Clinical Pharmacology For Anesthetists

CLINICAL PHARMACOLOGY
FOR ANESTHETISTS
By Mengesha A.
Clinical/Theoretical Instructor
Prepared by Mengesha Abate

1.. Drug: any chemical that can affect living processes
2. Pharmacology: the study of drugs and their
interactions with living systems
 Physical and chemical properties
 Biochemical and physiological effects
 Knowledge of the history, source, and use of drugs
 Absorption, distribution, metabolism and excretion
3. Clinical Pharmacology: study of drugs in humans
(patient and volunteers)
4. Therapeutics: use of drugs to diagnose, prevent and
treat illness

Drug Naming
Chemical Name - describe chemical structure (rarely
seen in medical literature)
Code Name - short letter-number combination used
for experimental drugs
Generic Name - a name assigned to drug that can be
used by anyone (not proprietary)
Trade Name - Proprietary name given to the drug by
the manufacturer

The study and evaluation of the effects of drugs in
humans.
1. Relating to the bedside treatment of a patient or to
the course of the disease.
2. Relating to the observed symptoms and
course of a disease.
Medication : Medication A substance administered for
the diagnosis, treatment, relief or prevention of
disease.

Overview
of CLINICAL PHARMACOLOGY
Pharmaceutics
Pharmacokinetics
Pharmacodynamics

Pharmaceutics
Different dosage forms have different pharmaceutical
properties.
Drug absorption of various preparations
Liquids Fastest
Powders
Tablets 
Enteric-coated tablets Slowest

Pharmacokinetics
Absorption
Bioavailability
First Pass Effect
Distribution
Metabolism
Excretion

Pharmacokinetics Cont’d

Pharmacodynamics
Onset, Peak, & Duration
Agonists & Antagonists
An agonist causes a particular effect by binding to the
correct “receptor”

Factors that determine the intensity of drug response

The Ideal Analgesic/Anesthesia
Safe with few side effects- Safe even at high
concentrations and for long periods of
administration
 Effective and rapid acting
 Easy to administer, store, and carry
 Not easily abused
 Selectivity:One that elicits only the response for which it
is given
Selective for specific reaction with no side effects

Additional Properties of Ideal Drug
 1. Reversible action
Effects be reversible
Example: General Anesthetic;
2. Predictability
Know how patient will respond
 3. Ease of Administration
Number of doses should be low and easy to administer
 decrease errors
 Diabetic patient: Multiple daily injection of insulin

Additional Properties of Ideal Drug (Continued)
 4. Freedom from drug interactions
 Should not augment or decrease action of other drugs or have adverse
combined effects
 5. Low Cost
 6.Chemical Stability
 7. Possession of a simple generic name

Easy to remember and pronounce

no drug is ideal
Because no drug is ideal…….
No medications are ideal
No drug is safe
All drugs produce side effects
Drug responses may be difficult to predict
Drugs may be expensive
Drugs may be hard to administer
All members of health care team must exercise
care to promote therapeutic effects and minimize
drug induced side efects
Dilemma of analgesia/Anesthesia
 Which agent/technique should I use?

What is the risk-benefit ratio?
 How much should I administer?
 When is analgesia/ Anesthesia required?

ANESTHESIA DEFINITION
Anesthesia: Loss of feeling or awareness.
 A general anesthetic puts the person to sleep.
 A local anesthetic causes loss of feeling in a part of
the body such as a tooth or an area of skin without
affecting consciousness.
Regional anesthesia numbs a larger part of the body
such as a leg or arm, also without affecting
consciousness.

Mechanism of Action O GA
UNKNOWN!!
Most Recent Studies:
General Anesthetics acts on the CNS by modifying the
electrical activity of neurons at a molecular level by
modifying functions of ION CHANNELS.
This may occur by anesthetic molecules binding directly
to ion channels or by their disrupting the functions of
molecules that maintain ion channels

Def cont’d
The term "conduction anesthesia" encompasses both local
and regional anesthetic techniques.
 Many surgical procedures can be done with conduction
anesthesia without significant pain.
In some situations, such as a C-section, conduction
anesthesia could be administered.

Thank you Anesthesia

General Anesthetics divided into 2 classes
Inhalation Anesthetics
 Gasses or Vapors
 Usually Halogenated
Intravenous Anesthetics
 Injections
 Anesthetics or induction agents

INTRODUCTION
Anesthesia is essential for the practice of
surgery.
 It is a great responsibility that we are
taken as anesthesia providers.
Patients undergoing surgery put their lives in our hands.
It is our duty:-
To protect the patient,
To give the patient our full attention, and
To administer the safest anesthetic possible .

Each of us must be vigilant to our pts care
Clinical pharmacology for anesthetists is both a basic
and an applied science.
The anesthetists are primarily concerned with the
applied aspects since it is the backbone of all courses
especially in anesthesia practice.

Goals For Anesthesia
Amnesia
unconsciousness
Analgesia
Muscle relaxation
Suppression of reflex activity
.

AMNESIA
ANALGESIA
Obtundention of refle
Anesthesia
xes
MUSCLE
RELAXATION
Anesthesia

History of Anesthesia
Ether synthesized in 1540 by Cordus
Ether publicized as anesthetic in 1846 by Dr. William
Morton
Chloroform used as anesthetic in 1853 by Dr. John
Snow
Thiopental first used in 1934
Curare first used in 1942 - opened the “Age of
Anesthesia”

Robert Hinckley's (1880’s)
"The First Operation with Ether"

Hx. of Anesthesia Cont’d…

Historical Awareness
Chloroform – one of the earliest anesthetic agents –
discontinued early 1900’s because of liver toxicity

Chloroform (CHCl3)
Cl
H C Cl
Cl
An early anesthetic agent.

Caused liver damage.
Mechanism of anaesthesia:-
The precise mechanism is unknown, but
theories as follows.
 Ascending reticular activating system is thought to
be the most likely site.

Stages Of Anesthesia
• The classic description of anaesthetic

stages was done by Guedel in 1937 in
unpremedicated patients, breathing
diethyl ether in air.
• Stage 1 - narcosis, analgesia
• Stage 2 - delirium, excitement

Stage of Anesthesia cont’d
• Stage 3 - surgical stage
• Plane 1 - loss of pain response
• Plane 2 - surgical plane
• Plane 3 - beginning of respiratory
paralysis/pupil dilation
• Plane 4 –cyanosis, non-responsive
pupils
• Stage 4 - paralysis of brain respiratory
centers

Stage of Anesthesia Cont…

• The study and evaluation of the effects of drugs .
1. Relating to the bedside treatment of a patient or to the
course of the disease.
2. Relating to the observed symptoms and
course of a disease.
• Medication : A substance administered for the diagnosis,
treatment, relief or prevention of disease.

Mechanism of drug action
The fundamental mechanism of drug actions
can be distinguished into four categories.
Physical action - by Osmotic activity (e.g.
mgSO4, manitol)
Chemical action - The drug reacts extracellularly
according to simple chemical equation e.g. antacids-
ALOH3 neutralizes gastric HCL.

Drug Mechanism Cont’d
Through enzymes - Stimulation
- inhibition
Through receptors - Two terms are important in relation to
drug / ligand
affinity - the ability to combine with the receptor
efficacy or intrinsic activity. The ability to produce a
response
Agonist - is an agent which has both affinity and intrinsic
activity

 Antagonist - has only affinity & no intrinsic activity -
i.e. it can only combine
Receptor Natural ligand Agonist Effect
B- Adrenaline Sulbutamol Bronchodiltation

adrenorece
ptor
Opiate Endorphins/ Morphine Analgesia

receptor Enkephalins

Receptors
Agonist
R1 R2
 Antagonist
Receptors: are specific proteins that interact selectively

with drugs.
Receptors :are believed to exist into interchangeable
states. R1 & R2. The agonist binds preferentially to R1 &
only this state the response while antagonist binds to R2
and no response results
Antagonist - agent binds to the receptor, but
unable to stimulate it.
 Pure antagonists - have no intrinsic activity
but only affinity) e.g. Naloxone is the
opioid pure antagonist. It occupies the
opiate receptor, produces no effect and
prevents the pharmacological actions of
the opioid agonist, morphine.

Drug antagonism:- When one drug opposes
the action of the other
I. Competitive antagonism - commonest type
II. Physiological antagonism:- opposing actions
are produced by binding at different
receptors.

Drug Interaction:
• Metabolic drug interactions:
Enzyme induction - drug A induces the body to
produce more of an enzyme which
metabolises drug B.
Enzyme inhibition - drug A inhibits the production of the
enzyme metabolising drug B

Competitive antagonists used in anaesthetic practice
Drugs Endogenous cpd
antagonised
 Atropine
 Hyocine - Ach at muscarinic
 Glycopyrrolate
 Pancuronium & D-tc - Ach at motor end plate
 Trimethaphane & D-tc - Ach at autonomic ganglia
 Naloxone - Endorphine
 Propranolol - Adrenaline & nore-adrenaline
 Metocloprimide & chlorpromazine - Dopamine


Drug interaction
Drug interaction can be defined as the
modifications of the effects of one drug by the
prior or concomitant of another drug

Drug interaction Cont’d
 Synergistic effect
Additive effect : 1 + 1 =2
Potentiation effect: 1 +1 > 2
Antagonism : 1-1 = 0

Drug interaction Cont’d
Pharmacokinetic interactions
 Absorption
 Distribution
 Biotransformation***
 Excretion
Pharmacodynamic interactions
 Receptor interaction
 Receptor sensitivity
 Neurotransmitter release/Drug transportation
 Electrolyte balance
Physiological interactions
Pharmaceutical interactions

Drug metabolism interaction
Enzyme inducers : increase metabolism of
concomitant drug therefore increase drug elimination
and decrease drug effect- Barbiturate, Phenytoin
Enzyme inhibitors : decresae metabolism of

concomitant drug therefore decrease
drug excretion and increase drug effect.-
Cimetidine,Diazepam
Pharmacodynam. interaction
 Receptor interaction
Competitive
Non-competitive
 Sensitivity of receptor
Number of receptor
Affinity of receptor
Alter neurotransmitter release /drug transportation
Alter water/electrolyte balance

Drug Interaction
Pharmaceutical interactions
 Outside the body, e.g. precipitation of
thiopentone/ suxamethonium mixture
Pharmacokinetics:- absorption, distribtion,
metabolism & excretion.
Absorption - is the movement of the drug from its site of
administration into the circulation.

Drug Interaction Cont’d
 The rate of absorption depends on the following
factors
Route of administration
Disease states affecting absorptive processes
Area of absorbing surface - larger its area is, faster
Vascularity of the absorbing surface

Distribution:- Once the drug has gained access to the
blood stream, it gets distributed to other tissues.
 The factors which influence drug distribution
are:-
Plasma protein binding
Rate of blood flow in various organs
Cellular binding
Concentration in fatty tissues
Blood-brain barrier

Plasma Protein Binding:- Most drugs in vascular
compartment bind reversibly to macromolecules in the
plasma
 Plasma protein binding
Drug binding (%) Plasma Protein
Diazepam, warfarin 95-99
Phenylbutazone, 98
Lignocaine 50

Pharmacodynamic interactions
Example: decreased requirement for anaesthetic agents
when opioids and
other sedatives are used.
 Sensitization of the myocardium to catecholamines

by halothane.


Interactions in GIT Absorption
Interactions at the receptor sites:-
 Interactions due to accelerated metabolism:-
Interactions due to inhibition of metabolism:-
Interactions due to protein binding

others hypertension large quantities
of
norepinephrine
Pethidine MAOI Hypertension, Unknown

stroke fever release of
convulsion norepinephrine
Barbiturates Inducing drugs Resistant to Induction of

such as CNS microsomal
phenytoin depressant enzymes of the
liver

Succinylcholin Echothiopate Prolonged Inhibition of
Drug Tolerance and Dependence
Types of Drug Tolerance:

• Metabolic tolerance
• Cellular-adaptive or pharmacodynamic tolerance
Metabolic Tolerance: the body produces increasing
quantities of drug-metabolizing enzymes. Thus, the drug
is metabolized at a faster rate, and more drug must be
administered to maintain the same level of drug plasma
levels in the body

Drug Tolerance Cont’d
 Cellular-adaptive or Pharmacodynamic Tolerance:
Receptors in the brain adapt to the continued presence
of the drug, with neurons adapting to excess drug
either by reducing the number of receptors available to
the drug or by reducing their sensitivity to the drug.

Drug Tolerance
Tolerance; The requirement of progressively
higher doses to produce a similar response
is termed as tolerance.
 Decreased effectiveness (or potency) of a drug after
repeated administrations
Increase in the dose in order to obtain the same effect
after repeated administration

 Mechanisms of Tolerance
Pharmacokinetic Tolerance
Enzyme Induction Effects.
 Pharmacodynamic Tolerance
NT depletion

Learned Tolerance - Learned behaviors
compensate for drug effects.
 Reward and punishment

•
Tolerance - Learned behaviors
• Practice effects.
• Reward and punishment

Drug Metabolism
Biotransformation of drugs may lead to the followings
Inactivation - most drugs & their active metabilites are
rendered inactive or less active. E.g morphine
Active metabolite from an active drug-
E.g Diazepam
Activation of inactive drug. Few drugs are inactive-
levodopa
The primary site for drug metabolism is liver.

Metabolism Cont’d
Phase I reaction involves oxidation, reduction &
hydrolysis
Phase II reaction involves in the combination of
unchanged drugs or the products & phase I reaction
with other groups e.g. glucoronide, sulfate, acetate,
glycine or methyl groups). The most important of
these reactions is glucoronide conjugation.

Metabolism Cont’d
Oxidation & conjugation are the most commonly
employed processes of the two phases of reactions.
 The hydrolysis is a phase I reactions that is
responsible for the metabolism of esters and amides.
It may occur in the smooth endoplasmic reticulum of
the liver and be dependant on microsomal enzyme
systems.

Drug Excretion
Drugs & their metabolites are excreted via
Urine, Feces
Exhaled air
Milk & Sweat
 The kidney is responsible for excreting all water
soluble substances.

Administration of drugs cont’d
To be effective a drug must enter the body and get to
its site of action
Best method of administration of a drug depends on
the drug
Most drugs dissolved in a fluid (saline) or contained in
a mixture as in pills or capsules – type of substance is
important
Injections tend to be fast acting, oral administration is

usually slow acting and of a longer duration

Routes Of Drug Administration
 Routes of drug administration broadly divided into:
Local routes
Systemic routes


Routes of administration – Enteral routes
Administered through the alimentary canal – oral
or anal
Common problem is that absorption rate can be
highly variable
Absorption of orally administered drugs is greatly
influenced by stomach contents
Hostile acid environment can interfere with absorption
Other problems:
Some people cannot take pills
Uncooperative patients may refuse or “cheek” them

Enteral routes cont’d
ORAL
 Advantages:
Convenient (storage, portability)
economical
non-invasive, often safer route
requires no special training

ORAL
Disadvantages:
drug delivery is often erratic and incomplete
highly dependent upon patient compliance
many drugs degrade in GI environment
exposes drugs to first-pass effect

Routes of administration – Parenteral routes
Injection
Intravenous – drug injected into vein
Advantages – fastest way administer drug and
dosage most accurate
Disadvantages – chance of infection if
conditions not sterile and no way to retrieve the
drug in case of allergic or toxic reaction
Intramuscular – drug injected into muscle mass – slower but
safer
Subcutaneous – injection under the skin or implanted under
the skin

Cont…
Intravenous Route:
Merits
 the action is almost immediate and thus it is valuable
in emergencies
avoids destruction of drug by gastric and intestinal
juices,
large volume of solutions can be infused
 can be given in unconscious patients,
irritant drugs can be given by this route.

IV
Demerits:
Once injected, it cannot be retrieved,
if injected too fast, there may be a sudden fall in the
blood pressure
intense irritation of the vein wall may lead to
thrombophlebitis,
if the drug extravasates there may be necrosis
accidental entry of air into the vein
self-medication is difficult.

IM
Intramuscular Route:The drug is injected into
one of the large skeletal muscles.
 gluteus maximus Muscle
 Deltoid muscle
 rectus femoris muscle
The volume injected should not exceed 10 ml.
The drawbacks with this route are pain at the site of
injection, abscess formation

Routes of administration – Parenteral routes
Subcutaneous (SC): hypodermic into subcutaneous tissue, just
below the skin.
A small amount of drug (2 ml. or less) may be injected.
The advantages are the route is reliable and self administration is
possible e.g. insulin. epinephrine (or adrenaline)
for emergency asthmatic attacks or allergic reactions
Normally given with the syringe held at a 45-degree angle

Intradermal (ID): is the administrating of a drug into the
dermal layer of the skin just beneath the epidermis, usually
small amount of liquid is used for example 0.1ml.
Advantage: absorption is slow (this advantage test for allergy).

Sc cont’d

– Parenteral routes cont’d

Routes of administration cont’d
Pulmonary routes – inhalation into the lungs
1.gaseous and volatile agents and aerosols
-rapid onset of action due to rapid access to
circulation
a. large surface area
b..high blood flow
Topical routes – placing drug on the surface

usually a surface with a mucous membrane

Drug Adm. Cont’d
Topical
 Mucosal membranes (eye drops,nasal, etc.)
 Skin- rubbing in of oil or ointment (local
action

Sublingual/Buccal
 Advantages:
rapid onset
avoids first-pass effect
ability to swallow is not required
 Disadvantages:
few drugs adequately absorbed
patients must avoid swallowing

Rectal
 Advantages:
can be used when patients cannot take oral meds- .
unconscious
good option in pediatric population
 may avoid first-pass metabolism
 if patient is nauseous or vomiting

Drug Administration Cont’d
• 5 Rights
• Right Patient
• Right Drug
• Right Route
• Right Time
• Right Dose

Weights and Measures
Metric system - The simplest and most exact system of
measurement.
Apothecary system
Common Household system

Weights and Measures Cont’d
Metric system
Basic Units
Meter (m)
Gram (g, Gm)
Liter (L, l)

Apothecary
Weight
(1.0 grain = 60 mg)
Volume
1 dram = 60 grains (= 4 ml)
(1 ounce = 30 ml)

Household
Tablespoon (T, tbs)

1 T = 15 ml
Teaspoon (t, tsp)
1 t = 5 ml
Drop (gtt)
60 gtts = 1 tsp

Drug Administration Cont’d
Intradermal injection:- A bleb is raised in the skin
by injecting the drug e.g. BCG vaccination.
Intra-arterial :-The drug is injected directly into the
artery. This route is dangerous and has specific
indications for diagnosis and treatment.
Intrathecal :-Injection of the drug into the
subarachnoid space of the spinal cord.

Basic Principles of drug calculation
The dose is the amount of drug taken at any

one time. This can be expressed as the
weight of drug (e.g. 250 mg), volume of
drug solution (e.g. 10 mL, 2 drop

Drug calculation Cont’d
Drug mass units
gram, milligram: microgram
1 gram = 1000 mg = 1000,000 microgram
Solution units = Liter; milliliter
1 liter = 1000 ml.
1 ml = 15 gtts in a normal IV infusion
1 ml = 60 microdrops in a paediatric microdrop IV
giving set

Metric conversions by moving
decimals
Remember:
1000mg = 1 gm = 1000ug = 1mg
To convert grams “large” to milligrams ”small,
multiply by 1000 or move the decimal point 3 places
to the right.
 Example: 5gm = 5.000 mg
0.2g = 200 mg

decimals
To convert milligrams “small” to grams “large”, divide
by 1000 or move the decimal point 3 places to the left.
Example: 250mg = 0.25g

20 mg = 0.02g

decimals
To convert milligrams “large” to micrograms “small”,
multiply by 1000 or move the decimal point 3 places
to the right.
 Example : 5mg = 5000ug

0.8mg = 800ug
0.05mg = 50ug

decimals
To convert micrograms “small” to milligrams “large”,
divide by 1000 or move the decimal point 3 places to
the left.
Example : 2500ug = 2.5mg

400ug = 0.4 mg
10ug = 0.01 mg

Percentages: to find the amount of mg in each ml. of
solution multiply %
strength by 10:
D = Desired strength of the drug
H = Strength of the drug available
q = Quantity of the drug (stock)
Q = Quantity of the solution to be made


Milliequivalent Measures (mEq)
mEq : represents the number of grams of solute
dissolved in a milliliter of solution.
mEq/L =mg % of a substance x valency x 10

Atomic wt. or MW

Questions
1. Prepare 0.9 % normal Saline solution from 100ml. of
5 % Nacl solution
2. Prepare 1:10,000 from adrenaline ampule


Percentages:
 To find the number of mg. in each ml. of a solution
multiply the % strength by 10;
e.g. o.1 % x 10 = 1 mg/ml.


1 ml. 10 ml. 100 ml. 1000
ml.
0.5 %
1%
2%

. Ratios:
 1:1000 is the same as a 0.1 % solution
1:1000 solution contains 1 mg. in 1 ml;
1:10,000 solution contains 0.1 mg. in 1 ml.


IV ANAESTHETIC AGENT
Objectives
1 Definition
2. Classification
3. Physical chemical properties
4. Pharmacokinetics
5. Pharmacodynamics
6. Dose and Administration
7. Indication, contraindication and precautions
8. Side Effects

Intravenous Anaesth etics

The first attempt at producing insensibility by means

of IV injection in 1656,
Injection of tincture of opium into the vein of a dog.
 It was not until the introduction of thiop. by Lundy
and Waters in 1934, that the intravenous method
began to achieve popularity.

Every IV anesthetic is very similar but also different

Properties of Ideal Intravenous
Anaesthetics
1. Rapid onset:- is achieved by an agent
which is mainly un-ionized at blood PH
2. Rapid recovery:- Early recovery of consciousness is produced
by rapid redistribution of the drug from brain into other well-
perfused tissues particularly muscles

Ideal Intravenous Anaesthetics
3. Analgesia at subanaesthetic
concentrations
4. Minimal CVS & respiratory depression
5. No emetic effects
6. No excitatory phenomena (e.g. coughing, hiccup, on
induction )
7. No emergence phenomena (e.g.nightmares)
8. No interaction with NMB drugs

Ideal Intravenous Anaesthetics
9. No interaction with NMB drugs
10. No pain on injection
11. Safe if injected inadvertently into an artery
12. No toxic effects on the other organs
13. No release of histamine
14. No hypersensitivity reaction
15. Long shelf-life

Pharmacokinetic of I.V. anaesthetic drugs
The anaesthetic effect is regulated by:
1. Protein binding:- Only unbound drug is
free to cross BBB.
Protein binding may be reduced by
displacement by other drugs
2. Extracellular PH of the drug :- only the non-ionized
fraction of the drug penetrates the lipid BBB.
3. The relative solubilities of the drug in lipid & water

4. Speed of injection :- Rapid I.V. administration results
in high initial concenterations of drug. This increases
speed of injection and also the extent of
cardiovascular and respiratory side effects.

N-ionized Ionized
Pharmacologic effect Active Inactive
Solubulity Lipid Water
Cross lipid barriers Yes No
Renal excretion No Yes
Hepatic metabolism Yes No


Uses of intravenous Anaesthetics
i. Induction of Anaesthesia - A single injection
to induce Anaesthesia
Ideally there should be an absence of pain on
injection and excitatory effects.
 Sleep should be produced in one arm -to-
brain circulation time.
ii. To supplement inhalation agents - used to supplement
low potency inhalational agents

Uses of intravenous Anaesthetics
iii. Total intravenous Anaesthesia (TIVA) - is
combined with a potent analgesics
iV. To produce sedation - in intensive care
units, regional Anaesthesia.
V. To control convulsions

Intravenous Anaesthetics Cont’d
Advantages
Induction is both rapid and pleasant
The procedure is extremely simple.
There is no problems regarding flammability of agents
Disadvantage
Irritant if injected extravascularly or intra-arterally.
Once the agent has entered the circulation, no means of
reducing the plasma level.

Vasomotor and respiratory center depression
The rapid loss consciousness is associated with the
rapid loss laryngeal and pharyngeal reflexes and
reduction in LEST - passive regurgitation.
Transmission of disease-HIV-AIDS


Parenteral anesthetics (IV):
These are used for induction of anesthesia.
Rapid onset of action.
Recovery is mainly by redistribution.
Also reduce the amount of inhalation anesthetic for
maintenance.
E.g., includes thiopental, midazolam propofol,
etomidate, ketamine

BARBITURATES

The barbiturates were first synthesized in the late 19th

century and introduced into medicine as hypnotics.
Classification:- classified according to the duration of
action (long, intermediate, short & ultra short acting).
Barbiturates are organic compounds derived from
barbituric acid. Barbituric acid is
 (A combination of urea & malonic acid)

BARBITURATES Cont’d

Barbiturates retaining an oxygen atom on the number
2 carbon of the barbituric acid ring are designated as
oxybarbiturates.
Replacement of this O2 atom with a sulfur atom results
in thiobarbiturates which are more lipid soluble than
oxybarbiturates.

R1 R2 R3 X
Thiopental Ethyl 1 methyl H S
butyl
Thiamylal Allyl 1 methyl H S

butyl
Methohexital Allyl 1 methyl 2 CH3 O

pentnyl

Mechanism of action
 Barbiturates depress polysynaptic responses in the
CNS, by means of pre-synaptic effects, to decrease
release of neurotransmitters such as acetylcholine.
produces hypnosis (sedation) with amnesia

 Metabolism
Oxybarbiturates are metabolized only in hepatocytes.
Thiobarbiturates also undergo breakdown to a small
extent in extra hepatic sites.
Side chain oxidation at the number 5 carbon atom of
the benzene ring.
This oxidation occurs primarily in the endoplasmic
reteculum of hepatocytes.

Barbiturate Addiction:- produces addiction.
Potentially life threatening include; anxiety,
restlessness, tremors, weakness, hyperreflexia,
insomnia, N & V, tachycardia, diaphoresis and
orthostatic hypotension.
The most serious problem associated with barbiturates
withdrawal is the occurance of grandmal seizure.

 Enzyme Induction
Activates the production enzymes which metabolize
barbiturate.
 Cross tolerance is found between barbiturates & ethyl
alcohol
Induce the enzyme system which producers porphyrin

Barbiturate poisoning:
Dangerous to the CNS & CVS.
patient becomes comatose & the respiration is affected
B/P falls owing to depression of cardiac contractility.

Treatment of Barbiturate poisoning
A. Emergency measures
i. Maintain adequate airway. Suctioning
the trachea.
ii. Maintain adequate O2 intake & CO2
removal if respiration is depressed
iii. Maintain blood pressure
iv. Induce emesis immediatey & follow
gastric lavage. If patient is depressed, intubate.

B. Antidote - No specific antidote is known
C. General measures: check & record the rate
& quality of the pulse, B/P,
colour of the skin (cyanosis)
 reaction of the pupil, respiration rate, temperature,
reflexes (corneal, papillary,
 response to painful stimuli.
Elevate the patient head (15 degrees) to reduce the
possibility of cerebral edema.


BARBITURATE POISONING
Cont’d
Endotracheal suction should be done hourly
Assess urine out put.
 administer IV fluids at 37 0C
Treat hypothermia
Treat aspiration pneumonia with specific
chemotherapy

THIOPENTONE
Thiopentone :- is a yellow hygroscopic powder with a
bitter taste
It is dissolved to produce a 2.5% sol. With a PH of
10.5 – 11.
Its high alkalinity makes it irritant to tissues – necrosis.
The Necrotisting action increases as the conc.
About 70% of Adm. Dose – bound to plasma protein

THIOPENTONE
The Ultra – short acting thiop is not due to rate of
metab.
( Metab. 10-15% per hr.) degraded in the liver
prolonged effect in liver disease.
 Activates the Production of enzymes which
metabolise Barb
distributed following a single IV injection into
vessel rich group.

THIOPENTONE
The maximum up take by fat does not occur until one
hour after uptake by muscles has ceased

uptake , distribution& elimination of thiopentone

Thiopentone
As with all lipid soluble anesthetic drugs, the
short duration of action of thiopentone is
almost entirely due to its redistribution away
from central circulation towards muscle and
fat tissue

Mechanism of action
Involves:
1. Enhancement of inhibitory neurotransmission by
GABAA receptor complex
2. Inhibition of excitatory transmission

How does Thiopentone work?
1. Activation of GABAA receptor complex
2. Enhancement of GABA-mediated Cl currents –
leading to hyperpolarization of neurons and reduced
excitability

THIOPENTONE
 Factors affecting the distribution of thiopentone
 Hypovolemia
Obesity
Acidosis
Hypoalbuminemia
Anxiety

THIOPENTONE
 Factors which  Protein binding of thiop
 Uremia.
Certain drugs
Hypovolemia – low plasma protein
Acidosis.

pharmacodynamics
CNS: barbiturates interact with chloride ion

channels by altering the duration they spend in an open
state
-this facilitates inhibitory neurotrasmitters such as
gama amino butyric acid(GABA)
-thiopental will decrease both cerebral electrical &

metabolic activity
So it can be used to stop seizures activity in
emergency situations

pharmacodynamics
Cont’d
CNS: Elevated ICP can quickly be reduced by

thiopental but the improvement of ICP requires
high dose of thiopental to be maintained
The reduction of ICP is due to cerebral
vasoconstriction, reduced cerb. Metabolism
&oxygen requirments associated with
dec.cerebral blood volume
-theopental has an an anti-analgesic effect,
since low dose may decrease pain threshold
Pharmacodynamics
Cont’d
CVS:-thiopental causes a dose related

depression of myocardial function as
measured by CO,SV, and blood pressure
-venous tone decreases (decreased preload)
And contributes to the increase in HR and
decrease in BP/reflex taccardia
-

Pharmacodynamics Cont’d
Respiratory:-induction of anesthesia with thiopental
may be associated with 2 or 3 large breaths followed
by apnea for less than 1min
-there is dose related depression of the respiratory
response to hypercarbia and hypoxia
-laryngospasm and bronchoconstriction may be

associated with light levels of thiopental and with
airway manipulation or intubation
-FRC is reduced by 20% with induction of anasthesia

GI: enzyme induction may occur with prolonged
high dose therapy
 Hypoalbuminemia will result in an increase in
unbound (free) thiopental and an increase in the
potency of thiopental
GU/pregnancy/fetus:
- Thiopental has little or no effect on the kidneys or
gravid uterus.

THIOPENTONE
 Pharmacodynamics
Skeletal muscle- initial redistribution
 Fat- rises 30 minutes after injection.
calculated according to lean body mass
Larynx:- Brewer - Luckhardit reflex
Bronchus:-Bronchoconstriction, brochospasm &
bronchoconsecretion

Skeletal muscle:- poor muscle relaxation
Hepato-renal function:-modest reduction in
renal blood flow & GRF
Eye:- IOP is reduced
Placenta:-crosses the placenta readily
Dosage & administeration:-administered IV as
2.5 % solution. Initial dose of 3 - 5 mg/ kg

Side effects of Thiop
1- hypotension :if thiopental is administered to
hypovolemic, shocked or previously hypertensive pt
2- respiratory depression :when excessive doses are
used
3- tissue necrosis : following venous infusion
4- laryngeal spasm
5- bronchospasm :unusual but may be precipitated in
asthmatics pts
6- allergic reaction : from cutaneous rashes to severe
anaphylactic shock with cvs collapse

Thiopentone- Indications
1- induction of anesthesia
2- maintenance of anesthesia for

short procedures
3- control of convulsive states
4- for supplement of regional

anesthesia or low potency
anesthesia

Complications of thiopentone
Skin sloughing
 Neuritis
 phlebitis
 arterial spasm
 precipitation of solid crystals of thiopentone
block, small arteries.


Arterial Injection As a Complication
Rarely, intra-arterial injection can occur.
The consequences of accidental arterial injection
may be severe.
The degree of injury is related to the
concentration of the drug.
Treatment consists of
1. dilution of the drug by the administration of
saline into the artery,
2. heparinization to prevent thrombosis, and
3. brachial plexus block.
Complications of thiopentone Cont,d
 Symptoms and signs of intra-arterial injection
The patient will feel intense pain.
The hand will be very pale or white.
The hand will be cold (arterial spasm).
The hand will be oedematous.
The pulse may be absent.

Treatment Of Thiopentone
Intra-arterial Injection
Leave the needle in the artery

Flush with N/S
inject lignocaine(10mls of 1%) into the artery.
Sympathetic nerve block (stellate ganglion block) – to
block SNS nerve supply to arm)
Horners Syndrome can be manifested.
Full heparinisation may be required
Thrombectomy may be required
Occasionally amputation is needed

Advantages of thiop. anaesthesia
It is an ultra short acting barbiturates

. absence of stage of delirium
 rapid recovery (with correct dosage)
 relative freedom from vomiting
ability to increase depth rapidly
Consciousness regained within 5-10 mins by
redistribution to skeletal muscle.
It does not increase ICP.
 It can be used for rapid control of seizures

Disadvantages Of Thiop
 Resp. depression
 Tendency to laryngeal spasm
 Circulatory depression in poor risk-patients
Laryngospasm: This may result from
a. direct stimulation by airway, laryngoscopy
b. stimulation some remote area

Pharmacokinetics
1. Mostly Hepatic metabolism by:
a) Oxidation
b) Desulfuration
c) Destuction of barbituric acid ring
2. Inactive metabolites excreted by kidney
3. Conjugated excreted in bile

Pharmacokinetics Cont’d
Chronic administration of barbiturates
Or
Other drugs that induce oxidative microsomal enzymes
(enzyme induction)
Enhances barbiturate metabolism

Contraindication Of Thiop
Absolute contraindications
1- airway obstruction
2- porphyria
3- previous hypersensitivity
4. Severe cardiovascular collapse or shock
5. Status Asthmatics
PRECUATIONS
1- CVS disease
2- severe hepatic disease

3- renal diseases
METHOHEXITONE
a methylated oxybarbiturate
used in 1 % solution: 1 to 2 mg/ kg/ IV
shorter elimination half time- 2- 4 hrs. while
thiop is 5- 12 hrs
Less imitating to tissues
 Cause less CVS depression
 Abnormal muscular movements with tremor
cause abnormal spike discharges in epileptic subjects

Propofol
Milk of Amnesia

Propofol
Propofol
Prepared by Mengesha Abateisa sweet drug in the OR, but
definitely not for home use.
Intravenous anesthetics Cont’d
 Propofol
This formulation supports bacterial growth and should be
used as soon as possible or within 6 hours of opening vial
Label syringe with expiration time and discard after 6
hours
appearance: milky white, slightly viscous
concentration= 1% or 10mg/mL; pH=7
properties: hypnosis, amnesia

Propofol (Diprivan):
Most commonly used IV anesthetic.
Unconsciousness in ~ 45 seconds and lasts ~15
minutes.
Anti-emetic in action.
Suited for day care surgery - residual impairment is less
marked.
sedation in the ICU
sedation for procedure under regional block

Pharmacodynamics Of Propofol
CNS effects
hypnosis, no analgesia
Decreased CBF & (CMRO2) (causing a decreased
ICP), similar to response caused by thiopental
Neuroprotective
Anti-convulsant

What is the effect on the CNS?
↓ CBF
↓ ICP and ↓ IOP
↓ CMRO2
But ↓ CBF and ↓ MAP can cause ↓↓ CPP

Neuroprotective for neurosurgical procedures

Pharmacody.. Of Propofol Cont’d
CV effects
compared with similar doses of other IV anesthetics, has the
most profound effect on blood pressure
depresses baroreceptor reflex, so only minimal if any
increase in HR (also contributing to low blood pressure)
profound vasodilation + direct myocardial depression
 both arterial and venous, causing drops in preload and afterload

Pharmacody.. Of Propofol Cont’
Respiratory effects
potent respiratory depressant, usually produces apnea with
induction dose
maintenance infusion will decrease MV by decrease in TV
(mostly) and RR
decreased ventilatory response to hypoxia and hypercapnia
great reduction in upper airway reflexes, more than with
thiopental
good for asthmatics and for insertion of LMA
can sometimes intubate without muscle relaxant
must be ready to “control the airway” once given even in
small doses
Propofol Cont’d
How To Use
Induction of anesthesia:
Dose = 2.5-3.5 mg/kg
reduce dose in elderly patients, hypovolemia, decreased
cardiac reserve, and when given with pre-medications
(benzo's or opioids)
maintenance of anesthesia
as part of a TIVA (along with opioids; or with nitrous oxide)
dose= 100-200 mcg/kg/min

Propofol Therapeutic Effect

Advantages of propofol
QUICK ONSET
QUICK OFFSET - quicker than thiopental, even if repeated
or continuous infusion
good for bronchospasm (vs. thiopental)
decreases ICP (neuroprotective)
decreased nausea and vomiting (vs. thiopental )
can be used as a maintenance anesthetic
no adrenal suppression (vs. etomidate)
can sometimes intubate without muscle relaxant
(thereby eliminating risks of SCh or NMB; no need to
“reverse”; patient may occasionally breathe
spontaneously
Termination of effect of propfol
Termination of effect is mainly caused by the
redistribution of propofol from the highly lipophilic
tissues (brain, spinal cord) to the inactive tissues like
the skeletal muscles and fat.

Disadvantages of propofol
pain on injection ** , up to 67% of patients
expensive
supports bacterial growth
decreases blood pressure (to a greater degree than
etomidate and thiopental)
Avoid with egg allergy
no analgesia (vs. ketamine)
+/- (depends on the situation) unlike volatile, does not
potentiate neuromuscular blockade

KETAMINE HYDROCHLORIDE(KETALAR)
 Ketamine, is primarily a non-competitive glutamate
NMDA receptor antagonist.
At low doses, the analgesia effects of ketamine are
mediated by antagonism on the NMDA receptors.

Pharmacodynamics
NMDA receptor antagonist
Reflexes are often preserved
Eyes open, pupils moderately dilated, nystagmic gaze,
lacrimation and salivation

Ketamine
It’s a dissociative anesthetic agent.
by dissociative we mean that the patient is

unconscious but appears awake and doesn’t feel
pain.
It has anesthetic and analgesic effect

KETAMINE Cont’d
 At high doses, ketamine has also been found to bind
to opioid mu receptors and sigma receptors.
This indicates that loss of consciousness at high doses
may be partially due to binding at the opioid mu and
sigma receptors.

KETAMINE Cont’d
hypnotic
Strong analgesic
amnesic
 Given by both IV 1 -2 mg/kg, IM 5-10mg/kg, IV drip
Available in different concentration.
Smooth induction but with emergence delirium
Unpleasant dreams (Hallucination) – upto 24 hrs .

Clinical Uses
1. Induction of anesthesia
2. Analgesia
3. Bronchodilator
4. Minimal resp depression

KETAMINE Cont’d
Ketamine :
• Produces - profound analgesia, immobility, amnesia
with light sleep.
• Acts by blocking NMDA receptors
• Heart rate and BP are elevated due to sympathetic
stimulation.
• Respiration is not depressed and reflexes are not
abolished.

KETAMINE Cont’d
 Emergence delirium, hallucinations and
involuntary movements occurs in 50% cases during
recovery.
It is useful for burn dressing and trauma surgery.
Dangerous for hypertensive and IHD.

KETAMINE Cont’d
Indications of Ketamine
As a sole agent for minor operation
As induction agent during G.A
When Maintenance of the B/P is important
- Shock,- poor risk Pt, - Elderly Pts.
For dressing of burns
For dealing for mass causalities

KETMINE
Indications Cont’d
1. sole anesthetic for diagnosis and surgical
procedures
2. to supplement regional or local anesthetic

techniques
4- for anesthetic induction in severe asthmatic pts.

Or patients with cardiovascular collapse requiring
emergency surgery

KETMINE Contraindications
1- lack of knowledge of the drug
2- lack of resuscitative equipment
3- inability to maintain a patent airways
4- allergy to ketamine
5- history of psychosis
6- Patients. For whom hypertention is hazardous

KETAMINE Cont’d
Ketamine IV drip
A continuous infusion of Ketamine once anaesthesia has
been induced.
500mg Ketamine added to 500ml of N/s

Administered at a rate of 1-2 ml/min
 ( Some may need as much as 4ml/min). 1gtt /
Kg/ min (60gtts / 60kg / 60 seconds)

KETMINE
Pharmacodynamics
CNS :
1. ketamine increases cerebral oxygen
consumption, cerebral blood flow, and
intracranial pressure
2- generalized increase in the muscle tone and
purposful movements.
3- Unpleasant dreams, hallucinations or frank delirium
(esp. females & large doze of ketamine).

KETMINE
Respiratory system:
It preserves laryngeal &pharyngeal airway
reflexes.
Ketamine is a potent bronchodilator.
FRC  unchaged.
Minute ventilation  unchanged.
Tidal volume  unchanged.
Ketamine causes increased secretions but
this can be limited by anti-cholinergic drugs.

KETMINE
CVS:
• It produces central sympathetic stimulation, which
increases:
1. arterial blood pressure, heart rate, and cardiac
output.
2. Pulmonary artery pressure.
3. Coronary blood flow.
4. Myocardail oxygen uptake.
It may cause myocardial depression if the
sympathetic nervous sys is exhausted or blocked.

GI: Minimal anorexia, nausea & vomiting.
GU: Placental transfer does occur, but neonatal

depression hasn’t been observed if the dose is
limited to < 1 mg/kg.
Muscle system: Generalized increase in skeletal
muscle tone.
Increases the effects of muscle relaxants.
Endocrine Sys: Increased sympathetic stimulation 
increased blood glucose, increased plasma cortisol,
increased heart rate.
KETAMINE-Contradication
 Absolute contraindications
Airway obstruction – inhalational gents should be
used for induction if airway obstruction is anticipated.
Raised ICP

KETMINE Contraindications
1- lack of knowledge of the drug
2- lack of resuscitative equipment
3- inability to maintain a patent airways
4- history of psychosis
5- cerebro-vascular disease
6- Patients. For whom hypertension is

hazardous
KETAMINE Cont’d
 Precautions
CVS - hypertersion, IHD or severe cardiac
decompensation
 - use of ergometrine with Ketamine is potentially
hazardous.
 Visceral stimulation - Ketamine suppresses poorly the
response to visceral stimulation
- Supplementation with opioids

KETAMINE Cont’d
Adverse effects
Emergence delirium, night mares
Hypertension & tachycardia
Prolonged recovery
Excessive salivation
Increase ICP

KETAMINEKetamine
Vs Thiopentone
THIOPENTONE
Analgesia
Resp.
Somatic – yes NO
Visceral – -↑ Broncho - Sec
minimal. -
-Bronchodilator spasm
-Minimal affected -
-Airway Constrict
maintained -Depressed
-Depressed R.c

Comparison b/t Ketamine Thiopentone
Ketamine - Thiopentone
CVS - Stimulated - ↑ B/p - Depressed - ↓ B/p

CNS- -↑ - ↓ CO
Protective CO - ↑ HR
Reflexes - ↑ - The Reverse of this
HR. - Obtunded
↑ CBF, ↑ Icp, ↑ O2
consumption
minimal

Skeletal Poor Fair
intravenous anesthetics Cont’d
ETOMIDATE:-
Hypnotic, but not analgesic properties, with minimal
cardiovascular effects
Concentration—0.2% (2mg/ml); pH=6.9
Properties—hypnosis
appearance—clear liquid

I
ETOMIDATE Cont’d
Pharmacokinetics
rapid onset
quick recovery due to redistribution to
inactive sites
metabolized by ester hydrolysis, excreted in urine and
bile
 usually not given as an infusion due to endocrine
response)

ETOMIDATE Cont’d
Pharmacodynamics
CNS
potent vasoconstrictor (decreased CBF, ICP, CMRO2)
spontaneous myoclonic activity (50% of patients)
CV
modest decrease in BP, minimal effect on HR and CO
Respiratory
less depression than thiopental/propofol

ETOMIDATE Cont’d
l
Endocrine
adrenocortical suppression by dose-dependent
inhibition of 11β-hydroxylase, an enzyme
needed to make cortisol
Effect lasts 4-8 hrs
not typically clinically relevant after one dose,
but be careful if patient is known to be septic
and with possible adrenal suppression.
Consider treating with steroids if unexplained
hypotension develops.
ETOMIDATE Cont’d
Induction of anesthesia
Dose=0.2-0.3 mg / kg IV
good for those patients with compromised myocardial

contractility (heart failure)

ETOMIDATE Cont’d
Advantages
minimal CV effect (vs. propofol and thiopental)
rapid onset
quick recovery (3-8 minutes

ETOMIDATE Cont’d
Disadvantages
adrenocortical suppression
no analgesia (vs. ketamine)
pain on injection
more PONV (vs. propofol and thiopental)
myoclonic movements during induction

IV Anesthetics
Anesthetic Duration Analgesia Muscle Others
I.V mins relaxation
Thiopental 5 - 10 --- --- Respiratory

depression
Propofol 5-10 --- --- Respiratory

depression
Ketamine 5-10
+++ --- Hallucinations
Intravenous anesthetics
Neuroleptanalgesia :
It is characterized by general quiescence, psychic
indifference and intense analgesia without total loss of
consciousness.
Combination of Fentanyl and Droperidol as Innovar

Neurolept analgesia Cont’d
Neurolept analgesia:- combined use of a neuroleptic
agent with potent analgesic usually fentanyl
- to produce sedation & analgesia
 Each milliter of this preparation contains Fentanyl 50
mic/gram and Droperidol 2.5 mg
Neurolept anaesthesia :- Nevolptic agent + opioids +
N2O + O2 + muscle relaxants

Neuroleptic Drugs (Butyrophenones)
They are powerful antiemetic drugs.
Produce dopaminergic blocking effects with
extraryramidal effect
Haloperidol – Long acting neurolept agent antipsychotic
Neuroleptic drugs – antiemetic, antihistaminic effects,
able to potentiate analgesics, sedative & GA

 Droperidol:- IM or IV use tranquilizer, used in
anaethesia
- Antipsychotic
- ant emetic
-reduce emergence reaction after
Ketamine
-has weakly blocking effect on alpha adrenergic
receptors

Benzodiazepines-Mode of action
1 – They inhibit the actions of glycine (by
increasing the conc. Of a glycine inhibitory
neurotransmitter) which will lead to antianxiety
and skeletal muscle relaxant effects.
2 – They facilitate the actions of the inhibitory
neurotransmitter GABA which results in the
sedative and anticonvulsant effects.
Benzodiazepines are highly lipid soluble.
They are highly protein bound (albumin).
They are metabolized by the liver through conjugation with
glucoronic acid and excreted by the kidneys.
BENZODIAZEPINES (BNZ)
Cont’d
Midazolam and diazepam
- Sedative – hypnotic
- anxiolytic
-Anticonvulsant
- Muscular relation
-Amensia

BNZ Cont’d

Midazolam vs diazepam
1- Midazolam is 2-3 times more potent than
diazepam:
2- The dose for IV conscious sedation: 0.5 – 3 mg
up to 0.1 mg/kg for midazolam, and 1-10 mg for
diazepam.
3- The dose for inducing anesthesia: 0.2 – 0.4
mg/kg for midazolam , and 0.15-1.5 mg/kg for
diazepam.
4- Midazolam has a more rapid onset, greater
amnestic effect, less postoperative sedative
effects
Prepared bythan diazepam
Mengesha Abate .
Midazolam vs diazepam cont’d
5- Pain on injection and subsequent thrombophlebitis is
less likely with midazolam (an emulsion of diazepam)
6- Midazolam is more costly than diazepam).
7- Midazolam’s duration of action is less than diazepam
8- Elimination half time for midazolam range from 1-4
hours, and for diazepam from 21-37 hours.
9- Midazolam is supplied as a clear liquid

GABA and the GABA Receptor
GABA is a neurotransmitter that has an inhibitory
effect on neurons.
When GABA attaches to its receptor on the
postsynaptic membrane, it allows Cl- ions to pass into
the neuron.
This hyperpolarizes the postsynaptic neuron to
inhibit transmission of an impulse.

BNZ Cont’d
Mechanism of action:-
Exert their antianxiety and skeletal muscle relaxing effects by
increasing the availability of glycine inhibitory
neurotransmitter
Sedative and anticonvulsant effects reflect the availability of
BZDs to facilitate action of inhibitory transmitter.
Occupation of BZD receptors by diazepam enhances the
affinity of GABA for its receptors, with resulting inhibition of
nerve conduction that manifests as a sedative effect.

BNZ Cont’d
Anaesthetic Uses
Premedication - diazepam, lorazepam
Sedation - diazepam, midazolam
Anticonvulsant - diazepam
Induction of anaesthesia - midazolam

BNZ Cont’d
Antagonists
Flumazenil – a specific BZD antagonist
has little intrinsic activity ( practically no
effect on normal subjects) but competes
with agonists
the CNS actions of BZDs antagonized within 2 min
following the intravenous administration of flumazenil
BZD overdose can be reversed by Physiostigmine –
nonspecific antagonist

BNZ Cont’d
Drug interactions
 Synergetic effect with alcohol and other CNS
depressant drugs
- Cimetidine - delays the hepatic clearance of BZDs.
Depression of ventilation & production of hypotension
less than barbiturates
Reduce CBF & CMRO2 .

BNZ Cont’d
CNS - ↓ cerebral metabolic 02 requirement.
- Depression – sedation
On large doses – Anaesthesia – Onset slow
In small doses - ↓ MAC value of inhalational
anaesthetics.
- Ameliorate unpleasant dreams ,following ketamine
-Muscular relaxation
-Amnesia

BNZ Cont’d
CVS - Large doses ↓CO & B/P
-Combined with opiate analgesics, diazepam &
midazolam safe in the MX of poor risk pts- Heart
surgery.
Resp. minimal depressant effects
Tolerance :- addiction Liability is Less.
* There is no evidence as causing enzyme
induction.


BNZ Cont’d
Clinical uses of BNZ
- pre- operative medication
- Iv sedation
- induction of anaesthesia
- maintenance of anaesthesia
- suppression of seizure activity

BNZ Cont’d
 Diazepam – available oral & intravenous forms
- The use of IV use ↓ed . because of the
advent of midazolam.
-Dilution with water causes cloudiness.
-IV or IM injection is painful & thrombophebitis
propylene glycol
-Can be minimized by dilution & use large veins

BNZ Cont’d
Diazepam Indication
- Premedication
- for induction of anaesthesia for poor risk.pts.
- sedation during regional anaesthesia
- to reduce hallucination after Ketamine &
control post-op restlessness.
-Anticonvulsants.
-For skeletal muscle relaxation.

BNZ Cont’d
Midazolam
– faster onset of action after IV adm
_water soluble– Its solubility is PH dependent
.When exposed to physiologic PH- ↑ lipid Solub.
Premedication – 0.07 – 0.1mg/kg IM 30-60 min
preoperatvely
Induction: 1-2.5mg lv .0.02 – 0.1mg/kg/hr continuous
IV infusion.


BNZ Cont’d
 Midazolam
Conscious sedation
Minimally depressed level of consciousness
Independently and continuously maintain an airway and
adequate cardiorespiratory function.
Respond to tactile stimulation and/or verbal command.
Tolerate the unpleasant procedures.

Midazolam Cont’d
Rapid onset. (i.v. 1-3 min, i.m. 5 min)
Shorter duration.
No pain on injection
Existence of antagonist- Flumazenil
Anxiolytic
Muscle relaxant
Anticonvulsant
Sedative
Hypnotic
Amnesia

Side effects of midazolam
Respiratory depression * Short-lived.
* Respond to verbal stimulation
Rare:
* Hiccups.
* Cough.
* Nausea/Vomiting.

Drug interaction of midazolam
• Drugs that inhibit the metabolism of midazolam
* Cimetidine
* Ranitidine
* Omeprazole
* Oral contraceptives
• Drug that enhance the metabolism of midazolam
* Rifampin

OPIOID ANALGESICS
Opium derived from dried juice of poppy

plant which contains over 20 plant
alkaloids. including morphine
OPIOID ANALGESICS
 History of Opioids
Opium is extracted from poppy seeds (Papaver
somniforum)
Used for thousands of years to produce:
Euphoria
Analgesia
Sedation
Relief from diarrhea
Cough suppression

History of opioids cont’d
Used medicinally and recreationally from early Greek
and Roman times
Opium combined with alcohol were used to treat
almost all known diseases
Morphine was isolated from opium in the early 1800’s
and since then has been the most effective treatment
for severe pain

History of opioids cont’d
Invention of the hypodermic needle in 1856 produced
drug abusers who self administered opioids by
injection
Controlling the widespread use of opioids has been
unsuccessful because of the euphoria, tolerance and
physiological dependence that opioids produce

Terminology
“opium” is a Greek word meaning “juice,” or the
exudate from the poppy
“opiate” is a drug extracted from the exudate of the
poppy
“opioid” is a natural or synthetic drug that binds to
opioid receptors producing agonist effects

Terminology cont’d
Pure Agonist: has affinity for binding plus efficacy
Pure Antagonist: has affinity for binding but no efficacy;
blocks action of endogenous and exogenous ligands
Mixed Agonist-Antagonist: produces an agonist effect at
one receptor and an antagonist effect at another
Partial Agonist: has affinity for binding but low efficacy

opioids cont’d
Natural opioids occur in 2 places:
1) In the juice of the opium poppy (morphine and
codeine)
2) As endogenous endorphins
All other opioids are prepared from either morphine
(semisynthetic opioids such as heroin) or they are
synthesized from precursor compounds (synthetic opioids
such as fentanyl)

What are Opioids?
Opioids are a class of drugs that act primarily on the
body’s opioid receptors.
Opioids are often referred to as narcotics.
They act by blocking μ, κ, sigma and possibly delta
receptor classes.
Most opioid receptors are found in the central nervous
system and in the gastrointestinal tract.
Opioids are used primarily for their analgesic effects
but also for their cough suppressant properties.

CLASSIFICATION OF OPIOIDS
Strong Intermediate Naturally Occurring
Morphine Pethidine Morphine
Fentanyl Pentazocine Codeine

Sufentanil Butorphanol Papavarine
 Alfentanil Nalbuphine
 Remifentanil

Pharmacologic Effects (Opioids)
Acute Effects
1. Analgesia
2. Sedation and euphoria
3. Respiratory depression
4. Antitussive actions
5. N & V
6. Gastrointestinal effects
7. Smooth muscle
8. Miosis

Pharmacologic Effects (Opioids
Chronic Effects
1.Tolerance - marked tolerance develops to the
above acute pharmacologic effects with the
exception of miosis and constipation.There is
cross tolerance between different opioids
2. Dependence - psychologic and physical
dependence


Clinical Uses of opioids
1. Analgesia - moderate to severe pain relief
parenterally, epidural (Morphine, Fentanyl)
2. Anti-tussive – e. g, codeine
3. Rx. of diarrhea
4. Mx. of acute pulmonary edema
5. Anesthesia - used as adjunctive agents
Opioid dependence- methadone is one of the longer
acting opioids is used in the management of opioid
withdrawal states

Toxicity of opioids
1. Overdose - coma with marked respiratory depression

and fatal if untreated
2. Drug interactions - concomitant use of
certain opioids (e.g. meperidine) with MAO
inhibitors


opioids cont’d
Pharmacological Effects
 Sedation and anxiolysis
 Drowsiness and lethargy
 Apathy
 Cognitive impairment
 Sense of tranquility
 Depression of respiration
 Main cause of death from opioid overdose
 Combination of opioids and alcohol is especially dangerous
 Cough suppression
 Opioids suppress the “cough center” in the brain
 Pupillary constriction
 pupillary constriction in the presence of analgesics is characteristic of
opioid use

Pharmacological effects of opioids cont’d.
 Nausea and vomiting
 Stimulation of receptors in an area of the medulla called the
chemoreceptor trigger zone causes nausea and vomiting
 Unpleasant side effect, but not life threatening
 Gastrointestinal symptoms
 Opioids relieve diarrhea as a result of their direct actions on the
intestines
 Other effects
 Opioids can release histamines causing itching or more severe
allergic reactions including bronchoconstriction
 Opioids can affect white blood cell function and immune function

Mechanism of action of opioids
Activation of peripheral nociceptive fibers causes
release of substance P and other pain-signaling
neurotransmitters from nerve terminals in the dorsal
horn of the spinal cord
Release of pain-signaling neurotransmitters is

regulated by endogenous endorphins or by exogenous
opioid agonists by acting presynaptically to inhibit
substance P release, causing analgesia

Three Opioid Receptors
Mu
Kappa
Delta

Mu-Receptor: Two Types
Mu-2
Mu-1
Located throughout
CNS
Located outside
Responsible for
spinal cord
Responsible for respiratory
central interpretation depression, spinal
of pain analgesia, physical
dependence, and
euphoria

Mu and Kappa Receptor Activation
Response Mu-1 Mu-2 Kappa
Analgesia
Respiratory
Depression
Euphoria
Dysphoria
Decrease GI
motility
Mu and Kappa Receptors
DRUGS MU KAPPA
Pure Agonists Agonist Agonist
Agonist- Antagonist Agonist

Antagonist
Pure Antagonist Antagonist

Antagonists
Agonists cont’d
*Morphine
*Heroin
*Hydromorphone
*Fentanyl
*Codeine

Antagonists
Naloxone
Naltrexone
EFFECTS
 *Reverses the effects of opiate agonists.
 * Reverses hypotension and cardiovascular
instability
 *inhibits Mu, Delta, and Kappa receptors.

Antagonists Cont..
Naloxone:- Competitive antagonist on all types of opioid
receptors
 Devoids agonist activity
Used:- Treat opioid induced depression &
ventilation in the newborn due to maternal
administeration of drug
 facilitate treatment of deliberate opioid overdose
 detect suspected physical dependence.
dose 0.4 mg IV or IM

Opioid poisoning
Opioid poisoning: N & V, respiratory depression,
hypotension, pinpoint, pupils & coma
. Mx. - supportive- includes gastric lavage, IV
fluids, O2 therapy & IPPV
Naloxone 0.4 - 2.0 mg. IV. repeatedly after
2 – 3 min. to a total of 10 mg.
 Side effects :- Reversal of analgesia.


Antagonists Cont..
Naltrexone is an opioid receptor antagonist used
primarily in the management of alcohol
dependence and opioid dependence.. It should not
be confused with naloxone, which is used in
emergency cases of overdose rather than for
longer term dependence control

opioids cont’d
Morphine is a highly potent opiate analgesic drug and
is the principal active agent in opium and the
prototypical opiate.
Morphine acts directly on CNS to relieve pain.
Morphine is highly addictive when compared to other
substances, and tolerance and physical and
psychological dependences develop very rapidly.

Mechanism of Action
• It is a CNS depressant that acts on the opiate receptors in
the brain, providing both analgesia and sedation. It
increases peripheral venous capacitance and decreases
venous return. This effect is sometimes called a chemical
phlebotomy.
• decreases systemic vascular resistance

Morphine cont’d
Morphine:-is the principal drug (proto type), derived
from popy seeds. Isolated in 1803.
- The standard drug against which other opioids are
compared
Has depressant & stimulant action on CNS
- Depression of Respiratory center, cough reflex, pain
sensation,
 ACTH, metabolic rate, vasomotor center

Morphine cont’d
Stimulation of
 CTZ, parasympathetic nucleus of the 3rd
cranial nerve causing- miosis
 vassopressin release
 Muscle rigidity following high doses –
thought to be caused by central
interference with motor function
 May cause addiction

Administration of Morphine
Parenterally as subcutaneous, intravenous, or
epidural injections. When injected, particularly
intravenously, morphine produces an intense
contraction sensation in the muscles due to
histamine release and also produces a very
intense 'rush' which is mediated by several
different receptors in the CNS.

Pharmacodynamics of Morphine
CNS
Analgesia - strong analgesic - dull, poorly localized
pain relieved better
Sedation - Drowsiness, higher doses progressively
cause sleep & coma. It has anticonvulsant action -
Causes euphoria
Respiratory center:- depression, rate & VT depressed

Pharmacody.. of Morphine Con’t
Cough center:- depressed
Temperature regulating center - Depressed
hypothermia occurs in cold environment.
Vasomotor center:- depressed at higher doses &
contributes to fall in B/P
Edinger Westphal Nucleus stimulated – miosis CTZ -
Cemoreceptor Trigger Zone,
 N & V occurs


Pharmacody.. of Morphine Co
CVS: morphine causes vasodilation due to:
direct action, decreasing tone of blood vessels
histamine release
depression of vasomotor center
 There is a shift of blood from pulmonary to
systemic circuit due to greater vasodilation
in the latter.
 GIT - Constipation is a prominent feature -
. Decrease in all gastrointestinal secretions & addicts
remain chronically addicted

Side Effects of morhine
Other central nervous system side effects of morphine are
cough suppression, sedation, and dependence leading to
addiction.
Morphine also has an effect on the muscle of the bowel
and urinary tract, causing the sphincter to contract and
reduce the peristalsis (the wavelike movements of the
bowel muscle that propel its contents forwards). This
results in a delayed emptying of the stomach, constipa
tion, and may also lead to urinary retention.

Morphine dosage
Biotransformation - morphine is conjugated with
glucuronic acid in the liver.
Suggested dose 0.1 - 0.2 mg/kg IM.
2 to 3 mg/ epidural/ intrathecal
 Morphine is supplied in 10 mg injections. This may
be in a vial or pre-filled syringe.
Oral absorption is unreliable - first pass metabolism


Side Effects of morhine
Morphine can also cause histamine release, which
causes itching of the skin and nose and a mild flushing
of the skin.

Contraindications
Because of the hemodynamic effects descried earlier,
morphine should not be used in patients who are volume
depleted or severely hypotensive. Morphine should not
be administered to any patient with a history of
hypersensitivity to the drug or to patients with
undiagnosed head injury or abdominal pain.
Precautions: special considerations are involved in the
handling of the drug b/c of high tendency for addiction.

Precautions morphine cont.
Infants & elderly pts.
Patients with respiratory insufficiency
Bronchial asthma - precipitates an attack
Head injury
Hypotensive states & hypovolemia exaggerate
fall in B/P
Undiagnosed acute abdominal pain

Codeine:
Codeine:- Occurs naturally in opium
 It is less potent than morphine (1/10 as
analgesic)
 More selective cough suppressant
 Codeine has very low affinity for opioid
receptors
 Has good activity by oral route & can also
administered IM

Meperidine
Meperidine( pethidine): Synthetic analgesic drug
was synthesized as atropine substitute & has some
action like it.
It is the most popular narcotic analgesic used during
labour
The side effects can be categorized as maternal &
foctal effects.

Principal differences between morphine & pethidine
No Morphine Pethidine
1 Equipotent adult 10 mg. 100 mg.

dose
2 Cortical effects Sedation Sedation less marked
3 Pupillary effects Miosis Atropine-like effects
4 Smooth muscles Spasmogeni ceffect Less marked spasm

constipation constipation unlikely
5 CVS Bradycardia Slightly fall Significant fall in B/P,

in B/P
Prepared by Mengesha Abate tachycardia
Fentanyl
 First synthesized in Belgium in the 1950’s for
anesthesia
 Trade Name “Sublimaze”
 It is a potent synthetic narcotic with properties similar
to those of morphine
 Chemically unrelated to morphine, but 50 to 100 times
more potent
 Duration of action is considerably shorter than
morphine – from 30 to 60 minutes

Fentanyl Cont..
Fentanyl:- synthetic opioid. Analgesic potency 100
times that of morphine
 Single dose - rapid onset of action (within 30
seconds)
A medication that is easily dosed
1 microgram per kilogram
Almost exclusively used in anaesthesia alone as well
as in combination with droperidol

Fentanyl Considerations
 Parenteral dose may be given diluted or undiluted
 Administer IV over 1 to 2 minutes
 Protect from light
 Closely monitor vital signs
 Respiratory depression may out last the analgesic
effect
 Effects may be reversed by naloxon (Narcan®)

Fentanyl Adverse/Side Effects
 Sedation
 Euphoria Nausea
 Dizziness Vomiting
 Diaphoresis Laryngospasm
 Delirium Respiratory depression
 Hypotension
 Bradycardia

Opioids Cont
 Narcotics are indicated for relief of pain that can not
be relieved by non-narcotic analgesics
used for Rx of pain with limited life expectancy
 The administration of narcotics intrathecal or
epidural spaces for the relief of pain has recently
gained popularity in clinical practice.

"Drug dependence"
"Drug dependence" - replaced the older terms
habituation & addiction –
where a state arising from the repeated use
 of drugs on a continuous bases
develop from the use or abuse of many drugs
morphine- type, amphetamine - type, barbiturate-type
or the like
Dependence refers to a state resulting from habitual use of a
drug, where negative physical withdrawal symptoms
result from abrupt discontinuation

"Drug dependence"
Subdivided: psychic dependence - occurs when a person
habitually & compulsively uses a drug & receives
gratification thereby
Physical dependence - a biochemical or physiologic
adaptation of tissues whereby continued administration is
necessary for normal function
Withdrawal (Abstinence) syndrome - withdrawal of the
drug precipitates an abnormal response

Neuromuscular Blocking Agents
Brief physiology of neuromuscular transmis..

 Synthesis, storage release and destruction of
acetylcholine
 Receptor theory
 Types of muscle relaxants
Depolarizing muscle relaxants
Non depolarizing (competitive) muscle
relaxants

The process of chemical NT can be
divided into five steps
1. Synthesis of the neurotransmitter in the presynaptic neuron
2. Storage of the neurotransmitter and/or its precursor in the
presynaptic nerve terminal
3. Release of the neurotransmitter into the synaptic cleft
4.Binding and recognition of the neurotransmitter by target
receptors
5. Termination of the action of the released transmitter

Acetylcholine synthesis
Acetylcholine:- Acetylcholine is synthesised, stored
and released from the nerve terminal, diffuses across th
junction to combine with a specific receptor and is
destroyed finally by a specific enzyme.
Synthesis:- Acetylcholine is synthesised in the
cytoplasm of the nerve terminal from choline and
acetyle coenzyme under the control of a specific
enzyme, choline acetyltransferase.

Storage & Release of ACh:-
Storage:- There is some free acctyl choline present in
the nerve terminal, the majority is packed into vesicles.
Release of ACh:- Arrival of a nerve impulse and
subsequent entry of calcium ion causes the release
hundreds of quanta of ACh which bind to nicotinic
cholinergic receptors on post synaptic membranes
causing a change in membrane permeability to ions.

Destruction of acetylcholine:-
Destruction of acetylcholine:- the enzyme which
facillitates the hydrolysis of ACh is acetylcholinsterase .
This enzyme is particularly concentrated at the post
junctional membrane.
This enzyme destructs it rapidly (within 15 milli seconds)
to acetic acid and choline. Choline can re-enter the motor
nerve ending to again participate in the synthesis of new
acetylcholine.


Types of cholinsterases
There are two main cholinsterases in the body.
 Acetylcholinsterase- This is present at NMJ
and at autonomic synapses.
i. At NMJ - it is localized at the post
junctional membrane
ii. At cholinergic synapses - both at the pre- &
post junctional membrane
Pseudo or plasma cholinsterase - it occurs in the blood
plasma and is produced by the liver

Ach Cont..
Ach has a positively charged “head” consists of a
quaternary amonium group and a negatively charged
‘tail” which includes a ketone group. The head of the
acetylcholine molecule, being positively charged, attaches

to a negatively charged (anionic) receptor site on the post
junctional membrane.
The tail of the Ach attaches to a receptor site. his latter
probably accomodates the Keto-oxygen group and is
therefore best called a cationic receptor site.

The cholinergic receptor can be blocked by binding
with a competitive inhibitor, preventing receptor
activation by acetylcholine. This is the primary
mechanism by which NDM act


Ach with its specific receptor

Receptor:
Receptor:- is a glycopritein with subunits of the
receptor arranged such that the channel is formed that
allows the flow of ions along a concentration gradient.
. These channels open in the active state.
It is postulated that acetylcholine produces its
neuromuscular transmission effects by attaching to
specific receptor sites on the post junctional membrane
and thus depolarizing the membrane.

Summary of neurotransmitter
1. Impulse from action potential opens ion channels
for Ca++
2. The increased Ca++ concentration in the axon
terminal initiates the release of the
neurotransmitter (NT)
3. NT is released from its vesicle and crosses the “gap”
or synaptic cleft and attaches to a protein receptor
on the dendrite

Summary of NT Cont..
4. Interaction of NT and protein receptor open post-
synaptic membrane ion channel for Na+
5. After transmission the NT is either degraded by an
enzyme or taken back into the pre-synaptic
membrane by a transporter or reuptake pump

Neurotransmission impaired
 Transmission may be impaired by:
 inhibition of Ach synthesis by Hemicholinium
 inhibition of release by botulism, aminoglycoside
antibiotics
 blockade of Ach receptors by neuromuscular blocking
drugs, receptor destruction in
myasthenia gravis
 Acetylcholinsterase inhibitors

Action of Ach
Muscarnic effects Nicotinic effects
1. Myocardium - brady cardia 1. Autonomic Ganglia -

2. Gut - contraction stimulated
3. Bronchioles - constriction 2. Skeletal muscle -
4. Pupil - constriction Stimulated
5. Salivary glands - mucus ++
6. Sweat glands - stimulated
7. Bladder contracted

Types of receptors
Post- junctional receptors
Pre-junctional Receptors
Extrajunctional receptors
Post- junctional receptors:- consists of five subunits

(channel is formed) . The two alpha subunits are the
binding sites for Ach and are the sites occupied by muscle
relaxants.

Types of receptors
Pre-junctional Receptors:- on motor nerve endings
influence the synthesis and release of NT blocked
byaminoglycoside and polymxin antibiotics.The action of
polymxin here is due to competition with Ca++.
Extrajunctional receptors :- are normally not present in
large numbers
When the muscle is denervated or deprived of nerve
stimulation, by injury, burn, stroke become more responsive
than junctional receptors to agonists and less responsive to
antagonists.

Extrajunctional receptors Cont..
Found throughout skeletal muscle.
Suppressed by neural activity
Prolonged inactivity
Sepsis
Denervation or trauma (burn)
When activated, stay open longer & permit more flow
of ions -> HyperK+ with SCh.
Proliferation accounts for resistance to nondepol
arizing muscle relaxants.

Neuromuscular Junction
Axon of motor
neuron
Myelin sheath
Motor Neuron
Synaptic cleft
Muscle fibre
Post Junctional Membrane

Muscle Relaxants

South American Indian Preparing Curare
Muscle Responses
Rapid onset at glottis muscles is due to rapid
equilibrium (more blood flow)
Dose required for diaphragmatic block is twice the
dose required for similar block @ adductor pollicis
Sequence of onset: small muscles (eyes, digits) 
trunk & abdomen  diaphragm

Sequence of Paralysis
Fingers, orbit (small muscles)
limbs Trunk neck
Diaphragm Intercostals
Diaphragm Recovery in Reverse

Muscle Relaxants
Muscle Relaxants are classified as:
I)Peripherally acting
A.Neuromuscular blocking agents:-
1) Depolarizing muscle relaxants.
2) Non-depolarizing muscle relaxants
B.) Directly acting: Dantrolene, Quinine
II)Centrally acting
o Diazepam, Baclofen, Tizanidine,

Muscle Relaxants
Spsmolytics NMB’s

Muscle Relaxants
Spasmolytics
Drugs that used to relieve skeletal muscle spasm & bring
them from hypertonic state to normal muscle tone
Neuro-Muscular Blocking Agents
Drugs that completely paralyze skeletal muscles (from
normal tone to zero) by interfering with acetylcholine at
neuromuscular jnx.

The Muscle Relaxants(NMBD)
Interrupt transmission of nerve impulses at the NMJ

thereby produce paralysis of skeletal muscles.
Two types:
Depolarizing (Mimic ACh)
Non-depolarizing (Interfere with actions of ACh)
They have neither anaesthetic nor analgesic properties.

NMBD’s Cont..
Clinical uses of NMBD’s
Skeletal relaxation for facilitation of tracheal intubation
and to provide optimal surgical working conditions.
Can be used in CPR situations, and ICU’s to facilitate
mechanical ventilation.
Intra-op evaluation by visually monitoring a mechanical
response (Twitch)
Usually ulnar and facial nerves.

How to choose NMBD’s
This is influenced by speed of onset, duration of
action, route of elimination, and associated side effects
For example, SCh is a great drug for tracheal
intubation
Rapid onset and brief duration of muscle paralysis
Rocuronium can also be used; however, duration of
action is much longer.

Structure
Quaternary ammonium compounds which has one (+)
charged nitrogen atom that binds to the α-subunit
SCh is like two ACh linked by a methyl group.
Aminosteroid Compounds:
Pancuronium, Vecuronium, & Rocuronium.
Benzylisoquinolinium Compounds:
Atracurium, Cistracurium, Mivacurium
Most likely to release histamine

Depolarizing NMBD
Succinylcholine
 Biphasic action— initial contraction followed by relaxation
 not susceptible to hydrolysis by acetylcholinesterase
Depolarization of the endplate
Opening of the sodium channels
Depolarization
Failure to remove the relaxant from the cleft

sodium channels remain inactive
muscle paralysis or relaxation
Depolarizing NMBD Cont’d
SCh: Only one used clinically
Rapid onset: Paralysis in 30-60 seconds
Duration: 5-10 min
Phase I block: is depolarizing NMB.
Phase II block:
When postjxnal membranes are repolarized but do not respond
to ACh.
Cause- unknown.Occurs when dose exceeds 5 00mg

Depolarizing NMBD (Cont’d)
Metabolism by pseudocholinesterase produced by the
liver.
Plasma cholinesterase not present in the NMJ,
therefore, blockage terminated by diffusion.
Atypical Plasma Cholinesterase
Lacks ability to hydrolyze ester bonds in drugs like SCh
and Mivacurium.
Recognized after prolonged paralysis (>1hr)
Dibucaine #:LA that inhibits normal plasma activity by
~80%

succinylcholine
The only depolarizing NMBA currently used
Only NMBA with short onset (< 1 min) & short
duration (5 – 10 min)
Almost exclusively used to counteract laryngospasm
(0.1 mg/kg)
IV injection – small fraction reaches NMJ
Depolarizing effect within 20-40 sec (fasciculations)
followed by relaxation (< 60 sec)

Dibucaine number % inhibition
Dibucaine number for Duration of Dibucaine
various types sera Suxs induced number %
relaxation inhibition of
enzyme activity
A.Normal Homozygote 5-10 min. 70 – 85

(twonormal genes) NN
B. Prepared
Heterozygote
by Mengesha Abate
(one 20 min. 50 – 65
Hydrolysis of Sch
Succinyl Dicholine ( Rapid) Succinyl monocholine +
choline
Plasma cholinasterase
Succinyl monocholine (Slow) Succinic acid and choline
Specific liver enzyme

Phase I block - Block due to dicholine
Phase II block Block due to monocholine
Dual block - Phase I and Phase II block
Mixed block - which is blockade partly to a
depolarizing relaxant partly to a NDM
action of succinylcholine will be prolonged
Absence of pseudocholinsterase - liver disease,
malnutrition
Block of pseudocholinsterase activity -
anticholinserase drugs
Abnormal (atypical pseudocholinsterase
- NN which occurs in about 96 % of the population -
hydrolysis of sux effectively
NA - 4 % - prolonged period relaxation (5-20 mins)
AA occurs in about 1 in 3200 of the population

Characteristics of Depolarizing MR
Cause muscular fasciculation.

The depolarized muscle fibres are unresponsive to other
stimuli. The Na+ channels are blocked open.
Repolarization is interfered with.
Not reversed by anticholinesterases
In partial paralysis, the neuromuscular monitoring
shows: (i) depression of muscle twitch, (ii) no 'fade', but
a well sustained response, (iii) no post-tetanic facilitation
Repeated or continuous use leads to 'phase II block'.
Characterstics of phase II block resemble those
considered typical of NDM blockade
MECHANISM OF ACTION SUX cont’d
Block transmission by causing prolonged
depolarization of endplate at neuromuscular junction.
Manifestation by initial series of muscle twitches
(fasciculation) followed by flaccid paralysis.
It immediately metabolize in plasma so to prevent its
metabolism in plasma it should be given at faster rate.

Depolarizing NMBD (Cont’d)
Adverse Side Effects:
Not be given to pts 24-72 after major burns, trauma,
extensive denervation of skeletal muscle.
Sinus bradycardia, and even sinus arrest.
 Action at cardiac postganglionic muscarinic receptors.
Faciculations
Hyperkalemia
Myalgia
Myoglobinuria
Increase Intraocular pressure
Increase Intragastric pressure
Malignant Hyperthermia

CONTRAINDICATIONS of Sux
 Hyperkalemia: Serum K > 5.5 is an absolute contraindication for use
of Sch.
 Head Injury : It increases ICP
 Newborns and infants: These have extrajunctional receptors which
are sensitive to depolarizing agents & Sch can produce severe
hyperkalemia by interacting with these receptors.
 Glaucoma & eye injuries.
 Up to 2-3 months after trauma, Up to 6 months after
hemiplegia/paraplegia, Up to 1 year after burns. In these conditions
the denervated/regenerating nerve develops extra junctional
receptors which can produce hyperkalemia.
CONTRAINDICATIONS of Sux
cont’d
Renal Failure : If associated with yperkalemia.
Prolonged intra abdominal infection can be associated
with hyperkalemia.
Diagnosed case of atypical/low
pseudocholinestrase .
Tetanus.
Guillian Barre Syndrome
Metabolic Acidosis/shock :Acidosis is associated with
hyperkalemia.
Spinal cord injury.

Non-depolarizing NMBD’s
Act by competing with ACh for α-subunits
Because of quaternary ammonium groups
No CNS effects
Renal tubular reabsorption is minimal
PO ineffective and does not cross to fetus
Renal disease alters only long acting, e.g. Pancuronium
Metabolism by plasma cholinesterase, e.g. mivacurium
Hofmann Elimination, e.g. Atracurium & Cisatracurium

Non-depolarizing NMBD’s (cont’d)
Enhancement by volatile anesthetics
Enhance: Aminoglycosides,, local anesthetics,
antiarrhthymics, dantrolene, Mg++, Li+,..
Diminish: Ca++ & Anticonvulsants
Resistance in burn injury and skeletal muscle affected by
CVA
Some Hypotension with Mivacurium & Atracurium
NMBD’s are the triggering drugs for anaphylatic rxns.

Non-depolarizing NMBD’s (cont’d)
Long Acting
Pancuronium
 Bisquaternary aminosteroid
 Onset in 3-5 min
 Duration of 60-90 min
 80% excreted in urine unchanged
 10-20% deacetylated in the liver
 10-15% increase in HR (atropine-like effect) mainly SA

Non-depolarizing NMBD’s (cont’d
Intermediate Acting
Vecuronium
 Monoquaternary aminosteroid
 Dose 0.5 mg/kg
 Onset in 1-2 min
 Duration 20-35 min
 Both hepatic and renal excretion
 Suitable in anephric patients
 Suitable in patients with atypical cholinesterase

Rocuronium
 Monoquaternary Aminosteroid
 Onset of 1-2 min
1.2 mg/Kg) resembles onset of SCh with duration of action like
pancuronium

Atracurium
 Onset 3-5 min
 Duration of action 20-35 min
 Clearance by Hofmann elimination ester hydrolysis
 Laudanosine is major metabolite that can cause CNS stimulation
 Slight histamine release

Cisatracurium
 Onset of 3-5 min
 Primarily undergoes Hofmann elimination to laudanosine

Mivacurium:
Short acting muscle relaxant with the duration of
action approximately that of sux.
Duration of action may be prolonged when plasma
cholinesterase is low.
 Onset 2-3 min
 Hydrolysis by plasma cholinesterase
 Slight histamine release

Differences between Depolarizing & Non-
depolarizing block
Depolarizing Nondepolarizing
Also called Phase I block -
Block preceded by muscle No fasciculations

fasciculations
Depolarizing blocking drugs Called pachycurare

are called Leptocurare
Does not require reversal Reversed by cholinesterase

rather cholinesterase inhibitors like Neostigmine.
inhibitors (Neostigmine)
Prepared by Mengesha Abate can
prolong the depolarizing
Monitoring the effects
Peripheral Nerve Stimulator is most reliable method
Facial nerve
Orbicularis oculi muscle
More closely reflects the onset of blockade in the larynx
with nondepolarizing NMBD.
Ulnar nerve
Adductor pollicis muscle is innervated solely by ulnar
nerve

Patterns of Stimulation
Train of Four (TOF): Four electrical stimulations 2 Hz
delivered every 0.5 seconds.
Based on concept that ACh is depleted by successive
stimulations.
The height of the 4th twitch compared to the 1st twitch
allows calculations of TOF ratio (fade).
The TOF ratio remains near 1.o for SCh because the
twitch for all 4 twitches are decreased by a similar
amount (Phase I blockade)

Patterns of Stimulation
Tetanus
Continuous or tetanic electrical stimulation for 5 sec at
about 50 Hz.
Presence of NMBDs causes tetanus to not be sustained
(fades)

Train of Four Ratio

Patterns of Stimulation Cont’d

Factors which prolonging neuromuscular blockade
 Decreased synthesis or release of Ach

↓synthesis and release of Ach thus,
hypoperfusion, hypoxia or acidosis
 Decreased ionized calcium –Massive bld trans.
• Antibiotic------ Aminoglycosides.
 metabolism or excretion of the muscle relaxant is decreased.
 atypical pseudochbinsterase
 ↓ ed U.O
 . Overdose, or if the muscle relaxant is given too close too the
end of the procedure
 Neonates,Old age
 Inhalational agents
 Hypermagnesemia & Calcium channel blockers
Prevention and Rx of prolonged relaxation
treat pre-existing disease

If massive transfusion (> 1500 ml.) - add Ca++
Use muscle relaxants judiciously
Avoid the use of sux towards the end of the procedure
if a NDM has been used
 Never administer NDM until it is obvious the
patient shows signs of recovery from

Suxamethonium.

Methods of use of NDMR
At the end of the operation signs of spontaneous

respiration are awaited before giving anticholinsterases
Reversal of the effects of sux are awaited before giving
NDMR


Signs of Incomplete Reversal
(1) Shallow respiration. (2) Jerky respiration. (3) '

Tracheal tug', and 'see-saw' respiration, where, as the
abdomen moves out, the chest moves in. (4) Cyanosis.
(5) restless, struggling patient, who says that he
cannot breathe. (6) Diplopia. (7) Inability to raise
head or extrude tongue

Mx of Incomplete Reversal
1. IPPV is given with mask and O2
2. If mild, more anticholinsterase given
3. If severe intubation (IPPV). Acid base & electrolytes
status is determined
4. Alternative diagnosis overdose of inhalation agents,
opioids, antibiotics or barbiturates, renal failure,
botulism, myasthenia gravis, myasthenic syndrome,
hypothermia, overdose of relaxant.


Rx.of prolonged apnea
1. Supportive
2. Specific Rx - repeat anticholinsterase
↑ IV fluid - increase urine output
 Wait until patient shows signs of recovery of muscle
power before giving the reversal dose of neostigmine
and atropine

(
Anticholinsterases
 Uses of anti-ChE agents
 Clinical applications (Neostigmine Physostigmine)
reversal of neuromuscular blockade
Rx of central nervous system effects
produced by certain drugs
Rx of mystenia gravis
Rx of glaucoma
 Insecticides (organophosphate
 Nerve gas (e.g. Sarin

Neostigmine (prostigmine)
Can cause its own a depolarizing type of block
It has nictotinic effects and has a direct stimulation on the
muscle
It has muscarinic properties:
bradycardia, intestinal peristalsis and spasm,
bronchial and salivary secreation, brochospasm,
stimulation of the sweat glands, contraction of the pupil,
contraction of the bladder


Side Effects of Neostigmine
Salivation
flushing
Bradycardia, decrease blood pressure
abdominal pain , nausea
bronchospasm ,
urinary urgency
Meiosis
Sweaty skin

Anticholinsterase drugs cont’d
These agents except physostigmine are quarternary
ammonium compounds so they do not cross blood
brain barrier.
The biggest disadvantage is that these agents also
increase the acetylcholine level at muscarinic receptors
producing muscarinic side effects like bradycardia,
bronchospasm.
So, to prevent these muscarinic effects some anti
cholinergic like atropine or glycopyrrolate is to be
given with cholinesterase inhibitors

Anticholinsterase Drugs Cont’d
Pyridostgmine - used in the Rx of myasthenia gravis. Its
duration of action (6 hrs. > makes it suitable for reversal
of relaxants in case of renal failure
 Dose 10 mg.
Physiostigmine:- tertiary amine structure used to treat
anticholinergic syndrome.
 It does not adequately antagonize neuromuscular block.

Anticholinsterase Drugs Cont’d
Edrophonium ( Tensiolon) :-
 quicker onset, brief duration.
 Its pattern of reversal suggests that it acts at
prejunctional receptors.
it is useful in the diagnosis of mystenia gravis or in
determining the type (depolarizing/ nondepolarising)
of relaxation.

SIGNS OF ADEQUATE
Regular respiration REVERSAL
with adequate tidal volume i.e.
patient is able to maintain oxygen saturation on room
air.
Spontaneous eye opening
Spontaneous limb movement
Able to protrude tongue
Upper airway reflexes returns like patient is able to
cough & spit.
Able to lift head for more than 5 seconds. This is the
best clinical sign.
return of full muscular activity shown after electrical
nerve stimulation
CAUSES OF INADEQUATE
REVERSAL
Inadequate dose of neostigmine.
Overdose of inhalational agents/opioids.
Renal Failure,Hepatic failure
Hypothermia &Shock
Electrolyte abnormalities (Hypokalemia, Hypocalcemia)
Associated neuromuscular diseases.
Acid Base abnormalities especially acidosis. It is
impossible to reverse a patient with pCO2 more than
50mmHg.

Drugs which antagonise Neuromuscular
Blockade
Phenytoin
Calcium
Cholinesterase inhibitors
Steroids.

Centrally acting muscle relaxants
These are drugs which produce muscle relaxation through
central mechanism both at supraspinal & spinal level
It also produces sedation
Uses
Muscle spasms.
Tetanus : IV diazepam is most effective.
Spastic neurological diseases like cerebral palsy,Spinal
injuries.
Close reductions & dislocations in orthopedics.

Organophosphorus Poisoning
 Organophosphates are used world wide

 Common cause of poisoning in the developing
world-----Malathion
Absorption route;
INGESTION(ACCIDENTAL OR SUICIDAL)
INHALATION
INJECTION

Pathology
 Organophosphate are absorbed via the skin
lungs & GI tract
 The principal effect is inhibition of
cholinesterase enzymes, particularly AChE. This
leads to accumulation of acetylcholine at;
1. Muscarinic receptors- in cholinergic
receptor cell.
2. Nicotinic receptors – in skeletal
neuromuscular junction and autonomic
ganglia
3. CNS.

Clinical Features
1. History of
 Ingestion
 Inhalation
 Dermal absorption
2. Features of intoxication are delayed i.e. because it

requires biotransformation to become active

Organophosphorus Poisoning
3.Muscarinic effects of Poisoning are characterized by;

 Anxiety
 Restless
 Tiredness
 Vomiting
 Abdominal colic, cramps
 Diarrhea
 Tenesmus
 Sweating
 Rhinorrhoea
 Bronchorrhoea
 Dyspnoea due to bronchoconstiction
 Chest tightness, wheezy
 Nausea,
 Urinary and fecal incontinence,
 Lacrimation, miosis
Nicotinic effects organo..
Nicotinic effects
Muscle fasciculation
Flaccid paralysis
Limbs muscles
Respiratory muscles
Extra ocular muscles
Weakness
Fatigue
Tremor
Nicotinic effects organo..
Respiratory system
Respiratory failure – worsened/exacerbated by
development of rhinorrhoea and pulmonary Oedema.
7. CNS – occur in severe poisoning
Coma
Convulsions
Headache
Lossof memory
Anxiety
Drowsiness

Treatment
1. Mild
 No specific treatment
 Clearing the Airway,
 Adequate ventilation-consider oxygenation
 Remove soiled clothes
 Wash contaminated skin to prevent further
absorption.

Treament Organo. poisoning Cont’d
. with systemic featurePatients
i) IV atropine 2mgs every 15 minutes till signs of atropinization are seen (DRY
SKIN, DILATED PUPILS)
ii) Reduces - Bronchorrhoea & Rhinorrhoea & wheezing
 It is a beta adrenoceptor blocking drug.
ii) Add e.g. Pralidoxime

 Dose – Slow IV injection 30mg/kg every 4-6 hours i.e. 1-2gms IV
- or infusion 8-10mg/kg/h i.e. 200-400mgs/h
- Prevents permanent binding of the organophosphate to cholinesterase.
iii) Gastric lavage within an hour followed by activated

Charcoal administered via nasogastric tube
iv) Wash the patient – to prevent dermal absorption
v) Wash soiled clothes
vi) Monitor
Preparedpatient 2 hourly
by Mengesha Abatein left lateral position
Cholinergics and Anti-cholinergics
 Cholinergic Drugs
Parasympathomimetics or cholinomimetics
Stimulate parasympathetic nervous system in same
manner as does acetylcholine
May stimulate cholinergic receptors directly or slow
acetylcholine metabolism at synapses (affect the enzyme
acetylcholinesterase)
Useful in treating Alzheimer’s Disease, Myasthenia gravis
and to tx atony of the smooth muscle of the GI system or
urinary system

Cholinergic Drugs
Normal neuromuscular function, acetylcholine binds to
nicotinic receptors on cell membranes of muscle cells to
cause contraction
Myasthenia gravis autoantibodies presumably destroy
nicotinic receptors; thus, acetylcholine less able to
stimulate muscle contraction. Results in severe muscle
weakness.
Acetylcholine stimulates cholinergic receptors in the
urinary system to promote urination
Results in contraction of the detrusor muscle and
relaxation of the urinary sphincter to facilitate emptying of
the urinary bladder

Acetylcholine
One of the main neurotransmitters of the ANS is
acetylcholine
Acetylcholine is released at preganglionic fibers of both
the sympathetic and parasympathetic nervous system
Also released from postganglionic sympathetic neurons
that innervate the sweat glands
Acetylcholine stimulates cholinergic receptors in the
urinary system to promote urination
ladder

Acetylcholine cont’d
 Nicotinic receptors are located in motor nerves and
skeletal muscle
Stimulation results in muscle contraction
 Muscarinic receptors are located in most internal organs.
This includes the cardiovascular, respiratory,
gastrointestinal, and genitourinary.
 Stimulation of the muscarinic receptors may result in
either excitation or inhibition, depending on the organ
involved.

ANS Phy.

Mechanisms of Action—Direct Acting
Cholinergics
Direct acting cholinergics are lipid insoluble
Do not readily enter the CNS
Resistant to metabolism by AchE
Effects are longer acting
Widespread systemic effects when they combine with
muscarinic receptors in cardiac muscle, smooth
muscle, exocrine glands and the eye

Direct-acting Cholinergic Drugs
Effects
Decreased heart rate, vasodilation effects
Increased tone and contractility in GI smooth muscle,
relaxation of sphincters, increased salivary gland and GI
secretions
Increased tone and contractility of smooth muscle in
urinary bladder and relaxation of the sphincter
Increased tone and contractility of bronchial smooth
muscle
Increased respiratory secretions
Constriction of pupils (miosis)

Indirect-Acting Cholinergic Drugs
Action is by decreasing the inactivation of Ach in the
synapse by the enzyme AchE
Accumulation of Ach then occurs which enhances the
activation of the nicotinic and muscarinic receptors
AntiAchE drugs are either reversible or irreversible
inhibitors of acetylcholinesterase
Reversible agents are such drugs as:edrophodium
(Tensilon). Used to diagnose myasthenia gravis and for
reversal of NDMB

Indirect-acting agents cont’d
Neostigmine (Prostigmine)—prototype anticholinesterase
agent.
 Used for long-term tx of myasthenia gravis and as an
antidote for non-depolarizing agents
Pyridostigmine is the maintenance drug of choice for
patients with Myasthenia gravis.
Physostigmine —only antiAchE capable of crossing the
BBB.
 Used as an antidote for overdosage of anticholinergics
such as: atropine.

Specific Conditions—Cholinergic vs.
Myasthenic Crisis
Distinction between cholinergic crisis and a myasthenic
crisis
Myasthenic crisis requires more anticholinesterase drug
whereas cholinergic crisis requires discontinuation of the
anticholinesterase drugs
Diagnosis can be made by evaluating patient patient
response to their medication
Need to distinguish as require opposite treatment
measures

Toxicity of Cholinergic Drugs
Atropine is the specific antidote to cholinergic agents
Atropine reverses only the muscarinic effects of
cholinergic drugs; heart, smooth muscle, and glands.
Atropine cannot reverse the nicotinic effects of skeletal
muscle weakness or paralysis due to overdose of
indirect cholinergic drugs.

Toxicity of Irreversible
Anticholinesterase
These agents are lipid soluble
Can enter the body by several routes.
Organophosphate insecticides (malathion, parathion) or
nerve gases (sarin, tabun, soman)
 cause excessive cholinergic stimulation (muscarinic) and
neuromuscular blockade
Cholinergic crisis occurs because the irreversible
antiAchE poison binds to the enzyme acetylcholinesterase
and inactivates it

Anti-cholinergic Drugs
 Atropine , Scopolamine and Glycopyrrolate
Atropine is an alkaloid found in atropa belladona

An ancient women found it fashionable to instill the
exctract in their eyes.
It is a competitive antagonist for the muscarinic
acetylcholine receptor
Because it’s a tertiary amine, atropine is relatively lipid
soluble and cross BBB and it’s well distributed through
the CNS

Effects of atropine :
CVS : bradycardia at low doses , tachycardia
at high doses
EYE : mydriasis, cycloplegia, increase IOP,
reduce lacrimal secretion
GIT : reduce the activity of GI
Urinary system : relaxation of smooth muscles in
urinary tract
Respiratory bronchodilation ,reduction in secretions
Salivary glands : xerostomia
Sweat glands :inhibition of secretion can cause

hyperthermia
Effects of atropine modified
A.EXOCRINE GLANDS
-salivary secretion is impaired
-gastric secretion is decreased
-bronchial secretion is impaired
-sweating is impaired
B. SMOOTH MUSCLES
- GIT-abolishes tone & motility
- Biliary Tract-relaxing action
- Urinary Tract- decreases the tone

Effects of atropine cont’d
C. Bronchial Tree - relaxation
D. Heart -large doses of atropine (2mg) –
increases HR by 40 to 50 beats\min.
Small doses (o.2mg) decreases HR by 10 to
15 beats\min.
therapeutic dose ( .5 to 1mg) has dual effect
first decrease & then increase
E. Eye -Mydrasis & Cycloplegia
F. CNS -Stimulatory but disorientation
with large dose

OVER DOSE OF ATROPINE
Dry as a bone-Salivary inhibition
 Red as a beet root –Facial vasodilation
Mad as a hatter- Central stimulation
 Hot as a hen -Inhibition of sweating
 Blind as a bat-Paralysis of accomudation
Anticholinergic overdose syndrome is characterized by:
Hyperthermia, delirium, dry mouth, tacycardia, ileus,
urinary retention. Seizures, coma and respiratory arrest
may occur.

Clinical uses:
Blocks the effect of Ach that result from cholinesterase
inhibitors like Neostigmine
Blocks secretions prior to surgery
Ophthalmic: mydiasis and cycloplegia to examine retina

and optic disc
GIT:antispasmodic agents
Urinary: reduce hypermotility of urinary bladder and
occasionally used in enuresis
In CNS disorder: Parkinson and motion S
Antidote for organophosphate

Atropine cont’d
Atropine ：
Block the M1 class receptors
reduce acid production
abolish gastrointestinal spasm
relatively unpopular as a first choice because of high

incidence of anticholinergic side effects (dry mouth
and blurred vision

Contraindications of atropine
BPH
Myasthenia gravis
Hyperthyroidism
Glaucoma
Tachydysrhythmias
Not in situations whereby delaying of gastric emptying
is a concern

Preop
Help prevent vagal stimulation and potential
bradycardia
Reduce respiratory secretions as well
Atropine is commonly used in an intravenous dose of
0.01-0.02mg/kg to treat bradycardia during
anaesthesia.
Adult dose 0.6 - 1 mg


SCOPOLAMINE (HYOSCINE)
A belladona alkaloid
Produces peripheral effects similar to atropine but it has
greater action on CNS
Longer duration of action that atropine
More effective in motion sickness
Produce sedation but at higher doses can cause excitement
The amnesic action of scopolamine makes it an important
adjunct drug in anesthetic procedures
Side effects same as atropine but with more effect on CNS

Effects of SCOPOLAMINE cont’d
atropine and scopolamine differ in their antimuscarinic
effects. Scopolamine has a stronger effect on the eye and
exocrine glands and is a more powerful antisialagoque
than atropine,
The effects of scopolamine on the heart rate are less
strong than atropine.
scopolamine may cause restlessness, hallucinations and
delirium. This syndrome occurs more often in the elderly.
The adult parenteral dose is 0.2 to 0.6 mg

Glycopyrrolate
It is a synthetic quaternary amonium compound.
Doesn’t cross BBB so no CNS effect
It has longer duration of action than atropine
Produce less cardiovascular stimulation than atropine

more potent anti-sialogogue than atropine,
The usual adult dose , 0.1 mg IV at induction

Commonly used parasympatholytic drugs,
routes and doses
Route given Dose given (average adult)
Bolus
Atropine IM/IV 0.015-0.02mg/kg
Oral 3mg for total vagal
blockade
Glycopyrrolat IM/IV 0.2-0.4mg

e
Hyoscin SC/IM 0.2-0.6mg
ePrepared by Mengesha
OralAbate (pre-med)
0.3mg qid
COMPLICATIONs OF ANTICHOLIN. DRUGS
1. Central anticholinrgic Syndrome ;

Delirium,restlessness,confusion.
2. LES relaxation
3. Increases IOP via mydrasis & cycloplegia
4. Bronchial smooth muscle relaxation-results in
increased dead space
5. Drying & Thickening of secretions
6. Potential problem with CF Pts.
7. Interference with sweating mechanism
8. Increased HR-Atropine greater than glycopyrolate or
scopolamine

Introduction To ANS
The ANS coordinates cardiovascular, respiratory,
digestive, excretory and reproductive systems.
The ANS consists of two divisions, sympathetic and
parasympathetic, which normally exert antagonistic
effects on many of the same target organs.

Comparison of Somatic and Autonomic Nervous Systems
 SNS provides motor fibers to skeletal muscle fibers. ANS

provides motor fibers to smooth and cardiac muscles and
glands.
 In Somatic NS, a single motor neuron forms the efferent
[pathway from the CNS to effectors. In ANS efferent
pathway consists of a two neuron chain, the preganglionic
neuron in the CNS and postganglionic in a ganglion.
 Acetylcholine, the neurotransmitter of somatic neurons is
stimulatory to skeletal muscle fibers. Neurotransmitters
released by ANS motor neurons-acetylcholine and
norepinephrine -may cause excitation or inhibition

ANS

Pharmacology of the SNS

Synthesis of adrenal hormones
Stimuli Part Principal
product
Angiotensin II Zona Aldosterone

glomerulosa
ACTH Zona Cortisol

fasiculata & Adrenal
reticularis androgens

SNS vs. PNS Divisions
 The PS or craniosacral division (resting-digesting
system)conserves body energy and maintains body
activities at basal level. Effects include pupillary
constriction, increased digestive tract mobility, and smooth
muscle activity leading to defecation and urination.
 The S or thoracolumbar division(fight-or-flight system)
activates the body under conditions of emergency.
Responses include dilated pupils, increased heart and
respiratory rates, inc. BP, dilation of bronchioles, inc. blood
glucose and sweating.

Anatomy of-craniosacral division
PS division-PS preganglionic neurons arise from the rain
stem and from the sacral region (S2- S4) region of the
spinal cord.
The preganglionic fibers are long and the post are short.
The preganglionic neurons synapse wit postganglionic
neurons in terminal ganglia located in or close to their
effector organs.
Neurons are cholinergic and the effects of stimulation are
brief and restricted to specific
sites

Physiology of PS division
All parasympathetic preganglionic and postganglionic
fibers release Ach at synapses and neuroeffector junctions.
The effects are short-lived because of the actions of
cholinesterase.
Stimulation of muscarinic receptors produces a longer
lasting effect than does stimulation of nicotinic receptors.
The effects produced by the PS division center on
relaxation, food processing and energy absorption

Anatomy of -thoracolumbar division
Preganglionoic sympathetic neurons arise from the
lateral horn of the spinal cord from the level of T1 to
L2.
Preganglionic fibers are short and postganglionic
fibers are long.
Two types of sympathetic ganglia-paravertebral and
prevertebral.
Preganglionic axons leave the cord and enter the
paravertebral ganglia(sympathetic chain ganglia)in the
sympathetic trunk.

Physiology of SNS
Stimulation of S division has two distinctive results:
release of NE at specific locations and secretion of E
and NE into the general circulation. Two types of
receptors alpha-for NE and E and beta-for E.
most postganglionic fibers are adrenergic, few
cholinergic Postganglionic fibers that innervate
smooth muscle in the walls of small arteries in skeletal
muscles.

Neurotransmitters and receptors
Ach and NE-major ones. Neurons are either adrenergic or
cholinergic.
Ach is released by all preganglionic fibers and all
parasympathetic postganglionic fibers. NE is released by
all sympathetic postganglionic fibers except sweat glands,
some blood vessels that release Ach.
Neurotransmitter effects depend on the receptor to which
the transmitter binds. Cholinergic receptors (Ach) are
classified as nicotinic and muscarinic. Adrenergic (NE)
are alpha 1 & 2 and beta 1 & 2

Interactions of the ANS
Most visceral organs are innervated by both types of
nerves.
Most blood vessels are innervated only by sympathetic
nerves. PS activity dominates the heart and GI tract.
Activation of the sympathetic division causes wide
spread, long-lasting mobilization of the fight-or-flight
response. PS effects are highly localized and short
lived.

CATHECHOLAMINES SYNTHESIS


Termination of the action of catecholamines
1. Reuptake into nerve terminals

2. Extra neuronal uptake
3. Diffusion

Sympathomimetics
 Sympathomimetics.
I. CATECHOLAMINES
 a. Epinephrine
 b. Norepinephrine
 c. Dopamine
 d. Isoproterinol
 e. Dobutamine


Sympathomimetics Cont’d
II. NON-CATECHOLAMINES
 a. Ephedrine
 b. Amphetamines
 c. Metaraminol (aramine)
 d. Phenylephrine (neosynephrine)
 e. Methoxamine (vasoxyl)
Sympathomimetics can be classified into
Naturally occurring
Synthetic

Sympathomimetics Cont’d
Naturally occuring
Epinephrine
• Synthetic
Norepinephrine – Dobutamine
Dopamine – Dopexamine
– Phenylephrine
– Metaraminol
– Ephedrine

Inotropes & Vasopressors
 Inotropes:
Drugs that affect the force of contraction of myocardial
muscle
Positive or negative
Term “inotrope” generally used to describe positive effect
Vasopressor:
Drugs that stimulates smooth muscle contraction of the
capillaries & arteries
Cause vasoconstriction & a consequent rise in blood
pressure

Which adrenoceptor mediates cardiac muscle
contraction?
65% 1. 1
2. 2
3. 1
4. 2
12% 12% 12%
1 2 3 4

Which adrenoceptor mediates vascular
smooth muscle contraction?
58%
1. 1
2. 2 38%
3. 1
4. 2
4%
0%
1 2 3 4

Main classes of Adrenoceptor
 receptors
1 Located in vascular smooth muscle
 Mediate vasoconstriction
2 Located throughout the CNS, platelets

 Mediate sedation, analgesia & platelet aggregation
 receptors
1Located in the heart
 Mediate increased contractility & HR
2Located mainly in the smooth muscle of bronchi
 Mediate bronchodilatation
 Dilatation of coronary vessels
 Dilatation of arteries supplying skeletal muscle

Organ Receptor subtype Adrenergic Cholinergic
Heart B1 HR Heart rate

Force of contraction Force of contraction
Automaticity and conduction Conduction velocity
velocity
Arteries Alpha1 Constriction Dilatation

Beta2 Dilatation
Veins
Alpha1
Constriction ++
Dilatation +
B2
Lung
- bronchial B2 Relaxation + Contraction ++
muscles ? (? inhibition) Stimulation +
- bronchial
glands
GI Tract
- motility B2 Decrease Increase +++
- sphincters (Alpha) Contraction Relaxation
Kidney B2 Renin Secretion
Bladder
- detrusor B2 Relaxation Contraction +++
Epinephrine Mechanism of Action
Alpha adrenergic action (vasoconstrictive)

increases systemic vascular resistance
elevates the systolic and diastolic blood pressure
reduces blood flow to the splanchic, renal, mucosal, and
dermal vascular beds
B- adrenergic receptor action
increases myocardial contractility
increases heart rate
relaxes smooth muscle in the skeletal muscle vascular bed
and bronchi

Epinephrine mechanism of Action, cont’d
increased heart rate
increased cardiac automaticity
increased myocardial contractility
increased systemic vascular resistance
increased blood pressure
increased myocardial oxygen requirements

Epinephrine
Stimulates  &  receptors
Predominantly  effects at low doses and  effects at
high doses
Clinical uses
Cardiac arrest
Anaphylaxis
Low cardiac output states
Upper airway obstruction
Combination with local anaesthetics

Epinephrine Cont’d
 Side effects
• Increase in myocardial oxygen consumption
Post-resuscitation hypertension
tachycardia
headache
nausea
vasoconstriction severe enough to decrease peripheral
blood flow

Epinephrine‚
Implications
Effects of Epinephrine are depressed in acidosis.
Extravasation may cause local ischemia and tissue

necrosis.
assure patent IV
preferably a central line
Monitor patient status q. 1 - 5 mi

Epinephrine Special Note
It is important to note that the volume of epinephrine
administered is 0.1 mL/kg whether conventional or high
dose epinephrine is provided.
The dose of epinephrine is determined by the
concentration of the drug (conventional dose = 0.1 mL/kg
of 1:10,000 and high dose = 0.1 mL kg of 1: 1,000).
All endotracheal doses of epinephrine are high dose (= 0.1
mg/kg of 1: 1,000).

Epinephrine Implications
Effects of Epinephrine are depressed in acidosis.
Extravasation may cause local ischemia and tissue

necrosis.
assure patent IV
preferably a central line
Monitor patient status q. 1 - 5 min.

Dopamine / Inotropin‚
uses and effects are dose related
is not a drug of choice in hypotension associated with

hypovolemia
is not a drug of choice in treating hypovolemic shock
is a potent venoconstrictor

Dopamine / Inotropin cont’d
dopaminergic 1-2 mcg/kg/min (kidney)
inotropic beta1 adrenergic 2-10 mcg/kg/min
increasing alpha adrenergic 10-20 mcg/kg/min
predominate vasoconstriction > 20 mcg/kg/min
Dopaminergic receptors: DA receptors have been

identified largely in the CNS and also in the kidneys
and mesentric vessels.

Dopamine Mechanism of Action
chemical precursor of epinephrine
possesses alpha and beta receptor-stimulating actions
low doses are mainly dopaminergic and stimulate renal
vasodilation
higher doses produce cardiac stimulation
increases cardiac output with minimum increase in
myocardial oxygen consumption

Dopamine clinical Use
hypotension with poor peripheral perfusion
shock which fails to respond to volume loading
Routes of Administration--IV drip

Dopamine Side Effects
In high doses, causes excessive vasoconstriction which
can lead to:
decreased peripheral perfusion
decreases renal blood flow
tachycardia
nausea
vomiting
ectopic beats
arrhythmias
Inactivated by alkaline solutions

Dobutamine
acts mainly on beta1 receptors in the heart to increase the
force of myocardial contraction with minimal increase in
heart rate
usually results in an increase in cardiac output, stroke
volume, and ventricular function
typical dosage is 1 to 20 mcg/kg/minute
Direct-acting inotropic agent possessing beta-stimulator

activity.
Induce short-term increases in cardiac output by
improving stroke volume

Isoproterenol (synthetic catechol..)
is a potent balanced B1 and B2 receptor agonist with no
vasoconstrictor effects.
Isoproterenol has powerful effects on all Beta
receptors and almost no action at alpha receptors.
relaxes almost all varieties of smooth muscle
It prevents or relieves bronchoconstriction.

Ephedrine:-
tic n
A stimulant that acts on the sympathetic nervous system .
 It induces pre-synaptic terminals norepinephrine into the
synaptic space.
Secondary effect of increasing circulating adrenaline
throughout the body.
Binds directly to beta-receptors, in place of
norepinephrine, on the surface of adipocytes.
Results in the increased production of cyclic AMP within
the effector cell.

Ephedrine cont’d
 A stimulant that acts on the sympathetic
an indirectly acting sympathomimetic. It is taken up into
presynaptic nerve terminals, thereby displacing
noradrenaline resulting in alpha mediated
vasoconstriction.
Ephedrine also has a direct beta agonist effect increasing
heart rate and cardiac output, the overall effect increasing
blood pressure
ephedrine has been used in the treatment of asthma
Weight loss

Ephedrine cont’d
is a sympathomimetic amine commonly used as a
stimulant, appetite suppressant, concentration aid,
decongestant, and to treat hypotension associated with
anaesthesia.
repeated doses have a gradually decreasing effect
(tachyphylaxis).
 Ephedrine is similar in structure to the derivatives of
amphetamine .
 Chemically, it is an alkaloid derived from various plants
in the genus Ephedra

Amphetamines
 Amphetamines are drugs that are classified as

Central Nervous System (CNS) Stimulants.
 Amphetamines are also drugs that induce
false feelings strength and enhanced
motivation.
Amphetamines are designated as an illegal
substance

Amphetamines cont’d
 Orally – In pill, tablet or liquid form

 Snorted – This can cause severe damage to the
interior and exterior of the nose.
 Injection –
 Into the blood stream
 Into muscle tissue
 Smoked

Amphetamines cont’d short term
effects
 Dilated Pupils
 Increased Blood
Pressure
 Increased Heart Rate
 Decreased Appetite
 Dry Mouth
 Tremors
 Dizziness / Nausea

Ampheta. long term effects
amphetamine use can cause the users to have long term
problems with high blood pressure, irregular heartbeats, and
severe sleeping disorders

Malnutrition – Because Amphetamines reduce the users appetite,
Chronic Anxiety/Tension - To combat this users often turn to alcohol
barbiturates for help. Chronic Anxiety may also lead to violent
Brain Damage – can cause damage to the brain, specifically areas tha
deal with memory and everyday thinking

Amphetamines cont’d
Euphoria
Increased alertnessBruxism
Altered mental status
Tachycardia
Hypertension
Diaphoresis
 Palpitations
chest pain
Amphetamines can be detected in urine for 2-3
days after ingestion.

Isoprenaline
Isoprenaline: the first synthetic beta receptor agonist
for clinical use, stimulating both beta-1 and -2
receptors.
 Usually given as an infusion because of its short
duration of action.
Used mainly to treat bradyarrhythmias and as a
bronchodilator.
 Now largely replaced as a bronchodilator by beta-2
selective drugs because of the risk of cardiac
arrhythmias.

Salbutamol
Salbutamol: predominantly a beta-2 agonist used in
the treatment of asthma, both administered
intravenously and by inhalation.
Also slows peristalsis and causes muscle tremor in
large doses. Alternatives include terbutaline

Ritodrine:
Ritodrine: a beta-2 agonist used as a uterine relaxant
(tocolytic) to prevent premature labour. Given i.v.
initially followed by oral maintenance therapy.
Salbutamol is also used for the same effect.

Alpha agonists
Ephedrine
Phenylephrine
Metaraminol
Methoxamine
Clonidine

Beta Agonists
Adrenaline Predominantly beta 1 & 2 effects at low

dose
Increasing alpha effects at higher dose
Useful “rescue inotrope” in resuscitation
situations
Noradrenaline Alpha & beta effects at very low dose. Alpha

effects quickly predominate as dosage
increases.

Dobutamine Potent beta 1 agonist. Some beta 2 mediated
Alpha Methoxamine
 Phenylephrine
 Norepinephrine
  Epinephrine
 Ephedrine
 Dopamine
 Dobutamine
 Isoproterenol
Beta

PHARMACOLOGY OF SNS
Direct - acting sympathomimetics
Non-selective: NE, EPI
Alpha1 agonists: methoxamine,
phenylephrine
Alpha2 agonists: clonidine
Beta1 agonist: NE, EPI, dobutamine,
dopamine
Beta2 agonists: albuterol, metaproterenol,
terbutaline
 Indirect - acting Sympathomimetics:
tyramine, ephedrine, amphetamine
 Catecholamine
tricyclic antidepressants
uptake inhibitors: cocaine,
PHARMACOLOGY OF SNS
 Alpha-adrenergic antagonists
Non-selective: phenoxybenzamine, phentolamine
Alpha1 antagonists: prazosin
 Beta-adrenergic antagonists
Non-selective: propranolol, pindolol, nadolol,
timolol
Beta1 antagonists: atenolol, esmolol
Mixed alpha/beta antagonsits: labetalol
 Reducers of Central Sympathetic Outflow:
methyldopa, clonidine
 Blockers of Norepinephrine Release: guanethidine
Corticosteroids

Group Hormone
Glucocorticoids • Cortisol
• Corticosterone
Mineralocorticoids • Aldosterone
• 11- deoxycorticosterone
Sex Hormones
•Androgen
•Progestogen
•Oestrogen
Pharmacological Actions of cort..
Direct Actions
Permissive Actions
 Lipolytic effects
 Effect on BP
 Effect on bronchial muscles
(e.g.,sympathomimeti

Pharmacological Action cort..
1. Carbohydrate
2. Protein
3. Lipid
4. Electrolyte & water
5. CVS
6. Sk. Muscle
7.Stomach
8. Blood
9. Anti-inflammatory
10. Immunosuppressant
Clinical use of corticosteroids
Deficiency state (Replacement therapy)

Cerebral edema
Asthma
 Organ transplantation
Shock especially for septicshock. Maintains the normal
circulatory function. norma l myocardial
contractility and vascular resist.
 Gout and rheumatoid
 Acute anaphylaxis

Side effects of cort..
1. Susceptable to infection

2. Delayed healing process
3. GI bleeding due to reactivation of peptic
ulceration and GIT perforation
4. Impaired electrolyte imbalance

Contraindication of cort.
 Systemic infection
 peptic ulcer
Renal dysfunction
 Diabetes mellitus
 Hypertension


Naturally occuring cortcosteroids
a. Cortisol (hydrocortisone)
b. Cortisone
c. Corticosterone
d. Desoxycorticosterone
e. Aldosterone


Synthetic Corticosteroids

a. Prednisolone
b. Prednisone
c. Beta methasone
d. dexamethasone - commonly choosen to
treat cerebral edema
e. Hydrocortisone (cortisol)
 Glucocorticoids appear to increase the efficiency of cellular
function by :
Their ability to increase peripheral vascular resistance and decrease
capillary permeability and decrease exudation of colloid in
inflammatory states.

Posterior Pitutary Hormones
1. Antidiuretic hormone (ADH)

2. Oxytocin
Vasopressin:- is the exagenous preparation of ADH
used for the treatment of diabetes insipidus and
management of uncontrolled emorrhage from
esophageal varicies

Oxytocin:
Induction of labor – in case of postmaturity or
prematurely in
 toxemia of pregnancy, diabetic mothers,
erythroblastosis,
 placenta insufficiency Slow IV infusion, 5 IU is diluted
in
 500 ml. Glucose or N/S solution
Started at low rate and progressively accelerated
Before starting infusion, check there is no CPD
no foetal distress and no uterine scar
Oxytoxine cont’d
Uterine inertia – when uterine contractions are table
and labour is not progressing
Oxytocin is preferred over ergometrine
 because of short half – life time
 action can be controlled or quickly terminated
 low conc – allow normal relaxation between contractions
 lower segement is not contracted, foetal descent is not
compromised
 Post partum haemorrhage, cesarean section for immediate
response

Ergometrine
increase force, frequency and duration of uterine
contraction
Cautious when use in:
Patients with vascular disease, hypertension, toxemia
Liver and kidney disease
Contraindicated before 3rd stage of labour


Ergometrine cont’d
 Clinical Use
To control and prevent postpartum haemorrhage 0.5
mg IV is recommended
 After C-section/ instrumental delivery – to prevent
uterine atony
preparations of oxytocin used clinically are synthetic
and their potency is described in units.


Increase Corticosteroids
Gluconeogenesis
Glycogen deposition in liver
Redistribution of Fat
 Buffalo hump
 Moon face
Electrolyte and water balance--Aldestrone

 Na+ reabsorption
 Urinary excretion of K+ and H+

Actions: Cardiovascular system
Restrict capillary permeability

Maintain tone of arterioles
Myocardial contractility
 Stomach:
Aggravate peptic ulcer. May be due to
 Acid & pepsin secretion
 immune response to H.Pylori

Immunosuppressive
allergic actionsImmunosuppressive
unosuppressive
Suppresses all types of hypersensitivity & allergic
phenomenon
At High dose: Interfere with all steps of immunological
response
Transplant rejection: antigen expression from grafted
tissues, delay revascularization, sensitisation of
lymphocytes etc

Actions: Growth & Cell divis
Inhibit cell division or synthesis of DNA
Delay the process of healing
Retard the growth of children
 Intestinal absorption
 Renal excretion
 Excessive loss of calcium from spongy bones
(e.g., vertebrae, ribs et

Antihypertensive Drugs
Hypertension
Primary – 90-95% of cases – also termed
“essential” or “idiopathic”
Secondary – about 5% of cases
Renal
Endocrine disease
Phaeochomocytoma
Cushings syndrome etc..

Renin-angiotensin system
Kidneys and blood vessels strive to regulate and
maintain a “normal” BP.
The kidneys regulate blood pressure via the renin-
angiotensin system.
Renin stimulates production of angiotensin I & then
AT- II (a potent vasoconstrictor), causes the release of
aldosterone (adrenal hormone that promotes sodium
retention ).

Renin-angiotensin system cont’d

Angiotensin II formation

Hypertension
Diagnosis- 3- 6 independent measurements
Determination of primary vs. secondary Hx.
If secondary, treat underlying pathology
Non-Pharmacological - Should be first line of treatment.
If successful, no meds. may be needed.
* Stress reduction techniques, exercise, salt restriction, no
smoking, wt. reduction less alcohol, diet etc..
Systolic pressure >140 mm/hg = antihypertensive meds
started

Pharmacological Treatment
 Classes of Antihypertensive Agents

. Diuretics
. Peripheral a-1 Adrenergic Antagonists
. b-Adrenergic Antagonists
. Anti-angiotensin II Drugs
. Ca++ Channel Blockers
. Vasodilators

Diuretics
Promote Na depletion  dec. in ECF
* First line drug for Rx of mild HTN
Thiazides: hydrochlorothiazide (Esidrix) (most
common)
Generally used to treat mild to moderate HTN
Use with lower dietary Na+ intake, and K+ supplement
 Loop diuretics:furosemide);ethacrynic acid

 Osmotic: mannitol ; urea
 Other: acetazolamide (Diamox)

Diuretics cont’d
. Site of Action: Renal Nephron
Mechanism
Na excretion

Antihypertensive drugs
Beta-Adrenergic Blockers (Beta Blockers)
Atenolol - Beta-1 cardio selective
Propranolol (Inderal) -Nonselective Beta-1, Beta-2
Nonselective = inhibits Beta-1 (heart) & Beta-2 (bronchial)
receptors
- HR slows & BP decreases
- Bronchoconstriction occurs
Cardio selective - Preferred - acts mainly on Beta-1
receptors

Antihypertensive
Agents
Adrenergic Neuron Blockers (Peripherally acting
sympatholytics)
* Potent drugs that block norepi. form sympathetic
nerve endings  a dec. in norepi.  dec. in BP
* Decrease in both cardiac output & peripheral
vascular resistance
Reserpine (Serpasil) & guanethidine (Ismelin) -
Potent - used for severe HTN

 prazosin
Site of Action- peripheral arterioles, smooth muscle
Blocks alpha adrenergic receptors vasodilatation & a dec.
in BP
- Helps maintain renal blood flow
Competitive antagonist at a-1 receptors on vascular
smooth muscle.
Effeccts:Vasodilation, reduces peripheral resistance

Central Sympatholytics (a-2
Agonists)
clonidine (Catapres), methyldopa (Aldomet)

clonidine; direct a-2 agonist
- Stimulate Alpha-2 receptors  dec. sympathetic
activity dec. epi., norepi. & dec.renin release 
dec. peripheral vascular resistance


Antihypertensive
Agents
Direct - Acting Arteriolar Vasodilators - potent
Hydralazine (Apresoline) -
Sodium Nitroprusside (Nipride) - Very potent - for
hypertensive Emergencies
- Act by relaxing smooth muscles of bld. vessels - mainly
arteries  vasodilation 
- Increase blood flow to brain & kidneys
- With vasodilation the BP dec., Na & H2O retained 
peripheral edema.
- SE = numerous - tachycardia, palpitations, edema

Antihypertensive Agents
Angiotensin Antagonists - Angiotensin-Converting
Enzyme Inhibitors (ACE inhibitors)
Captopril , Enalapril
- Prevents conversion of Angiotensin I to angiotensin II
(vasoconstrictor) & blocks release of aldosterone.
. Block aldosterone & Na excreted, but & K retained
- - SE = hyperkalemia

Angiotensinogen plus Renin

Angiotensin I

Converting enzyme Captopril
Angiotensin II
Vasoconstriction Aldestrone secretion

SPR Na - water retention
Systemic Hypertension

Antacids
Inhibitors of gastric acid production
H2-receptor antagonists
Proton pump inhibitors
Muscarinic antagonists
Mucosal Protectants
Anti-Helicobacter pylori. drugs

H2-receptor antagonists
Cimetidine （ Tagamet® ）
Ranitidine （ Zantac® ）
Famotidine
Nizatidine
Roxatidine

Dopamine antagonists :
 Metoclopramide
D2-receptor antagonist (periphery)
A weaker antiemetic, fewer extrapyramidal effects.
Accelerates gastric emptying; has little effect on the
colon

States of matter :exists inthe solid, the liquid and

gaseous state depending upon the temperature and
pressure
Vaporizer:-
used to convert liquids into vapour
 It should yield a constant concentration of anaesthetic
agent
 agent calibrated, flow compensated and temperature
compensated

Soda-lime canisters
are constructed of metal or plastic and contain granules of
soda-lime
Consistency (Hardness):- must have specified size,
consistency and degree of hydration
Size:- the granules through wire mesh, they have sizes
between 4 and 8 mesh
Too large granules - will have inadequate surface area
Too small granules - excessive resistance to gas flow


Granules cont’d
Consistency (Hardness):- Exhaust prematurely
Hydration:- For CO2 to react with soda lime a certain
amount of moisture must be present (14-19 %) of
water is incorporated into the soda-lime granule

Chemical neutralization of CO2
Carbon dioxide Elimination
The CO2 absorbents are soda lime and Barlyme.
Soda lime:- A mixture of 90% Ca (OH)2, 5 % NaOH, 1 %
KOH with silicates to prevent powdering
The hydroxides combine with CO2 in the presence of
water to form carbonates

Chemical neutralization of CO2 cont’d
CO2 + H2O → H2CO3
H2CO3 + NaOH → Na2CO3 (rapid) + 2H2O +heat
H2CO3 + Ca (OH)2 CaCO3 (slow) 2H2O + Heat


Signs of exhaustion of Soda-lime
Change of colour of granules and coldness of the canister

Rise in measured ETCO2 on the capnography
Clinically-rise in B/P followed by a fall, ↑ HR
Increased oozing of blood from wound and perhaps
sweating
Application
 Economy in use of gases
Less pollution of the theatre atmosphere
Humidification and warming of inspired gas


Channeling:- is the preferential passage of exhaled
gases via canister via pathways of low resistance such
that bulk of the CO2 absorbent granules are bypassed.
 Scavenging:- is the term applied to collection and
removal of excess gases that normally exit via the
overflow valve of the anaesthetic breathing.


System Gas Rebreathin Chemical Fresh gas

reservoir g of neutralizat inflow rate
bag exhaled gas ion
1. Open No No No Unknown
Insuflation
And open
drop)

2. Semi Yes No No High
The effect on CNS depends on:-

solubility of the agent

The potency of the agent
 The time for which the agents acts on the cell

The main target of inhalation
anesthetics is the brain.

Inhalation anesthetics:
Advantage of controlling the depth of anesthesia.

Metabolism is very minimal.
Excreted by exhalation.

Inhalation anesthetics cont’d
Non-halogenated gas:
Nitrous oxide
Halogenated hydrocarbons:
Halothane
Enflurane
Isoflurane
Desflurane
Sevoflurane
Methoxyflurane – nephrotoxicity.

The important characteristics of Inhalational
anesthetics which govern the anesthesia are :
Solubility in the blood
(blood : gas partition co-efficient)
Solubility in the fat
(oil : gas partition co-efficient)
Alveolar concentration represents brain concentration
after a short period of equilibration

MAC value
MAC value is a measure of inhalational anesthetic
potency.
It is defined as the minimum alveolar anesthetic
concentration ( % of the inspired air) at which 50% of
patients do not respond to a surgical stimulus.
MAC values are additive and lower in the presence of
opioids.

OIL GAS PARTITION CO-EFFICIENT

Inhalation Anesthetic MAC value Oil: Gas
% partition

Nitrous oxide >100 1.4
Desflurane 6 23
Sevoflurane 2 53
Isoflurane
1.15 91
MAC, BP, VAPOR PRESSURE
MAC BP(0C) VP (200C)
Halothane 0.77 50.2 241 mmHg
Enflurane 1.7 56.2 175 mmHg
Isoflurane 1.15 48.5 238 mmHg
Sevoflurane 2.0 58.5 160 mmHg
Desflurane 6.0 23 664 mmHg
N2 O 104

UPTAKE AND DISTRIBUTION
Concentration Effect: The inspired anesthetic
concentration also determines the rate of rise of
alveolar concentration toward inspired concentration
(FA/FI) ratio. The greater the inspired concentration,
the more rapid is the rate of rise in FA/FI ratio. It results
from two factors:
1. A concentrating of the residual gases
2. Increase in inspired ventilation

UPTAKE AND DISTRIBUTION
 Second Gas Effect: Factors governing concentration
effect also influence concentration of any gas given
concomitantly with N2O (Second gas effect
The uptake of one agent may be accelerated if given in
association with high concentration of another agent
(e.g. halothane and N2O).

Second Gas Effect cont’d
Situation A Situation B
N2O 50 % 75 %
O2 49 % 24 %
Halothane 1% 1%

Factors that↑ speed of induction

Inhaled concentration of vapor

Hyperventilation to increase alveolar ventilation
circulation to non-vital organs, shock, dehydration, old
age
High gas flow systems


Characteristics of an ideal inhaled anaesthetic agents
1.A stable molecule, not broken down by light, not

requiring preservatives
2. Non- flammable
3. Low blood solubility to assure rapid induction and
recovery as well as rapid response to changes in

inhaled concentration
4. Pleasant and non- irritating to inhale
5. Devoid of organ-specific toxicity
6.Prepared
Lackby of toxic effect when inhaled in low doses by
Mengesha Abate
Characteristics of an ideal inhaled anaesthetic agents
cont’d
7. Should not undergo metabolism in the body
8. Absence of excessive myocardial depression
9. Should provide analgesia and skeletal muscle
relaxation
10. CNS effects should be readily reversibly
11. Compatible with catecholamines
12. Suppresses excessive SNS activity
13. No interaction with other drugs
14. Cheap to manufacture

Pharmacodynamics of Ether and Halothane

 Halothane Ether
 Myocardial contractility ↓ ↓
 Blood pressure ↓ -
 Cardiac output ↓ -
 Heart rate ↓ ↑
 Sensitization to catechol ++ -
 Bronchodilation ++ +
 CBF ++ +
 Gravid uterus Relaxes Muscle tone
inhibited
↑ PPH as anesthesia
Halothane Metabolism
Undergoes with oxidative and reductive pathways of
metabolism
 halothane preferentially undergoes oxidative
metabolism.
Oxidative metabolites are not likely to be toxic
 reductive metabolism of halothane may
produce hepatotoxicity. in the presence
inadequate O2 delivery to hepatocytes.


Methoxyflurane & N2O Metabolism:
 Undergoes oxidative metabolism with an estimated of 50
% The most significant metabolite is fluoride which is
toxic to the kidneys.
 N2O Undergoes reductive metabolism (0.004 % of an
absorbed dose) to nitrogen is gastrointestinal tract by
anaerobic bacteria

Blood : gas partition co-efficient:
It is a measure of solubility in the blood.
the rate of induction and recovery of Inhalational
anesthetics.
Lower the It determines blood : gas co-efficient –
faster the induction and recovery – Nitrous oxide.
Higher the blood : gas co-efficient – slower induction
and recovery – Halothane.

Blood : gas partition co-efficient:
cont’d

UPTAKE AND DISTRIBUTION of
anesthetics
Tissue Groups: Three tissue groups form depots for
anesthetic within the body.
Vessel rich group (VRG) : Brain, heart, splanchnic
bed, liver, kidney and endocrine
Equilibrates with blood in 4-8 minutes
Muscle group (MG) : Muscle
Fat group (FG) : Equilibration: 70-80 min
 Vessel poor group (VPG)) : Bone , cartilage,
ligaments, tendons-no uptake

STRUCTURE OF DIETHYL ETHE

F H
F – C – C* – Br Halothane
F Cl
F H F
F– C – C* – O – C – H Isoflurane
F Cl F

Halothane (CF3 CHClBr)
Halothane -2-Bromo 2-chloro-1,1;1,trifuoroethane.

Synthesized in 1956 by Suckling
Halogen substituted
Volatile liquid easily vaporized,
 stable, and nonflammable

Properties Of Halothane:-
 Colorless, liquid, sweet, pleasant
MW 197, specific gravity 1.86, BP 50.20C,
SVP 243 mmHg ,MAC 0.75
Partition coefficients:- B/G 2.3, oil/gas 225
Non-inflammable, corrode aluminum, tin and certain
alloys in the presence of moisture.
Decomposed by light (stabilized by 0.01 % thymol),
stored in amber coloured bottles.
Absorbed into rubber

Halothane
Most potent inhalational anesthetic
MAC of 0.75%
Efficacious in depressing consciousness
Very soluble in blood and adipose
Prolonged emergence
Inhibits response to painful stimuli
Inhibits sympathetic driven baroreflex response
(hypovolemia

Halothane cont’d
It is a potent anesthetic.
Induction is pleasant.
It sensitizes the heart to catecholamines.
It dilates bronchus – preferred in asthmatics.
It inhibits uterine contractions.
Halothane hepatitis and malignant hyperthermia can
occur.

Pharmacodynamics:-
CNS:- Smooth rapid induction with rapid

recovery
Potent anaesthetic but not a good analgesic
↑ CBF and ↑ CSF
CVS:- Myocardial depression, -- lowers BP and
slows
conduction
bradycardia via increased vagal tone
Mild peripheral vasodilation.
 central vasomotor depressant actions.
 Mild peripheral vasodilation
Pharmacodynamics cont’d:-
Rs:- Non-irritant, pharyngeal, laryngeal and

cough reflexes are abolished early,
respiratory depressant, bronchodilation
dose dependent uterine relaxation - cause uterine
atony and PPH, useful if used in low con. (0.5 %)
Shivering: immediate post op.
Halothane hepatitis -- 1/10,000 cases fever,
jaundice, hepatic necrosis, death

The risk of liver dysfunction is increased in the
following
Hypoxemia
Obesity
Short interval between halothane anaesthesia
Severe circulatory shock
 avoidance of halothane previous exposure within 3
months
history of unexplained jaundice after previous
exposure to halothane


Halothane Side Effects
Malignant Hyperthermia-- 1/60,000
Classic-- rapid rise in body temperature,
muscle rigidity, tachycardia, acidosis,
hyperkalemia, DIC
most common masseter rigidity,family history
diagnosis--previous symptoms, increase CO2, rise in
CPK levels, myoglobinuria, muscle biopsy
physiology--hypermetabolic state by inhibition of
calcium reuptake in sarcoplasmic reticulum

Treatment of MH-
-early detection, d/c agents, hyperventilate, bicarb, IV
dantrolene (2.5 mg/kg), ice packs/cooling blankets,
lasix/mannitol/fluids. ICU monitoring
Susceptible patients-- preop with IV dantrolene, keep
away inhalational agents and succinylcholine

Enflurane:
Developed in 1963 by Terrell, released for use in 1972

Stable, nonflammable liquid
Pungent odor MAC 1.68%
Sweet and ethereal odor.
Generally do not sensitizes the heart Cathec..
Seizures occurs at deeper levels –contraindicated in
epileptics.
Caution in renal failure due to fluoride.

Enflurane cont’d:
Metabolism one-tenth that of halothane-- does not

release quantity of hepatotoxic metabolites
Metabolism releases fluoride ion-- renal toxicity
Epileptiform EEG patterns

Isoflurane
Synthesized in 1965 by Terrell, introduced into
practice in 1984
Not carcinogenic
Nonflammable,pungent
Less soluble than halothane
MAC of 1.30 %

Isoflurane cont’d
Depresses respiratory drive and ventilatory responses--
less than enflurane
Myocardial depressant-- less than enflurane
Inhibits sympathetic baroreflex response-- less than
enflurane
Sensitizes myocardium to catecholamines -- less than
halothane or enflurane
 coronary steal syndrome, increased ICP
Excellent muscle relaxant-- potentiates effects of
neuromuscular bloc

Isoflurane cont’d
Little metabolism (0.2%) -- low potential of
organotoxic metabolites
No EEG activity like enflurane
Bronchoirritating, laryngospasm

Comparisono of halothane
isoflurane and enflurane
Feature Halothane Isoflurane Enflurane
Thymol Yes No No
required
Solubilityin ++ + +
rubber
Decompsed Yes No No
by light
Irritant to No Yes Yes

airways
Cardiac
Prepared by output ↓↓
Mengesha Abate ↓ ↓↓↓
Sevoflurane and Desflurane
Low solubility in blood-- produces rapid induction and
emergence
Minimal systemic effects-- mild respiratory and
cardiac suppression
Few side effects
Expensive

Sevoflurane:
Induction and recovery is fast.

It is pleasant and acceptable due to lack of pungency.
It does not cause air way irritation.

Desflurane:
It is delivered through special vaporizer.

It is a popular anesthetic for day care surgery.
Induction and recovery is fast, cognitive and motor
impairment are short lived
It irritates the air passages producing cough and
laryngospasm.

Ethers R-O-R
CH CH -O-CH CH (diethyl ether)
3 2 2 3
 very important organic solvent,
 Bp = 35o.
Very flammable & forms explosive peroxides.
Synthesis for diethyl ether:

 2 CH3CH2-OH + H2SO4, 140oC  CH3CH2-O-
CH2CH3 + H 2O

Nitrous Oxide
Prepared by Priestly in 1776
Anesthetic properties described by Davy in 1799
Characterized by inert nature with minimal
metabolism
Colorless, odorless, tasteless,not support burn
Not metabolized
Only anesthetic agent that is inorganic

Nitrous Oxide cont’d
Major difference is low potency
MAC value is 105%
Weak anesthetic, powerful analgesic
Needs other agents for surgical anesthesia
Low blood solubility (quick recovery
Minimal effects on heart rate and B/P
Little effect on respiration
Safe, efficacious agent

Nitrous Oxide cont’d
Large volumes of gases can be used
Beginning of case: second gas effect
End of case: diffusion hypoxia
Inhibits methionine synthetase (precursor to DNA
synthesis)
Inhibits vitamin B-12 metabolism
Dentists, OR personnel at risk
Caution about diffusional hypoxia megaloblastic
anemia

Disadvantages of Nitrous Oxide
Weak anaesthetic agent

Deep plane of anaesthesia is very difficult
Diffusion hypoxia
Effect on closed gas spaces
Toxicity:- N2O affects vit B12 synthesis
Teratogenic Changes

Nitrous oxide
May see transient decrease in Oxygen
Use of pulse ox upon discontinuing
of Nitrous Oxide (wash out effect)
Always monitor with pulse ox and
provide appropriate supplemental
oxygen if needed!

Nitronox-Properties
Blended mixture of 50% nitrous oxide and
50% oxygen
 Also known as “laughing gas”
 Produces sedation and analgesia
 Colorless, odorless, heavier than air
Nonexplosive, nonflammable
Readily diffuses through membranes
(rapid onset, short duration after inhalation
is stopped)

Nitronox- Properties (cont.)
 Diffuses through tissues more easily than oxygen

 Should not be used in conditions where there may be
abnormal collections of air
 Gas may collect in these areas and make condition
worse
 *COPD (blebs)
 *pneumothorax
 *bowel distension due to bowel obstruction

Oxygen
1. Oxygen is a colorless, odorless, and tasteless gas
2. Oxygen makes up 21% of the atmosphere
5. Oxygen supports combustion but does not burn
6. It is an extremely active chemical
7. Oxygen can form compounds with almost all elements
except inert gases
8 Oxygen is denser than “air”
9. It is a gas at room temperature

Oxygen Preparation
Oxygen was discovered in 1772 by priestley. Oxygen
is manufactured commercially by fractional distillation
of liquid air.
 prepared by fractional distillation- Before liquefaction
of air, carbon dioxide is removed and liquid oxygen and
nitrogen are separated by means of their different boiling
points.
 (Oxygen - 183 0C, Nitrogen - 195 0C).

gas

Oxygen is available as the compressed gas in steel

cylinders.
Pipe lines from central gas supply tank.
O2 concentrators at 137 bar.
 Oxygen cylinders are colour coded and some form of
mechanical indexing of valve connections

Therapeutic Uses of oxygen
Correction of hypoxia
Reduction of the partial pressure of nitrogen
Oxygen as a carrier
Hyperbaric Oxygen:- In carbon monoxide poisoning,
hemoglobin becomes unavailable for O2 binding because of
the high affinity of CO for these patient.
Oxygen transport in the blood into two forms
 a. In chemical combination with Hgb
b. Physically dissolved in plasma

Oxygen cont’d
Dissolved Oxygen:- Only about 1 % of the oxygen
carried in the blood is in the dissolved state and the
remainder is carried by Hgb
Oxy - hemoglobin dissociation:- Oxygen that remains
bound to Hgb can not participate in tissue metabolism
 The relationship between the O2 carried in combination
with Hgb and the PO2 of the blood is described by oxygen -
hemoglobin - dissociation curve.
 The curve is S-shaped with the top flat portion representing
the binding of O2 to the hemoglobin in the lung and steep
portion representing its release into the tissue capillaries
The oxygen-hemoglobin
dissociation curve

. Effect of Carbon Monoxide (CO)
CO combines Hb at the same point as does O2, and can
displace O2 from hemoglobin.
CO binds with about 250 times as much tenacity as O 2.
Therefore, a PCO only a little greater than 0.4 mmHg

can be lethal.

Calculating oxygen content
With the Hb concent . Oxygen combines chemically
with the hemoglobin in a unit volume of blood;
It amounts to 1.34 ml of O2 per gm of Hb or 20 ml of
O2 per 100 ml of blood.
 Gram percent (gm.%) = grams of Hb. Per 100 ml. of
blood. Volume percent (vol.%) = milliliters of O2 per
100 ml. of blood.

Calculating oxygen content cont’d
Steps:-
 Hb. Content (gm%) x 1.34 x SO2 = Oxygen
attached to Hb. (Vol%)
 PO2 x 0.003 = Oxygen dissolved in plasma (Vol.
%)
Steps 1 + 2 = Oxygen content (Vol. %)
Example: Hb. 15 gm.%, PO2 100 mm Hg, SO2
100%.
 15 x 1.34 x 1.00 = 20.10 Vol. %
100 x 0.003 = 0.30 Vol. %
 Oxygen content = 20.40
Oxyhemoglobin Formation

 An oxygen molecule reversibly attaches to the heme

portion of hemoglobin.
 The heme unit contains iron ( +2 ) which provides the
attractive force.
 The iron stays in the ferrous state, so that the
reaction is an oxygenation, not an oxidation

Methaemoglobin:- consists of Hb. in which the iron
is present in the ferric (Fe+++) form rather than ferrous
form (Fe++) & is unable to combine with O2.
It shifts the oxy-Hg. dissociation curve to the left
making it more difficult for Hb. to release O2 to
tissues.
Treated by administration methylene blue (1-5 mg/kg.
IV) or with ascorbic acid (2 mg/kg).

Types of O2 lack (Hypoxia
 HYPOXic Hypoxia (DECREASED TISSUE OXYGEN
TENSION)
 CAUSES:
 A. V/Q MISMATCH
 B. SHUNT (EX: ATELECTASIS, PULM. EDEMA)
C. HYPOVENTILATION (EX: DRUG INDUCED
 . ANEMIC HYPOXIA (DEFICIENT OXYGEN-
CARRYING CAPACITY of the blood
 CAUSES:
A. ANEMIA (DECREASED HEMOGLOBIN)
 B. CARBON MONOXIDE POISONING
 C. METHEMOGLOBIN

TYPES OF HYPOXIA
CONTINUED
 CIRCULATORY HYPOXIA (DECREASE
PERIPHERAL CAPILLARY BLOOD FLOW)
CAUSES:
CO & Vascular insufficiency
Histotoxic hypoxia--- cyanide toxicity

Oxygen toxicity
Pulmonary Oxygen Toxicity

Retinopathy of prematurity (ROP)
CNS toxicity

compressed gas (oxygen)

1.Never permit oil or grease combustable

material to come in contact with cylinder
2. Note the cylinder contains sufficient gas
3. There should always be one full cylinder in
addition to the cylinder being used
Never permit oil or grease combustable material to
come in contact with
 4. Never lubricate regulators or gauges
5. Never drape a cylinder with sheets

Recommended cont’d
6. Open the valve on the cylinder before
connecting the apparatus to the patient
7. Open cylinder valve slowly
8. Turn on the flowmeters and see the bobbin
spins freely. If the bobbin is not spinning, it may be

stuck to the walls of the tube and the flow rate may be
inaccurate.

Blood and Blood Product Transfusion
You should be familiar with each of these blood
products. What are their indications and the
complications associated with them?
Whole Blood
Packed Cells
Platelets
Fresh Frozen Plasma (FFP)
Cryoprecipitate

Blood Type
categorized according to antigens on red blood cells
Type A: A antigens
Type B: B antigens
Type O: no antigens (universal donor)
Type AB: A and B antigens (universal recipient)
D antigen, third antigen; may be present on the red
blood cells
a. Rh factor positive: D antigen is present
b. Rh factor negative: D antigen is not pres

The Principle Aims of Blood
Transfusion
(1) Improve oxygen carrying capacity of

blood.
(2) Symptomatic improvement.
(3) Reduce hypovolaemia.

 1 UNIT of Blood should increase the Hb
by approx.1g/dL.
 If no improvement or reduction in Hb –
think about ongoing blood loss or
destruction.
 You need treat the underlying cause.
Indications for Blood Transfusion
Acute Anaemia
(1) Symptomatic hypovolaemia and blood loss.
(2) Peri-operative – ‘replacing losses’
(3) Haemolysis (treat the underlying cause)
(4) Severe, critical illness.
 Increase oxygen carrying capacity of blood
- Young adults can tolerate 30 – 40% volume loss with

adequate crystalloid replacement alone

‘Keep the Hb ≥ 10 g/ dL’
(2) Peri -operative
Much quoted by Anesthesia Providers still - ‘Keep the
Hb ≥ 10 g/ dL
- but- believed Patients tolerated Hb 8 – 10
g/dL
(3) Severe and critical illness
Oxygen delivery is dependent on:
(a) Cardiac output (c.o.)
(b) Oxygen content of blood

Blood transfusion Cont’d
Blood transfusion:- Blood is normally transfused to
provide Hgb for transportation of O2 to the tissues.
Sometimes blood or blood products are given to
provide clotting factors or platelets in patients with
coagulation failure.
Autologous Transfusion:- The patient’s own blood
can be retransfused during surgery

Autologous Transfusion cont’d
The blood in the peritoneal cavity is collected less than 6
hours old and not contaminated by bile or intestinal
contents. patients with ruptured spleen, ruptured ectopic
pregnancy are the most suitable.
Never leave a unit of blood out of fridge for longer than
30 minutes.
 Check that the blood is the correct group and the name,
expiration date and number on both the label and the form
match with the patient card number.

Methods of autotransfusion

A. Pre-deposit
B. Salvaging of blood at the operation
Pre-deposit of blood:- Collection of the patients own
blood prior to elective surgery
The deficit is normally corrected within 3 to 5 days
Check the Hb. conc. immediately prior to operation to
ensure that the patient has
 compensated for the deficit
-

Methods of autotransfusion cont’
Useful:-
i. Where there is a refusal of patients
ii. Patients requiring transfusion with a rare blood
group & donors of compatible blood
cannot find
iii. Where there are no or only limited blood bank
facilities available

The salvaging of blood lost into body cavities & its

subsequent re-infusion back into the patient can be a
lifesaving measure
useful in severe blood loss where there are delays in
obtaining compatible blood from donors

Salvaging of blood cont’d
v. The blood being salvaged should be sterile - there
should be not contamination with
the contents of the bowel or other sources of infection

Changes to blood due to storage

 Oxygen - carrying capacity is reduced due to

deteriorating red cell function during storage.
 Platelet function declines rapidly so that after 48 -
72 hours of storage
 Hyperkalemia. plasma contains 3.5 meq./L
 Deterioration of cougulation factors
 Citrate toxicity: Ca being tied up with citrate
 . Hypothermia

Changes to blood due to storage
cont’d
 Fall in 2, 3 DPGs
 Massive transfusion
 Circulatory overload
 . Metabolic acidosis

Some information about blood
donors
1.Health persons -18 to 60 years of age.
2. Should not donate greater than 2 to 3 times\year.
3. Hypertensive donors are always at risk
4 Avoid donors suffering from infectious diseases such as:-
HIV, Hepatitis, Malaria, Syphilis, CA etc..
5. Donors should have a light meal 2hrs before donation
6. Blood should be taken from the donor by skilled personel.


Blood may be collected in CPDA (ACD old system

* The first step is proper identification of the unit & pt.
* Medictons should not be given with blood
* Once released from the blood bank donate (within 30
minutes)
* Special transfusion sets are used
* The set should have special micro-aggregate filters (special
filters with size 20 - 40 microns.
* Pressure is not required for ordinary Trans.

Transfusion &Tech.Of Admin.cont

* If pressure is required, simple elevation of the bag

When large unit to be given rapidly, special pressure
devices
* B/p cuff does not exert a uniform pressure
Warm the blood (370C) before adm.
 Many physiological solutions are not compatible
(except N/S).


Ringer lactate causes clotting, Dextrose solutions
(cause clumping of cells)
* Identify immediate adverse reactions
* Sudden fall of B/p and profuse bleeding from
operation site in anaesthesized patient

Blood transfusions are run through specific giving sets

with a filter included in the chamber and wide bore
tubing.
You can NOT run them through a normal giving set as
without the filter the blood will coagulate.

To calculate drip rates / transfusion rates
For any giving set the tubing will have its own drop
factor. This is the number of drops in 1ml.
The drop factor is written on the packaging and is
dependent on the bore of the tubing.
Common drop factors are 10, 15 and 20 gtt / min
Paediatric drips commonly have a drop factor of 60 gtt
/min

Blood type and crossmatch
Blood type and Rh factor status crossmatched
Blood transfusion reactions:

Fever and chills within first 15 minutes
hives and itching during or after transfusion

Hemolytic reaction
most dangerous: ABO incompatibility
RBCs clump and block capillaries
decreased blood flow to vital organs
Manifestations: lumbar, abdominal and/or chest pain,
fever, chills, urticaria, nausea and vomiting
Occurs after 100 – 200 ml of incompatible blood
infused

Blood transfusion cont’d
Signs of incompatible blood transfusion
In anaesthesized patient.
 hypo tension, tachycardia, cyanosis, skin rash
 engorgement of neck veins- circulatory overload
oozingof blood from wound
collapse and renal failure (most serious complications)


Blood transfusion
Assessment of vital signs prior to transfusion
2 health personnels verify correct client and unit of
blood are correctly matched
Direct observation of client during first 15 minutes of
infusion
Check vital signs according to protocol

Mx of Blood transfusion reaction
1. Stop transfusion immediately
2. Continue IV infusion with normal saline
3. Provide care for client as indicated
4. Complete reaction form according to institution
protocol.
5. Obtain urine specimen from client and send for free
hemoglobin.
6. . Frusemide 80 mg. IV

Mx of Blood transfusion reaction
cont’d
5. O2 and steroids in high dose
6. Treat bronchospasm
7. The following must be sent to the boratory
 The remaining blood in the bottle
 A sample of the patients blood
 A sample of the patients urine

Fluid Management and
Replacement
Division of Adult Fluid Compartment
Based on Body Weight
40% of body weight -Intracellular Fluid
15% of bodyweight -Interstitial Fluid
5% of body weight -Blood Plasma

Intraoperative Fluid Requirement
4 ml per kg per hour for 1-10 kg
 2 ml per kg per hour for 11-20 kg
 1 ml per kg per hour for 21 kg and up

EG: fluid maintenance requirements for 60 kg .
The first 10 kg multiplied by 4 ml and equals 40 ml.
For kg 11-20, multiply 10 kg by 2 ml per kg. equals 20
ml.
The remaining 40 kg is multiplied by 1 ml equals 40 ml.
40 + 20+ 40 = 100 ml.
The patient should receive 100 ml per hour in
maintenance fluid.

Insensible Fluid Loss
This fluid is lost by evaporation from the
respiratory tract, sweating, and elimination. Insensible
fluid loss is calculated by multiplying 2 ml per kg per
hour of surgery.
Fluid Replacement Based on Surgical Trauma
Minimal Trauma 3-4 ml/kg/hour
Moderate Trauma 5-6 ml/kg/hour
Severe Trauma 7-8 ml/kg/hour

Blood Loss
Blood loss is replaced with 3 ml of IV solution for
every 1 ml of blood loss.
Blood loss is replaced with 3 ml of IV fluid for every 1
ml of blood loss

Putting It All Together
Fasting Fluid Deficit
1 ml per kg per hour for 21 kg on up
Maintenance Fluids
1 ml per kg per hour for 21 kg on up
Insensible Fluid Loss 2 ml per kg per hour

Fluid Requirements Based on
Surgical Trauma
minimal trauma = 3-4 ml per kg per hour
moderate trauma= 5-6 ml per kg per hour
Trauma severe trauma = 7-8 ml per kg per hr
Example: calculate the fluid requirement for 60kg
patient

Total fluid replacement.
1st Hour 2nd Hour 3rd Hour 4th Hour
Fluid Deficit
Maintenance
Fluid
Surgical
Trauma
Blood Loss

Total
Fluid Management and
Replacement
Calculate the fasting fluid deficit for a patient who
weighs 60 kg. The patient has fasted
for 8 hours.
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Clinical Pharmacology For Anesthetists

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Clinical Pharmacology For Anesthetists

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CLINICAL PHARMACOLOGY

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 7. Possession of a simple generic name

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 Which agent/technique should I use?

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An early anesthetic agent.

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• The classic description of anaesthetic

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Receptor Natural ligand Agonist Effect

B- Adrenaline Sulbutamol Bronchodiltation

Opiate Endorphins/ Morphine Analgesia

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Receptors: are specific proteins that interact selectively

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Enzyme inhibitors : decresae metabolism of

Alter neurotransmitter release /drug transportation

Alter water/electrolyte balance

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 Plasma protein binding

Drug binding (%) Plasma Protein

Diazepam, warfarin 95-99

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 Sensitization of the myocardium to catecholamines