GENERAL ANESTHETICS

INHALATION AGENT (I.A)

GENERAL INFO.  Because of their unique route of administration, I.A has useful pharmacological properties not
shared by other anesthetic agents.
 Exposure to the pulmonary circulation allows a more rapid appearance of the drug in arterial
blood than intravenous administration.
 The most important route for elimination of inhalation anesthetics is the alveolus.

ACTIONS Immobility
 It can be measured. Minimal alveolar concentration (MAC) measures the potency of an
General inhalational anesthetic. 1.0 MAC is the partial pressure of an inhalational anesthetic in the alveoli
anesthetics work of the lungs at which 50% of a population of patients are immobile at the time of a skin incision
by altering the
flow of sodium Amnesia
molecules in to  The ablation of memory arises from several locations in the CNS, including the hippocampus,
nerve cells or amygdala, prefrontal cortex, and regions of the sensory and motor cortices. (0.2–0.4 MAC)
neurons through
the cell membrane Unconsciousness
 Cerebral cortex, the thalamus, and the reticular activating system Malignant hyperthermia:

RESPIRATION  Depressed respiration and response to CO2 *All Inhalation agents, worst
with Halothane.
KIDNEY  Depression of renal blood flow and urine output
MUSCLE  High concentrations relax skeletal muscle *Treatment
CVS  Reduction in arterial pressure , peripheral vascular resistance. : Rapidly cool the individual
CNS  Increase cerebral blood flow and decrease cerebral metabolism. : Administer Dantrolene
 Halothane to be used with caution in Intracranial mass lesion.
UTERUS & FOETUS  Dose dependent relaxation of uterus, depresses fetus
EXAMPLES INDICATION M.O.A SIDE EFFECTS
Halothane Generally used as maintenance agent but also for induction in *Sensitizes the heart to
(Halogenated children Adrenaline ® risk of arrhythmia.
alkene) Potent, non-irritant, sweet smelling halogenated hydrocarbon (Use Adrenaline with care).
Excellent anesthetic but no analgesia. *Repeated use may cause
Dose-dependent depression of CVS and RS hepatitis
↓ airway resistance, bronchodilator

Isoflurane Potent Anesthetic, Quick induction, Irritant  Cause coronary steal.

(Halogenated CNS: Little analgesia,↑ CBF  Metabolized in liver.
Ether) CVS : ↓ SVR → ↓ B.P  Excreted as Fluorinated
Does not sensitize myocardium to cause arrhythmias compounds.
→ Renal toxicity.

Sevoflurane Rapid action, recovery, non irritant Less nausea, sedation,

Does not cause coronary steal hypotension

Desflurane Rapid onset, recovery Requires special electrically

Protect from light heated vaporizer
Minimum Atmospheric pollution
Good analgesia , anesthesia
Bronchodilatation

Nitrous oxide Anesthetic gas with mild analgesic potency May ↑ PVR in pts with
(Inorganic gas) Must be combined with other sedatives, analgesics, and anesthetic Pulmonary hypertension
medicines to provide full general anesthesia. Diffuse into air filled spaces
Used as carrier gas for anesthetic vapors and as a supplement to 34x faster than Nitrogen
anesthesia bowel, middle ear,
50% mixture in O2 (Entonox) used in obstetric analgesia, dentistry, pneumothorax, ↑ size of air
emergency & disaster medicine embolus (increased air in closed
air spaces)
Megaloblastic anemia
with long term use of N2O  pernicious anemia
peripheral neuropathy
 GENERAL ANESTHETICS

Inhalation B:G PC O:G PC Features Notes

Anesthetic
Halothane 2.3 220 PLEASANT Arrhythmia
Hepatitis
MH
Enflurane 1.9 98 PUNGENT Seizures
MH
Isoflurane 1.4 91 PUNGENT Widely used
MH
Sevoflurane 0.62 53 PLEASANT Ideal
MH
Desflurane 0.42 23 IRRITANT Cough
MH

Nitrous 0.47 1.4 PLEASANT Anemia

MH

Intravenous Duration mins Analgesia Muscle Others

anesthetic relaxation
Thiopental 5 - 10 --- --- Respiratory
depression
Propofol 5-10 --- --- Respiratory
depression
Ketamine 5-10 +++ --- Hallucinations
Midazolam 5-20 --- +++ Amnesia
Fentanyl 5-10 +++ --- Respiratory
depression

INTRAVENOUS AGENT
 GENERAL ANESTHETICS
USES  Induction
 Maintenance and supplement
 Sedation
 Control blood pressure
 Status epilepticus

EXAMPLES INDICATION M.O.A SIDE EFFECTS

Thiopentone  Ultra-short acting (redistribution of peripheral) barbiturate, no  Anaphylaxis
(barbiturates) analgesia, can cause anti Analgesia. (↑pain sensitivity)  bronchospasm
 Administered usually I.V. inducing sleep within 30 sec. Effect lasts  Intra arterial
20 mins. injections can
 Recovery fast but depends on its redistribution to less perfused cause tissue
tissues (fat). necrosis
 Metabolized by liver.  Acute intermittent
 Depresses heart, respiration in a dose dependent manner porphyria in
Hypotension, and tachycardia. suspected
 ↓ cerebral blood flow, ↓ ICP, used in Status epilepticus. individuals

Propofol White milky emulsion, no preservative PROPOFOL INFUSION

(barbiturates) Facilitation of inhibitory neurotransmission mediated by GABA. SYNDROME:
 Rapid onset (11-15 s) & recovery
 No anti analgesic effect  rhabdomyolysis
 Depresses resp; apnea of 30 - 60 s may occur  acute renal failure
 Causes hypotension  metabolic acidosis
 98% protein bound; highly lipophilic  hyperkalemia
 Rapid recovery, no nausea / hangover ® day case  ventricular
 Can be used as an anti epileptic agent in Status Epilepticus arrhythmia
 Propofol is rapidly metabolized by hepatic and extra-hepatic  hyperthermia
metabolic pathways. Recovery is rapid due to its short distribution  death
half life
 Propofol is non cumulative. Thus it can be used for prolonged
anesthesia by intermittent injection or by continuous infusion
 Used in the ICU for sedation

Etomidate  Appears to bind to a subunit of the GABA type A receptor  suppression of

(barbiturates)  Rapid onset adrenal cortex-
 Safe cardiovascular profile, useful in haemodynamically unstable sepsis (long term
patients. use)
 Limited suppression of ventilation, lack of histamine liberation and
protection from myocardial and cerebral ischemia.
 Only anesthetic agents able to decrease intracranial pressure and
maintain a normal arterial pressure.
 Useful in Traumatic Brain Injury.
Ketamine:  Potent analgesic and amnestic  Causes
Phencyclidine  Hallucinogenic hallucination
derivative  Blocks CNS excitatory (NMDA) receptor  But ↓ with BDZ
(non-  Causes dissociative anesthesia (sensory loss, analgesia, amnesia, (e.g. midazolam)
barbiturates) paralysis of movement without actual loss of consciousness)
 Characterized by active pharyngeal and laryngeal reflexes,
bronchial dilatation (useful in asthmatics)
 Sympathetic activity ® BP, TPR, HR, ICP and respi. rate
(Useful in hypovolemia / hypotensive pts and c/i in ICP)
 Common procedures undertaken with ketamine anesthesia include
minor orthopedic surgery (especially distal arm or lower leg
surgery including manipulation of fractures), gynecological surgery
(eg. dilatation and curettage) and other minor surgical procedures
(drainage of abscesses, debridement of burns, change of dressings)
and minor dental procedures, as well as a variety of examinations
under anesthesia.
 GENERAL ANESTHETICS

Midazolam  Only BDZ used as induction agent. ANTEDOTES:

(benzodiazepine)  Main use: hypnotic, sedative  Benzodiazepines
 anxiolytic are reversed with:
 Anterograde amnesia FLUMAZENIL
 anticonvulsant (Anexate,
 centrally acting muscle relaxant Romazicon).
 Acts on BDZ receptor
 Sleep dose 0.3 mg/kg (onset of sleep 2-5minutes) *(sodium amobarbital
 Lower doses (0.05 – 0.1 mg/kg) for sedation and amnesia 200mg)*
 More potent than DIAZEPAM OR LORAZEPAM and has quick
 Some anxiogenic &
recovery
pro-convulsant
 May depress respiration when used with narcotics and in large
activity (esp in Pt
doses
on tricyclic
 Minimal cardiac effects
antidepressants)
 Water soluble (diazepam not so)
 Used in hepatic
 Can be given by intranasal and buccal routes apart from IV, IM.
encephalopathy /
 Premedication alcohol-induced
 Anticonvulsant in status epilepticus or as anti-hallucinatory with coma
ketamine
 Highly protein bound ® effect in hypoalbuminaemia
 Metabolized in liver to 4-hydroxymidazolam (not active)
 Prolonged elimination in elderly and major surgery (due to
¯hepatic blood flow)
 No irritant effect i.v.

Narcotics  Used for years for analgesic action-- civil war for wounded soldiers  effects nausea
agonist (opiods)  Predominant effects are analgesia, depression of sensorium and  chest wall rigidity
respiration  seizures
 Mechanism of action is receptor mediated  constipation,
 Minimal cardiac effects-- no myocardial depression urinary retention
 Respiratory depression  Bradycardia in
 Reduce cerebral oxygen consumption, cerebral blood flow, and large doses
intracranial pressure, but to a much lesser extent than barbiturates
or benzodiazepines.
 Some peripheral vasodilation and histamine release – hypotension
 For postoperative pain relief and as adjunct to other anesthetic
agents
 MORPHINE, ALFENTANIL, FENTANYL, SUFENTANIL ,
REMIFENTANIL are commonly used usually in combination with
another agent like midazolam.
 NALOXONE is a pure antagonist that reverses analgesia and
respiratory depression.
 REMIFENTANIL can be administered as part of an anesthesia
technique called TIVA (Total Intravenous Anesthesia) using
computer controlled infusion pumps in a process called target
controlled infusion or TCI. A target plasma concentration is entered
as ng/ml into the pump, which calculates its infusion rate
according to patient factors like age and weight.
 GENERAL ANESTHETICS

DEFINITION OF G.A:
 Agents which produce reversible loss of consciousness by modifying the function of ligand gated ion channels of
nerve cell membranes are called General Anesthetic
 General anesthesia: Altered physiological state characterized by reversible LOC, analgesia of entire body, amnesia &
some muscle relaxation.

ESSENTIAL COMPONENT OF G.A:

 Analgesia
 Unconsciousness
 Amnesia
 Muscle relaxation
 Inhibition of autonomic reflexes * these terms together emphasize the role of immobility and of insensibility!

MODE OF ACTION:
 General anesthetics ↓ response to noxious stimulation by ↓neurotransmission at multiple sites in the cerebral
cortex, brain stem, and thalamus
 Spinal cord
 I.V agents through GABA receptors.
 Inhalation through GLYCINE receptors
 Multiple molecular targets are involved
 The targets are protein sites, mostly ion channels

MOLECULAR SITE OF ACTION:

 Chloride channels –GABAA (by increasing conductance through Chloride channels) and glycine receptors
 Potassium channels (K2P, possibly Kv, and KATP channels) remain the primary inhibitory ion channels.
 Excitatory ion channel targets include those activated by acetylcholine (nicotinic and muscarinic receptors), and
N-methyl-D-aspartate [NMDA] receptors), or by serotonin (5-HT2 and 5-HT3) receptors
 GENERAL ANESTHETICS

PRACTICAL APPROACH TO G.A:

 Premedication
 Induction of anesthesia (usually with i.v. anesthetics).In children halothane, sevoflurane
 Maintenance of anesthesia (usually with inhalational + opioid+ intravenous agents)
 Termination/ reversal of anesthesia. Switch off all agents. Reverse effects of muscle relaxants.
 Post-op analgesia