INHALATION ANESTHETICS

PRECEPTOR:
dr. Ernita, Sp.An

BY:
Putri Anggraeni Kusumawardhani
161 0221 026
Definition
• agent that possess anaesthetic qualities that are
administered by breathing through an
anaesthesia mask or ET tube connected to an
anaesthetic machine the substances that are
brought into the body via the lungs and are
distributed with the blood into the different
tissues
• 5 inhalation agents continue to be used in
clinical anesthesiology:
▫ nitrous oxide (N2O)
▫ Halothane
▫ Isoflurane
▫ Desflurane
▫ sevoflurane
• Administration via the pulmonary circulation 
more rapid appearance of the drug in arterial
blood than intravenous administration
Pharmacokinetics
• There are many steps in between the anesthetic
vaporizer and the anesthetic’s deposition in the
brain
• >> the fresh gas flow rate  << the breathing
system volume & <<the circuit absorption the
closer the inspired gas concentration will be to
the fresh gas concentration
Alveolar gas concentration

Uptake

• Concentration of a gas  directly

proportional to its partial pressureslow to
rise
• The alveolar partial pressure determines
the partial pressure of anesthetic in the
blood in the brain  directly proportional
to its brain tissue concentration 
determines clinical effect.
Uptake

• 3 factors affect anesthetic uptake:

• Solubility in the blood
• alveolar blood flow
• difference in partial pressure
between alveolar gas and
venous blood.
Solubility in the blood
• Nitrous oxide << soluble in blood
than halothane
• >> the blood/gas coeffi cient the
greater the anesthetic’s solubility
 the greater its uptake by the
pulmonary circulation
• consequence of >> solubility 
alveolar partial pressure rises
more slowly induction is
prolonged

blood/gas solubility :
• ↑ by postprandial
lipidemia
•↓by anemia
 Alveolar blood flow

• Cardiac output >>  anesthetic uptake increases 

the rise in alveolar partial pressure slowsinduction
is delayed
The partial pressure difference between
alveolar gas & venous blood
• If anesthetics did not pass into organs  no pulmonary
uptake
• The transfer of anesthetic from blood to tissues is
determined by three factors :
•Tissue solubility of the agent (tissue/blood partition
coefficient)
•Tissue blood flow
•The difference in partial pressure between arterial blood
and the tissue.
Ventilation

• The effect of increasing

ventilation will be most obvious
in raising the Fa /Fi for soluble
anesthetics
• Anesthetics depress
spontaneous ventilation (eg,
ether or halothane) will ↓ the
rate of rise in alveolar
concentration
Concentration

• The concentration effect is more

significant with NO than with the
volatile anesthetics
• ↑ concentration of NO will augment
not only its own uptake, but
theoretically that of a concurrently
administered volatile anesthetic
• Recovery from anesthesia depends on lowering
Elimination
the concentration of anesthetic in brain tissue
• Can be eliminated by:
▫ Biotransformation  Igreatest impact is on the
elimination of soluble anesthetics that undergo
extensive metabolism (eg, methoxyfl urane)
▫ Transcutaneous loss  insignificant
▫ Exhalation  most important route
• Elimination of N2O is so rapid that alveolar
oxygen and CO2 are diluted
• diffusion hypoxia is prevented by
administering 100% oxygen for 5–10 min
after discontinuing NO
• Inhalational agents interact with numerous ion
Pharmacodynamic
channels present in the CNS and peripheral nervous
system
• Mechanism:
▫ Inhibit N -methyl- D -aspartate (NMDA) receptors
(excitatory receptors in the brain)
▫ Gamma-aminobutyric acid [GABA]-activated Cl-
channel conductance
▫ Act on multiple protein receptors that block
excitatory channels and promote the activity of
inhibitory channels affecting  neuronal activity
▫ Nicotinic acetylcholine receptors
ANESTHETIC NEUROTOXICITY
• In animal studies :
▫ Isoflurane exposure promotes neuronal apoptosis
and subsequent learning disability.
▫ Volatile anesthetics have been shown to promote
apoptosis by altering cellular calcium homeostatic
mechanisms
MINIMAL ALVEOLAR CONCETRATION
• The alveolar concentration that prevents
movement in 50% of patients in response to a
standardized stimulus (eg, surgical incision)
NITROUS OXIDE (N2O)
• Physical Properties:
▫ Colorless
▫ Odorless
▫ Nonexplosive
▫ Nonflammable
▫ Inexpensive anesthetic
• Efects on organ systems:
▫ Cardiovascular  arterial
blood pressure, cardiac output,
and heart rate are essentially
unchanged or slightly
elevated because of its
stimulation of catecholamines
▫ Respiratory 
 Tachypnea
 decreases tidal volume as a
result of CNS stimulation
▫ Neuromuscular 
 Doesn’t provide significant
muscle relaxation
▫ Renal 
 increasing renal vascular
resistance  decrease renal
blood flow
 drop in glomerular filtration
rate and urinary output
▫ Gastrointestinal 
 postoperative nausea and
vomiting
• Biotransformation and toxicity:
▫ Eliminated by exhalation
▫ small amount diffuses out
through the skin
▫ Biotransformation  0.01%
▫ Irreversibly oxidizing the
cobalt atom in vitamin B 12
 inhibits enzymes that are
vitamin B 12 dependent:
 Methionine synthetase
myelin formation
 Thymidylate synthetase
DNA synthesis
▫ Prolonged exposure 
 bone marrow
 neurological deficiencies
(peripheral neuropathies)
▫ Teratogenic eff ects
 avoided in pregnant patients
who are not yet in the third
trimester
▫ Alter the immunological
response to infection:
 Affecting chemotaxis
 Motility of PMN leukocytes
• Contraindications:
▫ Venous or arterial air
embolism
▫ Pneumothorax
▫ Acute intestinal obstruction
with bowel distention
▫ Intracranial air
(pneumocephalus following
dural closure
▫ Pulmonary air cysts,
▫ Intraocular air bubbles, and
tympanic membrane
• Drug Interaction:
▫ influence the concentration of
volatile anesthetic delivered
HALOTHANE
• Physical properties
▫ Carbon–fluoride bonds 
nonflammable and
nonexplosive nature
• Effects on organ systems
▫ Cardiovascular
 Cardiac depression
 Drop in systemic arterial
pressure
 ↑ heart rate
 Slowing of SA node
conduction bradhycardia
▫ Respiratory
 rapid, shallow breathing
 due to central (medullary
depression) & peripheral
(intercostal muscle
dysfunction) mechanisms
 Potent bronchodilator  e.c
inhibiting intracellular calcium
mobilization airway reflexes 
relaxes bronchial smooth muscle
 ↓clearance of mucus from the
respiratory tract (mucociliary
function)  postoperative hypoxia
and atelectasis
▫ Cerebral
 Dilating cerebral vessels 
increases CBF
▫ Neuromuscular
 Relaxes skeletal muscle
▫ Renal
 ↓ renal blood flow
 ↓ glomerular fi ltration rate
 ↓ urinary output
 ▫ Hepatic • Drug Interaction
 The metabolism and ▫ Myocardial depression 
clearance fentanyl, halothane + β-adrenergic-
phenytoin, verapamil blocking agents or with
impaired by halothane Calcium channel-blocking
• Biotransformation & toxicity agents
 Oxidized in the liver by a ▫ ventricular arrhythmias
particular isozyme of CYP halothane + aminophylline
(2EI)
 Halothene hepatitis 
 ↑ serum alanine
 ↑ aspartate transferase
 ↑ bilirubin (leading to
jaundice)
 Encephalopathy
• Contraindication
▫ Hypovolemic patients
▫ Reductions in left ventricular
function
ISOFLURANE
• Physical Properties
▫ Nonflammable volatile
anesthetic
▫ Ethereal odor
• Effects on Organ Systems:
▫ Cardiovascular:
 ↑Heart rate
 Dilates coronary arteries
▫ Respiratory:
 Respiratory depression
 Bronchodilator
▫ Cerebrovascular:
 ↑ CBF & intracranial
pressure
 ↓ cerebral metabolic oxygen
requirements
▫ Neuromuscular:
 Relaxes sceletal muscle
▫ Renal:
 ↓ renal blood fl ow,
glomerular fi ltration rate,
and urinary output
▫ Hepar:
 ↓ Total hepatic blood flow
(hepatic artery and portal
vein flow)
• Biotransformation & toxicity
▫ metabolized to trifluoroacetic
acid
▫ Prolong sedation  without
renal and hepar impairment
• Contraindication
▫ Hypovolemia  not tolerate
vasodilating effects
DESFLURANE
• Physical properties: ▫ Cerebrovascular:
▫ Low solubility  very rapid  vasodilates the cerebral
induction vasculature
▫ 17 times more potent than  ↑ CBF, cerebral blood
nitrous oxide volume, and intracranial
pressure at normotension
• Effects on organ systems:
and normocapnia
▫ Cardiovascular:
▫ Renal:
 fall in arterial blood pressure
 no evidence of any
▫ Respiratory: significant nephrotoxic
 ↓tidal volume ▫ Hepar:
 ↑respiratory rate  risk of anesthetic- induced
 depresses the ventilatory  hepatitis  minimal
↑ Pa co 2
• Biotransformation and toxicity
▫ minimal metabolism
▫ insignificant percutaneous
loss
▫ degraded by desiccated CO 2

absorbent  CO 
carboxyhemoglobin may be
detectable by arterial blood
gas analysis
• Contraindications:
▫ severe hypovolemia
▫ malignant hyperthermia
▫ intracranial hypertension
SEVOFLURANE
• Physical properties:
▫ solubility in blood is slightly
greater than des flurane
▫ Rapid increases in
alveolar anesthetic
concentration make
sevoflurane an excellent
choice for smooth and
rapid inhalation
inductions in pediatric
and adult patients
• Effects on organ systems:
▫ Cardiovascular
 mildly depresses
myocardial contractility
 may prolong the QT
interval
• Respiratory:
▫ depresses respiration
▫ Reverses bronchospasm
• Cerebrovascular:
▫ slight increases in CBF and
intracranial pressure
▫ High concentrations (>1.5
MAC)  impair
autoregulation of CBF
• Neuromuscular:
▫ adequate muscle relaxation
for intubation of children
• Renal:
▫ slightly ↓renal blood flow
• Hepar:
▫ ↓portal vein blood flow
▫ ↑hepatic artery blood flow
• Biotransformation
▫ liver microsomal enzyme P-
450 (specifically the 2E1
isoform)
• Contraindication
▫ severe hypovolemia,
▫ malignant hyperthermia
▫ Intracranial hypertension
• Drug interaction:
▫ It does not sensitize the
heart to catecholamine-
induced arrhythmias
THANK YOU