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Inhalational agents

General principles
Classification of Inhalational agents
Commonly used Newer agents Commonly not used
Halothane Sevoflurane Ether
Isoflurane Desflurane Chloroform
Nitrous oxide Cyclopropane
• Maintenance of anesthesia
• Inhalational induction, esp in children
• As sole agent for small procedures (ether)
• Bind to cellular proteins altering enzyme
• Theory of fluidization: expand cellular
membrane (fluidization)---block Na+ channel
• Increase concentration of inhibitory
neurotransmitter (GABA, adenosine) &
enhance their effect
• Decrease excitatory neurotransmitter
(Adrenaline, norepinephrine, acetylcholine,
Site of action
• CNS -----unconsciousness, amnesia, m/s
• Dorsal horn cells of spinal cord ---analgesia
• Synapses: pre/post synaptic level; higher dose
cause axonal transmission block
• Molecular level: all inhalational agents have
same lipophilic (lipid soluble) binding site
(unitary theory of narcosis)
• Meyer Overton rule: potency directly
proportional to lipid solubility (oil gas partition
• Exceptions to the rule
Meyer Overton Exceptions
All isomers have Isoflurane, enflurane, desflurane; cuttinf effect: homologous
same potency series of compound with increasing lipid solubility should be
more potent but its opposite
All lipid soluble Some lipid soluble agents produce convulsions (does not
agents produce produce immobility or anesthesia): non-immobilizers
All inhalational Some bind to hydrophilic sites causing expansion (volume
agents bind to expansion theory) and can be reversed by increasing pressure
lipophilic sites (pressure reversal theory of anesthesia)
Minimum Alveolar concentration
- Minimum concentration of inhalational agent that produces immobility in 50%
subjects exposed to noxious stimuli (surgical skin incision in humans)
- MAC 95 = 1.3 X MAC 50
- More the MAC, less is the potency
- Eg: nitrous oxide with 104% MAC is least potent; halothane with MAC 0.74% is more
- Factors not affecting MAC: obesity, sex, thyroid d/s (hypo/hyperthyroidism)
- Factors increasing MAC (requiring increased dose/concn of inhalational agent):
hyperthermia (>42.C); hypernatremia; chronic alcohol & amphetamine abuse; cocaine
& ephedrine; increased barometric pressure (reversal theory of anesthesia)
- Factors decreasing MAC: increasing age; pregnancy; anemia (Hb<5gm%); severe
hypoxia (<40mmHg) & hypercarbia (>95mmHg); hypothermia & rise of temp upto
42.C; hyponatremia; hypercalcemia; hypermagnesemia; alpha 2 agonist; acute
alcohol/amphetamine intoxication; IV/LA (except cocaine)
Uptake & distribution
• Delivery: vaporizers + carrier gas (O2 alone/02
• Concn in brain determines effect of
inhalational agent

• Uptake increased----blood concn increase-----

slow induction & recovery
Factors affecting uptake & distribution
FI (inspired concentration) Depends upon concn delivered by vaporizers,
ventilation, fresh gas flow, absorption by bretahing
FA (alveolar concentration) After blood-brain equilibrium is achieved (4-8mins);
the alveolar conc represents concn in brain
Blood gas partition coefficient High: slow induction & recovery (halothane)
Low: fast induction & recovery (desflurane)
Cardiac output High---slow induction
Alveolar to venous partial High venous pressure ---- less uptake ---fast induction
Ventilation Affects high B/G coeff::::blood uptake increased---
alveolar concn decreased----room for inhalational
agent (slow induction)
Uptake = (B/G x Q x (Pa-Pv) ) / B/G::: lambda: blood gas coefficient
Pa-Pv: alveolar to venous pressure
P: barometric pressure
3 effects of N20 (nitrous oxide)
Concentration effect 2nd gas effect Fink effect
Augmented inflow effect Same effect as Diffusion hypoxia
concentration effect
N20 at higher conc (66%) -- N20 also increases End of Sx----sudden
--in every breath----taken concentration of other stppage of N20----gush of
up in blood (large uptake)-- inhalational agent used N20 diffuse from blood to
-- (void/gradient created) -- with it like halothane (i.e. alveoli-----displace O2
--more indraw of N20 from one inhalational agent (hypoxia)
machine---increased increases/effects concn of
alveolar concentration other known as the 2nd gas
Avoided by 5min of 100%
O2 after discontinuing N20
• Decreased brain concentration
• Depends upon
a) Excretion
- Pulmonary exhalation of agent
- Transcutaneous loss/excretion (only with N20)
b) Metabolism
- Oxidation mostly (dealkylation/dehalogenation) or reduction
- Liver
- Phase I rxn: Cytochrome-P450 enzyme (enzyme inducers: isoniazid,
phenytoin, phenobarbitone, ethanol, diazepam---increase metabolism)
- Phase II rxn: conjugation
- no metabolism with N20
- negligible metabolism: desflurane (<1%)
- maximum metabolism: halothane (20%)
Systemic effects
System Effects
Eye Decrease IOP
Teratogenic Inconclusive; chronic N20 use in pregancy ---sponatenous
abortion & congenital abnormalities
Amnesia All except N20
Analgesia Not good (except Ether, N20, xenon, max with Trielene)
Metabolic Hyperglycemia (profound: chloroform, mild: cyclopropane,
desflurane by sympathetic stimulation, ether by mobilizing liver
Uterus Relaxant (equally; previously max with halothane)

Neuromuscular Central acting m/s relaxant (except N20 which is not a m/s
relaxant); max. (ether, desflurane)
Spinal cord Prolonged N20 exposure: inhibit thymidate production---
impaired myelin production---subacute degeneration of SC
Systemic effects
Systems Effect
Hematopoietic Prolonged N20 exposure---inhibited one carbon moiety
pathway (inhibited methionine synthetase)----imapired
thymidate & DNA formn----megaloblastic & aplastic anemia
Inflammability Inflammable (ether, cyclopropane, ethylene, ethyl chloride):
avoid cautery use in 25 cm vicinity; made non-inflammble by
adding fluorine atoms
Renal By decreased RBF; direct nephrotoxic (inorganic F- ion in
fluorinated compounds)::vasopressin resistant polyuric renal
failure; methoxyflurane;;;;;fluoride level >renal threshold
(50um); sevoflurane at renal threshold is nontoxic as it has low
B/G coeff---faster action & elimination
CNS Decreased cerebral metabolic rate & O2 consumtion with
higher dose; Increased ICT;;;;; at clinical conc: isoflurane---
minimal ICT increase & decreased CBR & 02 so, agent of
choice in neurosx
Liver Hepatotoxic

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