INHALATIONAL ANAESTHETICS PHARMACOLOGY.pptx

Pharmacology of inhalational anaesthesia

1. INHALATIONAL ANAESTHETICS Dr Aishwarya Nikose Second Year Resident Department of Pharmacology LTMMC & GH, Mumbai Date: 12-07-2021 1

2. Introduction to Anaesthesia History of Anaesthesia Types of Anaesthesia Inhalational Anaesthesia: Classification of inhalational anaesthetics Pharmacodynamics & pharmacokinetics Specific Inhalational anaesthetics Summary 2 OVERVIEW

3. 3 Greek word, “ AN ” – Without; “ AESTHESIA ” – Sensation Loss of sensation Components of anaesthetic state: Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill. ANAESTHESIA

4. 4 N2O – First prepared by Priestley in 1772 In 1799, Sir Humphrey Davy called N2O – Laughing gas In 1844, Dr. Horace Wells established use of N2O in surgery On 16th October, 1846, Dr. William Morton – public demonstration of ether anaesthesia David E. Golan., Ehrin J. Armstrong., April W. Armstrong. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 4e. 4th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 2017. HISTORY OF ANAESTHESIA USE

5. 5 First Public Demonstration of anaesthesia - 1846

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7. GENERAL ANAESTHESIA: Intravenous Anaesthesia Inhalational Anaesthesia LOCAL OR REGIONAL ANAESTHESIA: Spinal Anaesthesia Epidural Anaesthesia Regional Nerve block Topical Anaesthesia 7 TYPES OF ANAESTHESIA Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

8. 8 ANAESTHETICS INHALATIONAL INTRAVENOUS GAS VOLATILE LIQUIDS CLASSIFICATION Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

9. 9 MINIMUM ALVEOLAR CONCENTRATION (MAC) – The minimum alveolar concentration that prevents movement in response to surgical stimulation in 50% of subjects Smaller MAC, more potent anaesthetic Higher lipid solubility, lower MAC MAC not influenced by sex, species, acid-base balance & arterial BP POTENCY OF INHALED ANAESTHETICS Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

10. 2 . OIL : GAS PARTITION COEFFICIENT Measures lipid solubility Higher lipid solubility (↑ oil : gas partition coefficient) more is potency Methoxyflurane – highest oil : gas partition coefficient – most potent N20 – lowest oil : gas partition coefficient – least lipid soluble & least potent 10 POTENCY OF INHALED ANAESTHETICS Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

11. 11 PHARMACOKINETICS Uptake in the blood: - Passive diffusion - Blood-gas partition coefficient Distribution and uptake into the brain: - Cerebral perfusion - Blood-brain partition coefficient Onset of effect: Metabolism: Elimination: by the lungs Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

12. 12 DRUG BLOOD-GAS COEFFICIENT BLOOD-BRAIN COEFFICIENT MAC Nitrous oxide 0.47 1.1 >104% Desflurane 0.42 1.3 6-7% Sevoflurane 0.69 1.7 2% Isoflurane 1.40 2.6 1.4% Enflurane 1.80 1.4 1.7% Halothane 2.30 2.9 0.75% PHARMACODYNAMIC & PHARMACOKINETIC VALUES David E. Golan., Ehrin J. Armstrong., April W. Armstrong. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 4e. 4th ed. Baltimore, MD: Lippincott, Williams & Wilkins; 2017.

13. Unconsciousness High density of γ -amino butyric acid (GABA-A), N-methyl-D-aspartate (NMDA) and acetylcholine (Ach) receptors in Cerebral cortex, thalamus, and reticular formation Amnesia Hippocampus, amygdala and prefrontal cortex causing neurotransmission depression 13 MECHANISM OF ACTION Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

14. Analgesia Blockade at Glutamate, GABA-A receptors in spinal cord Immobility GABA-A receptor & Glutamate receptors for NMDA, alpha-amino-5-methyl-3-hydroxy-4-isoxazole propionic acid (AMPA) and kainite in sensory & motor neurons 14 MECHANISM OF ACTION Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

15. 15 Nitrous oxide Xenon Isoflurane Sevoflurane Desflurane Halothane Enflurane Methoxyflurane SPECIFIC INHALATIONAL ANAESTHETICS

16. Colourless, odourless, heavier than air, non-inflammable, non-irritating gas Significant analgesic effect Second gas effect & diffusion hypoxia Used as carrier & adjuvant to other anaesthetics- mixture of 70% N2O + 25-30% O2 + 0.2-2% other potent anaesthetic 16 NITROUS OXIDE(LAUGHING GAS) Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

17. Nitrous oxide ( Laughing gas) Colourless, odourless, heavier than air, non-inflammable, non-irritating gas Significant analgesic effect Second gas effect & diffusion hypoxia Used as carrier & adjuvant to other anaesthetics- mixture of 70% N2O + 25-30% O2 + 0.2-2% other potent anaesthetic 17 NITROUS OXIDE(LAUGHING GAS) Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

18. Quick Induction & smooth with rapid recovery Used for Outpatient dentistry No adverse effects on CVS, respiratory system, kidney & liver Risk of abortion and birth defects PNEUMOTHORAX Vitamin B12 deficiency – Malnutrition, alcoholism 18 NITROUS OXIDE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

19. Inert gas, expensive & limited Analgesic and anaesthetic effects Rapid induction & recovery Administered with 30% O2 or IV anaesthetic Well tolerated in old age 19 XENON Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

20. Volatile liquid at room temperature, non-inflammable, non-explosive, pungent odour Induction- within 10 mins with 1.5%–3% isoflurane in O2 Maintenance of anesthesia – 1-2% Faster induction & recovery 99% excreted unchanged by lungs 20 ISOFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

21. CVS: arterial BP; Vascular resistance, reflex tachycardia CORONARY STEAL – Myocardial ischaemia RS: Airway irritant CNS: ICP in Intracranial Hypertension MUSCLE: Relaxes Uterine smooth muscle RENAL: Oliguria LIVER & GIT: Splanchnic & hepatic blood flow 21 ADR OF ISOFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

22. Clear, colorless, volatile liquid at room temperature and stored in a sealed bottle, nonflammable, nonexplosive Outpatient anesthesia Ideal Induction agent- 2%-4% Preferable agent in patients prone to myocardial ischemia 22 SEVOFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

23. CVS: decreases arterial BP RS: tidal volume & tachypnoea CNS: ICP in patients with poor intracranial compliance & delirium in children MUSCLE: effect of neuromuscular blocking agents RENAL: potential nephrotoxicity 23 ADR OF SEVOFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

24. Highly volatile, non-inflammable and nonexplosive Used for outpatient surgery Airway irritant – maintenance of anaesthesia (6% -8%) Rapid induction & recovery 99% of absorbed - eliminated unchanged through the lungs 24 DESFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

25. CVS : hypotension & transient tachycardia RS : strong airway irritant CNS : ICP with poor intracranial compliance MUSCLE : effect of neuromuscular blocking agents No nephrotoxicity & no hepatotoxicity Hypercarbia 25 ADR OF DESFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

26. Volatile liquid, light-sensitive, non-inflammable, non-explosive Maintenance of anaesthesia HALOTHANE HEPATITIS – Immune response to hepatic proteins that become trifluoro acetylated causing fulminant hepatic necrosis Malignant hyperthermia Trigger postpartum haemorrhage 26 HALOTHANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

27. Colourless, clear, volatile liquid, sweet odour, non-inflammable & non-explosive Maintenance of anaesthesia – 0.5% to 3% Induction in less than 10 min – 2% to 4.5% Potential nephrotoxicity & proconvulsive CYP2E1 activation 27 ENFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

28. Slow induction & recovery Hepatotoxic & nephrotoxic 28 METHOXYFLURANE Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

29. FDA approved - a general anesthetic and sedation agent in the operating room Use in the intensive care unit (not an FDA-approved indication) The primary applications in the ICU - sedation, refractory bronchospasm, and control of status epilepticus unresponsive to anticonvulsant medications.     29 Clar D, Patel S, Richards J. Anesthetic Gases [Internet]. Ncbi.nlm.nih.gov. 2021 [cited 16 June 2021]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537013 OTHER INDICATIONS OF INHALED ANAESTHETICS

30. 30 SUMMARY CONDITION DRUG OF CHOICE Outpatient surgery Desflurane Neurosurgery Isoflurane Children Sevoflurane Asthmatics Halothane Myocardial ischaemia Sevoflurane Brunton L, Hilal-Dandan R, Knollmann B. Goodman & Gilman's the pharmacological basis of therapeutics. 13th ed. new york: Mcgraw Hill.

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