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Pharmacology of therapeutic gases and inhalational anesthetics
- 1. Pharmacology of Therapeutic Gases and Inhalational Anesthetics www.freelivedoctor.com
- 5. O 2 Delivery Devices www.freelivedoctor.com 100% O 2 Flow Rate (L/min) Estimated FiO 2 Nasal Cannulae 1 0.24 2 0.28 3 0.32 4 0.36 5 0.40 6 0.44 Simple Facemask 5–6 0.40 6–7 0.50 7–8 0.60 Mask w/ Reservoir Bag 6 0.60 7 0.70 8 0.80 9 ≥ 0.80 10 ≥ 0.80
- 6. Hemoglobin O 2 Saturation Curve www.freelivedoctor.com
- 10. THERAPEUTIC GASES: CO Potential signaling pathways activated by CO leading to tissue protection Ryter, S. W. et al. Physiol. Rev. 86: 583-650 2006 www.freelivedoctor.com
- 16. “ Gentlemen, this is no humbug.” www.freelivedoctor.com
- 25. Unitary Hypothesis General anesthesia can be caused by a remarkable number of structurally diverse molecules www.freelivedoctor.com
- 26. Meyer-Overton Correlation 1903: Meyer and Overton note very strong correlation between solubility in olive oil and anesthetic potency www.freelivedoctor.com
- 27. Meyer-Overton rule The correlation of anesthetic potency with lipid solubility provides a means of predicting anesthetic potency. This correlation has traditionally been interpreted as meaning that primary anesthetic action sites are lipid portions of nerve membranes . Molecular Actions of General Anesthetics www.freelivedoctor.com
- 28. Nonspecific Theory Unitary hypothesis + Myer-Overton Rule = Anesthetics act nonspecifically on hydrophobic lipid components of cells www.freelivedoctor.com
- 29. General anesthetic potencies in animals can be correlated well with their ability to inhibit the activity of certain soluble enzymes, such as firefly luciferase. The finding shook the foundation of lipid theory, and opened a new chapter for protein theory. Proteins: molecular targets of general anesthetics Franks & Lieb 1984 Nature. 310:599-601 www.freelivedoctor.com
- 30. Protein Theory of General Anesthesia www.freelivedoctor.com
- 32. Molecular Mechanism(s) of General Anesthesia www.freelivedoctor.com Xe Isoflurane Halothane ...... Cellular (synapses) Molecular (lipids & receptors)
- 36. Properties of Inhaled Anesthetics Less potent More potent www.freelivedoctor.com ANESTHETIC MAC(atm) (oil/gas) (oil/gas) x MAC Nitrous oxide 1.01 1.4 1.4 Desflurane 0.06 19 1.1 Sevoflurane 0.02 51 1.0 Ether 0.019 65 1.2 Enflurane 0.0168 98 1.6 Isoflurane 0.0114 98 1.1 Halothane 0.0077 224 1.7
Editor's Notes
- -focus on inhaled anesthetics -lung is ideal for delivering gases to blood
- -one of the greatest discoveries in medicine of all time -made modern surgery possible -rare to go through life without being anesthetized at least once -scary: low TI, unknown mechanism of action
- Most anesthetic procedures today involve the combination of different anesthetic drugs which are being used in concentrations that are considerably smaller than those needed if the drug were to be used all by itself. Halogenated anesthetics: (1) rapid and pleasant induction of, and recovery from, anesthesia; (2) rapid changes in the depth of anesthesia; (3) adequate relaxation of skeletal muscles; (4) the absence of toxic effects or other adverse properties in normal doses; (5) a wide margin of safety. Advantages of using intravenous drugs: (1)high potency and rapid reversibility (2) adds flexibility and permits the administration of lower doses of inhalational agents; (3) permit more precise control of the effect required.
- Most anesthetic procedures today involve the combination of different anesthetic drugs which are being used in concentrations that are considerably smaller than those needed if the drug were to be used all by itself. Halogenated anesthetics: (1) rapid and pleasant induction of, and recovery from, anesthesia; (2) rapid changes in the depth of anesthesia; (3) adequate relaxation of skeletal muscles; (4) the absence of toxic effects or other adverse properties in normal doses; (5) a wide margin of safety. Advantages of using intravenous drugs: (1)high potency and rapid reversibility (2) adds flexibility and permits the administration of lower doses of inhalational agents; (3) permit more precise control of the effect required.
- Besides conventional EC50 for the drug potency measurement, MAC is more popularly used in the field.
- Different size, different chemical properties. Suggests single site, common mechanism.
- This famous plot demonstrates an amazing correlation between gA potency and their solubility in lipid. The more…the more. The correlation lasts 6 order of magnitudes.
- The difficulty to determine the site of action in the CNS for GA: we have no consensus of opinion regarding the region or regions of the brain responsible for the maintenance of consciousness. the brain area responsible for the control of consciousness: cerebral cortex? No. Large regions of the cortex could be ablated without loss of consciousness brainstem? No. Although much data exist on anesthetic effects in various brain regions, no set is sufficiently complete or consistent to allow one to conclude that exert their actions through one specific effect in one CNS region. Since it’s difficult to define gA comprehensively and quantitatively, there has been from the beginning a search for in-vivo and in-vitro model systems capable to either reflect gA completely, to describe partial aspects of it or to measure it indirectly.
- What this means is that at 1MAC the concentration of anesthetic in brain is nearly the same for all anesthetics.