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ANESTHETICS
Dr.Shadi- Sarahroodi
Pharm.D & PhD
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General Anesthetics
Signs and Stages of Anesthesia (Somewhat related to the response from Diethyl Ether):
Stage I—Analgesia
Stage II—Excitement
Stage III—Surgical anesthesia
Stage IV—Medullary paralysis
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3. Patient Factors in Selection of Anesthesia
Liver and kidney
Respiratory system
Cardiovascular system
Nervous system
Pregnancy
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4. Summary of anesthetics
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MOA
modulating ligand-gated ion channels
activating GABA channels (hyperpolarizing cells)
blocking excitatory receptors (like NMDA-glutamate receptors).
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7. Inhalation Anesthetics
Modern inhalation anesthetics are nonflammable, nonexplosive
nitrous oxide
halothane, desflurane, enflurane, isoflurane, sevoflurane, and methoxyflurane (easily vaporized liquid halo-genated hydrocarbons)
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8. Inhalation Anesthetics
ether [which is highly flammable]
chloroform [which has toxic properties]
are no longer used as general anesthetics
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important concepts
minimal alveolar concentration (MAC)
blood:gas partition coefficient
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10. MAC(minimal alveolar concentration)
concentration of anesthetic agent that renders 50% of patients immobile during surgery
this is measured as the percentage of the agent in inspired air
MAC is a direct measure of the potency of a drug
influenced by the age and physiologic state of the patient and by the presence of other pharmacologic agents
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12. blood:gas partition coefficient
solubility of the agent in blood
and is a measure of how quickly the inhalation anesthetic will equilibrate between lungs and blood and ultimately the target site in the brain
low blood:gas coefficient (e.g., desflurane) equilibrate quickly
lower the blood:gas coefficient faster the induction and the faster the recovery
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14. speed of induction of anesthetic effects
Solubility
Inspired gas partial pressure-high partial pressure in the lungs rapid achievement of anesthetic levels in the blood
Ventilation rate
Pulmonary blood flow—high pulmonary blood flows onset of anesthesia is reduced.
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15. Alveolar Blood Concentration
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16. Blood: Gas Partition Coefficient Minimum Alveolar Concentration (%)*
Anesthetic
Blood: Gas Partition Coefficient
Minimum Alveolar Concentration (%)*
Metabolism
Nitrous oxide
0.47
>100
None
Desflurane
0.42
6.5
<0.1%
Sevoflurane
0.69
2.0
2-5% (fluoride)
Isoflurane
1.40
1.4
<2%
Enflurane
1.80
1.7 8%
Halothane
2.30
0.75
>40%
Methoxyflurane 12
0.16
>70% (fluoride)
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elimination
redistribution of the drug from the brain to the blood and elimination of the drug through the lungs.
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desflurane, sevoflurane low blood solubility shorter recovery
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19. effects of inhaled anesthetics
CNS effects:
decrease brain metabolic rate.
reduce vascular resistance increase cerebral blood flow.
High concentrations of enflurane may cause spike-and-wave activity and muscle twitching,
nitrous oxide has low anesthetic potency (ie, a high MAC), it exerts marked analgesic and amnestic actions.
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20. effects of inhaled anesthetics
Cardiovascular effects
decrease arterial blood pressure moderately
Enflurane and halothane: myocardial depressants
isoflurane, desflurane, and sevoflurane: peripheral vasodilation
Nitrous oxide: less likely to lower blood pressure
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21. effects of inhaled anesthetics
Respiratory effects:
dose-dependent decrease in tidal volume and minute ventilation increase in arterial CO2 tension
Bronchodilation except desflurane(pulmonary irritant).
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Toxicities
Halothane: Postoperative hepatitis (rarely)
(formation of reactive metabolites that cause direct toxicity or initiate immune-mediated responses.)
Methoxyflurane, enflurane and sevoflurane: Fluoride release renal insuffi­ciency
nitrous oxide: megaloblastic anemia
anesthetics + neuromuscular blockers (Susceptible patients): malignant hyperthermia
mutations in the gene loci corresponding to the ryanodine receptor (RyRl)
Dantrolene
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24. Intravenous Anesthetics
Barbiturates: Thiopental and methohexital
Benzodiazepines: Midazolam
ketamine
Opioids: Morphine and fentanyl
propofol
etomidate
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Barbiturates
high lipid solubility rapid entry into the brain surgical anesthesia in one circulation time (< 1 min).
short surgical procedures
hepatic metabolism
respiratory and circulatory depressants
depress cerebral blood flow
decrease intracranial pressure.
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26. Redistribution of Thiopental
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Benzodiazepines
The onset of its CNS effects is slower than that of thiopental
flumazenil, accelerates recovery from midazolam and other benzodiazcpines.
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ketamine
dissociative anesthesia
patient remains conscious
marked catatonia, analgesia, and amnesia.
phencyclidine (PCP)
cardiovascular stimulant
increase in intracranial pressure.
disorientation, excitation, and hallucinations occur during recovery
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opioids
Morphine and fentanyl
Intravenous opioids :chest wall rigidity
Respiratory depression
Neuroleptanesthesia (state of analgesia and amnesia): fentanyl is used with droperidol and nitrous oxide.
Alfentanil and remifentanil (NEW)
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propofol
Rapid as the intravenous barbiturates
antiemetic
prolonged sedation
marked hypotension during induction of anesthesia
Total body clearance is greater than hepatic blood flow, suggesting elimination includes other mechanisms in addition to metabolism by liver enzymes.
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etomidate
rapid induction
minimal change in cardiac function
minimal change in respiratory rate
not analgesic
cause pain and myoclonus on injection and nausea postoperatively
Prolonged administration may cause adrenal suppression.
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