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):

1.

Stage IAnalgesia

2.
3. 4.

Stage IIExcitement
Stage IIISurgical anesthesia Stage IVMedullary paralysis

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Patient Factors in Selection of Anesthesia

Liver and kidney Respiratory system Cardiovascular system Nervous system Pregnancy

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Summary of anesthetics

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MOA

modulating ligand-gated ion channels activating GABA channels (hyperpolarizing cells) blocking excitatory receptors (like NMDAglutamate receptors).

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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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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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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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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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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 flowhigh pulmonary blood flows onset of anesthesia is reduced.
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Alveolar Blood Concentration

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Anesthetic
Nitrous oxide Desflurane Sevoflurane Isoflurane Enflurane Halothane Methoxyflurane

Blood: Gas Partition Coefficient

0.47 0.42 0.69 1.40 1.80 2.30 12

Minimum Alveolar Concentration (%)* >100 6.5 2.0 1.4 1.7 0.75 0.16

Metabolism None <0.1% 2-5% (fluoride) <2% 8% >40% >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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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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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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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)

Methoxyflurane, enflurane and sevoflurane: Fluoride release renal insufficiency nitrous oxide: megaloblastic anemia anesthetics + neuromuscular blockers malignant hyperthermia
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(formation of reactive metabolites that cause direct toxicity or initiate immune-mediated responses.)

(Susceptible patients)

mutations in the gene loci corresponding to the ryanodine receptor (RyRl) Dantrolene

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Intravenous Anesthetics

BARBITURATES: Thiopental and methohexital BENZODIAZEPINES: Midazolam

OPIOIDS: Morphine and fentanyl

KETAMINE

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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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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