General Anesthetics (Inhalation)
General anesthetics - inhalation, p. 143-161
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- decrease
- ____ rate of induction: increase solubility of anesthetic in blood (blood/gas partition coefficient), increase cardiac output
- nitrous oxide
- disadvantages: relatively weak; post-op N&V; hypoxia during recovery; chronic exposure -> vitB12 deficiency
- uniquely titratable
- general property of inhalation anesthetics: by altering partial pressure in inspired air; moment-to-moment control
- pulmonary blood flow
- esp. important factor for anesthetics w/ moderate-high blood solubility; INCREASE this, DECREASE rate of induction (b/c more blood for gas to dissolve into)
- recovery
- affected by: 1) pulmonary blood flow, 2) pulmonary ventilation, 3) solubility of anesthetic in various tissues (+ duration of exposure), 4) solubility of anesthetic in blood (if less soluble, this is faster); metabolism NOT usually a factor
- Minimum Alveolar Concentration (MAC)
- values INCREASE (potency decreases) with desensitization to CNS depressants (chronic alcoholism), CNS stimulants (e.g. amphetamine, cocaine); INDEPENDENT of gender and weight!
- therapeutic index
- general property of inhalation anesthetics: this is low, has a low margin of safety (2-4)
- sevoflurane
- disadvantages: CV and respiratory depression; expensive (b/c new); can be chemically unstable w/ exposed to CO2 adsorbents -> compound that may be nephrotoxic
- slow acting
- include: enflurane, isoflurane, halothane
- fast acting
- include: nitrous oxide, desflurane, sevoflurane
- isoflurane
- advantages: stable cardiac rhythm, quite rapid onset and emergence; minimal metabolism; muscle relaxant; use for MAINTENANCE; most widely used anesthetic in adults!
- mole fraction
- one way of expressing MAC (the other is partial pressure in alveolar gas); partial pressure as a % of total gas pressure
- oil/gas partition coefficient
- indicates relative SOLUBILITY of anesthetic in membranes relative to air; directly related to potency
- membrane proteins
- volatile and IV anesthetics act DIRECTLY on these by binding to specific hydrophobic sites to change their function
- dantrolene
- drug of choice for prevention and treatment of malignant hyperthermia; skeletal muscle relaxant that blocks Ca release from SR
- inspiration
- 1st step in getting I.A. to brain; affected by concentration in inspired gas, pulmonary ventilation (# respirations- increase that, increase uptake)
- systemically depressant
- general property of inhalation anesthetics: depress respiratory and CV systems
- stage III
- stage of anesthesia: "surgical anesthesia"- regular breathing, unconsciousness, decreased eye mvmt; loss of eyelash reflex
- malignant hyperthermia
- lethal, acute disorder developing during or after general anesthesia; massive increase in metabolic rate caused by uncontrolled Ca2+ efflux from SR -> muscle tetany and ____
- cellular effects
- 1) hyperpolarize neurons, 2) decrease synaptic transmission- modulation of synaptic transmission occurs at lower concentrations, POST-synaptic actions dominate
- stage IV
- stage of anesthesia: "medullary depression"- respiratory arrest, cardiac depression and arrest, no eye mvmt
- glycine receptors
- inhalation anesthetics, propofol, barbiturates enhance capacity for these receptors to be activated
- presynaptic nerve terminal
- actions here: interfere w/ NT release (potentiate inhibitory synapses, inhibit excitatory synapses); alter reuptake
- complete anesthetics
- general property of inhalation anesthetics: cause loss of consciousness, immobility, amnesia, analgesia, skeletal muscle relaxation at high doses
- increased intracranial pressure
- toxic effect of inhalation anesthetics, from increased cerebral blood flow; risk in pts. w/ brain tumor or head injury; reduce risk is pt. is hyperventilated before anesthesia
- desflurane
- advantages: rapid onset, recovery; high potency; minimal metabolism; use for OUTPATIENT anesthesia
- stage I
- stage of anesthesia: "analgesia"- conscious, but no pain; analgesia, amnesia, euphoria; muscles and airways not relaxed
- halothane
- disadvantages: slow induction, recovery; high metabolism -> fatal hepatotoxicity, side effects; CV and respiratory depression; arrhythmias
- GABA-a receptors
- halogenated anesthetics, propofol, barbituates, etomidate increase sensitivity of these receptors, enhance INHIBITORY neurotransmission, depress nervous system activity
- intraoperative awareness
- patient becomes conscious during procedure, has recall of events; rare occurrence; no pain; risks: genetics, age, cardiac reserve, substance abuse
- second gas effect
- uptake of a large volume of primary gas (low potency, e.g. N2O) accelerates uptake of a 2nd gas (more potent, smaller amounts)
- desflurane
- disadvantages: CV and respiratory depression; expensive (b/c new); VERY pungent, irritating (bad for asthma); laryngospasms; tachycardia
- blood/gas partition coefficient
- indicates relative solubility of anesthetic in blood relative to air; when this is higher, more anesthetic must be dissolved in blood to raise pp in gas phase
- isoflurane
- disadvantages: CV and respiratory depression; pungent odor; airway irritant (bad for asthma!); coughing, laryngospasms
- nitrous oxide
- only inhalation anesthetic that does NOT DECREASE respiration, decrease bp, increase PVR
- blood flow to brain
- increase this, have faster equilibration of CNS w/ alveolar partial pressure
- blood/gas partition coefficient
- physicochemical property of inhalation anesthetics that predicts RATE OF INDUCTION (how fast it works); ratio of anesthetic concentrations in compartments when pp of anesthetic is equal in them
- balanced anesthesia
- a combination of drugs is used to provide more satisfactory anesthesia than from just 1 drug - use desirable properties, minimize adverse actions (b/c of lower dose)
- lambda
- solubility of anesthetic in blood; is primary determinant of rate of onset/offset of anesthesia; affects passage from alveoli to blood in pulmonary capillaries (2nd step in getting I.A. to brain)
- lipid solubility
- potency of inhalation anesthetics directly correlated to this (Meyert-Overton rule); suggests hydrophobic site of action
- stage II
- stage of anesthesia: "excitement"- excitement, delirium, combative behavior, irregular breathing
- postsynaptic nerve terminal
- actions here: interfere w/ NT binding to receptors; interfere w/ ionic conductance
- uterine relaxants
- include halothane, enflurane, and isoflurane; useful for fetal manipulations; may increase bleeding postpartum or during therapeutic abortion
- Minimum Alveolar Concentration (MAC)
- the concentration of anesthetic at 1atm which prevents mvmt in 50% of people exposed to noxious surgical stimulus; is an indication of POTENCY (lower this, higher potency); effective anesthetic concentration is 1.2-1.5x this
- oil/gas partition coefficient
- physicochemical property of inhalation anesthetics that predicts POTENCY; is inverse of MAC value; ratio of anesthetic concentrations in compartments when pp of anesthetic is equal in them
- malignant hyperthermia
- genetic predisposition (AD inherited disorder- mutations in SR CA channel- ryanodine receptor) and triggering agents (halogenated volatile anesthetics - NOT N2O, depolarizing muscle relaxants) necessary to evoke this
- K+ channels
- halogenated inhalation anesthetics activate these channels; set resting membrane potential- activation leads to hyperpolarization
- sevoflurane
- advantages: fast induction, recovery; high potency; less irritating vapor; use for OUTPATIENT anesthesia, induction, esp. in kids
- increase
- ____ rate of induction: increase concentration of anesthetic in inspired-gas mixture, increase alveolar ventilation
- nitrous oxide
- advantages: no odor; fast induction and emergence; minimal cardiopulmonary depression; good analgesic; use for minor surgery, combination (2nd gas effect)
- anesthetics
- most dangerous drugs- low therapeutic indices, steep dose-response curves, no pharmacological antagonists to correct high doses
- halothane
- advantages: pleasant odor, nonirritating vapor; bronchodilator (good for asthma!); use for KIDS; MAINTENANCE of anesthesia; asthma pts.
- Minimum Alveolar Concentration (MAC)
- values DECREASE (potency increases) with increasing age, pregnancy, hyPOthermia, hyPOtension, adjuvants (e.g. CNS depressants)
- NMDA receptors
- ketamine, NO, cyclopropane INHIBIT these receptors