General anesthetics Flashcards
clinically effective concentration range
1-100mM. no single “receptor”
property determining general anesthetic potency
high lipid solubility
Lipid theory of general anesthesia
volatile general anesthetics exert their effects by partitioning into the lipid component of the nerve cell membrane
Protein theory of general anesthesia
volatile anesthetics act via interactions with hydrophobic pockets in membrane proteins
General anesthetic action in nervous system
potentiation of GABAa receptor activity, inhibition of excitatory synapses –> increased duration of inhibitory postsynaptic potentials –> greater inhibition in CNS, depression of neuronal excitability
Describe action potential conduction in the peripheral nervous system of anesthetized patients
Normal conduction. conduction block only appears at doses well above the clinical range
Sequence of general anesthesia progression
loss of fine motor function and coordination –> altered consciousness and analgesia –> loss of temp regulation –> unconsciousness –> effects on eye motion, pupil size, and light reflex –> loss of muscle tone –> respiratory failure –> cardiovascular failure –> coma and death
Stage I anesthesia
analgesia
Stage II anesthesia
excitement, delirium
Stage III anesthesia
surgical anesthesia
plane 1: regular metronomic respirations
plane 2: onset of muscle relaxation, fixed pupils
plane 3: good muscular relaxation, depressed excursion of intercostal muscles during respiration
plane 4: diaphragmatic breathing only, dilated pupils
Stage IV anesthesia
medullary paralysis
Stage able to be reached by N2O gas
Stage II
Time course of surgical anesthesia
Induction (time until stage III is reached)
Maintenance (surgery)
Recovery (termination to complete recovery from anesthesia)
steady state anesthesia
anesthetic gas partial pressure in lung = anesthetic gas partial pressure in blood = anesthetic gas partial pressure in body tissues
Four phases of uptake of volatile anesthetic
lung factors, uptake from alveoli to blood, uptake from blood to tissues, tissue distribution
lung factors for uptake
rate of partial pressure increase in proportional to rate of ventilation
Determinants of uptake rate from alveoli to blood
solubility of gas in blood, pulmonary blood flow
effect of higher gas solubility in blood
need more gas dissolved in blood to produce anesthesia. less solubility –> more rapid anesthesia
Higher lung blood flow
slower achievement of anesthesia
higher tissue blood flow
faster anesthetic delivery
Estimation of anesthetic potency
1/MAC
MAC = minimum alveolar anesthetic concentration = alveolar concentration that prevents gross skeletal muscle response to painful stimulus
Major elimination route for general anesthetics
lungs
determinants of lung excretion
cardiac output and respiratory rate
distribution to vessel-rich group
brain, heart, kidney, liver, endocrine glands. anesthetic effects in minutes
distribution to muscle group
muscle and skin. uptake in 2-4h due to lower perfusion than vessel-rich group
distribution to fat group
very slow uptake due to low perfusion and high lipid solubility. Eventually dominates rate of uptake into total body tissue
fat group effects on recovery
longer duration of anesthesia –> higher fat load of anesthetic –> long recovery from anesthesia
volatile anesthetics
xenon, nitrous oxide, diethyl ether, cyclopropane, chloroform, halothane, enflurane, isoflurane, desflurane, sevoflurane
IV anesthetics
thiopental, propofol, etomidate
IV adjuncts
ketamine, d-tubocurarine, morphine, fentanyl, diazepam, ondansetron, glycopyrrolate
treatment of malignant hyperthermia
dantrolene
nitrous oxide
advantages: excellent analgesia, rapid on/off, less increased cerebral blood flow (head injuries)
disadvantages: low potency –> not general anesthetic
contraindications: respiratory obstruction, pregnancy
Diethyl ether
advantages: complete anesthetic
disadvantages: flammable and explosive, slow induction/recovery
Chloroform
no longer used due to hepatoxocity and arrhymogenicity
Halothane
Advantages: mid-high potency, fast on/off, non-explosive, non-irritant
Disadvantages: not good analgesic, can produce respiratory and cardiac failure, can cause liver damage, can trigger malignant hyperthermia (excessive Ca release from ryanodine receptors)
Enflurane
Advantages: excellent analgesic, moderately fast on/off, good muscle relaxant
Disadvantages: can trigger seizures during induction/recovery
Isoflurane
Advantages: more potent than enflurane, little hepato/renal toxicity, does not trigger seizures, fast on/off, minimal direct cardiac depression, good muscle relaxant. Most widely use inhalational anesthetic
Disadvantages: can trigger coughing (use IV to overcome)
Desflurane
Advantages: fast recovery from extended anesthesia, similar pharmacokinetics to N2O with higher potency
Disadvantages: pungent odor –> airway irritation and cough. Requires special vaporizer
Contraindications: patients with predisposition to malignant hyperthermia
Sevoflurane
Advantages: high potency, fast on/off, rapid adjustment of anesthetic depth, no coughing or airway irritation (can be used for induction of anesthesia)
Disadvantages: chemically unstable. releases F ions –> renal toxicity
Thiopental
Advantages: Very short-acting barbiturate (potentiates GABAa), very rapid onset (15-20s) and offset (reawaken in 3-5 min)
Propofol
Potentiates GABAa
Advantages: loss of consciousness in seconds, recovery faster than thiopental, less nausea post-op, no involuntary movements seen with etomidate
Etomidate
Nonbarbiturate hyponotic. Potentiates GABAa
Advantages: minimal depression of CV and respiratory function, larger safety margin than thiopental, fast on/off
Disadvantages: involuntary movements during induction, high incidence of nausea, vomiting, pain on injection
Ketamine
PCP derivative
glu-NMDA antagonist
Advantages: potent bronchodilator –> indicated for asthmatics
Disadvantages: catatonia, amnesia, disorientation and hallucination (reduced with IV diazepam), slow effect IV
Use of neuromuscular blocking adjuvants
vecuronium and D-tubocurarine –> competitive antagonism of Ach at NMJ –> relaxation of skeletal muscle
Common in abdominal surgeries. relaxed abdominal wall –> lower dose of volatile anesthetic required –> reduced danger of anesthetic overdose
