General Anesthetics Flashcards
components of anesthetic state
amnesia, immobility in response to noxious stimulation, attenuation of autonomic responses to noxious stimuli, analgesia, unconsciousness
measurement of inhalational anesthetics
MAC units
minimum alveolar concentration= prevents movements in response to surgical stimulation in 50% of subjects (use about 1.3-1.5 MACs)
can be monitored continuously (end-tidal anesthetic concentration) and correspond with free concentration in blood
modern anesthesiology relies on
combinations of iv and inhaled drugs to balance properties
minor superficial surgery or invasive diagnostic procedures
general anesthesia not necessary
local anesthesia, analgesia or sedation
retention of patients ability to maintain airway, respond to verbal commands
extensive surgical procedures
begin with preoperative benzodiazepines
induced with an intravenous agent (eg, thiopental or propofol)
maintained with a combination of inhaled (eg, volatile agents, nitrous oxide) and/or IV drugs (eg, propofol, opioid analgesics)
How do GA enhance inhibitory activity
Chloride channels (volatile and IV) Activation of two-pore domain K channels (volitile)
How do GA inhibit excitatory activity
AMPA, NMDA (glutamate) - ketamine, nitrous oxide
Nicotinic and muscarinic receptors (Ach)
Volatile anesthetics
Halothane, enflurane, isoflurane, desflurane, sevoflurane
Low vapor pressures, high boiling points
Liquids at room temperature (20°C)
Administered using vaporizers
Gaseous anesthetics
Nitrous oxide
High vapor pressure, low boiling point
Gas at room temperature
factors controlling uptake of inhaled anesthetics
inspired concentration and ventilation
Solubility
Alveolar-venous partial pressure difference
alveolar venous partial pressure difference
Dependent mainly on uptake of the anesthetic by the tissues, including nonneural tissues
Influenced by tissue:blood partition coefficients, rates of blood flow to the tissues, and concentration gradients.
4 stages of CNS depression
analgesia (some amnesia) excitement (delirious, rapid respiration, hr and bp inc) surgical anesthesia (slowing of respiration and hr) medullary depression (require circulatory and respiratory support)
barbiturates examples
thiopental, methohexital
largely replaced as induction agents by propofol
barbiturates MOA
Combination of enhancement of inhibitory and inhibition of excitatory neurotransmission
Inhibitory transmission: activation of the GABAA receptor complex
Effects on excitatory transmission are less well understood
barbs PK
Pharmacokinetics
Hepatic metabolism
Thiopental is metabolized more slowly, long elimination half-time
Recovery after single bolus is comparable for thiopental and methohexital - depends on redistribution to inactive tissue sites rather than on metabolism
barbs effects
CNS - sedation to GA
no analgesia, may reduce pain threshold
CD - decrease BP d/t vasodilation
Respiratory depressants
benzodiazepines examples
midazolam, lorazepam, diazepam
desired effects benzos
Most desired effects are anxiolysis and anterograde amnesia
action of benzos terminated by
selective antagonist, flumazenil
pk benzos
Highly lipid-soluble, rapidly enter the CNS, rapid onset of action
Followed by redistribution to inactive tissue sites and termination of effect
Midazolam has the shortest context-sensitive half-time
Only benzodiazepine drugs suitable for continuous infusion
benzos act through
GABA receptors
etomidate desired effects
hypnotic but not analgesix
etomidate mechanism
Likely acts through potentiation of GABAA-mediated chloride currents, like most other intravenous anesthetics.
etomidate pk
Induction dose of etomidate produces rapid onset of anesthesia
Recovery depends on redistribution to inactive tissue sites
Larger doses, repeated boluses, or continuous infusions can safely be administered
Because (1) minimal effects on hemodynamics and (2) short context-sensitive half-time
etomidate effects
cerebral vasoconstrictor
cv stability
some resp depression
adrenocortical suppression
Hghly lipid-soluble phencyclidine (PCP) derivative producing significant analgesia
Ketamine
kind of anesthesia ketamine does
“dissociative anesthesia,”
patient’s eyes remain open with a slow nystagmic gaze (cataleptic state)
moa ketamine
inhibition of nmda receptor complex
pharmacokinetics ketamine
High lipid solubility of ketamine ensures a rapid onset of its effect
Metabolism occurs primarily in the liver
Effect of a single bolus injection terminated by redistribution to inactive tissue sites
ketamine effects
amnesia (not as complete as benzodiazepines)
cerebral vasodilator
unpleasant emergence reactions
transient but significant inc bp, hr, co
no resp depression, bronchodilation
opioid analgesics distinct how
Recall not reliably prevented unless hypnotic agents such as benzodiazepines are also used
Postoperative analgesia and intraoperatively as part of a balanced anesthesia
fentanyl is a
opioid analgesic
___ + ____ = GA state
Large dose opioids + large dose benzodiazepines
AE opioid analgesics
Hemodynamic stability - good for patients with compromised myocardial function
Respiration must be maintained artificially and may be depressed into the postoperative period
Can induce chest wall (and laryngeal) rigidity, acutely impairing mechanical ventilation
May speed up tolerance, complicate postoperative pain management
how do inhaled anesthetics affect cardiovascular
Halothane, enflurane, isoflurane, desflurane, and sevoflurane all depress normal cardiac contractility (at some level)
Tend to decrease mean arterial pressure in direct proportion to alveolar concentration
Halothane and enflurane → myocardial depression (reduced CO) (little change in vascular resistance)
Isoflurane, desflurane, and sevoflurane produce greater vasodilation with minimal effect on CO (preferred for patients with impaired myocardial function)
Nitrous oxide also depressed myocardial function in a concentration-dependent manner (may be offset by activation of SNS → preservation of CO)
