General Anesthetics Flashcards
What is anesthesia
Anesthesia IS a medication-induced, reversible depression of the central nervous system such that the perception of all senses is ablated
Desirable components of anesthesia
Amnesia
Hypnosis
Analgesia
Immobility
Brain areas targeted by general anesthesia
vSpecific brain areas affected by various anesthetics include the reticular activating system, cerebral cortex and hippocampus
Stages of anesthesia
Stage 1: Induction – analgesia and euphoria
Stage 2: Excitement – involuntary movement
Stage 3: Surgical anesthesia – unconsciousness and muscle relaxation
Stage 4: Medullary depression – apnea and cardiovascular depression
Characteristics of the Ideal Anesthetic
Smooth and rapid – ideal for induction and loss of consciousness
Physiologically stable – does not cause large variation in blood pressure, heart rate, etc.
Reversible and/or metabolized – allows for rapid return of cognitive function when discontinued
Safe – devoid of adverse effects and with a wide margin of safety
What is Context sensitive half-time
Time required for concentration of a drug to decrease by 50% after discontinuation of an infusion
The context-sensitive half-time cannot be predicted by the elimination half-life because it depends on distribution/redistribution
In general, drugs which are more lipid soluble have a longer context-sensitive half-time
Barbituates MOA and metabolism
GABA agonists
Produce rapid loss of consciousness – historically used as an induction agent
Hepatic metabolism to inactive metabolites
Relatively short elimination t1/2, unless repeat dosing or infusion
Barbituates effects on CNS, cardiovascular, resp
CNS effects
- Cerebral vasoconstrictors therefore decrease CBF, ICP and CMRO2
- Protective against focal ischemia
- Anti-epileptic (except methohexital)
- No associated analgesia or muscle relaxation
Cardiovascular effects
- Peripheral vasodilation
- Negative inotropic effect
- Blunts baroreceptor response, transient hypotension
Respiratory effects
- Decreases tidal volume and respiratory rate as well as decreased response to hypoxia and hypercarbia
- Dose-dependent apnea
- Does not depress airway reflexes (may have laryngospasm during use)
Barbituates examples
Sodium thiopental
vHistorically used as “truth serum”
vUsage declined with increasing use of propofol and etomidate
vNo longer manufactured or imported in the US due to association with lethal injection
Methohexital remains available
vActivates epileptic foci
Benzodiazapenes MOA
GABA Agonist
Produce anxiolysis and antegrade amnesia – often used as premedication prior to induction
Benzodiazapenes examples
Midazolam: most lipophilic, onset <5 minutes, half-life 2 hours
Lorazepam: onset <30 minutes, half-life 12-18 hours
Diazepam: onset 1-5 minutes, half-life extremely variable (20-100 hours) due to active metabolites
Benzodiazapenes metabolism
Liver metabolism, active metabolites (diazepam) and inactive metabolites (midazolam) excreted in urine
Reversal agent: flumazenil
Benzodiazapenes effects on CNS, cardiovasc, resp
Ketamine MOA and use
NDMA Antagonist
Functionally dissociates the thalamus from the limbic cortex; patients may appear conscious but are unable to process or respond to sensory input
Used for induction or in smaller doses as an adjunct anesthetic or analgesic
Ketamine metabolism
Midazolam mitigates unpleasant emergence hallucinations
Liver metabolism to minimally active metabolite, urine excretion
Ketamine effects on CNS, cardiovasc, resp
Propofol MOA and use
GABA Agonist
Also used as a continuous infusion for conscious sedation, general anesthesia or in the ICU
Propofol metabolism
Induction dose: 1-2.5mg/kg IV
Pain on injection
Liver and extrahepatic metabolism to inactive metabolites
Rapid induction and emergence
Propofol effects on CNS, cardiovasc, resp, GI
Propofol adverse effects
Anaphylaxis
Hypertriglyceridemia
Propofol Infusion Syndrome
Rare but serious syndrome that results after long-term, high-dose propofol infusion
More common in pediatric population
Critically ill patients receiving vasopressors and/or glucocorticoids seem to be at higher risk
Signs and symptoms:
Metabolic acidosis and hyperkalemia
Rhabdomyolysis leading to renal failure
Lipemia
Cardiac failure
Green urine may be a herald sign
MOA of etomidate
GABA Agonist
vRapid induction and emergence
vPain on injection and myoclonus frequently observed
Etomidate effects on CNS, cardiovasc, resp, endocrine
Dexmedetomidine MOA and use
Selective CNS α2 adrenergic agonist, Related to clonidine
Often used as a continuous infusion for conscious sedation in OR/ICU, or as an adjunct to general anesthesia
Prevents memory formation
Dexmedetomidine metabolism
Liver metabolism, long context specific half life
Dexmedetomidine effects on CNS, cardiovasc, resp
Major opioid receptors and fucntion
μ –analgesia, respiratory depression, dependence, constipation, urinary retention, euphoria
κ – analgesia, sedation, dysphoria, miosis
δ –analgesia, dependence, respiratory depression, urinary retention
Opioid effects on CNS, cardiovasc, resp, GI
How do vaporizers work
What is the partition coefficient
The ratio of concentration of anesthetic in blood vs in the lung when steady state is reached: Pblood / Palveolar