Ketamine
Sat, 11/03/2007 - 13:31 — oxygen
KETAMINE
Listen to Audio
mechanism of action
structure-activity relationships
pharmacokinetics
effects on organ systems
drug interactions
MECHANISM OF ACTION
-dissociative amnesia which dissociates the thalamus from the limbic system
-primary receptor involved: NMDA receptor antagonist
-other possible receptors involved:calcium regulated receptors, muscarinic receptors, opiod receptors, monoamine oxidase receptors
STRUCTURE-ACTIVITY RELATIONSHIPS
-phenycyclidine structural analogue
-probable stereotactic receptor involvement with increased potency and and decreased psychotomimetic side effects
PHARMACOKINECTICS
Absorption
-administered either intravenously or intramuscularly
-intramusclular administration leads to peak plasma levels within 10 - 15 minutes
Distribution
-rapid brain uptake due to high lipid solubility, less protien binding and equally ionized at physiologic pH
-ketamine-induced increased CBF and cardiac output contribute to increased brain uptake
-distribution half life is 10 - 15 minutes
Biotransformation
-biotransformation occurs in the liver
-some metabolites may retain anesthetic activity ex. norketamine: approximately 1/3 the anesthetic potency of ketamine
-multiple doses may induce hepatic enzyme activity which may develop tolerance
-relatively short elimination half time (2 hours) due to a high hepatic uptake
-hepatic extraction ratio of 0.9
Excretion
-excretion by kidneys
PHARMACODYNAMICS
Effects on Organ Systems
Central nervous system
-increases CMR02
-increases CBF
-increases ICP
-therefore should be avoided in patients with space occupying lesions
-increased subcortical electrical activity associated with myoclonus activity
-possibe undesirable psychotomimetic side effects during induction or emergence
-premedication with benzodiazepines helps to lessen or avoid the undesirable side effects
Cardiovascular system
Indirect cardiovascular effects by:
-central stimulation of the sympathetic nervous system
-inhibiting reuptake of norepinephrine
-therefore indirectly increases mean arterial pressure, heart rate, and cardiac output
Ketamine avoided in patients with CAD, uncontrolled hypertension, heart failure, and arterial aneurysms because:
-increased pulmonary artery pressure associated with increased sympathetic tone
-increased myocardial work associated with increased sympathetic tone
Direct myocardial depressant effects of large doses of ketamine may be due to:
-calcium transient inhibition
-may unmask the blocked sympathetic tone which occurs in cases such as spinal cord transection
-exhaution of catecholamine stores which may occur in cases of severe end stage shock
-ketamine may be considered an induction drug of choice in acute hypovolemic shock patients such as trauma patients
Respiratory system
-generally induction doses of ketamine used alone has minimal effects on ventilatory drive
-potent bronchodilator: good induction agent for asthmatic patients
-upper airway reflexes generally stay intact although patients at risk of aspiration should be intubated
-associated with increased salivation therefore premedication with an anticholingeric agent (ex.glycopyrrolate) may be useful
Drug Interactions
-ketamine may prolong the effects of nondepolarizing muscle relaxants (NDMR)
-ketamine with theophylline combination may predispose patients to seizure activity
-ketamine may have less indirect cardiostimulatory effects when used with diazepam
-ketamine may have a prolonged elimination half life with use of diazepam
-ketamine generally has a more cardiodepressant effect when used with volatile anesthetics (especially halothane)
-ketamine may have a prolonged duration when used with lithium
KETAMINE
Listen to Audio
mechanism of action
structure-activity relationships
pharmacokinetics
effects on organ systems
drug interactions
MECHANISM OF ACTION
-dissociative amnesia which dissociates the thalamus from the limbic system
-primary receptor involved: NMDA receptor antagonist
-other possible receptors involved:calcium regulated receptors, muscarinic receptors, opiod receptors, monoamine oxidase receptors
STRUCTURE-ACTIVITY RELATIONSHIPS
-phenycyclidine structural analogue
-probable stereotactic receptor involvement with increased potency and and decreased psychotomimetic side effects
PHARMACOKINECTICS
Absorption
-administered either intravenously or intramuscularly
-intramusclular administration leads to peak plasma levels within 10 - 15 minutes
Distribution
-rapid brain uptake due to high lipid solubility, less protien binding and equally ionized at physiologic pH
-ketamine-induced increased CBF and cardiac output contribute to increased brain uptake
-distribution half life is 10 - 15 minutes
Biotransformation
-biotransformation occurs in the liver
-some metabolites may retain anesthetic activity ex. norketamine: approximately 1/3 the anesthetic potency of ketamine
-multiple doses may induce hepatic enzyme activity which may develop tolerance
-relatively short elimination half time (2 hours) due to a high hepatic uptake
-hepatic extraction ratio of 0.9
Excretion
-excretion by kidneys
PHARMACODYNAMICS
Effects on Organ Systems
Central nervous system
-increases CMR02
-increases CBF
-increases ICP
-therefore should be avoided in patients with space occupying lesions
-increased subcortical electrical activity associated with myoclonus activity
-possibe undesirable psychotomimetic side effects during induction or emergence
-premedication with benzodiazepines helps to lessen or avoid the undesirable side effects
Cardiovascular system
Indirect cardiovascular effects by:
-central stimulation of the sympathetic nervous system
-inhibiting reuptake of norepinephrine
-therefore indirectly increases mean arterial pressure, heart rate, and cardiac output
Ketamine avoided in patients with CAD, uncontrolled hypertension, heart failure, and arterial aneurysms because:
-increased pulmonary artery pressure associated with increased sympathetic tone
-increased myocardial work associated with increased sympathetic tone
Direct myocardial depressant effects of large doses of ketamine may be due to:
-calcium transient inhibition
-may unmask the blocked sympathetic tone which occurs in cases such as spinal cord transection
-exhaution of catecholamine stores which may occur in cases of severe end stage shock
-ketamine may be considered an induction drug of choice in acute hypovolemic shock patients such as trauma patients
Respiratory system
-generally induction doses of ketamine used alone has minimal effects on ventilatory drive
-potent bronchodilator: good induction agent for asthmatic patients
-upper airway reflexes generally stay intact although patients at risk of aspiration should be intubated
-associated with increased salivation therefore premedication with an anticholingeric agent (ex.glycopyrrolate) may be useful
Drug Interactions
-ketamine may prolong the effects of nondepolarizing muscle relaxants (NDMR)
-ketamine with theophylline combination may predispose patients to seizure activity
-ketamine may have less indirect cardiostimulatory effects when used with diazepam
-ketamine may have a prolonged elimination half life with use of diazepam
-ketamine generally has a more cardiodepressant effect when used with volatile anesthetics (especially halothane)
-ketamine may have a prolonged duration when used with lithium
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