(from my master's thesis....a memorial day special!)

Ketamine (my favorite drug)
Ketamine is a racemic mixture of an R (-) and S (+) optical isomers. The S (+) isomer has been shown to be more potent than the R (-) isomer. It has also been shown to have fewer side effects than either the R (-) isomer or the racemic mixture (Kohrs & Dureux, 1998). Ketamine has a rapid onset (30 seconds), relative short duration (5-15 minutes), high lipid solubility and a low degree of plasma protein binding (12 %) (White, 1997). These properties are reflected in the following parameters from Goodman and Gillman (1996). Ketamine has a molecular weight of 238. It has a pKa of 7.5, elimination half-life of 2.3 +/- 0.5 hours, volume of distribution of 1.8+/- 0.7 L.kg-1, clearance of 15+/- 5 ml.min.kg-1. The drug is extensively metabolized in the liver via the cytochrome P-450 enzymes. Ketamine undergoes N-demethylation to form norketamine, an active metabolite that is one fifth to one third as potent as the parent drug (Stoelting, 1991). Norketamine is then hydroxylated on the cyclohexanone ring in two places. This forms hydroxynorketamine metabolites III and IV. These metabolites can be further metabolized by heat to metabolites II or conjugated to inactive glucuronide metabolites (White, 1997). The metabolites and a small amount of the drug are excreted in the urine.
Ketamine affects the CNS, producing a state of dissociative anesthesia. Ketamine appears to work at the thalamoneocortical projection system and in the medial medullary reticular formation. These actions play a pivotal role in emotional components of nociception from the spinal cord to the brain (Miller, 2000). Ketamine produces profound analgesia but the patient’s cough, corneal and swallowing reflex often remain intact. Lacrimation and horizontal nystagmus are present and airway secretions increase. Purposeful movements, not related to painful stimuli, occur and skeletal muscle tone increases. Ketamine increases cerebral blood flow (CBF) 60% to 80% but blood flow returns to normal within approximately half an hour after administration. This increase in CBF causes both the metabolic oxygen consumption and intracranial pressure to increase. Electroencephalogram can determine ketamine’s effects. Alpha waves give way to
theta-waves while the drug is active and return to alpha-waves upon emergence. Ketamine, at high doses, may cause emergence delirium, night terrors, sympathetic stimulation and hallucinations.
Ketamine stimulates the cardiovascular system. This drug has direct myocardial depressant effects but is offset by the centrally produced sympathetic outflow. There is a subsequent increase in heart rate, blood pressure, and cardiac output. These affects on the cardiovascular system can be attenuated with the use of α and β-adrenergic antagonists (Miller, 2000). Inhalational agents will also blunt the cardiovascular response of ketamine (Miller, 2000). Catecholamine-depleted patients may exhibit a decline in blood pressure and cardiac output (White, 1996).
Ketamine has minimal effects on the respiratory system, airway reflexes are relatively preserved and the carbon dioxide response is not blunted. There is an increase in tracheal, bronchial and salivary gland secretions. The use of an antisialogogue may be necessary to attenuate increased secretions. The increase of circulating catecholamines is thought to give ketamine its bronchodilating properties.
Kohrs and Durieux (1998) reported that ketamine’s antagonistic action at the NMDA receptor accounts for most of the anesthetic properties of the drug. It is at the phencyclidine site, on the NMDA receptor, that ketamine non-competitively inhibits the action of glutamate. Ketamine also acts at opioid, nicotinic, muscarinic, monoaminergic and non-NMDA glutamate receptors.