Ketamine

Drug Profile Check Sheet

Name(s):

Common Brand Name: Ketalar, Chemical Name Ketamine or 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone, Street Name(s): K, Super C, Cat Valium, Jet, Super acid Green, Puprle and Special K.

Drug Classification

Classified as a Psychotomimetic, Dissociative Anaesthetic, and a Hallucinogen (National Highway Traffic Safety Administration, n.d)

Mythos

Users engage in illegal activities, promotes illegal behavior, main cause for psychosis, can be mixed with alcohol safely, provides insight into the universe, cannot make one sick, addicted users do not need treatment. Other myths include; it is safe, natural and Non addictive (Lockwood, 2006).

History

Ketamine has a history of human usage as a hallucinogen. The interest in the drug developed gradually from Ancient Greece attributed by the visions and omens that were evident after the inhalation of a dissociative anesthetic, nitrous oxide   (TD Consultancy, 2017). The drug has seen popularity as an illicit drug in China (BBC News, 2017) and Egypt (Samy, 2015).

Chemistry

Ketamine is synthesized from the reaction between cyclopentyl Grignard and o-chlorobenzonitrile, which produces o-chlorophenyl-cyclopentyl ketone. This was then brominated and then reacted with methylamine forming 1-Hydroxycyclopentyl-(o-chlorophenyl)-ketone-N-methylimine. Heating the product forms Ketamine through novel alpha-hydroxyimine rearrangement.

Ketamine can achieve purification by using Isopropyl alcohol

Undergoes degradation by the use of heat or treatment with an acid or base

Synthetic

Starting reagents used to synthesize Ketamine are cyclopentyl Grignard and o-chlorobenzonitrile

Mechanism of action (MOA)

Ketamine undergoes interaction with N-methyl-D-aspartate (NMDA) receptors, monoaminergic receptors, opioid receptors, muscarinic receptors and voltage sensitive Ca ion channels. Does not interact with GABA receptors.

Neurotransmitter system(s) affected

Dopamine, Noradrenaline, glutamate, GABA, serotonin, Ach, Histamine, Glycine &>200 others

Disorder used to treat OR Addictive liability

Schizophrenia, depression, bipolar, PTSD, Obsessive Compulsive Disorder, fibromyalgia, neuropathic syndromes, severe anxiety and drug addiction

Efficacy (if therapeutic)

Low, moderate or high depending on the therapy employed

Pharmacokinetics

The bioavailability of ketamine after different dosages in various sites of action are as follows: an intramuscular 93%, intranasal 25-50%, and oral 20±7%.  The drug is rapidly distributed into the brain and other highly perfused tissues. Ketamine is 12% bound in plasma (plasma’s half life is 2.3 ± 0.5 hours. Oral administration results in peak concentrations of ketamine that is lower.

Solubility

Ketamine is lipophilic.

Common Route(s) of administration

Intravenous, intranasal, sublingual, intramuscular, oral and rectal means

Usual dose-range (by route)

Intranasal dosage is 10-250mg/kg between 5 and 15mins. Oral is 40 to 500+mg/kg between 5 and 20mins. Rectal is 40-500+mg/kg between 5 and 20mins. IM is 10-200mg between 1 and 5mins. I.V is 1- 4.5mg/kg between 1 and 4mins.

Metabolism/Excretion

Undergoes first pass metabolism upon oral administration. The drug then goes to the liver where biotransformation to norketamine and dehydronorketamine takes place using CYP3A4, CYP2B6, and CYP2C9.

Major effects (desired)

Pain management and dissociative aesthetic state.

Side-effects (undesirable)

Bluish skin,  blurry vision, difficulty breathing, convulsions, itching, urination urge, unusual weakness, unusual senses, loss of consciousness, death

Lethality (toxicity) method

Suffocation (loss of consciousness), liver damage (evidenced by biliary and hepatic complications)

Usual Cause of death

Overdose or chronic use, resulting in respiratory complications which lead to death.

Tolerance

Cellular tolerance where damaging effects evident on brain cells that secrete neurotransmitters. Metabolic tolerance in the sense that cell structures break thus becoming less sensitive to the effects of ketamine. Behavioral tolerance in the form of alterations of sensory perceptions resulting in the ingestion of larger ketamine doses to maintain hallucinogenic effect.

Physical dependence

Can be low, moderate or high depending on the frequent of usage of ketamine.

Psychological dependence

Craving for the drug may be low, moderate or high depending on the frequency of usage of the drug

Withdrawal symptoms

Paranoia, depression, emotional and physical imbalance in nature. Actual symptoms may include; muscle cramps, headache, tremors, rapid breathing, loss of hearing, double vision, accelerated heart beat and loss of coordination and motor ability.

Psychological effects on consciousness

Hallucinatory effects occur where a lessening, or heighten of confusion may be experienced.

Uses

Medical, hallucinogen or a Psychotomimetic agent

Behavioral tests

Activity (swimming and maze tests), Analgesia, SD, ICSS, CPP

Assessment instruments

Rating scales, which take note of psychiatric, visual and mood measurements.