Ketamine

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Ketamine
Ketamine.svg
Ketamine3Dan.gif
Systematic (IUPAC) name
(RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
Clinical data
AHFS/Drugs.com Consumer Drug Information
Licence data US FDA:link
Pregnancy cat. B3 (AU) C (US)
Legal status Controlled (S8) (AU) Schedule I (CA) CD (UK) Schedule III (US)
Dependence liability Moderate
Routes IV, IM, Insufflated, oral, topical
Pharmacokinetic data
Metabolism Hepatic, primarily by CYP3A4[1]
Half-life 2.5–3 hours.
Excretion renal (>90%)
Identifiers
CAS number 6740-88-1 YesY
ATC code N01AX03
PubChem CID 3821
DrugBank DB01221
ChemSpider 3689 YesY
UNII 690G0D6V8H YesY
KEGG D08098 YesY
ChEBI CHEBI:6121 YesY
ChEMBL CHEMBL742 YesY
Chemical data
Formula C13H16ClNO 
Mol. mass 237.725 g/mol
Physical data
Melt. point 262 °C (504 °F)
 YesY (what is this?)  (verify)

Ketamine is a drug used in human and veterinary medicine, mainly for starting and maintaining general anesthesia. Other uses include sedation in intensive care, as a pain killer (particularly in emergency medicine), and treatment of bronchospasm. This drug is sometimes used recreationally. Like other drugs in its class such as tiletamine and phencyclidine (PCP), ketamine is classified as a dissociative agent.[2] The state it induces is defined as "a trancelike cataleptic state characterized by profound analgesia and amnesia, with retention of protective airway reflexes, spontaneous respirations, and cardiopulmonary stability."[3] Studies have shown that respiratory function is unchanged with the administration of ketamine.[4] Though its impact on respiratory function is favorable, ketamine can still cause adverse effects which will be discussed below.

Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist but does have some activity at other receptors..[5] It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a health system.[6]

Medical use[edit]

One 10 ml vial of 1000 mg ketamine

Indications for use as an anaesthetic:

In medical settings, ketamine is usually injected intravenously or intramuscularly.[7] Since it suppresses breathing much less than most other available anaesthetics,[8] ketamine is still used in human medicine as an anesthetic; however, due to the hallucinations it may cause, it is not typically used as a primary anesthetic, although it is the anaesthetic of choice when reliable ventilation equipment is not available.

Ketamine is frequently used in severely injured patients. It is the drug of choice for patients in traumatic shock who are at risk of hypotension.[9] Hypotension is extremely dangerous in patients with severe head injury[10] and ketamine is anaesthetic agent least likely to precipitate hypotension, often even able to prevent it.[11][12] For years medical myth has held that ketamine was dangerous in patients with head injury over concerns that it might transiently increase the pressure inside the skull. This small transient effect is completely outweighed by the devastation caused by hypotension in severely head injured patients. Air medical services and paramedics are using this drug with increasing frequency.[citation needed]

Ketamine tends to increase heart rate and blood pressure. Because it tends to increase or maintain cardiac output, it is sometimes used in anesthesia for emergency surgery when the patient's fluid volume status is unknown (e.g., from traffic accidents). Ketamine can be used in podiatry and other minor surgery, and occasionally for the treatment of migraine. Research is ongoing in France, the Netherlands, Russia, Australia and the US into the drug's usefulness in pain therapy, depression,[13] and for the treatment of alcoholism[14] and heroin addiction.[15]

Ketamine may be used in small doses (0.1–0.5 mg/kg·h) as a local anesthetic, particularly for the treatment of pain associated with movement and neuropathic pain.[16] It may also be used as an intravenous coanalgesic with opiates to manage otherwise intractable pain, particularly if this pain is neuropathic (pain due to vascular insufficiency or shingles are good examples). It has the added benefit of counteracting spinal sensitization or wind-up phenomena experienced with chronic pain. At these doses, the psychotropic side effects are less apparent and well managed with benzodiazepines.[17] Ketamine is a coanalgesic, so is most effective when used alongside a low-dose opioid; while it does have analgesic effects by itself, the higher doses required can cause disorienting side effects.[17] The combination of ketamine with an opioid is, however, particularly useful for pain caused by cancer.[18]

The effect of ketamine on the respiratory and circulatory systems is different from that of other anesthetics. When used at anesthetic doses, it will usually stimulate rather than depress the circulatory system.[19] It is sometimes possible to perform ketamine anesthesia without protective measures to the airways. Ketamine is also a potent analgesic and can be used in subanesthetic doses to relieve acute pain; however, its psychotropic properties must be taken into account. Patients have reported vivid hallucinations, "going into other worlds" or "seeing God" while anesthetized, and these unwanted psychological side effects have reduced the use of ketamine in human medicine. They can, however, usually be avoided by concomitant application of a sedative such as a benzodiazepine.[17]

Low-dose ketamine is recognized for its potential effectiveness in the treatment of complex regional pain syndrome (CRPS).[20] Although low-dose ketamine therapy is established as a generally safe procedure, reported side effects in some patients have included hallucinations, dizziness, lightheadedness and nausea. Therefore, nurses administering ketamine to patients with CRPS should do so only in a setting where a trained physician is available if needed to assess potential adverse effects on patients.[21]

In some neurological intensive care units, ketamine has been used in cases of prolonged seizures. Some evidence indicates the NMDA-blocking effect of the drug protects neurons from glutamatergic damage during prolonged seizures.[22]

Ketamine is a "core" medicine in the World Health Organization's "Essential Drugs List", a list of minimum medical needs for a basic healthcare system.[23]

Pain[edit]

The dissociative anesthetic effects of ketamine have also been applied for postoperative pain management. Low doses of ketamine have been found to significantly reduce morphine consumption, as well as reports of nausea following abdominal surgery.[24]

Oral ketamine[edit]

Ketamine can be started using the oral route, or people may be changed from a subcutaneous infusion once pain is controlled. Bioavailability of oral ketamine hydrochloride is approximately 20%

Converting from a 24-hour subcutaneous ketamine infusion to oral ketamine[edit]

  • Oral ketamine is easily broken down by bile acids and thus has a low bioavailability (~20%). Oftentimes lozenges or "gummies" for sublingual or buccal absorption prepared by a compounding pharmacy are used to combat this issue.
  • Some specialists stop the subcutaneous infusion when the first dose of oral ketamine is given. Others gradually reduce the infusion dose as the oral dose is increased.[25]

Recreational use[edit]

Ketamine poured onto glass and left to dry.

Unlike the other well-known dissociatives PCP and DXM, ketamine is very short-acting. It takes effect within approximately 10 minutes,[26] while its hallucinatory effects last 60 minutes when insufflated or injected and up to two hours when ingested orally. The total experience lasts no more than a few hours.[27]

At subanesthetic doses, ketamine produces a dissociative state, characterised by a sense of detachment from one's physical body and the external world which is known as depersonalization and derealization.[28] At sufficiently high doses, users may experience what is called the "K-hole", a state of extreme dissociation with visual and auditory hallucinations.[29] John C. Lilly,[30] Marcia Moore[31] and D. M. Turner[32] (amongst others) have written extensively about their own entheogenic use of, and psychonautic experiences with, ketamine. Both Moore and Turner died prematurely in a way that has been indirectly linked to the sedative properties of ketamine.[33]

Side effects[edit]

These include:[34]