Ketamine is a drug used in human and veterinary medicine developed by Parke-Davis (today a part of Pfizer) in 1962. Its hydrochloride salt is sold as Ketanest , Ketaset , and Ketalar . Pharmacologically, ketamine is classified as an NMDA receptor antagonist. At high, fully anesthetic level doses, ketamine has also been found to bind to opioid μ receptors and sigma receptors. Like other drugs of this class such as tiletamine and phencyclidine (PCP), it induces a state referred to as "dissociative anesthesia" and is used as a recreational drug.
Ketamine has a wide range of effects in humans, including analgesia, anesthesia, hallucinations, elevated blood pressure, and bronchodilation. Ketamine is primarily used for the induction and maintenance of general anesthesia, usually in combination with some sedative drug. Other uses include sedation in intensive care, analgesia (particularly in emergency medicine), and treatment of bronchospasm. It is also a popular anesthetic in veterinary medicine.
Ketamine is a chiral compound. Most pharmaceutical preparations of ketamine are racemic; however, some brands reportedly have (mostly undocumented) differences in enantiomeric proportions. The more active enantiomer, ( S )-ketamine, is also available for medical use under the brand name Ketanest S . Ketamine is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.
History
Ketamine was developed by Dr. Craig Newlands of Wayne State University. It was then developed by Parke-Davis in 1962 as part of an effort to find a safer anesthetic alternative to phencyclidine (PCP), which was likely to cause hallucinations, neurotoxicity and seizures. The drug was first given to American soldiers during the Vietnam War. It is still widely used in humans. There may be some evidence that ketamine has the potential to cause emergence phenomena because of the drug's possible psychotomimetic effects. It is also used widely in veterinary medicine, or as a battlefield anesthetic in developing nations.
The drug was used in psychiatric and other academic research through the 1970s, culminating in 1978 with the publishing of John Lilly's The Scientist and Marcia Moore and Howard Alltounian's Journeys into the Bright World , which documented the unusual phenomenology of ketamine intoxication.
The incidence of recreational ketamine use increased through the end of the century, especially in the context of raves and other parties. The increase in illicit use prompted ketamine's placement in Schedule III of the United States Controlled Substance Act in August 1999. In the United Kingdom, it became outlawed and labeled a Class C drug on 1 January 2006. In Canada ketamine is classified as a Schedule I narcotic, as of August 2005. In Hong Kong, as of year 2000, ketamine is regulated under Schedule 1 of Hong Kong Chapter 134 Dangerous Drugs Ordinance . It can only be used legally by health professionals, for university research purposes, or with a physician's prescription.
Naming
Ketamine was invented as CL369, and it was referred to as CI 581 (clinical investigation 581) during development at Parke-Davis. Commercial brands of ketamine include "Ketalar, Ketaset, Ketmex, Ketotal, Ketamine-500 (Astrapin) and Imalgen".
Production for recreational use has been traced to 1967, when it was referred to as "mean green" and "rockmesc". Recreational names for ketamine include "K", "Ket", "Special K", and "Vitamin K".
Medical use
Indications for use as an anaesthetic:
- Paediatric anaesthesia (as the sole anaesthetic for minor procedures or as an induction agent followed by muscle relaxant and endotracheal intubation)
- Asthmatics or patients with chronic obstructive airway disease
- In emergency medicine in entrapped patients suffering severe trauma
- Emergency surgery in field conditions in war zones
- To supplement spinal / epidural anaesthesia / analgesia utilizing low doses
Effects
Impairs all senses, especially:
- Sight
- Balance
- Sense of time
Cardiovascular:
- Partial depressant
Gastrointestinal:
- Nausea
Musculoskeletal:
- Relaxant
Neurological:
- Analgesia
Respiratory:
- Partial depressant/stimulant
In medical settings, ketamine is usually injected intravenously or intramuscularly, but it is also effective when insufflated, smoked, or taken orally.
Since it suppresses breathing much less than most other available anaesthetics, ketamine is still used in human medicine as an anesthetic, however, due to the hallucinations which may be caused by ketamine, it is not typically used as a primary anesthetic, although it is the anaesthetic of choice when reliable ventilation equipment is not available. Ketamine tends to increase heart rate and blood pressure. Because ketamine 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. There is ongoing research in France, the Netherlands, Russia, Australia and the US into the drug's usefulness in pain therapy, depression suppression, and for the treatment of alcoholism and heroin addiction.
In veterinary anesthesia, ketamine is often used for its anesthetic and analgesic effects on cats, dogs, rabbits, rats, and other small animals. Veterinarians often use ketamine with sedative drugs to produce balanced anesthesia and analgesia, and as a constant rate infusion to help prevent pain wind-up. Ketamine is used to manage pain among large animals, though it has less effect on bovines. It is the primary intravenous anesthetic agent used in equine surgery, often in conjunction with detomidine and thiopental, or sometimes guaifenesin.
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. It may also be used as an intravenous co-analgesic together 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 counter-acting 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. Ketamine is a co-analgesic, and 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. The combination of ketamine with an opioid is, however, particularly useful for pain caused by cancer.
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. 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 sub-anesthetic 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.
Low-dose ketamine is recognized for its potential effectiveness in the treatment of complex regional pain syndrome (CRPS), according to a retrospective review published in the October 2004 issue of Pain Medicine. 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 only do so in a setting where a trained physician is available if needed to assess potential adverse effects on patients.
Experimental antidepressant use
When treating patients suffering from complex regional pain syndrome (CRPS) with a low-dose (subanesthetic) ketamine infusion, it was observed that some patients made a significant recovery from associated depression. This recovery was not formally documented, as the primary concern was the treatment of the patient's pain. It was not possible to quantify to what degree depression recovery was secondary to the patient's recovery from CRPS. Based on this result, it was thought that a low-dose (subanesthetic) infusion of ketamine was worth a trial in patients who were suffering from treatment-resistant depression without other physical or psychiatric illness.
Correll, et al. gave ketamine intravenously to patients commencing at 15–20 mg/h (0.1–0.2 mg/kg/h) and the dose increased until a maximum tolerated dose was achieved. This dose was assumed to be a therapeutic dose and w
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