Ketamine indications

Phencyclidine (l-[l-phenylcyclohexyl] piperidine, PCP) was originally developed as an intravenous anesthetic in the 1950s. Used for this indication, it causes a trance-like state without loss of consciousness and was hence classified as a dissociative anesthetic. However, it was soon withdrawn from human use because it produced unpleasant hallucinations, agitation, and delirium. The product was later used in veterinary medicine. Ketamine, a chemically closely related substance, was developed to replace PCP and is stiU in use as a dissociative anesthetic in children. Ketamine is less potent than PCP, and its effects are of shorter duration. However, it may also cause hallucinations (see the section on ketamine in Chapter 7, Club Drugs ). Much of the ketamine sold on the street (special K, cat Valium) has been diverted from veterinarians offices. 

No specific treatments for ketamine intoxication are currently indicated (Solh-khah and Wilens 1998). General supportive care, including providing the patient with a quiet, low-stimulus environment, can be helpful (Koestets et al. 

On the other hand, the results using the hippocampal seizure model revealed an interesting profile of anticonvulsant effects for PCP and ketamine, compared to several classical anticonvulsant compounds. When tested against the unkindled hippocampal seizure, the effects of behaviorally equivalent doses of PCP and ketamine were remarkably similar, but differed substantially from the effects of the anticonvulsant drugs. The compression of the entire EEG seizure episode to a shorter duration was unique to PCP and ketamine, and suggests an anticonvulsant effect. Conversely, the small prolongation of the initial AD episode, and the decreased duration of the postictal depression, could be reflective of pro-convulsive influences. There were, however, no other indications of enhanced seizure activity, such as the appearance of motor convulsions or spread of seizure activity to the cerebral cortex. 

Generalization tests indicated that a number of compounds were able to substitute for PCP (table 1). Ketamine and tiletamine, which are structurally similar to PCP, produced dose-dependent effects mimicking PCP. These compounds are interesting examples of the structural requirements of molecules for PCP-mimetic activity, demonstrating that neither the piperidine nor the phenyl moieties are absolutely necessary for activity. 

Ketamine and also tiletamine are structurally and pharmacologically related to phencyclidine. Its mechanism of action is not well understood. It has been suggested that it blocks the membrane effects of the excitatory neurotransmitter glutamic acid. Ketamine produces dissociative anesthesia, which means that the patient seems to be awake but there are no responses to sensory stimuli. Ketamine, which can be administered IV or IM, has strong analgesic activity. It is especially indicated for interventions of short duration without any need for skeletal... 

Barbiturates may precipitate episodes of acute intermittent porphyria (AIP) and their use is contraindicated in patients who are predisposed to this condition. Some animal models indicate that ketamine, etomidate, and the benzodiazepines may be porphyrinogenic and propofol is considered to be the intravenous anaesthetic of choice in AlP-prone patients. 

Intraocular pressure is slightly increased by ketamine. Uterine tone and intrauterine pressure are increased in both the non-pregnant and pregnant uterus, effects that may be harmful in abruptio placentae and cord prolapse. Ketamine rapidly crosses the placenta and equilibrates in fetal plasma. Transient rashes have been reported in 20% of patients although life-threatening reactions are rare. Indications... 

Ketamine has been approved for both human and animal use as an injectable anesthetic in medical settings since 1970. About 90% of the ketamine legally sold in the United States in 2001 was intended for veterinary use, and over the past several years medical usage of ketamine has remained fairly constant. Production of ketamine, however, has increased almost 40% over the last six years, indicating a great deal of the substance is being diverted for illegal use. 

Research continues to illuminate different aspects of ketamine pharmacology, some of it promising enough to indicate that new clinical uses (principally in the field of anesthesiology) for the drug will be approved. It is still used as a general anesthetic for children and geriatric patients because it is well tolerated. Benzodiazepine-based tranquilizers are used to keep the auditory and visual hallucinations to a minimum. 

Though data on the regular party-going subset of the gay community is comparatively sparse, the research that has been conducted indicates gay men of a much broader age demographic are users of ketamine and other club drugs. 

Among the drugs which are known to interact with barium, the barbiturates sodium pentobarbital and phenobarbital were found to have an increased depressive effect on the hearts of rats exposed to barium (Kopp et al. 1985 Perry et al. 1983, 1989). This hypersensitivity of the cardiovascular system to anesthesia was not observed in similarly treated animals that were anesthetized with xylazine plus ketamine. Results of the study indicated that the hypersensitivity was specific to the barbiturates and not a generalized effect of anesthesia (Kopp et al. 1985). 

Although chronic ketamine (repeated acute administration for 14 days) reportedly has no effect on the amplitude or latency of any ERP components, there does appear to be some lasting effects of chronic ketamine exposure (Maxwell et al., 2006b). In a study by Maxwell and colleagues, mice were treated with ketamine daily for 2 weeks, and then tested 1 week later. Ketamine decreased N40 amplitude, but not latency 7 days after last ketamine dose. These data indicate that chronic NMDA receptor hypofunction can lead to auditory processing deficits similar to those seen in schizophrenia patients (Maxwell et al., 2006b). 

In its powdered form, ketamine is often mistaken for cocaine or crystal methamphetamine. Reports also indicate that ketamine is sometimes sold as Ecstasy (MDMA) and mixed with other drugs. In all its forms, ketamine is usually sold for 25 to 50 per gram.52... 

People who use ketamine regularly can suffer psychological problems. Paranoia and delirium are the main difficulties.59 There are many reports of regular ketamine users starting to see patterns and coincidences (synchronicities) in the world around them. To users, these patterns indicate that they are somehow more important or integral to the world than other people, and this can also contribute to their feelings of paranoia. 

Since 1992, the DEA has received more than 500 reports of the sale and/or use of ketamine by minors on college campuses, at nightclubs, and at raves.63 Most DEA field divisions report that ketamine is available in their areas, while several indicate that availability is increasing.64 The sale of ketamine as a drug of abuse to undercover law enforcement officials has also been recorded. The DEA s STRIDE data have shown that since 1999 (the first year that ketamine was included in the STRIDE data system), there has been an upward trend in ketamine seizures. In 1999,4,551 dosage units ofketamine were seized, compared with... 

If Chiralpak AD shows an indication of separation, the Chiraleel OJ column should also be evaluated. It seems particularly appropriate for the following SAs (and compounds with similar structures) ibuprofen. ketamine, methadone, nicotine, steroids. 

Pathological bradyarrhythmias that affect cardiac output or peripheral perfusion require appropriate therapy. The primary aim of therapy should be the correction of the underlying disease mechanism electrolyte abnormalities should be corrected or the depth of anesthesia reduced as appropriate. An ct2 adrenoceptor antagonist (e.g. atipamezole) can be considered in animals sedated with the 02 adrenoceptor agonists but it should not be administered to animals anaesthetized with ketamine because of the risks of inducing ketamine-related excitement. Corticosteroids are indicated if myocardial inflammation is present. 

There is ample evidence that ketamine is an effective analgesic that acts at the level of both the spinal cord and the brain. In horses, epidural administration of ketamine provided perineal analgesia for up to 75 min (Gomez de Segura et al 1998). Epidural ketamine reduced the MAC of halothane for hind- but not forelimb procedures, indicating a localized effect in the spinal cord after epidural administration (Doherty et al 1997c). Constant rate i.v. infusions of ketamine caused a reduction in the MAC value for halothane in the horse when plasma ketamine concentrations exceeded 1 (ig/ml (Muir Sams 1992). 

The reference number and the technique are indicated parenthetically in the columns. The techniques are designated as follows a, tail cuff in conscious mice b, carotid artery in awake mice 24 h after surgery with isoflurane c, carotid artery in awake mice 3 h after surgery with halothane d, carotid artery in awake mice 24 h after surgery with pentobarbital e, carotid artery in mice under pentobarbital anesthesia f, telemetry in awake mice 1 wk after surgery with isoflurane g, echo under anesthesia h, echo in conscious mice i, femoral artery telemeter 10 d after ketamine and xylazine anesthesia j, femoral artery in awake mice 3 d after surgery with pentobarbital. 

The respiratory effects of ketamine are perhaps the best indication for its use. Induction doses of ketamine produce small and transient decreases in minute ventilation, but respiratory depression is less severe than with other general anesthetics. Ketamine is a potent bronchodilator due to its indirect sympathomimetic activity and perhaps some direct bronchodilating activity. Thus, ketamine is particularly well suited for anesthetizing patients at high risk for bronchospasm. 

Several investigations have studied the in vivo antidepressant activity of this herb and of compounds isolated from it. For example, a commercially available extract of the aerial parts of Hypericum perforatum LI 160 and hypericin, Fig. (13) showed pronounced activity in selected animal bioassays. These include the forced swimming test and the tail suspension test, used to determine antidepressant activity, and tests indicating activity on the central nervous system, such as body temperature and ketamine-induced sleeping time [231,232],... 

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