KETAMINE DRUGS

Ketamine

Ketamine in powder form

AKA: K, Special K, Vitamin K, K2

Price: $$$

Ketamine, sold under the brand name Ketalar among others, is a medication mainly used for starting and maintaining anesthesia.^[4] It induces a trance-like state while providing pain relief, sedation, and memory loss.^[5] Other uses include for chronic pain and for sedation in intensive care.^[6][7] Heart function, breathing, and airway reflexes generally remain functional.^[5] Effects typically begin within five minutes when given by injection with the main effects lasting up to 25 minutes.^[3][4]

Common side effects include psychological reactions as the medication wears off.^[8] These reactions may include agitation, confusion, or hallucinations.^[4][8][9] Elevatedblood pressure and muscle tremors are relatively common, while low blood pressure and a decrease in breathing are less so.^[4][9] Spasms of the larynx may rarely occur.^[4] Ketamine has been classified as an NMDA receptor antagonist; it also acts on opioid receptors and monoamine transporters among others.^[10]

Ketamine was discovered in 1962.^[3] It is on the World Health Organization's List of Essential Medicines, of the most important medications needed in a basic health system.^[11] It is available as a generic medication.^[4] The wholesale cost in the developing world is between 0.08 and 0.32 USD per dose.^[12] Ketamine is also used as arecreational drug.^[13]

Ketamine is perhaps best known as a horse tranquiliser although it was developed for human use. It was intended to replace PCP (Angel dust) as a shorter lasting anaesthetic and it is still used in certain situations. However, there are several side effects that come in to play as the drugs effects wear off, most notably hallucinations. These usually last less than 2 hours along with feelings of detachment, which can be fairly extreme.

Ketamine overdoses are potentially fatal and there is no effective antidote. A patient may need to be put on life support to maintain respiratory function until they can breath on their own. Possibly the greatest risk to users of ketamine though is the direct psychological effects or the “K-hole”. The user may become so detached from reality that they endanger themselves. For example two eminent ketamine experimentors wound up dead, one from hypothermia and the other drowning.

There is plenty of evidence of ketamine being addictive and once this happens tolerance soon builds up. Along with this go several side-effects such as bladder problems, memory loss and various other psychological impairments. Withdrawal may result in minor, but permanent nerve damage.

Ketamine, categorized as a “dissociative anesthetic,” is used in powdered or liquid form as an anesthetic, usually on animals. It can be injected, consumed in drinks, snorted, or added to joints or cigarettes. Ketamine was placed on the list of controlled substances in the US in 1999.

Short- and long-term effects include increased heart rate and blood pressure, nausea, vomiting, numbness, depression, amnesia, hallucinations and potentially fatal respiratory problems. Ketamine users can also develop cravings for the drug. At high doses, users experience an effect referred to as “K-Hole,” an “out of body” or “near-death” experience.

Due to the detached, dreamlike state it creates, where the user finds it difficult to move, ketamine has been used as a “date-rape” drug.

Side effects[edit]

Ketamine is generally safe for those critically ill, when administered by trained medical professionals.^[44] Even in these cases, there are known side effects that include one or more of the following:^[45]

• Cardiovascular: abnormal heart rhythms, slow heart rate or fast heart rate, high blood pressure or low blood pressure
• Central nervous system: Ketamine is traditionally avoided in people with or at risk of intracranial hypertension (ICP) due to concerns about ketamine causing increased intracranial pressure. It does not increase ICP more than opioids.^[46]
• Dermatologic: Transient erythema, transient morbilliform rash
• Gastrointestinal: Anorexia, nausea, increased salivation, vomiting
• Local: Pain or exanthema of the injection site
• Neuromuscular and skeletal: Increased skeletal muscle tone (tonic-clonic movements)
• Ocular: Double vision, increased intraocular pressure, nystagmus, tunnel vision
• Respiratory: Airway obstruction, apnea, increased bronchial secretions, respiratory depression, laryngospasm
• Other: Anaphylaxis, dependence, emergence reaction

In 10-20% of patients at anesthetic doses experience adverse reactions that occur during emergence from anesthesia, reactions that can manifest as seriously as hallucinations and delirium.^[8] These reactions may be less common in some patients subpopulations, and when administered intramuscularly, and can occur up to 24 hours postoperatively; the chance of this occurring can be reduced by minimizing stimulation to the patient during recovery and pretreating with a benzodiazepine, alongside a lower dose of ketamine.^[8] Patients who experience severe reactions may require treatment with a small dose of a short- or ultrashort-acting barbiturate.^[45]

Tonic-clonic movements are reported at higher anesthetic doses in greater than 10% of patients.^[47]

Neurological effects[edit]

In 1989, psychiatry professor John Olney reported ketamine caused irreversible changes in two small areas of the rat brain. However, the rat brain has significant differences in metabolism from the human brain, therefore such changes may not occur in humans.^[48]

The first large-scale, longitudinal study of ketamine users found current frequent (averaging 20 days/month) ketamine users had increased depression and impaired memory by several measures, including verbal, short-term memory, and visual memory. Current infrequent (averaging 3.25 days/month) ketamine users and former ketamine users were not found to differ from controls in memory, attention, and psychological well-being tests. This suggests the infrequent use of ketamine does not cause cognitive deficits, and that any deficits that might occur may be reversible when ketamine use is discontinued. However, abstinent, frequent, and infrequent users all scored higher than controls on a test of delusional symptoms.^[49]

Short-term exposure of cultures of GABAergic neurons to ketamine at high concentrations led to a significant loss of differentiated cells in one study, and noncell-death-inducing concentrations of ketamine (10 μg/ml) may still initiate long-term alterations of dendritic arbor in differentiated neurons. The same study also demonstrated chronic (>24 h) administration of ketamine at concentrations as low as 0.01 μg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal maintenance and development.^[50][51]

More recent studies of ketamine-induced neurotoxicity have focused on primates in an attempt to use a more accurate model than rodents. One such study administered daily ketamine doses consistent with typical recreational doses (1 mg/kg IV) to adolescent cynomolgus monkeys for varying periods of time.^[52] Decreased locomotor activity and indicators of increased cell death in the prefrontal cortex were detected in monkeys given daily injections for six months, but not those given daily injections for one month.^[52] A study conducted on rhesus monkeys found a 24-hour intravenous infusion of ketamine caused signs of brain damage in five-day-old but not 35-day-old animals.^[53] Some neonatal experts do not recommend the use of ketamine as an anesthetic agent in human neonates because of the potential adverse effects it may have on the developing brain. These neurodegenerative changes in early development have been seen with other drugs that share the same mechanism of action of NMDA receptor antagonism as ketamine.^[54]

The acute effects of ketamine cause cognitive impairment, including reductions in vigilance, verbal fluency, short-term memory, and executive function, as well as schizophrenia-like perceptual changes.^[55]

Urinary tract effects[edit]

A 2011 systematic review examined 110 reports of irritative urinary tract symptoms from ketamine recreational use.^[56] Urinary tract symptoms have been collectively referred as "ketamine-induced ulcerative cystitis" or "ketamine-induced vesicopathy", and they include urge incontinence, decreased bladder compliance, decreased bladder volume, detrusor overactivity, and painful haematuria (blood in urine). Bilateral hydronephrosis and renal papillary necrosis have also been reported in some cases.^[56][57] The pathogenesis of papillary necrosis has been investigated in mice, and mononuclear inflammatory infiltration in the renal papilla resulting from ketamine dependence has been suggested as a possible mechanism.^[58]

The time of onset of lower urinary tract symptoms varies depending, in part, on the severity and chronicity of ketamine use; however, it is unclear whether the severity and chronicity of ketamine use corresponds linearly to the presentation of these symptoms. All reported cases where the user consumed greater than 5 g/day reported symptoms of the lower urinary tract.^[56] Urinary tract symptoms appear to be most common in daily ketamine users who have used the drug recreationally for an extended period of time.^[57] These symptoms have presented in only one case of medical use of ketamine. However, following dose reduction, the symptoms remitted.^[57]

Management of these symptoms primarily involves ketamine cessation, for which compliance is low. Other treatments have been used, including antibiotics, NSAIDs, steroids, anticholinergics, and cystodistension.^[56]Both hyaluronic acid instillation and combined pentosan polysulfate and ketamine cessation have been shown to provide relief in some patients, but in the latter case, it is unclear whether relief resulted from ketamine cessation, administration of pentosan polysulfate, or both. Further follow-up is required to fully assess the efficacy of these treatments.^[56]

Liver problems[edit]

In case reports of three patients treated with esketamine for relief of chronic pain, liver enzyme abnormalities occurred following repeat treatment with ketamine infusions, with the liver enzyme values returning below the upper reference limit of normal range on cessation of the drug. The result suggests liver enzymes must be monitored during such treatment.^[59]

Interactions[edit]

Other drugs which increase blood pressure may interact with ketamine in having an additive effect on blood pressure including: stimulants, SNRI antidepressants, and MAOIs. Increase blood pressure and heart rate, palpitations, and arrhythmias may be potential effects.

Ketamine may increase the effects of other sedatives in a dose dependent manner, including, but not limited to: alcohols,^[60] benzodiazepines,^[61] opioids,^[62] quinazolinones, phenothiazines, anticholinergics andbarbiturates.^[63]