Ketamine

Ketamine: Uses, Mechanism of Action, Side Effects, and Contraindications

What is Ketamine and what does it feel like?

Non-barbiturate general anesthetic ketamine is a short-acting drug that is used to induce a kind of unconsciousness in patients where they feel no pain but appear to be awake. This state is called dissociated state and so does ketamine called dissociative anesthesia. Immobility, amnesia, and sedation are primary outcomes associated with the use of ketamine.

Calvin Stevens of Parke Davis Laboratories developed Ketamine in 1963 as a substitute for phencyclidine (PCP). It was first employed for veterinary purposes in Belgium, and it was observed in 1964 that it caused mild hallucinogenic effects and shorter psychotomimetic effects when compared to PCP.

It was licensed by the FDA in 1970 and has since been used as a local anesthetic for children and people having minor procedures and in animals. However, the drug is not used widely because it encourages postoperative hallucinations and an increase in cerebral blood flow.

Ketamine Mechanism of Action

By reacting with N-Methyl-D-aspartate (NDMA) receptors, the drug produces an analgesic effect. The aforementioned mechanism is also said to be involved in the neuroprotective mechanism of the drug. Ketamine stimulates central sympathetic flow, which stimulates the heart and increases blood pressure as well as cardiac output. Owing to this, the drug is a very suitable candidate for hypovolemic, asthmatic, and cardiogenic shock patients.

Ketamine Pharmacokinetics

Absorption

Ketamine is rapidly absorbed and has a bioavailability of roughly 93 percent. Only 17 percent of the prescribed dosage is absorbed after the first pass effect. It spreads quickly and has a distribution half-life of 1.95 minutes.

Plasma Protein Binding

53.3% of the administered dose is bound to plasma proteins.

Metabolism

The drug undergoes hepatic metabolism producing norketamine.

Mechanisms of biotransformation involved in the metabolism of ketamine may involve

  • N-dealkylation
  • Hydroxylation of the cyclohexane ring
  • Conjugation to glucuronic acid
  • Dehydration of the hydroxylated metabolites for the formation of cyclohexene derivatives

How Ketamine is Eliminated?

It is primarily eliminated from the body in urine. Some amounts of the drug are also excreted in bile and feces.

Ketamine Adverse Effects

Ketamine infusions at sub-anesthetic levels can cause a variety of side effects, most of which occur during the infusion phase and fade away quickly. Among the acute and transitory side effects are:

  • A rise in blood pressure
  • Perceptual disturbance
  • Drowsiness
  • Dizziness
  • Nausea
  • Vomiting
  • Dissociation
  • Floating sensation
  • Vivid pleasant dreams
  • Nightmares
  • Hallucinations
  • Delirium
Nausea

What is Ketamine Used for?

Historical uses associated with ketamine

For nearly 50 years, ketamine has been utilized in the operating room. In patients with asthma or life-threatening acute bronchial constriction, ketamine’s bronchial dilating characteristic makes induction and maintenance of anesthesia safer.

The drug is also one of the few medications that can be used to induce anesthesia during a cesarean section. It is the preferred agent in the treatment of children and burns sufferers. Additionally, ketamine treatment during induction may reduce postoperative delirium, particularly in patients on cardiopulmonary bypass.

Ketamine Current Uses

Ketamine has appeared as a promising medicine for nearly half a century after its discovery to treat

  • Preoperative and postoperative pain
  • Depression
  • Inflammation

Ketamine Contraindications

The use of the drug is contraindicated under the following conditions:

  • Hypersensitivity
  • Aortic dissection
  • Uncontrolled hypertension
  • Myocardial infarction
  • Aneurysms
  • Obstetrics
  • Pregnancy
  • Breastfeeding
  • Chronic alcoholics
  • Patients with acute Alcohol intoxication
  • Schizophrenia
  • Elevated levels of Cerebrospinal fluid (CSF)
Lactation

Ketamine Abuse

Ketamine and its synthetic analogs have become drugs of abuse having hallucinogenic effects, in addition to its legitimate, medical usage.  It is frequently insufflated (“snorted”) up the nose when abused in social contexts. It can also be injected, taken orally as a liquid, or smoked in the form of marijuana or tobacco. It’s commonly taken in conjunction with other drugs like cocaine or amphetamines. Multiple drug use has resulted in death.

Long-term usage can lead to psychological dependence. When chronic users stop taking the drug, they will suffer cravings, making it difficult to quit because their bodies are not accustomed to operating without it.

Ketamine Therapy

Ketamine is injected into a vein (IV) or a muscle (IM). The FDA recently approved a ketamine nasal spray for the treatment of patients with treatment-resistant depression.

How Long does Ketamine Stay in your System?

Ketamine is a short-acting anesthetic drug. Ketamine’s effects might last anywhere from 5 to 30 minutes, depending on how it’s administered.

Infusion

Ketamine has been proved to have antidepressant qualities in studies for decades. The United States Food and Drug Administration (FDA) has licensed ketamine for the induction and maintenance of anesthesia, as well as the treatment of psychiatric illnesses and chronic pain. Ketamine has been used to treat psychiatric diseases such as MDD, bipolar disorder, and post-traumatic stress disorder (PTSD), and post-operative and chronic pain management.

For the treatment of psychiatric problems, ketamine infusion therapy comprises giving a single infusion or a series of infusions. For example

  • Major depressive disorder
  • Post-traumatic stress disorder
  • Acute suicidality

Ketamine Brand Names

Following are some brand names containing Ketamine:

References

https://pubmed.ncbi.nlm.nih.gov/9707750/

Lippincott Illustrated Reviews: Pharmacology 4th edition

https://go.drugbank.com/drugs/DB01221
https://journals.sagepub.com/doi/10.1177/2045125320916657
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933765/
https://www.ncbi.nlm.nih.gov/books/NBK470357/
https://americanaddictioncenters.org/ketamine-abuse/how-long-does-ketamine-stay-in-your-system
https://www.apna.org/m/pages.cfm?pageid=6603

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.