Ketamine is classified as a Schedule 3 Compound that is used for starting as well as maintaining an anaesthesia. The drug class is an NMDA receptor antagonist that is used as a general anaesthesia (Tripathi, 2013). Ketamine is also classified as a dissociative which is the class of hallucinogen. The drug is also classified as a sedative, analgesic and antidepressants (Harold, 2015).
The chemical structure of Ketamine makes it be classified as an arylcyclohexylamine derivative. The drug has a chiral compound. The pharmaceutical preparations of this medicine are racemic but some preparations have differences in enantiomer proportions. The most active enantiomer is ketamine (S-Ketamine) and the less active enantiomer is ketamine (R-Ketamine) that is sold as an enantiopure drug used for clinical purposes (Harold, 2015).
The images below shows structural representation of ketamine (Katzung & Trevor, 2015).
Skeletal Formula of (R)-Ketamine
Ball-and-Stick Model of (R)-Ketamine
Skeletal Formula of (S)-Ketamine
Ball-and-Stick Model of (R)-Ketamine
The half-life of ketamine is between 2-3 hours and that of norketamine is about 12 hours. Ketamine takes almost 4 hours in the body before half of the drug is removed from the body such that the serum concentration is reduced due to metabolism and excretion (elimination).
Ketamine is legally marketed in most of the countries to be used for medical purposes. However, in many countries due to the use of the drug as a drug of abuse, it is a controlled substance (Rang, Ritter, Flower & Henderson, 2014). Therefore one to acquire ketamine in these countries where the substance is controlled, one has had a prescription and is illegal to sell, use or to possess the drug without a prescription. Ketamine is a substance that is availed for use, however, it requires restriction of the production, supply, distribution, ownership and use so that to decrease cases of ketamine abuse, misuse and also eradicate psychological or physical dependence. For instance, in Canada ketamine has been classified as a Schedule 1 narcotic since the year 2005. In Australia, ketamine is a schedule 8 controlled drug from October 2015 under the Poisons Standard. The drug is a frequently abused recreational drug as it has dissociative effects, tranquillizing as well as hallucinogenic effects hence there are many restrictions (Aan Het Rot, Zarate Jr, Charney & Mathew, 2012).
Ketamine is orally administered whereby 16% of the administered drug is absorbed. This means that about 5 mg of the administered 30mg is orally absorbed. Other routes of Ketamine administration include intravenous, subcutaneous, rectal, intranasal, epidural, sublingual and intramuscular.
How The Drug Gets From The Point Of Entry Into The Circulatory System
Ketamine is absorbed into the bloodstream after it is administered. When the drug is taken orally, it is absorbed through the walls of the stomach and small intestines. The medicine then passes through the liver where it is metabolized and then into the circulatory system. When the drug is administered through injections, it rapidly reaches the body tissues and organs via the bloodstream. When ketamine is administered through the rectal, epidural and sublingual routes it is absorbed through the tissues to enter the bloodstream.
When Ketamine reaches the bloodstream, it is taken to the heart where it is pumped to all other parts of the body including the brain (Katzung, Masters & Trevor, 2012). Before the drug can reach the brain, it must pass through the blood-brain barrier which is designed to prevent dangerous and poisonous substances from reaching the brain tissues. Ketamine has elevated lipid solubility and very little plasma protein binding of 12%. This enables the rapid transmission of the drug across the blood-brain barrier. The drug is primarily distributed to all the vastly perfused tissues such as the brain to reach levels that are 4-5 times those in plasma (Rang, Dale, Ritter, Flower & Henderson, 2012). When the medicine reaches the brain, it elicits various effects such as euphoria, sedation, pain relief among others. The drug is able to achieve these by affecting receptors and chemicals within the brain. Distribution of Ketamine is also associated with the many adverse effects that the drug has. Since the drug is distributed to all the body parts, it causes effects that are unwanted hence damaging many internal organs. The CNS effects reduce the redistribution to the less perfused tissues (the redistribution half-life is about 2.7 minutes).
Ketamine is an NMDA receptor antagonist. The drug has an influence on the glutamate binding sites N-Methyl-D-Aspartate (NMDA) and the non-NMDA receptors (Duman, Li, Liu, Duric & Aghajanian, 2012). The antipathy of the N-Methyl-D-Aspartate (NMDA) receptor is the reason for the specific ketamine properties such as loss of consciousness or anaesthesia, analgesia, amnesia, neuroprotection and psychosensory. The drug results in relaxation and relieves pain in both humans and animals. Ketamine is metabolized into an active metabolite referred to as norketamine that causes dissociative anaesthesia as it prevents sensory inputs from being perceived in association areas. The drug blocks the afferent signals from the spinal-reticular pathways but does not modify the conduction of spinothalamic pathways (Harold, 2015). Ketamine ensures that the medial reticular formation which is involved in pain perception and the medial thalamic nuclei are selectively depressed. The drug also stops the signal from the reticular formation and improves the descending inhibiting the serotoninergic pathway. These actions of Ketamine at the site of action is the cause of the effects elicited by the drug such as pain relief, hallucinations, vivid dreams, disturbances in photographic and auditive insights, disposition, time and body image. Ketamine has glutamate-independent mechanisms as it interrelates with numerous binding sites like opioids, nicotinic, muscarinic, cholinergic and monoaminergic receptors (Stone, Dietrich, Edden, Mehta, De Simoni, Reed & Barker, 2012).
Once Ketamine has been distributed to all the body parts, it is metabolized or broken down. The drug is taken by the circulatory system to the liver to be metabolized. The liver is the primary site of ketamine metabolism, but it is also metabolized by other tissues and organs like the skin, kidneys and the lungs. The drug is mostly metabolized by the liver through N-demethylation through hepatic phase 1 and phase 2. The major enzyme involved is CYP3A4 while the two minor enzymes are CYP2C9 and CYP2B6. Ketamine metabolites include norketamine, hydroxynorketamine, dehydronorketamine and conjugates (Murrough, Iosifescu, Chang, Al Jurdi, Green, Perez & Charney, 2013).
The last phase of ketamine drug within the body is excretion. This is the processes in which ketamine exits the body primarily through the urine and faeces (Katzung & Trevor, 2015). The metabolized drug from the liver is taken to the urinary bladder and to the large intestines where the blood carries the waste products out of the body. Elimination of Ketamine is mostly renal whereby almost 90% of the drug is really excreted. The elimination half-life of ketamine is 3-4 hours while that of norketamine is 12 hours. The drug is greatly biotransformed by the liver before its elimination. The drug is also excreted in faeces in small amounts of about 3%, milk, sweat and expired air. The Standard toxicology tests that are usually put into use do not deter Ketamine if a “date rape” is suspected a specific toxicology test is conducted to detect the initial drug or its metabolites ((Marland, Ellerton, Andolfatto, Strapazzon, Thomassen, Brandner & Paal, 2013).
References
Aan Het Rot, M., Zarate Jr, C. A., Charney, D. S., & Mathew, S. J. (2012). Ketamine for depression: where do we go from here?. Biological psychiatry, 72(7), 537-547.
Becker, D. E., & Reed, K. L. (2012). Local anesthetics: review of pharmacological considerations. Anesthesia progress, 59(2), 90-102.
Bell, R. F., Eccleston, C., & Kalso, E. A. (2012). Ketamine as an adjuvant to opioids for cancer pain. The Cochrane database of systematic reviews, 11, CD003351-CD003351.
Duman, R. S., Li, N., Liu, R. J., Duric, V., & Aghajanian, G. (2012). Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology, 62(1), 35-41.
Harold E.D, (2015). Concepts of Chemical Dependency 9th Edition pp. 66-77
Katzung, B. G., & Trevor, A. J. (Eds.). (2015). Basic & clinical pharmacology (pp. 753-756). New York, NY: McGraw-Hill.
Katzung, B. G., Masters, S. B., & Trevor, A. J. (2012). Basic and Clinical Pharmacology (LANGE Basic Science). McGraw-Hill Education.
Marland, S., Ellerton, J., Andolfatto, G., Strapazzon, G., Thomassen, O., Brandner, B., … & Paal, P. (2013). Ketamine: use in anesthesia. CNS neuroscience & therapeutics, 19(6), 381-389.
Morgan, C. J., Curran, H. V., & Independent Scientific Committee on Drugs (ISCD). (2012). Ketamine use: a review. Addiction, 107(1), 27-38.
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., … & Charney, D. S. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. American Journal of Psychiatry, 170(10), 1134-1142.
Rang, H. P., Dale, M. M., Ritter, J. M., Flower, R. J., & Henderson, G. (2012). Antidepressant drugs. Rang and Dale’s pharmacology. 7th ed. Edinburgh: Elsevier/Churchill Livingstone, 564-83.
Rang, H. P., Ritter, J. M., Flower, R. J., & Henderson, G. (2014). Rang & Dale’s Pharmacology E-Book: with STUDENT CONSULT Online Access. Elsevier Health Sciences.
Stone, J. M., Dietrich, C., Edden, R., Mehta, M. A., De Simoni, S., Reed, L. J., … & Barker, G. J. (2012). Ketamine effects on brain GABA and glutamate levels with 1H-MRS: relationship to ketamine-induced psychopathology. Molecular psychiatry, 17(7), 664.
Tripathi, K. D. (2013). Essentials of medical pharmacology. JP Medical Ltd.
Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., … & Dossou, K. S. (2016). NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature, 533(7604), 481.
Essay Writing Service Features
Our Experience
No matter how complex your assignment is, we can find the right professional for your specific task. Contact Essay is an essay writing company that hires only the smartest minds to help you with your projects. Our expertise allows us to provide students with high-quality academic writing, editing & proofreading services.
Free Features
Free revision policy
$10Free bibliography & reference
$8Free title page
$8Free formatting
$8How Our Essay Writing Service Works
First, you will need to complete an order form. It's not difficult but, in case there is anything you find not to be clear, you may always call us so that we can guide you through it. On the order form, you will need to include some basic information concerning your order: subject, topic, number of pages, etc. We also encourage our clients to upload any relevant information or sources that will help.
Complete the order form
Once we have all the information and instructions that we need, we select the most suitable writer for your assignment. While everything seems to be clear, the writer, who has complete knowledge of the subject, may need clarification from you. It is at that point that you would receive a call or email from us.
Writer’s assignment
As soon as the writer has finished, it will be delivered both to the website and to your email address so that you will not miss it. If your deadline is close at hand, we will place a call to you to make sure that you receive the paper on time.
Completing the order and download