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Carbamazepine
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| Systematic (IUPAC) name | |
| 5H-dibenzo[b,f]azepine-5-carboxamide | |
| Identifiers | |
| CAS number | 85756-57-6 (dihydrate) |
| ATC code | N03 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C15H12N2O |
| Mol. mass | 236. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 269 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 80% |
| Protein binding | 76% |
| Metabolism | Hepatic—by CYP3A4, to active epoxide form (carbamazepine-10,11 epoxide) |
| Half life | 25–65 hours |
| Excretion | 2–3% excreted unchanged in urine |
| Therapeutic considerations | |
| Pregnancy cat. |
C(US) |
| Legal status | |
| Routes | Oral |
Carbamazepine ("CBZ") is an anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism An epoxide is a cyclic Ether with only three ring atoms This ring approximately is an Equilateral triangle, i The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located A prescription drug is a licensed medicine that is regulated by legislation to require a prescription before it can be obtained The United States of America —commonly referred to as the In Pharmacology and Toxicology, a route The anticonvulsants, also called antiepileptic drugs (abbreviated "AEDs" are a diverse group of pharmaceuticals used in the treatment of epileptic This article refers to the medication For other uses see Stabilizer. Epilepsy is a common chronic Neurological disorder that is characterized by recurrent unprovoked seizures. It is also used to treat ADD, ADHD, schizophrenia, Phantom limb syndrome and trigeminal neuralgia. Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Schizophrenia ( from the Greek roots schizein (σχίζειν "to split" and phrēn A phantom limb is the sensation that an amputated or missing limb (even an organ like the appendix is still attached to the body and is moving appropriately Trigeminal neuralgia (TN, or Tic Doloureux, (also known as prosopalgia is a neuropathic disorder of the Trigeminal nerve that causes episodes of intense
Contents |
Trade names
Carbamazepine has been sold under the names Tegretol, Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Telesmin,Teril, Timonil, Trimonil, Epimaz, and Degranol (in South Africa)[1]. The Republic of South Africa (also known by other official names) is a country located at the southern tip of the continent of Africa
History
Carbamazepine was discovered by chemist Walter Schindler at J. R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953. Novartis International AG is a multinational Pharmaceutical company based in Basel Switzerland that manufactures drugs such as Clozapine "Basilia" redirects here For the Fly Genus, see Basilia (fly. Switzerland (English pronunciation; Schweiz Swiss German: Schwyz or Schwiiz Suisse Svizzera Svizra officially the Swiss Confederation [2] Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered.
Carbamazepine was first marketed as a drug to treat trigeminal neuralgia in 1962. Trigeminal neuralgia (TN, or Tic Doloureux, (also known as prosopalgia is a neuropathic disorder of the Trigeminal nerve that causes episodes of intense It has been used as an anticonvulsant in the UK since 1965, but only approved in the U.S. since 1974. The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located The United States of America —commonly referred to as the
In 1971, Drs. Takezaki and Hanaoka first used carbamazepine to control mania in patients refractory to antipsychotics (lithium was not available in Japan at that time). Dr. Okuma, working independently, did the same thing with success. As they were also epileptologists, they had some familiarity with the anti-aggression effects of this drug. Carbamazepine would be studied for bipolar disorder throughout the 1970s. [3]
Adverse effects
Carbamazepine is known to render many hormonal contraception products ineffective, due to its action as a cytochrome P450 enzyme inducer, which is the system that metabolizes many oral contraceptives. Hormonal contraception refers to Birth control methods that act on the hormonal system Carbamazepine causes more cytochrome P450 enzyme to be produced, which hastens removal of the contraceptive from the blood plasma although the clinical significance of this effect is debatable.
Common side effects include drowsiness, motor coordination impairment and/or upset stomach. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Gross motor coordination addresses the Gross motor skills walking running climbing jumping crawling lifting one's head sitting up etc Carbamazepine preparations may also greatly decrease a person's alcohol tolerance.
Less common side effects include cardiac arrhythmias, blurry or double vision and/or the temporary loss of blood cells or platelets and in rare cases can cause aplastic anemia. In Psychology, visual perception is the ability to interpret information from Visible light reaching the Eyes The resulting Perception is also A blood cell (also called blood corpuscle) is any cell of any type normally found in Blood. Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved With normal use, small reductions in white cell count and serum sodium are common, however, in rare cases, the loss of platelets may become life-threatening. This occurs commonly enough that a doctor may recommend frequent blood tests during the first few months of use, followed by three to four tests per year for established patients. In the UK, testing is generally performed much less frequently for long-term carbamazepine patients -typically once per year. Additionally, carbamazepine may exacerbate preexisting cases of hypothyroidism, so yearly thyroid function tests are advisable for persons taking the drug.
There are also reports of an auditory side effect for carbamazepine use, whereby patients perceive sounds about a semitone lower than their actual pitch. A semitone, also called a half step or a half tone, is the smallest Musical interval commonly used in Western tonal music and it is considered the Thus, middle C would be heard as the note B3 just below it, etc. C or Do is the first Note of the fixed-Do Solfege. In Western Music, the expression " Middle C " refers to the note Scientific pitch notation is one of several methods that name the Notes of the standard Western Chromatic scale by combining a letter-name accidentals This unusual side-effect is usually not noticed by most people, and quickly disappears after the person stops taking carbamazepine.
Oxcarbazepine, a derivative of carbamazepine, reportedly has fewer and less serious side effects. Oxcarbazepine (marketed as Trileptal by Novartis or Trexapin by Taro is an Anticonvulsant and mood stabilizing drug, used primarily
Carbamazepine may cause SIADH (syndrome of inappropriate anti-diuretic hormone), since it both increases the release and potentiates the action of ADH (vasopressin). Arginine vasopressin ( AVP) also known as vasopressin, argipressin or antidiuretic hormone ( ADH) is a Hormone found in
Carbamazepine may aggravate juvenile myoclonic epilepsy, so it is important to mention any history of jerking, especially in the morning, before starting to take this drug. Juvenile myoclonic epilepsy (JME also known as Janz syndrome is a fairly common form of Idiopathic generalized epilepsy, representing 5-10% of all epilepsies
Pregnant women taking carbamazepine put their fetuses at increased risk for teratogenic effects. As a result, they should be given folic acid supplementation and undergo prenatal ultrasonography for diagnosis. Folic acid (also known as Vitamin M and Folacin) and Folate (the Anionic form are forms of the water-soluble Vitamin B9
In addition, carbamazepine has been linked to serious adverse cognitive anomalies, including EEG slowing[4] and cell apoptosis. [5]
The FDA informed healthcare professionals that dangerous or even fatal skin reactions (Stevens Johnson syndrome and toxic epidermal necrolysis), that can be caused by carbamazepine therapy, are significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502. This allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. [6]
Mechanism of Action
The mechanism of action of carbamazepine and its derivatives is relatively well understood. Voltage-gated sodium channels are the molecular pores that allow brain cells (neurons) to generate action potentials, the electrical events that allow neurons to communicate over long distances. Sodium channels are Integral membrane proteins that form Ion channels, conducting sodium ions ( Na+) through a cell's Plasma membrane Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information In Neurophysiology, the action potential is a self-regenerating Wave of Electrochemical activity that allows Nerve cells to carry a signal Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information After the sodium channels open, to start the action potential, they inactivate, essentially closing the channel. Carbamazepine stabilizes the inactivated state of sodium channels, meaning that fewer of these channels are available to open, making brain cells less excitable.
Interactions
Valproic acid and valnoctamide both interact with carbamazepine, as they inhibit microsomal epoxide hydrolase (mEH), the enzyme responsible for the breakdown of carbamazepine-10,11 epoxide into inactive metabolites. Valproic acid ( VPA) is a Chemical compound that has found clinical use as an Anticonvulsant and mood-stabilizing drug, primarily in Valnoctamide ( INN, USAN) has been used in France as an Sedative - Hypnotic since 1964 Epoxide hydrolase (also known as Epoxide hydratase functions in Detoxication during Drug metabolism. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins [7] By inhibiting mEH, valproic acid and valnoctamide cause a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.
Carbamazepine interacts with multiple drugs and caution should be used in combining other medicines with it. Lower levels of carbamazepine are seen when administrated with phenobarbital, phenytoin (Dilantin), or primidone (Mysoline). Warfarin (Coumadin), phenytoin (Dilantin), theophylline, and valproic acid (Depakote, Depakote ER, Depakene, Depacon) are more rapidly metabolized with carbamazepine, while carbamazepine levels are elevated when taken with erythromycin, cimetidine (Tagamet), propoxyphene (Darvon), and calcium channel blockers. Carbamazepine also increases the metabolism (destruction) of the hormones in birth control pills and can reduce the effectiveness of birth control pills. Unexpected pregnancies have occurred in patients taking both carbamazepine and birth control pills
Carbamazepine,as CYP 450 inducer, may increase clearance of many drugs, decreasing their blood levels.
See also
References
- ^ Degranol® Tablets
- ^ Schindler W, Häfliger F (1954). Oxcarbazepine (marketed as Trileptal by Novartis or Trexapin by Taro is an Anticonvulsant and mood stabilizing drug, used primarily "Über Derivate des Iminodibenzyls". Helvetica Chimica Acta 37 (2): 472–83. Helvetica Chimica Acta is a Scientific journal founded by the Swiss Chemical Society. . doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.
- ^ Okuma T, Kishimoto A (February 1998). "A history of investigation on the mood stabilizing effect of carbamazepine in Japan". Psychiatry Clin. Neurosci. 52 (1): 3–12. PMID 9682927.
- ^ Salinsky MC, Binder LM, Oken BS, Storzbach D, Aron CR, Dodrill CB (2002). "Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers". Epilepsia 43 (5): 482–90. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12027908.
- ^ Gao XM, Margolis RL, Leeds P, Hough C, Post RM, Chuang DM (1995). "Carbamazepine induction of apoptosis in cultured cerebellar neurons: effects of N-methyl-D-aspartate, aurintricarboxylic acid and cycloheximide". Brain Res. 703 (1-2): 63–71. PMID 8719616.
- ^ MedWatch (December 12, 2007). Carbamazepine. 2007 Safety Alerts for Drugs, Biologics, Medical Devices, and Dietary Supplements. FDA.
- ^ Gonzalez, Frank J. ; Robert H. Tukey (2006). "Drug Metabolism", in Laurence Brunton, John Lazo, Keith Parker (eds. ): Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11th ed. Goodman & Gilman's The Pharmacological Basis of Therapeutics is an American Textbook of Pharmacology. , New York: McGraw-Hill, p. The McGraw-Hill Companies Inc, ( is a Publicly traded corporation headquartered in Rockefeller Center in New York City. 79. ISBN 978-0071422802.
External links
- Carbatrol website
- Equetro website
- TA warning
- Carbamazepine overview from PsychEducation. org
- U.S. Patent 2,948,718, August 1960
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