CARBAMAZEPINE

'Carbamazepine ("CBZ")' is an anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat ADD, ADHD, schizophrenia and trigeminal neuralgia.

Contents

Trade names

History

Adverse effects

Mechanisms

Interactions

See also

Notes

External links

Trade names

'Carbamazepine' has been sold under the names 'Tegretol', 'Biston', 'Calepsin', 'Carbatrol', 'Epitol', 'Equetro', 'Finlepsin', 'Sirtal', 'Stazepine', 'Telesmin', 'Timonil', 'Trimonil', 'Epimaz', and 'Degranol' (in South Africa)^[1].

History

Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953.^[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. It has been used as an anticonvulsant in the UK since 1965, but only approved in the U.S. since 1974.

Adverse effects

Carbamazepine renders certain methods of hormonal contraception ineffective because it is an enzyme inducer of the cytochrome P450 system which metabolises the oral contraceptive, leaving less active contraceptive in the plasma.
Common side effects include drowsiness, motor coordination impairment and/or upset stomach. Taken every twelve hours, the Tegretol XR or Carbatrol preparations can greatly decrease alcohol tolerance.
Less common side effects include cardiac arrythmias, blurry or double vision and/or the temporary or mild loss of blood cells or platelets. In rare cases the latter can be life-threatening if unnoticed, so frequent blood tests are required during the first few months' use, followed by three or four tests per year. In the UK testing would be less frequent in long-term use, typically once every year or two. Underactivity of the thyroid gland may be provoked, so thyroid function tests are advisable every year or two.
Small reductions in white cell count and serum sodium are common.
There are also reports of a bizarre auditory side effect, whereby patients perceive musical notes about a semitone lower than their actual pitch (so middle C would be heard as the note B3 just below it, etc).
Oxcarbazepine, a derivative of carbamazepine, has fewer and less serious side effects.
Carbamazepine may cause SIADH (syndrome of inappropriate antidiuretic hormone), since it both increases the release and potentiates the action of ADH (vasopressin).
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.
Pregnant women taking carbamazepine for seizures are putting their fetuses at increased risk for neural tube defects and should be given folic acid supplementation and undergo prenatal ultrasonography for diagnosis.

Mechanisms

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. 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.^[3] By inhibiting mEH, valproic acid and valnoctamide cause a buildup of the active metabolite, prolonging the effects of carbamazepine and delaying its excretion.
Carbamazepine greatly reduces serum concentrations of simvastatin and simvastatin acid.^[4]

See also

★ Oxcarbazepine

Notes

1. http://www.intekom.com/pharm/lennon/degranol.html
2. Schindler W, Häfliger F (1954). "Über Derivate des Iminodibenzyls". ''Helvetica Chimica Acta'' '37' (2): 472–483. .
3. Goodman & Gilman's The Pharmacological Basis of Therapeutics, , Frank J., Gonzalez, McGraw-Hill, 2006,
4. Carbamazepine markedly reduces serum concentrations of simvastatin and simvastatin acid, Ucar M ''et al.'', , , Eur J Clin Pharmacol, 2004

External links

★ Carbatrol website

★ Equetro website

★ TA warning

★ Carbamazepine overview from PsychEducation.org

★ U.S. Patent 2,948,718, August 1960