Pharmacology carbamazepine

Pharmacology Carbamazepine s mechanism of action is unknown. It appears to act... 

Outside of the evidence-based guidelines, other pharmacologic treatments are commonly used or avoided. For initial treatment of absence seizures, ethosuximide and valproate are commonly used, not only in the United Kingdom, but also in the United States. Zonisamide may be also used for initial treatment of absence and myoclonic seizures. In absence and myoclonic seizures, carbamazepine, oxcarbazepine, gabapentin, tiagabine, and pregabalin should be avoided, as they have been associated with an exacerbation of these types of seizures. 

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

Egnell, A.-C., Houston, B. and Boyer, S. (2003) in vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. The Journal of Pharmacology and Experimental Therapeutics, 305, 1251-1262. 

Oral absorption of carbamazepine is quite slow and often erratic. Its half-life is reported to vary from 12 to 60 hours in humans. The development of blood level assays has markedly improved the success of therapy with this drug, since serum concentration is only partially dose related. Carbamazepine is metabolized in the liver, and there is evidence that its continued administration leads to hepatic enzyme induction. Carbamazepine-10,11-epoxide is a pharmacologically active metabolite with significant anticonvulsant effects of its own. 

Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine. 

Bertschy G., C. Bryois, G. Bondolfi, A. Velardi, P. Budry, D. Dascal, C. Martinet, D. Baettig, and P. Baumann (1997). The association of carbamazepine-mianserin In opiate withdrawal A double blind pilot study versus clonidine. Pharmacological Research 35 451-456. 

Stemebring B., A. Linden, K. Anderson, and A. Melander (1992). Carbamazepine kinetics and adverse effects during and after ethanol exposure in alcoholics and healthy volunteers. European Journal of Clinical Pharmacology 43 393-397. 

Diagnostic boundaries in juvenile-onset BD need to be defined, since children with hypomania or manic-like symptoms may be increasingly treated with mood stabilizers. In parallel, this would require more complex algorithms because very few controlled trials have been reported (Walkup, 1995). In contrast to the studies of adults reported in the literature, the pharmacological treatment of childhood bipolarity with anticonvulsants remains an understudied area. Carbamazepine appears to be less efficacious than valproate in adult rapid cycling, yet no studies have identified predictors of treatment response to CBZ or any other mood stabilizer (besides lithium) in a pediatric population. 

Weaver, D.F., Camfield, P., and Fraser, A. (1988) Massive carbamazepine overdose clinical and pharmacologic observations in five episodes. Neurology 38 755-759. 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Post RM, Chuang D-M Mechanism of action of lithium comparison and contrast with carbamazepine, in Lithium and the Cell Pharmacology and Biochemistry. Edited by Birch NJ. London, Academic Press, 1991, pp 199-241 Post RM, Weiss SRB The neurobiology of treatment-resistant mood disorders, in Psychopharmacology The Fourth Generation of Progress. Edited by Bloom FE, Kupfer DJ. New York, Raven, 1995... 

ECT should be considered for more severe forms of depression (e.g., those associated with melancholic and psychotic features, particularly when the patient exhibits an increased risk for self-injurious behavior) or when there is a past, well-documented history of nonresponse or intolerance to pharmacological intervention. Limited data indicate that bipolar depressed patients may be at risk for a switch to mania when given a standard TCA. A mood stabilizer alone (i.e., lithium, valproate, carbamazepine, lamotrigine), or in combination with an antidepressant, may be the strategy of choice in these patients. Some elderly patients and those with acquired immunodeficiency syndrome may also benefit from low doses of a psychostimulant only (e.g., methylphenidate) (see also Chapter 14, The HIV-Infected Patient ). Fig. 7-1 summarizes the strategy for a patient whose depressive episode is insufficiently responsive to standard therapies. 

Bertilsson L, Tomson T. Clinical pharmacokinetics and pharmacological effects of carbamazepine and carbamazepine-10,11-epoxide. Clin Pharmacokinei 1986 11 177-198. 

The pharmacologic basis of these disorders is unknown, and there is no satisfactory medical treatment for them. A subset of patients respond well to levodopa medication (dopa-responsive dystonia), which is therefore worthy of trial. Occasional patients with dystonia may respond to diazepam, amantadine, antimuscarinic drugs (in high dosage), carbamazepine, baclofen, haloperidol, or phenothiazines. A trial of these pharmacologic approaches is worthwhile, though often not successful. Patients with focal dystonias such as blepharospasm or torticollis often benefit from injection of botulinum toxin into the overactive muscles. The role of deep brain stimulation for the treatment of these conditions is being explored. 

If these measures fail, clonidine, fluphenazine, clonazepam, or carbamazepine should be tried. The pharmacologic properties of these drugs are discussed elsewhere in this book. Clonidine reduces motor or vocal tics in about 50% of children so treated. It may act by reducing activity in noradrenergic neurons in the locus coeruleus. It is introduced at a dose of 2-3 mcg/kg/d, increasing after 2 weeks to 4 mcg/kg/d and then, if required, to 5 mcg/kg/d. It may cause an initial transient fall in blood pressure. The most common adverse effect is sedation other adverse effects include reduced or excessive salivation and diarrhea. Phenothiazines such as fluphenazine sometimes help the tics, as do dopamine... 

FIGURE 7—24. Shown here is an icon of carbamazepine s pharmacologic actions. By interfering with sodium and potassium, carbamazepine is thought to enhance the inhibitory actions of gamma aminobutyric acid (GABA). 

Albini, F. Carbamazepine clinical pharmacology - a review. Pharmacopsuchiat. 28 (1995) 235-245. 

Carbamazepine, phenytoin, phenobarbi-tal, and other anticonvulsants induce hepatic enzymes responsible for drug biotransformation valproate is a potent inhibitor. Combinations between anticonvulsants or with other drugs may result in clinically impor-Luellmann, Color Atlas of Pharmacology All rights reserved. Usage subject to terms... 

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