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Anti-Convulsant Drugs

The anti-convulsants, sometimes also called anti-epileptics, belong to a diverse group of pharmaceuticals used in prevention of the occurrence of epileptic seizures. Many typical anticonvulsants work by blocking voltage-sensitive sodium channels in the brain. They include Barbiturates, which are drugs that act as central nervous system (CNS) depressants, and by virtue of this they produce a wide spectrum of effects, from mild sedation to anesthesia. Some also are used as anticonvulsants.

They also include the Benzodiazepines, whcih are a class of drugs with hypnotic, anxiolytic, anticonvulsive, amnestic and muscle relaxant properties. They are believed to act on the GABA receptor GABAA, the activation of which dampens higher neuronal activity. They began to be widely prescribed for stress-related ailments in the 1960s and 1970s. Benzodiazepines are often used for short-term relief of severe, disabling anxiety. Long-term use can be problematic due to the development of tolerance and dependency. These drugs are preferred to the use of barbiturates because they have a lower abuse potential and relatively lower adverse reactions and interactions. However, drowsiness, ataxia, confusion, vertigo, impaired judgement, and a number of other effects are still common.

Two very important Anti-convulsant drugs used in neurosurgery are Phenytoin and Carbamazepine. See further information about them here.

Phenytoin

Phenytoin sodium (marketed as Dilantin® in the USA and as Epanutin® in the UK) is a commonly used antiepileptic or antiseizure drug. It can be injected or taken orally. It was first synthesized in 1908, but is was not until 1938 that scientists discovered phenytoin's usefulness for controlling seizures, without the sedation effects associated with phenobarbital. There are some indications that phenytoin has other effects, including anxiety control and mood stabilisation, although it has never been approved for those purposes by the USA FDA. It is used especially to prevent tonic-clonic (grand mal) epileptic seizures, and complex partial seizures (psychomotor seizures). It may be used alone or with phenobarbital or other anti-convulsants.

Dose

The dosing of phenytoin is very patient specific. It may be given once, twice, or three times daily. Doses are often adjusted to find the optimal dose, based on measurement of blood levels. Taking phenytoin with food may reduce some of the side effects. Elderly patients, debilitated persons, and patients with certain kidney or liver diseases may need lower doses. The suspension should not be given at the same time as tube feedings.

Drug Interactions

There are many potential drug interactions with phenytoin. Phenytoin can increase the metabolism (elimination) of many drugs, reducing their concentrations in the body. Drugs that may be affected include: digoxin, carbamazepine, clonazepam, corticosteroids (e.g. prednisone), cyclosporine, disopyramide, doxycycline, estrogens, felodipine, levodopa, lidocaine, methadone, mexiletine, oral contraceptives, paroxetine, quinidine, tacrolimus, theophylline, phenobarbital, and warfarin. Phenytoin can interact with these drugs not only when it is added to therapy but also when it is discontinued. In the latter case, the concentration of the other drugs may increase.

Phenytoin's metabolism may be affected by other drugs. Drugs that can reduce the amount of phenytoin in the body include rifampin and phenobarbital. Drugs that increase phenytoin concentrations include amiodarone, chloramphenicol, cimetidine, disulfiram, fluconazole, fluoxetine, isoniazid (INH), omeprazole, and paroxetine. Thus, measuring levels of phenytoin in the blood may be necessary when patients begin or discontinue other medications.

The oral absorption of phenytoin can be reduced by any of the following: antacids containing magnesium, calcium carbonate, or aluminum; calcium salts; or enteral feeding products (tube feedings). Separating the administration of phenytoin and enteral feeding products, antacids, or calcium salts by at least 2 hours will help avoid this interaction.

Adverse Reactions

Many varied adverse effects can occur during phenytoin therapy including dizziness, drowsiness, difficulty focusing (vision), unsteady gate, tiredness, abnormal involuntary movements, nausea, vomiting, constipation, abdominal pain, and loss of appetite. Children and young adults can develop overgrowth of the gums during long-term therapy which requires regular treatment by a dentist. Good oral hygiene and gum massage may reduce the risk. Rashes can occur in between 1 in 20 and 1 in 10 persons; some may be severe. Additionally, darkening coloration of the skin may develop (more commonly in women). Phenytoin can produce unusual growth of hair in some patients. This reaction most commonly affects the arms and legs but can also affect the trunk and face; it may be irreversible.

Various lymph node reactions have been reported with phenytoin therapy. Lymph nodes may swell up, sometimes painfully. Phenytoin cause serum glucose to rise. Thus, blood sugar should be monitored closely when phenytoin is administered to patients with diabetes. Phenytoin can potentially injure the liver although this is an uncommon occurrence. Phenytoin can cause the platelet or white blood cell counts to drop, increasing the risk of bleeding or infection, respectively. Phenytoin also can cause anemia. Because it interferes with vitamin D metabolism, phenytoin can cause weakening of the bones (osteomalacia). Phenytoin can cause sexual dysfunction including decreased libido, impotence, and priapism (painful, prolonged erections).

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Carbamazepine

Carbamazepine is an anti-seizure medication, and mood stabilising drug, used primarily in the treatment of epilepsy and bipolar disorder; but also used to treat schizophrenia and trigeminal neuralgia, a painful nerve condition of the face. Recurrent seizures (epilepsy) are divided into two main categories according to how much of the brain is involved, partial and generalized epilepsy (which includes petit mal, grand mal, and myoclonic epilepsy). Seizures are called "simple" if there is no loss of consciousness and "complex" if there is. Medicines that inhibit seizures are called anti-convulsants. Carbamazepine works as an anti-convulsant for partial and grand mal seizures by reducing or blocking certain responses in the brain. It is also used for treating trigeminal neuralgia. One dosage form, Equetro, has been approved for treating bipolar disorder.

Carbamazepine is used in the treatment of simple and complex partial seizures and in generalized seizures of the grand mal type.a. Equetrol is used to treat bipolar disorder.

Dose

Carbamazepine may be taken with or without food. Carbamazepine is excreted by the kidney and metabolized by the liver and dosages may need to be lowered in patients with liver or kidney dysfunction. Drug blood levels of carbamazepine can be followed.

Drug Interactions

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, or primidone. Warfarin, phenytoin, theophylline, and valproic acid are more rapidly metabolized with carbamazepine, while carbamazepine levels are elevated when taken with erythromycin, cimetidine, propoxyphene, 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.

Adverse Reactions

Serious side effects include dangerously low red and white blood cell counts. Severe skin reactions can occur as well as serious liver abnormalities, such as hepatitis, resulting in jaundice. Low sodium levels and thyroid abnormalities have been described. Minor more common side effects include dizziness, unsteadiness, nausea, and vomiting.

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