Anticonvulsants include-- Barbiturate, Oxazolidinediones- Miscellanous

Phenobarbitone Paramethadione Lamotrigine Trimethadione Primidone HYDANTOINS- Valproic acid Phenytoin

BENZODIAPINES- Cabamazepine Mephenytoin Clonazepam Phenacemide Ethotoin Clorazepate Felbamate Diazepam Gabapentin SUCCINIMIDES- Ethosuximide Methsuximide Phensuximide

Refer phenytoin sodium - 

   Patent Expiry Date of drugs (Ref - IDMA Publication)   

GI- Most common initial side effects are nausea, vomiting, and indigestion, usually transcient and rarely requiring discontinuation of therapy. diarrhea, abdominal cramps, constipation, anorexia, and weight loss and increased appettite with weight gain may occur. Use of delayed divalporex sodium may reduce GI side effects in some patients.

CNS- Sedation has occured(alone and in combination) and usually disappers upon reduction of anticonvulsant medication.

Tremor (may be dose related), ataxia, headache, nystagmus, diplopia, astterixis- spots on eyes- , dysarthia, dizziness, incordination, coma.

Psychiatric- emotional upset, depression, psychosis, aggression, hyperactivity, behavoiural deterioration

Dermatologic- Transcient hair loss, skin rash, petechiae, erythema multiforme, photosensitivity, generalised pruritus, Stevens- Johnson Syndrome

Hematologic- Valproic acid inhibits the secondary phase of platelet aggregation this may be reflected in altered bleeding time.Thrombocytopenia, bruising, hematoma formation, frank hemorrhage, relative lymphocytosis, macrocytosis, hypofibronogenemia, leukopenia, eosinophillia, anemia, bone marrow suppression, bone marrow toxicity suggestive of a myelodysplastic syndrome, acute intermittant porphyria.

Hepatic- minor elevatond of AST, ALT, and LDH are frequent and appear to be dose related, occassional increases in serum bilirubin and abnormal changes in other liver function tests ocur. Severe hepatotoxicity and death occur Endocrine- irregular menses, secondary amenorrhea, abnormal thyroid function tests, parotid gland swelling, breast enlargement, galactorrhea.

Respiratory- Dyspnea, rhinitis Special senses- abnormal vision, amblyopia, conjuntivitis, deafness , dry eyes, ear disorder, ear pain, eyepain, tinnitus

Metabolic- Hyperammonemia, hyponatremia, inappripiate ADH secretion, Fanconis syndrome (rare, and chiefly seen in children), hyperglycemia associated with a fatal outcome in a patient with preexistant nonketonic hyperglycinemia, hypocarnitinemia.

Body as a whole- Edema of extremities, weakness, acute pancreatitis, (including rare fatal cases) lupus erythematosus, enuresis, hearing loss.

Pre-existing hepatic dysfunction,women of child bearing age.

Special precautions:

Children with severe epilepsy associated with mental retardation,brain damage or congenital heart defects.In the 1st 6months perform liver function test in all and especially in those most at risk. Monitor platelet function.

Hematologic effects- thrombocytopenia, inhibition of the secondary phase of platelet aggregation, and abnormal ciagulation parameters have occured. Determine platelet counts and bleedingtime before intiating therapy, at periodic intervals and prior to surgery.

Hyperammonemia- with or without lethargy or coma may occur in the absence of abnormal liver functin tests. If elevation occurs, discontinue the drug.

Warnings-

Hepatotoxicity- usecaution in patients with a history of hepatic disease.

Children and patients with congenital metabolic disorders, anticonvulsants, those with severe seizure dosordes accompanied by mental retardation and those with organic brain disease may be a particular risk.

Long term use- safety and efficacy for long term use ( . 3 weeks) have not been systematically evaluated in clinical trials. Continually reevaluate the drugs usefulness fo extended periods

Fertility impairment- chronic toxicity studies in animals demonstrated reduced spermatosis and testicular atrophy.

Pregnancy- administer antiepiletic drugs to women of child bearing potentail only if they are clearly shown to be essential in the management of seizures.

Lactation- excercise caution when administering to a nursing woman

Children- safety and efficacy of diavalproex sodium for the treatment of acute mania has not been studied in individuals < 18 years of age

 Indications:

Petit mal, complex absence seizures.

Dosage:

Initial- 15 mg/kg/day. Increase at 1 week intervals by 5 to 10 mg/kg/day. Maximum recommended dose is 60 mg/kg/day.

Overdosage- Symptoms

Somnolence, heart block, and deep coma. Motor restlessness, visual hallucinations, asterixis, and death have also occured.

Treatment

1. Valproic acid is absorbed very rapidly.efficacy of gastric lavage varies with time since ingestion.

2. Use general supportive measures and carefully maintain adequate urinary output.

3. Hemodialysis and hemoperfusion have been used.

4. Nalaoxone has reveresed CNS depresant effects.

5. It could theoritically reverse anticonvulsant effects, use caution.

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

1.If GI upset occurs,take with food.

2. Do not chew tablets or capsules; swallow whole to avoid irritation of mouth and throat.

3. Diabetic patients- Medication may interfere with urine tests for ketones.

4. May cause drowsiness, observe caution while driving or performing tasks requiring alertness.

5. Allergies- tell your doctor if you have ever had any unusual or allergic reaction to divalproex or valproic acid. Also tell your doctor if you are allergic to any other substances, such as foods, presevatives or dyes.

6.Pregnancy- valproic acid and divalproex have been reported to cause birth defects when taken by the mother during the first 3 months of pregnancy.

7.Breast feeding- valproic acid and divalproex pass into the breast milk, but rheir effect on nursing baby is not known.

8.Children- children up to 2 years of age and those taking more than one medicine for seizure control may be more likely to develop serious side effects.

9. Elderly- elderly peole are especially sensitive to the effects of valproic acid and divalproex.

10. Other medicines - Tell your doctor if you taking Acetoaminopohen or Amiodarone or Anabolic steroids or Androgens or Anti-infective by mouth or injection or Anti-thyroid agents or Barbiturates or Carmustine or Chloroquine or Dantrolene or Daunorubicin or Disulfram or Estrogens or Etretinate or Gold salts or Hydroxychloroquine or Mercaptopurine or Methotrexate or Methyldopa or Naltrexone or Oral contraceptives or Phenothiazines or Plicamycin - there is an increased risk of serious side effects to the liver CNS depressants or Tricyclic antidepressants - valproic acid and divaloproex may increase CNS depressant effects Carbenicillin or Dipyridamole or Inflammation or pain medicine or Pentoxyfylline or Sulfinpyrazone or Ticarcillin - valproic acid or divalproex may increase the hance of bleeding because of decreased blood clotting abilty

Heparin - there is an increased risk of sidec effects that may cause bleeding Mefloquine - amount of valproic acid or divaloprex that you need to take may change Other anticonvulsants- increased erisk of seizures or other unwanted effects.

11. Other medical problems - Blood disease or Brain disease or Kidney disease - increased risk of serious side effects Liver disease - valproic acid or divaloprex may make the condition worse

12. Missed dose - If you miss a dose of this medicine, take it as soon as possible. however, if it is almost time for the next dose, skip the missed dose. Do not double doses.

13. Storage - Keep out of reach of children. Store away from heat or direct sunlight. Do not store the capsule in bathroom, near the kitchen sink, or in other damp places.

14. Outdated medicines - Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of reach of children.

Pharmacology:

Activity is related to increased brain level of gamma-aminobutryic acid(GABA).

Pharmacokinetics:

Valproic acid is rapidly absorbed orally. Peak serum levels occur approximately after 1 to 4 hours after a single dose. Metabolism; primarily metabolised in liver and excreted as glucuronide.

Slight delay in absorption of valproic acid may occur when with meals,but does not affect bioavailability..

Pregnancy:

The incidence of neural tube defects in the fetus may be increased in mothers receiving valproic acid during first trimester .

Lactation:

Excreted in breast milk,but not not known what effect it has on the nursing mother. Excercise caution.

Children-

Safety and efficacy of diavalproex sodium for the treatment of acute mania has not been studied in individuals < 18 years of age