epilepsy2

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General Principles of Management of Epilepsy : 

General Principles of Management of Epilepsy Educate Patient about the disease, duration of treatment and emphasize on compliance. Epilepsy

Avoid Precipitating Factors : 

Avoid Precipitating Factors Alcohol Stress

Slide 3: 

Irregular sleep Irregular eating habits fever Light signals

Give anticonvulsant Drugs : 

Give anticonvulsant Drugs The decision to give treatment after single seizure remains controversial Therapy should start with single, well-tried and relatively non-toxic drug. Start with 1/3 rd of anticipated dose and increase gradually over 3-4 weeks to reach anticipated dose. If fits are not controlled increase doses until fits stop or ADRs appear. If one drug fails, second drug of another chemical class should be tried. Doses can be administered in twice a day regime. SDCs should be measured when possible. Total duration of therapy is 2-3 years. Withdrawal of drug should be gradual

Plasma Drug Concentrations : 

Plasma Drug Concentrations 2-4 weeks after commencing therapy. When fits occur with standard dosage. When adverse effects occur. When sodium valproate is added to another drug. When sodium valproate is withdrawn Pregnancy Renal or hepatic disease

Monitoring Therapy : 

Monitoring Therapy 60-95% epileptics can be completely relieved within one year time. Drug withdrawal is associated with relapse in 20% patients during withdrawal and a further 20% relapse over 5 years. Relapse is more likely when disease is severe and prolonged. Withdrawal of medication should be slow.

Pregnancy and Epilepsy : 

Pregnancy and Epilepsy Pharmacokinetics is altered during pregnancy. Patient should be closely watched. Doses should be increased if fits occur more frequently than expected.

Breast feeding and Epilepsy : 

Breast feeding and Epilepsy Antiepileptic drugs pass into breast milk but total quantities ingested by baby are small. Breast feeding may be considered safe in general. Breast feeding is safer with Phenytoin and valproate.

Fetal abnormalities : 

Fetal abnormalities Children of mothers taking anti-epilepsy drugs show approximately X 2.5 increased rate of malformations at birth. Withdrawal of medication during early pregnancy is not recommended. Carbamazepine seems sensible choice. Folate supplement recommended Vitamin K

Contraception and epilepsy : 

Contraception and epilepsy Oral contraceptives in higher doses are needed If breakthrough bleeding occurs, a supplemental barrier method is necessary. Contraceptive failure has also been reported with the use of fixed subdermal levonorgestrel Contraceptive failure does not occur with valproic acid , gabapentin , lamotrigine or the benzodiazepines

Anticonvulsant Drugs : 

Anticonvulsant Drugs Mechanism of Action

Common mechanism of action : 

Common mechanism of action Many agents mediate their actions either by limiting the spread of discharge from a focus (e.g., carbamazepine, hydantoins) or by elevating the seizure threshold (e.g., succinimides, felbamate). Barbiturates appear to possess both mechanisms of action.

Mechanism of action continued : 

Mechanism of action continued Valproate might inhibit enzymes that metabolize GABA or block the reuptake of GABA into glia and nerve endings The action of benzodiazepines is mediated through central facilitation of GABA receptors.

MoA (contd) : 

MoA (contd) Carbamazepine and phenytoin, possess actions at neuronal sodium channels. Lamotrigine may also be acting at voltage-sensitive sodium channels. Felbamate antagonizes the effects of glycine by binding to the glycine receptor site of the NMDA receptor.

Adverse Effects of Anti-convulsants : 

Adverse Effects of Anti-convulsants CNS Hemtaological Skin Liver

CNS Effects : 

CNS Effects Nearly all anticonvulsants can cause CNS effects, ranging from drowsiness to drug-induced seizures if serum concentrations are high enough.

Skin : 

Skin Stevens-Johnson syndrome, although relatively uncommon, is a potentially serious complication of therapy with carbamazepine, ethosuximide, phenytoin, or phenobarbital cross-reactivity among these agents has been reported due to their ability to be metabolized to a common intermediate.

Hematological toxicity : 

Hematological toxicity Agranulocytosis during therapy with carbamazepine has been well described. Patients should undergo routine monitoring of hematologic function. Early symptoms of toxicity can include fever, sore throat, mouth ulcers, or unusual bruising or bleeding. Leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, and aplastic anemia have been reported with carbamazepine. Felbamate has been reported to cause aplastic anemia.

Hepatotoxicity : 

Hepatotoxicity Phenytoin can cause benign elevations of liver-function tests or more serious manifestations of hepatitis such as focal necrosis and hepatomegaly. Hepatotoxicity with valproic acid is most likely to occur within the first 6 months of treatment and more commonly occurs in children, especially age 2 years and under, and in those receiving multiple anticonvulsants or who have other complicating factors.

Individual Anti-convulsants : 

Individual Anti-convulsants Phenytoin Carbamazepine Barbiturates Valproate Benzodiazepines

Phenytoin : 

Phenytoin Phenytoin is used for many types of epilepsy but not in absence seizures. It acts by use dependent block of Sodium channels. Plasma concentrations vary widely due to saturation kinetics. Drug interactions common. Common ADRs include gum hyperplasia, drowsiness, confusion, anemia, skin rashes,osteomalacia and teratogenesis.

Phenytoin : 

Phenytoin Phenytoin tablets or capsules 100 mg/50 mg/ 30 mg. Phenytoin syrup 30 mg/ 5 ml. Phenytoin injection 100 mg/ ml. For IV administration. Undiluted into large vein. Maintenance Dosage: 3- 5 mg/Kg BW daily. Phenytoin Syrup 100 mg? 5 ml.

Carbamazepine : 

Carbamazepine It is effective in generalized and partial seizures. Impairs cognitive functions less than phenytoin. Auto-induction. Complex interactions ADRs include CNS symptoms, disturbances of AV conduction, GIT disturbances, Rashes, Liver and kidney dysfunctions.

Carbamazepine : 

Carbamazepine Tablets of 100 mg/ 200 mg. are available. Twice a day administration with food. No parenteral formulations. Syrup should not be administered with other syrups. Carbamazepine 100 mg/ ml. Carbamazepine tablets 200 mg

Phenobarbitone : 

Phenobarbitone Used to control tonic clonic, and simple partial seizures. Can be taken orally or by rectal suppository. It is usually given with other anti-epileptic medications. Common reactions may include drowsiness, headache, depression, insomnia, elation, confusion, breathing difficulty, high blood pressure, skin rash and an increased risk of liver disease.

Precautions with Phenobarbitone : 

Precautions with Phenobarbitone Long-term use of phenobarbital may result in addiction. Abrupt withdrawal may cause nightmares, forgetfulness, irritability, weight loss, and convulsions. Alcohol should be avoided (Potentiation of ADRs) Patients should not operate vehicle or other hazardous machinery Women should report pregnancy to their physicians promptly Dosage forms:Tablets: 15, 30 to 60 mg.Ampoules 200 mg / ml. for IM or IVinjection.

Drug interactions with Phenobabrbitone : 

Drug interactions with Phenobabrbitone Phenobarbitol may increase the action of acetaminophen (Tylenol®). Phenobarbital may decrease the action of oral contraceptives and verapamil. Antihistamines, corticosteroids, narcotic pain killers, tranquilizers, phenytoin and valproate may increase the action of phenobarbital. The therapeutic effect of phenobarbital may increase or decrease when taken with other anticonvulsants.

Other Anticonvulsants : 

Other Anticonvulsants Magnesium Sulfate: when given by injection in large doses , it causes CNS depression and blocks peripheral neuromuscular transmission, thus producing anticonvulsant effects. Its main use is in prevention and control of seizures in patients with preeclampsia and eclampsia. Magnesium sulfate is sometimes used to control seizures associated with other conditions. Benzodiazepines: Clonazepam, lorazepam, diazepam, and some others are sometimes used to manage absence and atypical absence seizures and nocturnal myoclonus. Limitation withbenzodiazepines is the rapid (weeks to months) development of tolerance and corresponding loss of seizure control.

Slide 29: 

Gabapentin is an analog of GABA (agonist) and possesses high lipid solubility . Gabapentin is renally eliminated, not metabolized by the liver, has no protein binding, and is devoid of the usual anticonvulsant drug interactions. Gabapentin has been shown to be effective in treating partial and generalized tonic-clonic seizures. Newer Anticonvulsants

Slide 30: 

Lamotrigine is derived from agents that inhibit dihydrofolate reductase.. Clinical trials of lamotrigine have been completed and show that it is effective in treating partial seizures. Felbamate is chemically similar to meprobamate. Compared with other anticonvulsants, believed to have a more desirable side effect profile, to be effective as both add-on and monotherapy, to have a broad spectrum of anticonvulsant activity, and to cause no apparent teratogenicity in animal screening. Post-marketing reporting of adverse effects, however, revealed there were 10 cases of aplastic anemia.

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