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Epilepsy and antiepileptic drugs Epilepsy: is a very common chronic disorder characterized by recurrent seizures. Seizure: excessive discharge of cortical neuron Convulsion: involuntary contraction of voluntary muscles Patients may have epilepsy or seizure disorders without convulsions 2 Any Seizure Result From 3 Types Of Ion Channels Ion Channels Voltage-gated Channels • • Ligand -gated channels Na+ & ca ++ depolarize the cell membrane (E) • • K+ hyperpolarize the cell membrane (I) 4 Glutamate (E) GABA (I) Classification of Seizures Seizures Loss of Consciousness? Yes No Generalized Seizures Partial Seizures Alteration of Consciousness? Yes No 5 Complex Partial Simple Partial I. Partial “focal” : In which the discharge involves one part of the cortex. A. Simple Partial Seizures B. Complex Partial Seizures II. Generalized In which the discharge involves the whole cortex 1. Tonic-Clonic: Grandmal seizures Tonic: abrupt loss of consciousness (less than 1 min) Clonic: jerking of body muscles with lip or tongue biting, fecal & urinary incontinence Generalized tonic clonic seizures (grand mal seizures) 9 2. Absence or petit mal: altering of consciousness lasting 10-30 seconds, onset of this type occurs from ages 3-16 years Generalized Seizure (Absence or Petit Mal ) 11 3. Myoclonic: Single or Multiple muscle jerking c. Status epilepticus: Series of seizures without recovery of consciousness between attacks It is life threatening emergency ATONIC SEIZURE • Are characterized by a sudden loss of postural tone so that the individual falls to the ground. Febrile seizures Young child (3 months to 5 years) frequently develop seizures with illness accompanied by high fever Treatment: acute case Diazepam rectally Diagnosis of specific seizure type is important for prescribing the most appropriate antiseizure drug Treatment may involve combination of drugs Aim of Treatment a: Complete suppression of fits and if not possible. b: Reduction of fit frequency as much as possible, with minimum and tolerable ADRs. The use of single or combination drug therapy using careful grading of drug dosage. Regular monitoring of drug toxicity. Regular monitoring of patient status regarding drug interactions. The management of patients with epilepsy is focused on 3 main goals: Improve Quality Of Life Goals Avoiding Side Effects Controlling Seizures 18 NURSING ASSESSMENT NURSING ASSESSMENT OF SEIZURE ACTIVITY SHOULD OCCUR AND BE DOCUMENTED IN THE NURSING NOTES. 1. Appropriate information about what occurred during the ictal (active seizure) phase should be documented. If the nurse does not actually witness the seizure, persons present should be consulted to obtain the information. 2.The individual should be monitored during the postictal phase of the seizure. The individual’s postictal condition and activity should be documented. 3. Any action taken, including a request for medical consultation, should be documented in the nursing notes. Etiology of epilepsy Some seizures arise secondary to other conditions. However, in most cases, the cause of the seizure is unknown. 1.Primary (idiopathic) seizures have no identifiable cause. 2.Secondary seizures (symptomatic or acquires seizures) occur secondary to an identifiable cause. Clinical evaluation History includes an evaluation of the seizure, including interviews of the patient’s family Laboratory test may also identify an underlying etiology Neurological imaging studies Special Cases: Pregnancy Seizures in pregnancy constitute major risk to mother and fetus Must maintain therapy Monotherapy usually better than drugs combination. Folic acid is recommended to be given for every pregnant women with epilepsy Teratogenicity Antiepileptic drugs associated with increased (2-3 fold) incidence of birth defects (cleft lip/palate and cardiac defects) Significant risk of neural tube defects Phenytoin, sodium valproate are absolutely contraindicated MOA of antiepleptic drugs: inhibitory tone by facilitation of GABA-mediated hyperpolarization-barbiturates, benzodiazepines axonal conduction by preventing Na' influx through fast Na channels-carbamazepine, phenytoin; also, at high doses, barbiturates and valproic acid presynaptic ca2 + influx through type-T channels in thalamic neurons-ethosuximide and valproic acid Classification of AEDs Newer Classical • • • • • Phenytoin Phenobarbital Carbamazepine Ethosuximide Valproate (valproic acid) Lamotrigine Felbamate Topiramate Gabapentin Vigabatrin Pharmacology of antiepileptic drug DRUG THAT BLOCK VOLTAGEDEPENDENT SODIUM CHANNELS 27 Block channels firing at high frequencies Inactivated channel Na+ Barbiturates Valproate Topiramate Carbamazepine Phenytoin Anti-epileptic drugs 1. Phenytoin MOA: blocks voltage gated sodium channels in neuronal membrane Clinical uses: partial seizures & generalized tonic-clonic seizures It has narrow therapeutic index Metabolized by MES Has high drug Interactions. S/Es 1. 2. 3. 4. CNS: diplopia, nystagmus Gingival hyperplasia Hairsutism Teratogenic effect (not given during pregnancy) Gingival hyperplasia 2. Carbamazepine MOA: blocks sodium channels Uses: as phenytoin & for Trigeminal Neuralgia & Rx of mania Similarities between phenytoin & carbamazepine: Both are liver enzyme inducers Both are not used in absence seizures S/Es Rashes, dizziness, blurred vision 3. Valproic acid MOA: Interfere with sodium channels at high doses Can potentiate the inhibitory effect of GABA Therapeutic uses: Generalized Tonic-Clonic, partial & can be used in absence seizure S/Es: Teratogenicity Weight gain.. Very rarely it causes liver damage T type Ca++ current inhibition: Ethosuximide MOA: act by blocking T-calcium channel The main drug used to treat absence seizures S/Es: gastric upset. Ca++ Reduction in the flow of Ca++ through T - type Ca++ channels in thalamus Gitanjali-15: Facilitation of GABA-mediated hyperpolarization Barbiturates: Phenobarbital clinical use: the same as phenytoin, for TonicClonic seizures. Alternative to phenytoin in treatment of status epilepticus. Benzodiazepines 1. Diazepam 2. Clonazepam 3. Lorazepam Other AEDs: New drugs (second generation) Have potential advantages in terms of pharmacokinetics, tolerability, and lesser risk for drug-drug interactions Vigabatrin : In all types, specially in pts resistant to other AEDs. Irreversible GABA transaminase inhibitor. Gabapentin In spite of its close structural relationship to GABA, gabapentin appears not to act on GABA receptors . Drugs Used in Seizure Disorders Tonic-Clonic & Partial Seizure Carbamazepine Phenytoin Valproic acid phenobarbital Absence Seizure Ethosuximide Valproic acid Clonazepam Myoclonic Clonazepam Valproic acid Management of status epilepticus 1.Establish airway, oxygenate, recovery position 2. Establish IV access and give IV lorazepam 2-4mg (IV diazepam 5-10mg alternative; 3. Check blood for: glucose, urea and electrolytes, Calcium, anticonvulsant levels, and arterial blood gas and pH. 4.If seizures continue, administer intravenous phenobarbital or phenytoin as second-line treatment 5. In sever status epilepticus especially that not respond to these meausres, general anesthesia and neuromuscular blocker and artificial respiration. It is important that anticonvuslants are not discontinued too suddenly as they may precipitate seizures. Patients with seizures should be warned against driving vehicles,swimming and working under conditions where a seizure could produce disaster. Attentions Selection of an appropriate antiseizure agent Use of single drug Withdrawal Toxicity Fetal malformations