Epilepsy treatment ppt.ppt

Epilepsy treatment Dr. Md. Shamshir Alam      Establish therapeutic goals. Discuss nonpharmacologic treatments and pharmacotherapeutic regimen. Select monitoring parameters for antiepileptic therapy. Recognize complications and drug interactions. Educate a patient or caregiver on epilepsy...

Epilepsy treatment Dr. Md. Shamshir Alam      Establish therapeutic goals. Discuss nonpharmacologic treatments and pharmacotherapeutic regimen. Select monitoring parameters for antiepileptic therapy. Recognize complications and drug interactions. Educate a patient or caregiver on epilepsy and pharmacotherapy for this  Primary goal is complete seizure freedom.  Secondary goals:  To control or reduce the frequency and severity of the seizures.  Minimize the side effects.  Ensure the compliance (60% patients are non-compliant).  Allowing the patient to live as normal a life Treatment Medical Surgical     Begin with monotherapy. 65% patients maintained on one ASD. 60% of patients noncompliant most common reason is treatment failure. When to start treatment:  Patients who have had two or more seizures. Basic rules for drug treatment Drug treatment should be simple, preferably using one anticonvulsant (monotherapy). “Start low, increase slow“. Add-on therapy is necessary in some patients… If pt is seizure-free for three years, withdrawal of pharmacotherapy should be considered. It should be performed very carefully and slowly! Mechanism of Action Current antiepileptic drugs are thought to act mainly by two main mechanisms: Reducing electrical excitability of cell membranes, possibly through inhibition of sodium channel. Enhancing GABA. This may be achieved by an enhanced pre- or post- synaptic action of GABA, by inhibiting GABA-transaminase, or by drugs with direct GABA-agonist properties. Strategies to accomplish the goals: - Modification of ion conductance (Na, Ca) - Increasing inhibitory (GABAergic) transmission - Decreasing excitatory (Glutamatergic/aspartate) activity Clinical Uses: Antiepileptic Drugs Tonic-clonic (grand mal) seizures: phenytoin, valproate. Use of single drug is preferred, when possible, because of risk of pharmacokinetic interactions. Partial (focal) seizures: Lacosamide, pregabalin, gabapentin, oxcarbazepine, phenytoin, and vigabatrin Alternative drugs: Carbamazepine, valproate, clonazepam. Clinical Uses: Antiepileptic Drugs  Absence seizures (petit mal): ethosuximide or valproate.  Valproate is used when absence seizures coexist with tonic-clonic seizures, since most drugs used for tonicclonic seizures may worsen absence seizures.  Myoclonic seizures: valproate or clonazepam.  Status epilepticus: must be treated as an emergency.  Lorazepam is preferred because of its rapid onset of action and is dosed at 0.1 mg/kg IV. No more than 2 mg should be administered per minute.  If lorazepam is not available, then diazepam can be used at 0.15 mg/kg IV up to a maximum of 5 mg per minute. Epilepsy - Treatment  The majority of patients respond to drug therapy (anticonvulsants).  In intractable cases surgery may be necessary.  The commonest drugs used in clinical practice are:  Carbamazepine, Sodium valproate, Lamotrigine (first line drugs)  Levetiracetam, Topiramate, Pregabaline (second line drugs)  Zonisamide, Eslicarbazepine, Retigabine (new AEDs) Epilepsy treatment and pregnancy The risk of teratogenicity is well known (~5%), especially with valproates, but withdrawing drug therapy in pregnancy is more risky than continuation. Epileptic females must be aware of this problem and thorough family planning should be recommended. Over 90% of pregnant women with epilepsy will deliver a normal child. Special considerations in the female patients Contraception: Estrogen: seizure-activating effect, progesterone: seizure protective Enzyme-inducing ASDs Phenobarbital, phenytoin, carbamazepine, topiramate, lamotrigine, and felbamate contraception failures in women taking oral contraceptives Catamenial epilepsy: Conventional ASDs should be tried first Intermittent higher-dose ASDs and Benzodiazepines should be considered. Progestational agents may also be effective.  Pregnancy  Women with epilepsy: If seizure free for 9 to 12 months before becoming pregnant have an 84% to 92% chance of being seizure free during pregnancy.  During Pregnancy clearance increases Clearance of Phenobarbital, phenytoin, carbamazepine, and valproic acid increases during pregnancy by 1055%. Protein binding may be reduced.  Oxcarbazepine levels decrease during pregnancy  Carbamazepine levels normal.  Serum concentrations may fluctuate: New anti-seizure medications, lamotrigine and levetiracetam are the most widely used due to their known safety during pregnancy. Valproic acid (Category D): Major congenital malformations (MCMs)x 4 times higher. an ↑ risk of neurodevelopmental effects including effects on cognition. In pregnancy, max. dose is 500-600 mg/day. Topiramate (Category C →D): associated with cleft palate and possibly low birth weight and Folic acid (0.4–5 mg/day): Women of child-bearing potential taking ASDs. Higher folate doses: Previously delivered a child with a neural tube defect and is on valproic acid. Neonatal hemorrhagic disorder Vitamin K (10 mg/day orally)- during the last month of pregnancy may prevent. Alternatively, parenteral vitamin K can PK and protein binding Conditions altering ASD protein binding include: Chronic renal failure and liver disease Hypoalbuminemia, burns, pregnancy Displacing drugs Age (neonates and the elderly) In Altered plasma protein binding: Measure free and not total serum concentrations.  Neonates and infants:  Decreased efficiency in renal elimination and metabolize drugs more slowly  Thus, require lower doses of ASD.   Children of age 2 or 3 years may metabolize drugs more rapidly than adults. Thus, children require higher doses Elderly and epilepsy More cautious dosing Monotherapy preferred More frequent SEs Comorbid medical problems/medicines Osteoporosis Cognitive decline Risk of falls/injury      Lower doses of ASDs due to compromised renal or hepatic function. More prone to neurocognitive effects and drug– drug interactions Hypoalbuminemia is common and highly bound ASDs (eg, valproic acid) can be problematic. The body mass changes affects elimination half-life and volume of distribution. Seizure Freedom with AED use 1st drug ------------- seizure free ( 47%) 2nd drug------------- seizure free ( 14%) 3rd drug------------- seizure free ( 3%) Medication resistant 36%  CNS side effects: frequent Sedation, dizziness, blurred vision, poor concentration and ataxia. Barbiturates:  more cognitive impairment, but in children paradoxical excitement. Newer generations less cognitive impairment except Topiramate. Idiosyncratic reactions: SJS/toxic epidermal necrolysis.  HLA-B*1502 in Asians and south Asians. > with carbamazepine  HLA-A*3101 is associated with carbamazepine        Long-term side effect: Osteomalacia or osteoporosis Because interfere with vitamin D metabolism  Phenytoin, phenobarbital, carbamazepine, oxcarbazepine, felbamate, and valproic acid  Patients should receive vitamin D supplementation and calcium Bone mineral density testing if other risk factors for osteoporosis are present. Laboratory tests:  ↑ Bone-specific alkaline phosphatase  ↓ serum Ca and 25-OH vitamin D,  But intact parathyroid hormone.  Cytochrome P450 (CYP450) inducers: Potent  Phenobarbital, phenytoin, primidone, and carbamazepine.  Devoid of enzyme inducing or inhibiting properties: Levetiracetam, Gabapentin and vigabatrin  Valproic acid inhibits many hepatic enzyme systems and displaces some drugs from plasma albumin.  Felbamate and topiramate can act as inducers Surgery Hemispherectomy • Hemispherotomy Vagus Nerve Stimulation Therapy (VNS) • • It is a primary communication pathways between body and brain. It is delivered by a surgically implanted generator and lead. Like a pacemaker. • Side Effects: – Cough – Hoarseness – Paraesthesia – Shortness of Breath – Vocal Cord Paralysis/weakness – Increased/Improved: Mood, Alertness and Memory