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EPILEPSY Seizures - Transient alteration of sensation, awareness or behavior due to disordered, abnormal firing of brain neurons. Epilepsy is a chronic.

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Presentation on theme: "EPILEPSY Seizures - Transient alteration of sensation, awareness or behavior due to disordered, abnormal firing of brain neurons. Epilepsy is a chronic."— Presentation transcript:

1 EPILEPSY Seizures - Transient alteration of sensation, awareness or behavior due to disordered, abnormal firing of brain neurons. Epilepsy is a chronic disorder characterized by recurrent seizures.

2 EPILEPSY FOCAL SEIZURES (PARTIAL) : Focal Seizures Without Dyscognitive Features (Simple Partial Seizures)  Eg., It include sensory, motor and psychic symptoms without impairment of cognition.  Focal Seizures With Dyscognitive Features (Complex Partial Seizures)  Focal seizures may also be accompanied by a transient impairment of the patient's ability to maintain normal contact with the environment.  The patient is unable to respond appropriately to visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase.  Eg., Psychomotor epilepsy – focus in temporal lobe. 

3 EPILEPSY GENERALIZED SEIZURES: Involve both the hemisphere from outset. 1.Generalized, Tonic-Clonic Seizures: 2.Absence Seizures: Typical absence seizures are characterized by sudden, brief lapses of consciousness without loss of postural control. The seizure typically lasts for only seconds, consciousness returns as suddenly as it was lost, and there is no postictal confusion.  3. Myoclonic Seizures: Myoclonus is a sudden and brief muscle contraction that may involve one part of the body or the entire body.

4 ANTIEPILEPTIC DRUGS Seizures: Defective synaptic function. Inhibition of inhibitory synapse. Excitation of excitatory synapse. Antiepileptic drugs act by restoration of normal synaptic activity. Activation of inhibitory synapse. Inhibition of excitatory synapse.

5 ANTIEPILEPTICS DRUGS Drugs acting by prolonging the inactivation of Na channels: Carbamazepine, Phenytoin, Valproate, Topiramate, Lamotrigine, Zonisamide Drugs enhancing GABA-A induced inhibition: Benzodiazepines, Barbiturates, Valproate, Topiramate, Gabapentin, Tiagabine, Vigabatrin Drugs affecting the ‘T’ Ca Current: Ethosuximide, Valproate Drugs inhibit glutamate synaptic function: Topiramate, Lamotrigine, Felbamate

6 ANTI EPILEPTICS Topiramate

7 ANTIEPILEPTIC DRUGS Phenytoin (Dilantin®) Zero order kinetics. Plasma monitoring. Enzyme inducer. Uses of Phenytoin: Generalized Tonic-Clonic Seizures. Partial seizures and Status epilepticus Fosphenytoin (Cerebyx®) is a prodrug used i.v as a substitute for phenytoin.

8 ANTIEPILEPTIC DRUGS Phenytoin, Carbamazepine and Valproate act by prolonging the inactivation of Na channels

9 ANTIEPILEPTIC DRUGS Phenytoin toxicity: Ataxia, vertigo and nystagmus. Gum hypertrophy, Hirsutism. Megaloblastic anemia / Osteomalacia. In pregnancy – fetal hydantoin syndrome – cleft lip and palate. Should not be used in absence seizures.

10 Phenytoin induced gum hyperplasia and coarsening of facial features

11 ANTIEPILEPTIC DRUGS BARBITURATES : Phenobarbital (Luminal®), Primidone (Mysoline®) It has specific anticonvulsant action. It is an enzyme inducer. It is contraindicated in acute intermittent or variegate porphyria. Long term administration cause behavioral abnormalities, impaired learning and memory.

12 ANTIEPILEPTIC DRUGS Carbamazepine (Tegretol®) Oxcarbazepine (Trileptal®) Prolong the inactivated Na channel. Antidiuretic effect by ↑ ADH action. Metabolized to toxic epoxide derivative. Enzyme inducer and auto-induction may need dose adjustments. Not to be used in absence seizures.

13 ANTIEPILEPTIC DRUGS Carbamazepine toxicity: Sedation, ataxia, vertigo and diplopia. SIADH – ADH action (Hyponatremia) Fetal malformations – craniofacial abnormality and spina-bifida. Fatal skin reactions (Stevens–Johnson syndrome) in HLA-B*1502. Agranulocytosis and aplastic anemia

14 ANTIEPILEPTIC DRUGS Uses of Carbamazepine (CBZ): Partial / Generalized tonic-clonic epilepsy. Trigeminal neuralgia. Bipolar disorder. Oxcarbazepine is an analog of CBZ. Less potent inducer of cytochrome P450 than CBZ.

15 ANTIEPILEPTIC DRUGS Valproate (Depakene) It is a broad spectrum antiepileptic drug. Mechanism of action: Prolong inactivated state of Na channel. Attenuation of calcium T Current. Inhibition of degradation of GABA by transaminase. Attenuates excitatory action of glutamate at NMDA receptors.

16 ANTIEPILEPTIC DRUGS VALPROATE TOXICITY: Acute pancreatitis Hepatotoxicity – in children < 2 years. Antagonist of folic acid – neural tube defects – spina bifida. It is an enzyme inhibitor.

17 ANTIEPILEPTIC DRUGS Uses of Valproate: Tonic-clonic seizures. Partial seizures. Absence seizures. Myoclonic seizures. Bipolar disorder. Migraine prophylaxis.

18 ANTIEPILEPTIC DRUGS ZONISAMIDE (Zonegran) Prolong the inactivated Na channel. Inhibits Ca ‘T’ currents. Add on therapy for Focal (Partial) seizures Ataxia and anorexia are the adverse effects.

19 ANTIEPILEPTIC DRUGS ETHOSUXIMIDE (Zarontin) Thalamus plays a role in 3-Hz spike-wave rhythms typical of absence seizures Primary action is on thalamocortical system involved in absence seizures. Acts by suppression of the ‘T’ Ca current. Used in absence seizures. Skin rash (SJS) and agranulocytosis.

20 ANTIEPILEPTIC DRUGS LAMOTRIGINE (Lamictal) Prolongs the inactivation Na channels. Inhibits Calcium channels. Block of glutamate receptors. Used in Partial epilepsy, GTC seizures, Myoclonic seizures, Absence seizures, Lennox Gastaut Syndrome and Bipolar disorder. Ataxia and SJS are adverse effects.

21 LAMOTRIGINE Lamotrigine (LTG) induced Stevens- Johnson Syndrome. Valproate added to lamotrigine increases LTG concentrations approximately two-fold.

22 ANTIEPILEPTIC DRUGS TOPIRAMATE (Topamax) Prolong the Na inactivated channels. Enhance GABA current. Blocks the AMPA (glutamate) receptor. Carbonic anhydrase inhibitor. Used in the treatment of Partial seizures, Generalized tonic-clonic seizures, Lennox- Gastaut syndrome and migraine prophylaxis. Weight loss and renal stones

23 ANTIEPILEPTIC DRUGS BENZODIAZEPINES Lorazepam, Midazolam, Diazepam, Clonazepam. Clonazepam – Absence and Myoclonic seizures. Lorazepam, Midazolam, Diazepam – Status epilepticus. Sedation and tolerance are the disadvantages on long term use.

24 ANTIEPILEPTIC DRUGS GABAPENTIN (Neurontin) and PREGABALIN (Lyrica) – Increased release of GABA – Inhibition of L-type Ca 2+ channels Gabapentin used for Neuropathic pain (Post-herpetic neuralgia) and Partial seizures. Pregabalin is approved for treatment of chronic pain disorders.

25 ANTIEPILEPTIC DRUGS VIGABATRIN (Sabril) A gamma vinyl analogue of GABA. Inhibitor of GABA transaminase. Used in refractory partial epilepsy Adverse effects includes – visual field defects (monitoring Q 6 months recommended) and psychosis.

26 ANTIEPILEPTIC DRUGS TIAGABINE (Gabitril) It ↑ GABA by blocking the GABA reuptake transporter. It is used in Partial seizures. Somnolence, Depression and impaired concentration are adverse effects.

27 TIAGABINE (Gabitril) increase GABA by blocking its reuptake.

28 ANTIEPILEPTIC DRUGS LEVETIRACETAM (Keppra) It modulates the release of glutamate and GABA. Approved in Partial seizures, Generalized tonic-clonic seizures and myoclonic seizures. Somnolence and ataxia are the adverse effects.

29 ANTIEPILEPTIC DRUGS Felbamate (Felbatol) It blocks NMDA receptors and potentiates GABA-A receptor response. Use of felbamate is restricted to patients with Lennox-Gastaut syndrome. Adverse effects includes aplastic anemia and hepatic failure.

30 DrugMech actionIndicationsToxicity TopiramateBlocks AMPA Block Na Channel ↑ GABA Partial seizures GTC seizures Weight loss Renal stones LamotrigineBlock glutamate Block Na channel Partial seizures GTC seizures Sedation, SJS FelbamateBlock NMDA Potentiate GABA Partial seizures Lennox Gastaut syndrome Aplastic anemia Hepatotoxicity Vigabatrin Inhibit GABA transaminase ↑ GABA Partial seizuresVisual defect Tiagabine Block reuptake GABA transporter ↑ GABA Partial seizuresSedation GabapentinPromote GABA release Chronic painSedation

31 EpilepsyPreferred choiceOthers Focal seizures (Partial) Carbamazepine Lamotrigine Topiramate Valproate Primary GTC Valproate Lamotrigine Topiramate Carbamazepine AbsenceEthosuximideValproate MyoclonicValproate Levetiracetam Topiramate Status epilepticus Lorazepam Midazolam Diazepam Phenytoin Phenobarbital

32 Focal (Partial) Simple Complex Generalized Absence Myoclonic Tonic-clonic Phenytoin Valproic acid Carbamazepine Ethosuximide Traditional AEDs

33 Partial Seizures Simple Complex Generalized Seizures Absence Myoclonic Tonic-Clonic Status epilepticus Lamotrigine Levetiracetam Topiramate Newer AEDs Benzodiazepine

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