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THE NERVOUS SYSTEM EPILEPSY

THE NERVOUS SYSTEM EPILEPSY. Epilepsy. The second most common neurological disorder affects 1% of population Characterized by short, recurrent attacks initiated by electrical discharges in the brain lights, noise, or smells may be sensed skeletal muscles may contract involuntarily

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THE NERVOUS SYSTEM EPILEPSY

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  1. THE NERVOUS SYSTEMEPILEPSY GoTafe/CShalders 2007

  2. Epilepsy • The second most common neurological disorder • affects 1% of population Characterized by short, recurrent attacks initiated by electrical discharges in the brain • lights, noise, or smells may be sensed • skeletal muscles may contract involuntarily • loss of consciousness

  3. Epilepsy • Epilepsy is a group of chronic neurological disorders characterized by sporadic recurrent episodes of convulsive seizures resulting from occasional excessive disorderly discharges in neuronal pathways across the cerebral cortex. GoTafe/CShalders 2007

  4. Epilepsy • The seizures can lead to a loss of consciousness, muscle jerking, sensory disturbances and abnormal behavior. • 70% of seizures do not have an identifiable cause and 30% have an underlying cause. Eg. Head injury, cerebrovascular infarct or hemorrhage, infection, brain tumour,drug toxicity or a metabolic imbalance.

  5. Epilepsy • Seizures vary from localized motor seizures to petit mals to grand mal tonic clonic seizures. • Status epilepticus is the term used when fitting persists for > 30 mins • This causes acute hypoxia and can be fatal

  6. Epilepsy • Epilepsy has many causes, including; • brain damage at birth, metabolic disturbances, infections, toxins, familiar disposition, head injuries, and tumors

  7. TYPES OF EPILEPSY • Partial complex (psychomotor) seizures are characterized by brief alterations in consciousness, unusual movements repeated over and over, changes in temperature, confusion and feeling of unreality. • Generalised absence seizures simple or complex most often seen in childhood and consist of temporary lapses of consciousness and last a few seconds GoTafe/CShalders 2007

  8. TYPES OF EPILEPSY • Partial simple motor epilepsy is described as a type of focal seizure, associated with irritation of a specific part of the brain. Consciousness may not be lost unless develops into a generalized convulsion. GoTafe/CShalders 2007

  9. TYPES OF EPILEPSY • Toni clonic (grand mal seizures) Often characterized by an aura, continuous tonic spasm (stiffening and increased muscle tone) and clonic (rapid synchronize jerking) • Status epilepticus is a clinical emergency. State of recurrent seizures for more than 30 minutes. A 10-20% mortality rate due to anoxia. GoTafe/CShalders 2007

  10. ABSENCE SEIZURES • ABSENCE SEIZURES • (PETIT MAL) • Ethosuximide • Valproate • Clonazepam GoTafe/CShalders 2007

  11. SIMPLE OR COMPLEX PARTIAL • SIMPLE OR COMPLEX PARTIAL • Carbamazepine • Phenytoin • Valproate • Lamotrigine GoTafe/CShalders 2007

  12. GENERALISED TONIC CLONIC • GENERALISED TONIC CLONIC • (GRAND MAL) • Carbamazepine • Lamotrigine • Phenytoin • Valproate GoTafe/CShalders 2007

  13. ANTIEPILEPTIC THERAPY • ANTIEPILEPTIC THERAPY • Secondary seizures usually respond to correction of the underlying cause. Primary recurrent seizures require long term antiepileptic therapy. If possible epilepsy is controlled with one antiepileptic drug. Only if seizures cannot be controlled with any one drug a second is added to the regime. • 70% of patients can be well controlled with one drug. Half of the remainder may require two. GoTafe/CShalders 2007

  14. Mechanisms of action • Anti seizure drugs suppress the over excitability of cortical neurones. • 1. stabilising the nerve membrane • 2. Altering movement of ions • 3. enhancing GABA • 4. inhibiting the action of glutamate GoTafe/CShalders 2007

  15. Medications in epilepsy • Used alone or as adjuvant therapy. Thought to block sodium and enhance GABA • Contra – Hepatic dys, preg • Prec – Abrupt with, RF, platelet dys, BF • AR – hepatic dys, neurological dys, pancreatitis GI • Inter – alcohol, other anticonvulsants, anticoags, psychotropics, CNS depressnats’ • Pre – 100 mg 200 mg 500 mg • Dose – Adults 600mg daily ^ 1-2g/day • Child 20-30mg/kg/day Available in syrup

  16. Medications in epilepsy • Phenytoin (dilantin) Acts to promote intracellular removal of sodium ions during refractory period, stabilizes cortical nerves against hyper excitability • Adverse effects • Gum overgrowth • Liver damage • Avoids St John Wart as can combine and reduce phenytoin levels • Also decreases effectivness of OCP GoTafe/CShalders 2007

  17. Medications in epilepsy • Phenytoin (dilantin) • Control of status epilepticus, tonic clonic seizures. Block sodium channels • Contra – cardiac arrhythmias • Prec – Hepatic impairment, IHD, diab abrupt withdrawal, CVD • AR – CNS, nystygmus, slurred speech, ataxia, GI upset, rash CNS depression CVS collapse

  18. Medications in epilepsy • Phenytoin (dilantin) Inter – antacids, OC’s anticoags,pethidine and loop diuretics • Pres – 30 mg 100 mg • Dose – Adults 4-5 mg/kg/day Max 600 mg/day • Child – 5mg/kg/day Max 300mg/day • Available as infatabs and pediatric suspension

  19. Medications in epilepsy • Phenobarbitone Used for grand mal and psychomotor epilepsy • Cont- resp dys, RF,hepatic dys,uncon diab • Prec – abrupt withdrawal, asthma, preg • AR – rash dependency, bradycardia,CNS dist

  20. Medications in epilepsy • Phenobarbitone • Inter - anticoags, anticonvulsants,corticosteroids,OC,opiods paracetamol antiarrythmics St Johns Wort Vit D • Pres – 30mg • Dose Adults – 60-240 mg/day in 2-3 divided doses • Child 1-6 mg/kg/day in 2-3 divided doses

  21. Medications in epilepsy • Carbamazepine (Tegretol) • Is a trycyclic related to an anti-depressant • Reduces neuronal excitability • Adverse effects • CVS disturbances, liver and kidney dysfunction, drowsiness, dizziness, blurred vision • Dose increased slowly to minimize effects • Blood test taken every two weeks for the two to three months of treatment GoTafe/CShalders 2007

  22. Medications in epilepsy • Carbamazepine (Tegretol) • Used for generalised epilepsy, neuralgia, and mania and bipolar management. Blocks sodium channels • Contra – AV block, SLE Hepatic dys • Prec – cardiac dys, resp dys, renal dys • AR – CNS disturbances, GI haem changes, rash

  23. Medications in epilepsy • Carbamazepine (Tegretol) • Inter – OC, anticoags, MAOIs anticoags, alcohol, tricyclic antidepressants, St Johns Wort, grapefruit juice, tramadol • Pres – 100 mg 200 mg • Dose Adults Start 100-200 mg 1-2 times daily^to 400mg 2-3 times daily • Chils start 50mg 2 times daily^gradually to max 100mg/daily

  24. Medications in epilepsy • Gabapentin • Used when treatment of partial epileptic seizures not well controlled by other ant epileptic drugs • Prec – Abrupt withdrawal, RF, preg, BF • AR – ataxia GI nystagmus • Inter – cimetidine, antacids • Pres 100 mg, 300 mg, 400 mg • Dose - >12yrs start at 300 mg ^ 300 mg over 3 days Usual effective range 900 – 1800 mg in 3 divided doses Max 2400mg/day

  25. Medications in epilepsy • Primodone (Mysoline) Used for grand mal seizures, myoclonic jerks • Contr – porphyria • Prec – Hepatic dys, renal dys, resp dys, abrupt with, preg, lact • AR – CNS dist, visual dist, ataxia rash, • Int – other anticonvulsants, anticoag, alcohol, CNS, depress • Pres – 250 mg • Dose Adults 125 mg init, Max 1.5g/day

  26. Medications in epilepsy • Valproate ( Epilum) • Slows recovery rate of voltage gated sodium channels and elevates brain GABA levels • Common side effect hepatoxicity • Absorbs moisture so packed in aluminium foil Therefore discard half tablets exposed to air • Take with food (GIT upset) • Treatment ceased with loss of seizure control bruising or bleeding GoTafe/CShalders 2007

  27. Medications in epilepsy Clonazepam (rivotril) Generalized epilepsy status epilepticus • Contra – resp failure, hepatic dys alcohol • Prec – abrupt with, renal dys, acute glaucoma, schizophrenia • AR – CNS disturbances, resp dep, ataxia

  28. Medications in epilepsy • Clonazepam (rivotril) • Inter – alcohol, anticonvulsants, cimetidine, CNS depressants, sodium valproate • Pres – 0.5 mg, 2 mg • Dose – Adults init 1mg/day Max 4-8 mg in 3-4 divided doses • Child init 0.3mg/day Max 0.5-6mg dep on age

  29. Central nervous system effects of selected anticonvulsants • Phenytoin • Fatigue, increased clumsiness, confusion, mood alterations, decreased attention span. learning, and ability to solve problems. • Sodium Valproate • Sedation, depression, increased appetite and weight, hyperactivity and aggression in children. • After a drug regime has been found to be successful, it is continued until the patient has been seizure free for 2-3 years. • Plasma levels of antiepileptic drugs are monitored frequently. Useful for establishing baseline data, predicting toxicity, checking compliance. GoTafe/CShalders 2007

  30. Phenytoin • Most useful in tonic clonic seizures, and partial and generalised seizures • Also used as antidysarhythmic • Do not give IV using 5% glucose a s crystallisation can occur, instead use saline GoTafe/CShalders 2007

  31. Levetiracetam • Recommended for adults and children over 12 years • Repetitive firing of neurons within the affected area of the cortex is suppressed • Adverse effects • Skin rash, (Stevens-Johnson syndrome) needs to be stopped immediately, dizziness headache and double vision GoTafe/CShalders 2007

  32. Levetiracetam • Excreted in breast milk • Caution in pregnant women • Drug withdrawal should occur gradually GoTafe/CShalders 2007

  33. Oxcarbazepine • Recommended for treatment of partail and generalised tonic clonic seizures • Blocks voltage gated sodium channels, therefore hyperexcitable neurons are stabilsed, nerve impulse transmission reduced and repetitive firing is inhibited GoTafe/CShalders 2007

  34. Oxcarbazepine • Adverse effects are transient • fatigue., skin eruptions, and gastrointestinal disturbances • Better tolerated in terms of adverse reactions and compliance therapy GoTafe/CShalders 2007

  35. Medications in epilepsy • Drug levels must be monitored to avoid toxic effects, and to adjust doses correctly • Some anti epileptic drugs are useful for pain management • Carbamazepine for neuralgia, sodium valproate for migraine, and gabapentin for diabetic neuralgia

  36. Medications in epilepsy • Benzodiazepines are also used in anti epileptic drugs, such as clonazepam and diazepam, nitrazepam • They inhibit the firing of hyperexcitable neurons through the enhancement of the action of GABA • Adverse effects • Fatigue, muscle weakness and vertigo • Not used for long term therapy

  37. Medications in epilepsy Barbiturates, phenobarbitone or primidone • Generally used as hypnotics • Increased activity or excitement altered sleep pattern, impaired judgment, and short term memory impairment decreased attention span. GoTafe/CShalders 2007

  38. Medications in epilepsy AMYLOBARBITONE Indicate for use as a sedative hypnotic and anti convulsant METHYLPHENOBARBITONE Is a barbiturate indicated for use only as anti convulsant. GoTafe/CShalders 2007

  39. Medications in epilepsy VIGABANTIN GABA mediated inhibitor, irreversible inhibitor of GABA transminase. Adverse reaction on vision LEVETIRACETAM New antiepileptic used for adjunct therapy. Common adverse effects headache, long term safety not yet known. GoTafe/CShalders 2007

  40. PARENTAL USE OF ANTIEPILEPTICS • Administered usually IV or IM in acute condition. Phenobarbitone, phenytoin and the benzodiazepines diazepam and lorazepam are given by injection • Anticonvulsant therapy should be tapered down slowly. If a patient is taking more than one, each drug is withdrawn separately and slowly. GoTafe/CShalders 2007

  41. PARENTAL USE OF ANTIEPILEPTICS • MECHANISM OF ACTION • There are three main groups of antiepileptic drugs • Those that enhance (GABA) mediated inhibition of neural activity. The benzodiazepines, barbiturates act by this mechanism. • Those that inhibit sodium channel function, thus blocking repetitive depolarization of neurons. Phenytoin, carbamazepine, sodium valproate and lamotrigine. • Miscellaneous drug with varying mechanisms. GoTafe/CShalders 2007

  42. Clinical considerations • Do not omit doses • Should not be withdrawn abruptly • Can increase metabolism of many drugs • Female contraceptives should be non hormonal • Advise during pregnancy • Do not drive a car when first put on therpay • Avoid alcohol

  43. Clinical considerations • Avoid hot baths tactile stimulus from hot water can provoke a seizure • Regular levels where appropriate

  44. References • Bryant, Knights, Salerno. 2nd Edition Toronto 2005 • Bullock, S. Manias, E. Galbraith, A. 2007. Fundamentals of Pharmocology 5th Edition. Pearson Education Australia. GoTafe/CShalders 2007

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