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Antiseizure drugs pres

Antiseizure drugs pres






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    Antiseizure drugs pres Antiseizure drugs pres Presentation Transcript

    • ANTISEIZURE DRUGS OR Antiepileptic drugs
    • Epilepsy
      • Chronic disorder characterized by recurrent seizures
      • Seizures is a sudden, excessive, abnormal discharge of cerebral neurons
      • Causes of seizures
      • Heredity – major contributing factor
      • may occur due to infection, neoplasm or head injury
      • Environmental causes-alteration in blood gases, pH, electrolytes, or glucose availability
    • Seizure classified into two broad groups
        • Partial: simple or complex
        • Generalized: absence, tonic, clonic, tonic-clonic, myoclonic, febrile
      • Simple partial seizures (without loss of consciousness)
        • confined to a single locus in brain
        • abnormal activity in one limb or muscles
        • With autonomic symptoms (nausea, blood pressure changes,...)
      • Complex partial seizures (with loss of consciousness)
        • Simple partial followed by a loss of consciousness
        • Impaired consciousness from the onset
        • Exhibits complex sensory hallucination
        • Motor dysfunction may involve chewing movements, diarrhea or urination
    • Generalized seizures
      • Electrical discharge spread to both hemisphere
      • May be convulsive (shaken repeatedly) or non convulsive
      • Immediate loss of consciousness occurs
      • Types
      • generalized tonic-clonic (grand mal) seizures
      • absence (petit mal) seizures
      • tonic seizures
      • atonic seizures
      • clonic and myoclonic seizures
      • febrile seizures
    • =======================
      • Partial Seizures localized onset of attack ascertained, either by clinical observation or by EEG – attack begins in a specific locus in brain
      • Simple Partial seizures – least complicated, characterized by minimal spread of abnormal discharge, normal consciousness and awareness are preserved – pt may have a sudden onset of clonic jerking of an extremity lasting 60-90 secs; residual weakness lasts for 15-30 mins after attack.
      • Pt completely aware of attack, can describe it in detail
      • EEG may show an abnormal discharge highly localized to the involved portion of brain
    • =======================
      • Complex Partial seizures – localized onset, discharge becomes more widespread (usually bilateral) and almost always involves limbic system
      • most (not all) CPS arise from one of the temporal lobes, possibly because of the susceptibility of this area to insults such as hypoxia or infection
      • Clinically, pt may have a brief warning followed by an alteration of consciousness during which some pts may stare and others may stagger or even fall
      • More, however, demonstrate fragments of integrated motor behavior called automatisms for which pt has no memory
      • after 30-120 secs, pt makes a gradual recovery to normal consciousness but may feel tired or ill for several hours after attack
    • Generalized Seizures Tonic-clonic seizures
      • characterized by
      • tonic phase  continuous rigidity of all extremities
      • clonic phase  massive jerking of body ( rapid contraction and relaxation)
      • Tongue or cheek bitten, urinary incontinence common
      • Seizure followed by period of confusion and exhaustion due to depletion of energy
    • Absence seizure (petit mal)
      • Typical absence seizures consists of staring for a few seconds (altered consciousness) then returning to full function, as if nothing occurred
      • Brief duration (< 10 secs)
      • ass with mild clonic jerking of eyelids, patient stares & exhibit rapid eye blinking
      • begin in childhood or adolescence and may occur up to hundreds of times a day
      • The patient has no recollection of the event.
    • Myoclonic seizures
      • Myoclonic jerking – seen in generalized tonic-clonic seizures, partial seizure, absence seizures, and infantile spasms
      • Short episode of muscle contractions
      • Occurs due to permanent nurologic damage due to hypoxia, uremia, encephalitis or drug poisoning
    • Atonic seizures
      • sudden loss of postural tone , if standing pt falls suddenly and may be injured, if seated, may suddenly drop forward
    • Infantile spasms
      • characterized clinically by brief recurrent myoclonic jerks of body with sudden flexion or extension of the body and limbs
      • 90% of affected pts have their 1 st attack before age of 1 yr
      • Most pts mentally retarded
      • cause  infection, kernicterus and hypoglycemia
    • Febrile fits
      • Frequently occurs in young children (6 months- 6 yrs) during high grade fever
      • Characterized by tonic clonic convulsions of short duration (1 to 5 min), eye rolling & unresponsiveness
      • Benign, do not cause death, nurologic damage, injury, or learning disorder
      • Status epilepticus
      • Continuous, rapid, recurrent seizures
    • Antiepileptic drugs
      • Primary drugs
      • Phenytoin
      • Carbamazepine
      • Clonazepam (BZ)
      • Clorazepate (BZ)
      • Diazepam (BZ)
      • Ethosuximide
      • Lorazepam (BZ)
      • Phenobarbital
      • Primidone
      • Valproic acid
      • Adjunct drugs
      • Fel bamate
      • Gaba pentin
      • Lamo trigine
      • Leve tira cetam
      • Tiaga bine
      • Topira mate
      • Zoni samide
      • Viga batrin
    • Pathophysiology of Seizures
      • Increased CNS excitability
        • Membrane depolarization
        • Increased excitatory input
        • Decreased inhibitory (GABA) input
    • Strategies in Treatment
      • Stabilize membrane by blockade of voltage gated channels (Na & Ca)  prevent depolarization by action on ion channels
      • Increase GABAergic transmission
      • Decrease Excitatory glutamate transmission
    • Classification of Anticonvulsants Felbamate Topiramate Benzodiazepines Barbiturates Valproic acid Gabapentin Vigabatrin Topiramate Felbamate Na + : Phenytoin, Carbamazepine, Lamotrigine Topiramate Valproic acid Ca ++ : Ethosuximide Valproic acid Inhibit glutamate Transmission Enhance GABA Transmission Action on Ion Channels
    • Phenytoin
      • Diphenylhydantoin – oldest antiseizure drug
      • Mechanism of action .
      • Blocks voltage gated Na+ channels in inactive state , slows recovery
      • blocks repetitive firing of action potentials, promotes stabilization of membrane, reduce propagation of abnormal impulse in brain
      • At higher dose blocks Ca 2+ conductance
      • Interfere with release of neurotransmitters norepinephrine, acetylcholine
      • Produces drowsiness and lethargy
    • Phenytoin /Clinical use
      • Highly effective in
      • Partial seizures (simple and complex)
      • Tonic-clonic seizures
      • Status epilepticus
      • Arrhythmia
      • Not effective in absence seizures
    • Phenytoin /Adverse effects
      • Depression of CNS  Sedation, Nystagmus, diplopia and ataxia, confusion & hallucination
      • Reversible Gingival hyperplasia and hirsutism
      • GIT  nausea & vomiting
      • Long term use
      • Coarsening of facial features occurs in children
      • Mild peripheral neuropathy  deep tendon reflexes in lower extremities
      • Osteomalacia due to abnormalities of vitamin D metabolism
    • Phenytoin /Adverse effects
      • Megaloblastic anemia due to folate deficiency
      • Inhibition of antidiuretic hormone secretion
      • Hyperglycemia and glycosuria   insulin secretion
      • Teratogenic effects  fetal hydantoin syndrome  includes cleft lip, cleft palate, congenital heart disease, growth retardation and mental deficiency
    • Phenytoin/ Drug Interactions
      • Phenytoin metabolism decrease by  Cimetidine, isoniazid, Chloramphenicol, dicumarol, sulfonamide
      • Phenytoin metabolism increase by Carbamazepine
    • Carbamazepine
      • M.O.A
      • By blocks sodium channels  reduce the propagation of abnormal impulses
      • inhibits high-frequency repetitive firing in neurons
      • decrease synaptic transmission, inhibits uptake and release of NE from brain
      • postsynaptic action of GABA potentiated
    • Carbamazepine /Clinical use
      • Drug of choice in all partial seizures
      • Highly effective in tonic–clonic seizures
      • Trigeminal neuralgia
      • Use in Manic depressive patient to decrease the symptoms
    • Carbamazepine Adverse effects
      • Respiratory depression
      • Drowsiness, vertigo, diplopia, blurred vision, ataxia & coma
      • Irritating to stomach  n & v may occurs
      • Serious liver toxicity
      • hyponatremia and water intoxication
      • Idiosyncratic blood dyscrasias,including fatal cases of aplastic anemia and agranulocytosis
      • Is an enzyme inducer
    • Drugs inhibiting metabolism of Carbamazepine
      • Cimetidine
      • Diltiazem
      • Erythromycin
      • Isoniazid
      • Propoxyphene
    • Phenobarbital
      • clinically useful as antiseizure drugs phenobarbital, mephobarbital, metharbital,
      • Mechanism of Action
      • Elevate seizure threshold
      • Limits the spread of seizure discharge in brain
      • Binds to a regulatory site on GABA receptor, prolonging the openings of Cl- channels
      • Blocks excitatory responses induced by glutamate
    • Phenobarbital/ clinical uses
      • Doc in children with febrile fits
      • Effective in simple partial seizures
      • Recurrent tonic clonic seizures
      • Relieve anxiety
      • insomnia
    • Phenobarbital adverse effects
      • Sedation
      • Ataxia
      • Nystagmus
      • Vertigo
      • N &v
      • Morbilliform rash (measles like)
      • Agitation & confusion
      • Rebound seizures can occur on discontinuation of drug
    • Primidone
      • 2-deoxyphenobarbital
      • Metabolized to Phenobarbital and phenyl-ethyl-malonamide
      • All 3 are active anticonvulsants
      • M.O.A. – similar to Phenobarbital
      • Effective against partial and tonic clonic seizures
    • Valproic acid
      • Drug of choice for myoclonic seizures
      • Effective in tonic clonic & absence seizures
      • Block sodium channels & enhance GABAergic transmission
      • Adverse effects  N, V, ataxia, sedation, tremors, rash & alopecia
    • Ethosuximide
      • Inhibit T-type calcium channels in brain  reduce propagation of abnormal electrical activity
      • First choice in absence seizures
    • Benzodiazepines
      • Benzodiazepines are safest antiepileptic drugs
      • Clonazepam  use for chronic treatment of absence & myoclonic seizures
      • Chlorazepate  effective in partial seizures
      • Diazepam & lorazepam  drug of choice in acute treatment of status epilepticus (interrupt repeated seizures)
      • A/E  sedation, drowsiness, fatigue, ataxia, respiratory and cardiac depression
    • Adjunct antiepileptic drugs
      • Newer agents
      • Use as add on therapy in refractory epilepsies
      • Also effective as monotherapy
    • Lamotrigine
      • M.O.A. –blocks sodium channels, voltage activated calcium channels & decreased synaptic release of glutamate
      • Add on therapy, monotherapy for partial seizures, absence and myoclonic seizures in children
      • Dizziness, headache, diplopia, nausea, somnolence, and skin rash – potentially life-threatening dermatitis develops in 1-2% of pediatric pts
    • Felbamate
      • Broad spectrum
      • Use only in refractory cases (may cause aplastic anemia & hepatic failure)
      • block sodium channels & inhibits glycin & glutamate transmission
      • Effective in partial seizures
    • Gabapentin
      • Amino acid, analog of GABA, effective against partial seizures
      • M.O.A. – in spite of its close structural relationship to GABA, it appears not to act on GABA receptors, interfere with voltage gated calcium channels
      • Used in Partial and G tonic clonic seizures, diabetic neuropathic pain, postherpetic neuroralgia in adults
    • To-pira-mate
      • Effective in refectory partial and secondary generalized seizures
      • M.O.A.
      • Blocks voltage dependent sodium channels
      • Potentiate inhibitory effect of GABA, acting at a site different from BNZs or barbs
    • Ti-aga-bine
      • M.O.A. – inhibitor of GABA uptake
      • Prolongs inhibitory action of synaptically released GABA
      • Indicated for adjunctive treatment of partial seizures
    • Zonisamide
      • Primary site of action is on sodium channel
      • Also act on voltage dependent calcium channels
      • Effective against partial and G tonic clonic seizures, also against infantile spasms and certain myoclonias
      • S/E – drowsiness, cognitive impairment, serious skin rashes
    • Levetiracetam
      • M.O.A. – unknown
      • Effective for the treatment of refectory partial seizures
      • S/E – somnolence, asthenia, dizziness
    • Acetazolamide
      • Inhibits carbonic anhydrase
      • Mild acidosis in brain – mech by which drug exerts its antiseizure activity
      • Used for all types of seizures
      • Use severely limited by rapid development of tolerance usually within weeks