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Undergraduate MBBS level Theory Class in Power Point presentation from drdhriti, NEIGRIHMS, Shillong, Meghalaya, India

Undergraduate MBBS level Theory Class in Power Point presentation from drdhriti, NEIGRIHMS, Shillong, Meghalaya, India

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  • .  A sudden outburst of emotion or action:  a paroxysm of laughter. 2.a.  A sudden attack, recurrence, or intensification of a disease. b.  A spasm or fit; a convulsion. [Middle English paroxism,  periodic attack of a disease , from Medieval Latin paroxysmus, from Greek paroxusmos, from parox nein,  to stimulate, irritate  : para-,  intensive pref. ; see  para- 1 + ox nein,  to goad, sharpen  (from oxus,  sharp ; see ak- in Indo-European roots).] par ox·ys mal  (- k-s z m l)  adj.
  • Congener of carbamazepine, only glucoronide conjugated not oxidized. Toxic effect due to epoxide are avoided risk of hepatotoxicity is less but hyponetrimia is more
  • Large number of BZDs have antiseizure properties but only few are used or approved
  • BDZs can be used orally but practically in therapeutics maximum use is IV. Redistribution like other lipid soluble drugs, central effect will be rapid but wanes soon. Redistribution half life – 1 hr NDD acts as partial agonist.
  • Because of the adverse effects it may require to withdraw or reduce the dosage
  • Lorazepam has more sustained effect. Diazepam action is short.
  • GABA agonist because of high lipid solubility
  • Structure and amino acid sequence is similar to L type of voltage sensitive Ca++ channel
  • 1. CBZ, Phenytoin and valproate has been traditionally used in these conditions. CBZ is preferred nyoung girls bcoz of toxicities of phenytoin. Valproate should be used cautiously bcoz of hepatotoxicity. However newer drugs can be used 2. Absence seizure – equally effective but valproate is used more to prevent kindling and GTCS Mixed absence and GTCS is more common than pure absence. 3. Carbamazepine is preferred drug in complex partial seizure. Newer drugs can also be used
  • Monotherapy should be instituted. If a drug fails to control seizures adequately even after administration of maximum tolerated dose then alternate with other drug. Combination therapy should be instituted with drugs of different mechanism of actions – for example – Na+ channel blockers with GABA drugs etc. Pharmacokinetic interactions are common among antiseizure drugs – dose adjustment is necessary. 5. Febrile convulsion – in children under 5 yrs, convulsions during fever. May become chronic everytime fever developes.
  • Though antiseizure drugs have teratogenic effects and other birth defects, it should not be stopped as there is increased incidence of status epilepticus. Antiseizure drugs that induce CYPs have been associated with vit. K deficiency in newborn which can result in coagulopathy and haemorrhage. Therefore treatment of epilepsy during pregnancy should be supplemented with 10mg/day of vit.k

Antiepileptics Antiepileptics Presentation Transcript

  • Antiepileptic Drugs Department of Pharmacology NEIGRIHMS, Shillong
  • SOME FAMOUS PEOPLE WHO WERE AFFLICTED
        • ALEXANDER THE GREAT
        • JULIUS CAESAR
        • NAPOLEON
  • What are Epilepsies?
    • Group of disorders of the CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizure) of loss of consciousness, with or without characteristic body movements (convulsions), sensory or psychiatric phenomena.
    View slide
  • What are seizures?
    • A seizure is a transient alteration of behaviour due to the disordered, synchronous, and rythmic firing of populations of brain neurones. Seizure can be nonepileptic and can be evoked in normal brain
    • A seizure is a paroxysmal behavioral spell generally caused by an excessive disorderly discharge of cortical nerve cells.
    View slide
  • What are Epilepsies – Clinically?
    • Epilepsy is a syndrome of two or more unprovoked or recurrent seizures on more than one occasion.
    • Epileptic seizures range from clinically undetectable (electrographic seizure) to convulsions.
  • How many types?
    • Generalized:
    • Generalized tonic-Clonic Seizures
    • Absence Seizure
    • Atonic Seizures
    • Myoclonic Seizures
    • Infantile Spasms
  • Types of seizures – contd.
    • 2. Partial (focal) Seizures
      • Simple Partial Seizures
      • Complex Partial Seizures
  • 1. Generalized seizures
    • A. Generalized tonic-clonic
    • GTCS/major epilepsy/grand mal
    • Commonest of all
    • Lasts for 1-2 minutes
    • Aura-cry-unconsciousness-tonic phase-clonic phase
    • Usually occurs in both the hemispheres
    • Manifestations are determined by cortical site of seizure occurence
    • Tonic phase:
    • - Sustained powerful muscle contraction (involving all body musculature) which arrests ventilation.
    • EEG: Rythmic high frequency, high voltage discharges with cortical neurons undergoing sustained depolarization, with protracted trains of action potentials.
    Generalized Seizures – contd.
    • Clonic phase:
    • - Alternating contraction and relaxation, causing a reciprocating movement which could be bilaterally symmetrical.
    • EEG: Characterized by groups of spikes on the EEG and periodic neuronal depolarizations with clusters of action potentials.
    Generalized Seizures – contd.
  • Generalized Seizures – contd.
  • Generalized Seizures – contd.
  • Generalized Seizures – contd.
    • B. Absence seizure:
    • Also called minor epilepsy/petit mal
    • Usually in Children and lasts for 1-2 minutes
    • Typical generalized spike-and-wave type discharges at 3 per second (3 Hz)
    • Momentary loss of consciousness, patient stares at one direction
    • No motor (muscular component)
    • No convulsions
    • Minor muscular twitching restricted to eyelids (eyelid flutter) and face.
    • No loss of postural control.
  • Generalized Seizures – contd.
    • C. Atonic Seizures:
    • Unconsciousness with relaxation of all muscles
    • Patient falls down
    • Loss of postural tone, with sagging of the head or falling
    • D. Myoclonic Seizures:
    • Isolated clonic jerks associated with brief bursts of multiple spikes in the EEG
    • Momentary contractions of muscles of limbs or whole body
    • No loss of postural control
  • Generalized Seizures – contd.
    • E. Infantile spasm:
    • An epileptic syndrome.
    • Characterized by brief recurrent myoclonic jerks muscle spasm) of the body with sudden flexion or extension of the body and limbs.
    • Progressive mental deterioration
  • 2. Partial (focal) Seizures
    • A. Simple partial seizure
    • Lasts for 20 – 60 seconds
    • Confined to a group of muscles or localized sensory disturbances depending on area of cortex involved
    • For example – if motor cortex of the left thumb then jerking movement of left thumb, and if it is sensory cortex then paresthesia of left thumb.
    • No alteration of consciousness
  • Partial (focal) Seizures – contd.
    • B. Complex partial seizure (temporal lobe/psychomotor epilepsy)
    • Focus is located in temporal lobe
    • Confused behaviour and purposeless movements and emotional changes lasting for 30 seconds to 2 minutes
    • An aura often present
    • Motor activity appears as non-reflex actions.
    • Automatisms (repetitive coordinated movements).
    • Wide variety of clinical manifestations
    • Consciousness is impaired
  • Complex partial seizure – contd. Deja vu
  • Partial (focal) Seizures – contd.
    • C. Secondarily generalized:
    • (Jacksonian)
    • Partial seizures initially
    • Followed by generalized tonic-clonic seizure
  • Secondarily generalized seizure
  • Partial (focal) Seizures – contd.
  • Types of Seizure: Summery:
  • Status epilepticus
    • Continuous seizure activity for more than 30 minutes, or 2 or more seizures without recovery of consciousness.
    • Emergency: Recurrent tonic-clonic convulsions without recovery in between.
  • Causes of Epilepsy
        • ACUTE
        • CONGENITAL
  • Causes of Epilepsy – contd.
        • ACUTE EPILEPSY
        • CORTICAL DAMAGE
        • TRAUMA
        • STROKE
        • NEOPLASM
        • AUTOIMMUNE EFFECTS
  • Causes of Epilepsy – contd.
        • Congenital:
        • Hippocampus DYSGENESIS (FAILURE OF CORTEX TO GROW PROPERLY)
        • VASCULAR MALFORMATIONS
        • AT LEAST EIGHT SINGLE LOCUS GENETIC DEFECTS ARE ASSOCIATED WITH EPILEPSY – motor cortex, somatosensory cortex, visual cortex, auditory cortex, temporal lobe cortex and olfactory.
  • Experimental Models
    • Maximal electroshock seizures: tonic phase abolished by drugs effective in GTCS
    • PTZ clonic seizures (Pentylenetetrazole): Can be prevented by drugs effective in absence seizure
    • Chronic focal seizure: alumina cream in monkey
    • Kindled seizures: bursts of weak electrical impulses – tonic-clonic seizure
  • Classification – antiepileptic drugs
    • Hydantoins: phenytoin , phosphenytoin
    • Barbiturates: phenobarbitone
    • Iminostilbenes: carbamazepine , oxcarbazepine
    • Succinimides: ethosuximide
    • Aliphatic carboxylic acid: Valproic acid , divalproex
    • Benzodiazepines : clonazepam, diazepam, lorazepam
    • New compounds: gabapentin, lamotrigine , tiagabine, topiramate, vigabatrin , zonisamide, felbamate
    • Most common ones:
    • Modification of ion conductance
      • Prolongation of Na + channel inactivation
      • Inhibition of `T` type Ca ++ current
    • Increase inhibitory (GABAergic) transmission.
    • Glutamate receptor antagonism (NMDA, AMPA, or kainic acid)
    • Genetic mechanism
    Mechanisms of seizure & antiseizure drugs:
    • The Sodium Channel:
    • Resting State
    • Arrival of Action Potential causes depolarization and channel opens allowing sodium to flow in.
    • Refractory State, Inactivation – reduce the rate of recovery.
    Na + Na + Na + Sustain channel in this conformation Anticonvulsant mechanism – contd.
  • The Sodium Channel – contd.
    • Drugs acting via this channel:
    • Phenytoin, Sodium Valproate, Carbamezepine, Lamotrigine, Topiramide and Zonisamide
  • Anticonvulsant mechanism – contd.
    • T type Ca ++ current inhibition:
    • T type current is responsible for 3 Hz spike-and-wave
    • Throughout the thalamus `T` current has large amplitudes
    • Bursts of action potential is by action of T current
    • In absence seizure
    • Drugs – ethosuximide, valproate and trimethadione
  • Anticonvulsant mechanism – contd.
    • The GABA mediated CL- channel opening
    • Drugs: barbiturates, benzodiazepines, vigabatrin, gabapentin and valproate
  • Individual Drugs
  • Phenobarbitone
    • First effective organic antiseizure agent
    • Mechanism:
      • Mechanism of CNS depression like other barbiturates, but less effect on Ca++ channel and glutamate release – less hypnotic effect
      • GABA A receptor mediated like other Barbiturates
      • Continued use – sedation effect lost but not anticonvulsant action
      • Raises seizure threshold and limits spread
      • Suppresses kindled seizures
    • Pharmcokinetics:
      • Slowly absorbed and long t 1/2 (80 – 120 hrs)
      • Metabolized in liver and excreted unchanged in kidney
      • Single dose after 3 wks. – steady state
  • Phenobarbitone – contd. (Gardenal/Luminal)
    • Adverse effects:
      • Sedation
      • Behavioural abnormalities
      • Hyperactivity in children
      • Rashes, megaloblastic anaemia and osteomalacia
      • Primidone: deoxybarbiturate
      • Phenobarbitone and PEMA Short half life 6-14 hrs
    • Uses:
      • Many consider them the drugs of choice for seizures only in infants
      • GTC
      • SP and CPS
    • Dose:
      • 60 mg 1-3 times a day
    • Child: 3-6 mg/kg/day
      • Available as tabs – 30/60mg, syr. and inj.
  • Phenytoin (Dilantin/Epsolin/Eptoin)
    • Pharmacological actions:
      • Not CNS depressant
      • But muscular rigidity and excitement at toxic doses
      • Abolish tonic phase of GTC seizure
      • No effect on clonic phase
      • Prevents spread of seizure activity
      • Tonic-clonic phase is suppressed but no change in EEG and aura
      • In CVS – depresses ventricular automaticity, accelerates AV conduction
  • Phenytoin sodium – contd.
    • Mechanism of action:
      • Prevents repetitive detonation of normal brain cells during ` depolarization shift`
      • Prolonging the inactivation of voltage sensitive Na+ channel
      • No high frequency discharges
      • Na+ channel recovers
      • No interference with kindling – only on high frequency firing
  • Phenytoin sodium – contd.
    • Pharmacokinetics:
      • Slow oral absorption
      • 80-90% bound to plasma protein
      • Metabolized in liver by hydroxylation and glucoronide conjugation
      • Elimination varies with dose – first order to zero order
      • T1/2 life is 12 to 24 hrs
      • Cannot metabolize by liver if plasma conc. Is above 10 mcg/ml
      • Monitoring of plasma concentration
  • Phenytoin sodium – contd.
    • Adverse effects:
    • Hirsutism, coarsening of facial features and acne
    • Gum hypertrophy and Gingival hyperplasia.
    • Hypersensitivity – rashes, lymphadenopathy
    • Megaloblastic anaemia
    • Osteomalacia
    • Hyperglycaemia
    • Cognitive impairment
    • Exacerbates absence seizures
    • Fetal Hydantoin Syndrome
  • Phenytoin sodium – contd.
    • Uses: It is the first line antiepileptic for
      • GTCS, no effect in absence seizure
      • Status epilepticus
      • Trigeminal neuralgia – 2 nd to Carbamazepine
    • Available as caps/tabs/inj
    • 25 to 100 mg caps and tabs.
  • Phenytoin sodium – contd.
    • Drug Interactions:
      • Phenytoin and carbamazepine increases each others metabolism
      • Induces microsomal enzyme – steroids, digitoxin etc
      • Phenytoin metabolism inhibition – by warfarin, isoniazide etc.
      • Sucralfate – decreases phenytoin ebsorption
  • Phenytoin sodium – contd.
  • Phenytoin sodium – contd. Phenytoin Toxicities Fetal Hydantoin Syndrome
  • Images of Phenytoin preparations
  • Carbamazepine (Tegretol/Tegrital)
    • Chemically related to imipramine
    • Trigeminal neuralgia
    • Resembles phenytoin in pharmacological actions
    • Unlike phenytoin – inhibits kindling, modifies electroshock seizures and raises threshold to PTZ and electroshock
  • Carbamazepine – contd.
    • Pharmacokinetics:
      • Poorly water soluble and oral absorption is low
      • 75% bound to plasma protein
      • Metabolized in liver: active 10-11 epoxy carbamazepine
      • Substrate and inducer of CYP3A4
      • Half life – 20 to 40hrs. Decreases afterwards due to induction
  • Carbamazepine – contd.
    • Adverse effects:
      • Autoinduction of metabolism
      • Nausea, vomiting, diarrhoea and visual disturbances
      • Hypersensitivity – rash, photosensitivity, hepatitis, granulocyte supression and aplastic anemia
      • ADH action enhancement – hyponatremia and water retention
      • Teratogenicity
      • Exacerbates absence seizures
  • Carbamazepine – contd.
    • Uses:
      • Complex partial seizure
      • GTCS and SPS
      • Trigeminal and related neuralgias
      • Manic depressive illness and acute mania
    • Available as tabs (100mg 200, 400 etc.) and syr.
    • Oxcarbamazepine
  • Carbamazepine – contd.
    • Interactions:
      • Enzyme inducer – reduce efficacy of OCPs and others
      • Metabolism is induced by – phenobarbitone, phenytoin, valproate
      • Inhibits its metabolism – isoniazide and erythromycin
  • Ethosuximide
    • Drug of choice for absence seizures
    • Does not modify maximal electroshock seizure or inhibit kindling
    • High efficacy and safety
    • Not plasma protein or fat binding
    • Mechanism of action involves reducing lowthreshold Ca2+ channel current (T-type channel) in thalamus
    • At high concentrations:
    • Inhibits Na+/K+ ATPase
    • Depresses cerebral metabolic rate
    • Potentiates GABA
        • Phensuximide = less effective
        • Methsuximide = more toxic
  • Ethosuximide – contd.
    • Toxicity:
      • Gastric distress, including, pain, nausea and vomiting
      • Lethargy and fatigue
      • Headache
      • Hiccups
      • Euphoria
      • Skin rashes
    • Doses:
      • 20-30mg/kg/day
      • Available as syr./caps.
  • Valproic acid (Encorate/Valparin)
    • Broad spectrum anticonvulsant
    • Effects on chronic experimental seizure and kindling
    • Potent blocker of PTZ seizure
    • Effective in partial, GTCS and absence seizures
    • Mechanism:
      • Na+ channel inactivation
      • Ca++ mediated `T` current attenuation
      • Inhibition of GABA transaminase
    • Pharmacokinrtics: well absorbed orally, 90% bound to plasma protein and completely metabolized in liver and excreted in urine t 1/2 is 10-15 hrs.
  • Valproic acid – contd.
    • Adverse effects:
      • Elevated liver enzymes including own – rise in serum transaminase
      • Nausea and vomiting
      • Abdominal pain and heartburn
      • Tremor, hair loss, weight gain
      • Idiosyncratic hepatotoxicity
      • In Girls – polycystic ovarian disease and menstrual irregularities
      • Negative interactions with other antiepileptics
      • Teratogenicity: spina bifida
    • Available as tabs. (200/300/500, syr. and inj.)
  • Valproic acid – contd.
    • Drug Interactions:
      • Valproate and carbamazepine induce each others metabolism
      • Inhibits phenobarbitone metabolism and increases its plasma level
      • Displaces phenytoin from protein binding sites and thereby decreases its metabolism – phenytoin toxicity
  • Benzodiazepines
    • Mainly used agents – Clonazepam, Diazepam, Lorazepam and Clobazam
    • Antiseizure properties:
      • Prevents PTZ induced seizures prominently and modifies electroshock seizure pattern
      • Clonazepam has potent effect on PTZ induced seizures but almost nil action on ME seiures
      • Suppress the spread of kindled seizures and generalized convulsions
      • Do not abolish abnormal discharges at site of stimulation
  • Benzodiazepines – contd.
    • Pharmacokinetic properties:
      • Well absorbed orally (peak 1-4 hrs)
      • IV administration – redistribution
      • Diazpam rapid redistribution (1 hr)
      • Diazepam – 99%, Clonazepam – 85% bound to plasma protein
      • N-desmethyldiazepam (metabolite) is less active than diazepam – partial agonist
      • Diazepam and NDD – hydroxylated to active metabolite – oxazepam – t 1/2 is 1 to 2 days
      • Clonazepam – reduction of nitro group to inactive 7-amino derivatives
      • Lorazepam – conjugation with glucoronic acid – t 1/2 is 14hrs
  • Benzodiazepines – contd.
    • Adverse effects:
      • Long term use of Clonazepam – drowsiness and lethargy – tolerance to antiseizure effects
      • Muscular incoordination and ataxia
      • Hypotonia, dysarthria and dizzziness
      • Behavoiural abnormalities in children – aggression, hyperactivity, irritability and difficulty in concentration
      • Increased bronchial and salivary secretions
      • Exacerbation of seizures
  • Benzodiazepines – contd.
    • Therapeutic uses:
      • Cloonazepam in absence seizure and myoclonic seizure in children (1 to 6 months)
      • Dose initial – 1.5mg/day, children – 0.01 to 0.03mg/kg/day
      • Status epilepticus – Diazepam Lorazepam may be used as alternative
  • Benzodiazepines – contd.
  • Gabapentin
    • GABA molecule covalently bound to a cyclohexane ring
    • Originally designed to be centrally active GABA agonist – rapid transfer across BBB
    • Pharmaqcological Effects:
      • Inhibits hindlimb extension in ME seizure
      • Inhibits clonic seizures induced by PTZ
      • Efficacy is equal to valproic acid but different from carbamazepine and phenytoin
  • Gabapentin – contd.
    • Mechanism of action:
      • Unknown
      • Does not mimic GABA
      • Probably, promotes nonvesicular release of GABA
      • Binds a protein in cortical membrane – similar to L type of voltage sensitive Ca++ channel
      • But, do not alter Ca++ currents
      • Does not reduce repetitive firing of action potentials
  • Gabapentin – contd.
    • Pharmacokinetics:
      • Absorbeed orally
      • Not metabolized in humans
      • Not bound to plasma proteins and excreted unchanged in urine
      • Half life is 4 to 6 hrs.
      • No known drug interaction
    • Uses:
      • Partial seizures with or without secondary generalization in addition to other drugs
      • 900-1800mg/day is equivalent to 300 mg/day of carbamazepine if used alone
      • Usual starting dose is 300mg/day
    • Adverse effects: somnolence, dizziness, ataxia etc.
  • Lamotrigine
    • Phenyltriazine derivative
    • Originally, as antifolate agent
    • Pharmacological Effects and Mechanisms:
      • Suppresses tonic hindlimb extension in ME seizure
      • Partial and secondarily generalized in kindling
      • No action on PTZ seizures
      • Delays recovery from inactivation of Na+ channels – carbamazepine and phenytoin
      • Effective against partial and secondarily generalized seizures
      • Broad spectrum activity – action in areas other than Na+ channels
      • Inhibition of glutamate release
  • Lamotrigine – contd.
    • Pharmacokinetics:
      • Completely absorbed from GIT and metabolized by glucoronidation
      • Plasma half-life – 15 to 30 hrs
      • Phenobarbitone, carbamazepine and phenytoin – reduces half life
      • Valproate – increases plasma concentration but its concentration reduces
      • Together with Carbamazepine – increase in 10,11-epoxide and toxicity
    • Uses: Monotherapy and add on therapy in simple partial and secondarily generalized seizures
  • Topiramate
    • Sulfamate substituted monosaccharide
    • Pharmacological effects and MOA:
      • Broad spectrum antiseizure drug
      • Carbonic anhydrase inhibitor
      • Antiseizure activity against PTZ, ME seizure and partial and secondarily generalized tonic-clonic kindling
      • Multiple actions – Na+ channel, K+ channel, GABA A , AMPA-kainate subtypes of glutamate
    • Pharmacokinetics:
      • Rapidly absorbed orally, 10-20% bound to plasma protein, excreted unchanged in urine
      • Metabolized by hydroxylation, glucoronidation and hydrolysis
      • Reduction in estradiol level
  • Major Drug Interactions
    • Phenytoin:
      • With P.barbitone – unpredictable overall reaction
      • With Carbamazepine – increases each other`s metabolism
      • With Valproate – displaces phenytoin from protein binding
      • Mainly significant interactions are due to displacement of protein binding - sulfonamides
    • Carbamazepine:
      • Increase in metabolism of other drugs like primidone, phenytoin, ethosuximide, valproic acid, and clonazepam
      • Phenobarbitone and Phenytoin increases its metabolism
      • Significant interactions are due to enzyme induction
  • Major Drug Interactions – contd.
    • Valproate:
      • Due to Protein binding and inhibition of metabolism
      • Phenytoin is displaced from binding
      • Inhibits metabolism of phenobarbitone, phenytoin and carbamazepine
    • Ethosuximide:
      • Valproate inhibits metabolism and clearance
  • Other uses of AEDs:
    • Gabapentin, carbamazepine — neuropathic pain
    • Lamotrogine, carbamazepine — bipolar disorder
    • Valproate, topirimate, gabapentin — migraine
    • Diazepam – Tetanus, eeclampsia and convulsant drug poisoning
  • Treatment of Epilepsies
    • Aim of the treatment:
      • Control and prevent all seizure activity (seizure - freedom and improvement in quality of life!)
      • To search the cause of epilepsy
      • Attempts to remove the causes
      • Symptomatic treatment with antiepileptic drugs
      • To consider status epilepticus as medical emergency and treat efficiently and promptly
    • Choice of Drugs: According to the seizure types.
  • Treatment of Epilepsies – Drug choices - Diazepam rectal 0.5mg/kg Febrile convulsions Phenytoin IV Phosphenytoin IV Diazepam Lorazepam Status epilepticus Lamotrigine Topiramate Valproate Myoclonic Gabapentin Lamotrigine Phenytoin, Carbamazepine and Valproate Complex partial seizure with or without generalization Ethosuximide Valproate Absence seizure Phenobarbitone and Valproate Carbamazepine, Phenytoin and Valproic acid Generalized tonic-clonic or simple partial seizure 2 nd choice 1 st choice Seizure types
  • Treatment of Epilepsies – contd.
    • 3. Initiation of treatment:
      • Initiate therapy even if it is isolated tonic-clonic seizure with family history of seizure, abnormal neurological examination, abnormal EEG and an abnormal MRI
      • Treat with monotherapy
      • Substitute another drug if fails
      • Combination therapy – only when all monotherapy fail
      • Therapeutic monitoring of drugs – dose adjustments
  • Treatment of Epilepsies – contd.
    • 4. Seizure diary
    • Withdrawal of drugs:
      • Gradual withdrawal
      • Prolong therapy – life long/3yrs after last seizure
      • Withdrawal – childhood epilepsy, absence of family history, primarily generalized tonic-clonic seizure and normal EEG
  • Treatment of Epilepsies – contd.
    • Antiepileptics and pregnancy
      • Drugs should not be stopped if conceive – status epilepticus
      • Fits during pregnancy – birth defects, mental retardation etc.
      • Folic acid and vit.K supplementation
    • Care during attacks: tonic-clonic seizures
    • Surgical removal
  • Generalized Onset Seizures
    • Tonic-clonic, myoclonic, and absence seizures: 1st line drug is usually valproate
    • Generalized seizures: Phenytoin and carbamazepine are effective on tonic-clonic seizures but not other types of seizures
    • Absence seizures: Valproate and ethosuximide are equally effective in children, but only valproate protects against the tonic-clonic seizures that sometimes develop.
    • Risk of hepatoxicity with valproate—should not be used in children under 2
  • Partial Onset Seizures
    • Without generalization
      • Phenytoin and carbamazepine may be slightly more effective
    • With secondary generalization
      • First-line drugs are carbamazepine and phenytoin (equally effective)
      • Valproate, phenobarbital, and primidone are also usually effective
    • Phenytoin and carbamazepine can be used together (but both are enzyme inducers)
    • Adjunctive (add-on) therapy: newer drugs felbamate, gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate, and zonisamide
    • Phenytoin and carbamazepine failure: Lamotrigine, oxcarbazepine, felbamate approved for monotherapy –
    • Refractory partial seizures: Topirimate can be effective.
    Partial Onset Seizures—New Drugs
  • Status Epilepticus
    • Defn.: Continuous seizure activity for more than 30 minutes, or 2 or more seizures without recovery of consciousness. Recurrent tonic-clonic convulsions without recovery in between
    • Goal of therapy: rapid termination of seizure activity – more difficult to control – permanent brain damage
    • Prompt treatment with effective Drugs
    • Attention to hypoventilation and hypotension
    • Treatment is IV only
  • Status Epilepticus – contd.
    • Diazepam 10mg IV bolus injection (2mg/min)
      • Fractional dose at every 10 min. or titrated dose by slow infusion
      • Lorazepam: 0.1mg/kg
    • Followed by Phenobarbitone IM/IV (100-200mg) or Phenytoin slow IV in saline (25-50mg/min)
    • Resistant cases (refractory): IV anaesthetics
    • General supportive measures
  • Attentions
    • Selection of an appropriate antiseizure agent
    • Use of single drug
    • Withdrawal
    • Toxicity
    • Fetal malformations
  • Thank You