Convulsion abnormal discharge motor neurons, contrac and relax,

1

• Convulsion abnormal discharge motor neurons,
  contrac and relax,
• Can NOT have convulsion w/o seizure
• Seizure orig in cortex, might or might NOT have
  motor SX
• Can have seizure w/o convulsions
• Epilepsy grp disorders
• Some form abnormal mvt, might or might NOT
  disturbance or loss consciousness
• Class Seizures
• Partial seizures most common 80
• Simple partial no impairment or LOC
• Complex partial impaired, or LOC
• Sensory illusions, hallucinations, pt wont
  remember event
• LOC Loss of Consciousness

2

• Gen convulsive seizures LOC usually
• Tonic rigid extension
• Myoclonic sudden contraction 1 or more mm
• Tonic-clonic grand mal, tonic ext followed by
  clunus
• Can become STATUS EPILEPTICUS medical
  emergency, one episode after another
• Infantile spasms short burst flex arms and
  trunk w ext legs
• Poor prognosis, MR
• Hypsarrhythmia chaotic EEG pattern
• Febrile seizures short bursts tonic-clonic,
  benign
• 3 mos to 5 yrs
• Gen non-convulsive seizures
• Absence petit mal pt may not be aware,
• no motor component, hard to TX, bilateral
• Hallmark bilateral spike wave activity at rate
  of 3 hz/sec, occ bt thalamus and cortex
• Atonic brief LOC drop attacks (not shop
  attacks)
• Most often in kids

3
Pathophysiology of epilepsy

• 2 main options
• Loss of GABAergic Fxn
• GABA tonic inhibitory control epileptics have
  INCREASED corticol activity
• A) Rxs that block GABA-A cause seizures
• B) Rxs that ? GABA trans have anti-convul efx
• BARBS, BZs
• Increased excitatory transmission
• Glu levels ? in some epileptics
• NMDA Glu receptor linked to ion channel that when
  stimulated, ?s gCa into cells
• A) too much Ca in cell cell death
• XS stim of NMDA R convulsions, death
• Drugs that block NMDA good anti-convulsants,
  eg Felbamate toxic, limited

4

• RXs used to TX Epilepsies
• Barbituates
• All have anticonvulsant activity, but many too
  sedating
• Phenobarbital often used in initial TX
  children, infants
• MOA binds to GABA-A??gCl- conductancehyperpolari
  zation
• Puts neuron to sleep, or whole brain
• BARBS keep channel open longer, BZs frequency
• Blox AMPA R (one of Glu Rs)
• Net Effect raise seizure level
• SEFX sedation, enz indxn, ?resp, hangover effect
• TX OD by making urine more basic
• Pentobarbital if strong sedative desired
• Mephobarbital
• Demethylated in liver to phenobarbital
• Do not use if LIVER DZ
• Primidone metab to 2 active metabolites
• Phenobarbital 5 active metabolite
• PEMA 35-40 active metabolite

5
BZs

• MOA ?gCl- by binding to interface bt alpha and
  beta subunits of GABA-A R complex gamma subunit
  required
• Net effect raise threshold
• Clonazepam long acting oral prep
• Tolerance develops sedation limiting factor
• Clorazepate ADJUNCT, Sedating, oral
• Diazepam - ADJUNCT,
• oral, IV or rectal for Status Epilepticus
• High lipid solub into and out of brain quickly -
  recurrences
• Lorazepam
• IV for status epilepticus
• Less lipid soluble longer acting, maintains
  control longer

6

• Phenytoin Orig drug (HYDANTOINS)
• Anti-epileptic mech blox VS Na channels
• ? Na influx ? no depolar inside stays negative
• IV status epilepticus
• IV Digoxin induced arrythmias
• Antiarrhytmic mechs
• Blox Na channels
• Inhibiting Ca influx
• Do not use if SINUS BRADYCARDIA
• OR 2ND 3RD DEGREE HEART BLOCK
• Major SEFX
• CNS - ? cerebellar and vestibular systems
• HIRSUTISM hairy lady
• GINGIVAL HEPERPLASIA altered collagen metab
• NV common, take with food or milk
• ENZ INDXN - ? metab other Rxs, NOT own
• P450 is family of enzymes, phen induces different
  enzyme
• Metab by hydroxylation saturation easy TOXIC
• Preg Category D D for DEFECT in fetus cleft
  lip, congenital heart dz, mental deficiencies

7

• FOSPHENYTOIN
• More soluble form of PHENYTOIN, IM use
• Pro-drug dose expressed as phenytoin equivs bc
  metab to phenytoin
• Use IV for STATUS EPILEPTICUS, non-ER main TX
• Give slowly to avoid arrhythmias

8

• Succinimides
• ETHOSUXIMIDE DOC for Absence
• MOA Blox T currents low thresh Ca currents
• SEFX NV, gastric pain, 1 case Steven-Johnsons
• Methsuximide more toxic
• MISC
• CARBAMAZEPINE
• Structurally related to TCAs
• MECH Blox VS Na channels
• SEFX most common diplopia ataxia
• Most serious aplastic anemia agranulocytosis
• ENZ INDXN ? own metab 3-4X/day dose
• Other uses
• Trigeminal neuralgiatic douloureux - V
• Glossopharyngeal neuralgia - IX
• Bipolar affective disorder Mech blox uptake NE
• CXN MAO-I NE gets too high - vasoconstriction

9

• OXCARBAZEPINE
• Pro-Drug monohydroxy deriv active form
• Mech and uses similar to CARBAMAZEPINE, less
  toxic, less ENZ INDXN
• ? metab oral contraceptives
• Unlabeled uses ATYPICAL PANIC DISORDER
• VALPROIC ACID DIVALPROEX
• Mech sim to carbamazepine
• Mech sim to ethosuximide
• Uses 2nd choice for ABSENCE (1st Ethosuximide)
• Manic phase bipolar disorder
• Prophylaxis of migraine
• SEFX NV most common, sed, ataxia, tremors
  SERIOUS hepatotoxic 50 deaths
• Pregnancy D Defect in fetus, ? spina bifida, CV,
  orofacial and digital abnormalities

10

• TRIMETHADIONE Absence,
• SEFX blood dyscrasias, hep, nephrosis
• MOA Inhibits T Currents
• LAMOTRIGINE weak antifolate
• Mech
• Blox Na channels
• ? release Glutamate
• Might inhibit T currents
• Uses
• TX Lennox-gastaut Syn dev in epil 1-8 yrs old
• Mult form seizures, delayed dev, behav dist, MR,
  caused by brain injury, brain, infxn, genetic,
  dev malform, etc
• SEFX Steven-Johnson Syndrome
• Life-threat rashes higher in kids, not approved
  for kids
• D/C in ANYONE who develops RASH, unless not RX
  related
• GABAPENTIN structurally similar to GABA
• USE adjunct in Partial tonic-clonic
• MOA ? GABA release
• Other uses
• neuropathic pain

11

• TIAGABINE adjunct for partial seizures
• MOA ? GABA uptake
• CXN in Absence
• facil spike-wave discharge in animals
• TOPIRAMATE monosaccharide
• MOA a) blox Na channels
• B) ? GABA transmission
• C) blox AMPA Glut receptor
• Uses partial/tonic-clonic
• Lennox-gastaut syndrome
• Wests syndromeencephalopathy in infants
  infantile spams, poor psychomotor devel
  hyperarrhthymia
• SEFX somnolence, dizzy, ataxia, psychomotor
  slowing
• FELBAMATE struc sim to MEPROBAMATE
• Hi rates aplastic anemia severe hepatitis,
  limited to severe and refractory cases of PARTIAL
  SEIZURES, partial generalized seizures assoc
  with LENNOX-GASTUAT Syndrome
• MOA blox glycine site R must bind glycine for
  Glu to activate NMDA stype Glu Rs

12

• Zonisamide Sulfonamide
• MOA
• Blox Na channels
• Blox T currents Absence
• CXN ? risk oligohidrosis, hyperthermia in kids
• LEVETIRACETAM Adjunct, MOA UK
• Magnesium Sulfate
• depresses all excitable tissues
• USE seizures assoc with pre-eclempsia, eclempsia
  pregnancy disorders
• Pre-eclempsia hyperTN, edema, proteinuria
• Eclempsia toxemia in pregnancy convulsions,
  death
• MOA competes w Ca in mm and nn to
• ? release Ach _at_ NMJ mm cant contract
• Blox Ca in contraction
• ACTH infantile spasms
• Hi doses blox GABA metab Inhibits GABA-Tase
• Acetazolamide carbonic anhydrase inhibitor
• Catamenial epilep seizures in menses
• Acidosis triggers GABA release