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Anticonvulsants


=Types of epileptic seizures and Clinical Manifestations 1.) Partial seizures -involve one side of the brain at onset A.)Simple partial seizure- pt. is conscious, limited to certain muscles or, specific sensory changes. B.)Complex partial seizure- pt. is conscious and impaired, experiences automatism (involuntary, and repetitive movements), autonomic dysregulation, psychotic like behavior (pt. may see aura beforehand). C.) Partial seizures that evolve to general seizures; see generalized seizures for clinical manifestations. 2.) Generalized seizures- involves both sides of the brain at onset A.)Tonic -clonic seizure (grand mal)- pt. is unconscious, loss of postural tone, tonic clonic contraction of skeletal muscles bilaterally (pt. may see aura). B.) Absent seizure (petit mal)- pt. is conscious but impaired (very short 5-10 sec.), most common in children, postural muscles not impaired, pt. experiences minor muscular twitching (eyelids or face). C.) Myoclonic seizures- pt. experiences sudden, brief contractions of individual muscles or groups producing shock like spasms in muscles of the face, trunk, and extremities. D.) Clonic seizures- pt. experiences repetitive clonic jerking, that can alternate between opposing muscles. E.)Tonic seizures- pt. experiences violent simultaneous muscular contractions (flexors and extensors), while limbs are in a strained position. F.) Atonic seizures (astatic)- pt. experiences sudden loss of muscle tone and consciousness (pt. sustain fall injuries). 3.) Unclassified seizures- cannot be classified because of insufficient data or atypical pattern of seizure -Anticonvulsants are CNS drugs -CNS (Depressed function, tolerance to the sedative effect , impaired learning & cognitive abilities) Gastrointestinal tract (Anorexia, Nausea, Vomiting) Dermatologic (Rash, Stevens-Johnson syndrome, Exfoliative dermatitis, Erythema multiforme, Drug induced systemic lupus erythematosus) Withdrawal- Abrupt withdrawal can cause seizures Categories of Anticonvulsant Drugs:

  1. Hydantions:
-Phenytoin (Dilantin) -Uses- Tonic -clonic seizures and partial seizures, Trigeminal neuralgia, Antiarrhythmic -Adverse Reactions- Gastrointestinal, CNS (Mental confusion, Ataxia, Slurred speech, Blurred vision, Dizziness, Insomnia)Dermatologic (Rash, Exfoliative dermatitis, Lupus erythematosus, Stevens-Johnson syndrome, Irreversible hypertrichosis , Hirsutism) Vitamin deficiency (Vitamin D and folate, Interferes with vitamin D metabolism) Congenital abnormalities, Gingival enlargement. When given intravenously- .thrombophlebitis, arrythemia, hypotension. Absorbtion- GI tract
  • Babiturates:
    (Phenobarbital)
    -Uses: Treatment of tonic-clonic seizures and partial seizures
    -Adverse Reactions- Sedation, Dermatologic (Exfoliative dermatitis, Erythema multiforme, Stevens-Johnson syndrome)

  • Carbamazepine:
    (Tegretol)
    -Other Uses: Trigeminal neuralgia, bipolar depression
    -Pharmacologic effects- Anticonvulsant, Anticholinergic , Antidepressant, Sedative, Muscle relaxant, Antiarrhythmic , Antidiuretic , Neuromuscular transmission inhibitory actions
    -Mechanism of action- Blocks sodium channels therefore blocks propagation of nerve impulses (LA). Also, inhibits high-frequency repetitive firing of neurons
    -Adverse reactions- CNS depression (Dizziness, Headaches, Vertigo, Nystagmus, Drowiness, Speech disturbances, Fatigue, Ataxia, Confusion) Gastrointestional tract (Vomiting, Nausea, Abdominal pain, Diarrhea, Constipation, Anorexia) Hematologic (Aplastic anemia, agranulocytosis , thrombocytopenia and leucopenia) Dermatologic (Rashes, Urticaria, Photosensitivity reactions, Altered skin pigmentation, Erythema multiforme, erythema nodosum, and systemic lupus erythematous) Oral (Xerostomia, Glossitis , Stomatitis) Other (Congestive heart failure, Abnormal liver function )

  • Valproic Acid:
    (dipropylacetic acid)

    -Pharmacologic effects-Anticonvulsant (used especially for abscence seizures), Antidepressant (used in bi-polar disorder), and reduction of migrane headaches.
    -Absorbtion: GI tract
    -Adverse effects: Appetite distubances, indigestion, heartburn, nausea, and weight change.
  • Succinimides:
    (Ethosuximide, methsuximide)

    -Pharmacologic effects: Anticonvulsant (Abssence seizures)
    -Mechanism of action: Inhibiion of low threshold Ca+ channels (not fully understood)
    -Absorption: GI tract, metabolized in liver, excreted: urine
    -Adverse effects: gastrointestinal distress, headache, dizziness, and skin rash. Potential fatal bone marrow depression.
    Patient with hematopoietic toxicity Adverse effects: fever, sore throat and coagulopathy.

    Drugs that affect the GABA transmission: Such as: Benzodiazepines, Vigabatrin, Tiagabine Neurosteriods, and GABAmimetic agents
    Miscellaneious Anticonvulsants: Such as Gagapentin, Febamate, Lamotrigine, Carbonic Anhydrase Inhibitors, Topiramate, Zonisamide, Levetiracetam, Magnesium Salts
    .



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  • Partial seizures:
    • Simple partial:
      • carbamazepine (Tegretol)
      • phenytoin (Dilantin)
      • phenobarbital (Luminal)
      • primidone (Mysoline)
      • valproic acid (Depakene, Depakote)
      • gabapentin (Neurontin)
      • lamotrigine (Lamictal)
    • Complex partial
      • carbamazepine (Tegretol)
      • phenobarbital (Luminal)
      • phenytoin (Dilantin)
      • primidone (Mysoline)
      • valproic acid (Depakene, Depakote)
      • lamotrigine (Lamictal)
    • Partial is secondarily generalized tonic-clonic seizures
      • carbamazepine (Tegretol)
      • phenobarbital (Luminal)
      • phenytoin (Dilantin)
      • primidone (Mysoline)
      • valproic acid (Depakene, Depakote)
      • gabapentin (Neurontin)
      • lamotrigine (Lamictal)
  • Antiepileptic drugs side effect profiles
    • Most antiseizure medications tend to be sedating, with drowsiness observed.
    • Often sedative effect diminish over time.
    • Other common side effects are referable to the gastrointestinal tract.
    • For most antiseizure agents, there are low frequency, but serious side effects.
    • Primidone (Mysoline)/phenobarbital (Luminal) side effects:
      • sedation
      • vertigo, nausea, vomiting, ataxia, nystagmus, diplopia. Feeling of intoxication immediately after ingestion.
      • Serious adverse effects are uncommon but include rash, leukopenia, thrombocytopenia, lupus, and lymphadenopathy.
      • Megaloblastic anemia which response to folate
      • Osteomalacia (response to high dose vitamin D)
      • Hypoprothrombinemia with hemorrhage in newborns of primidone (Mysoline)-treated mothers (vitamin K is effective for treatment or prophylaxis)
    • Carbamazepine (Tegretol):
      • Acute intoxication: stupor, coma, hyperirritability, convulsions, and respiratory depression
      • Long-term: drowsiness, vertigo, blurred vision
      • Serious hematological toxicity: aplastic anemia, agranulocytosis
    • Ethosuximide (Zarontin):
      • The most common complaint is gastrointestinal upset, including nausea, vomiting and anorexia, and CNS effects including drowsiness, euphoria, headache and hiccough. Some tolerance of these effects may develop.
      • Hematological disturbances include: leukopenia, thrombocytopenia and aplastic anemia. Bone marrow depression may be fatal, although very infrequently so.
      • Skin reactions, including Stevens-Johnson syndrome and exfoliative dermatitis have been reported




Types of seizures

Those that respond to pharmacotherapy:

Tonic-clonic seizures: include all the body, muscle rigidity, violent muscle contractions, and loss of consciousness.
Absence seizures: “petite mal” usually in children, it temporary disturbance of brain function, abrupt short-term lack of conscious activity (“absence”).
Status epilepticus: an acute or prolonged epileptic crisis there is a change in mental status.

Those that do not respond to pharmacotherapy:

Myoclonic seizures: are abnormal bilateral movements of the body, they are brief jerking movements that are either subtle or very dramatic.
Atonic seizures: usually begin in childhood, it is a brief lapse in muscle tone and many fall, sometimes called drop attacks, or drop seizures.