Anticonvulsants Flashcards
Epilepsy
a sudden, recurrent and transient disturbance of mental function or movements of the body that result from excessive discharging of groups of brain cells
imbalance between inhibitory and excitatory neurotransmission
disease of cerebral cortex, correlate with abnormal EEG activity
Idiopathic, Drug use, Hypoglycemia, Brain Injury, and Tumors
Types of Seizures
Convulsive - loss of consciousness, tonic, clonic, followed by confusion
Absence - brief abrupt loss of consciousness, early onset, staring/rapid eye blinking, distinct EEG
Myoclonic - short episodes of muscle contractions, more common on awakening, brief jerks of limbs
Atonic - loss of muscle tone, relatively short lived, can result in serious injuries
Febrile - common in young children with high fever, generalized tonic-clonic
Status Epilepticus - generalized tonic-clonic seizures so frequent that another seizure occurs before the patient returns to normal, Medical emergency because of hypoxia leading to brain damage
Treatment of Status Epilepticus
IV Lorazepam/ Diazepam/ Midazolam followed by IV phenytoin/fosphenytoin
If refractory give more phenytoin and BDZ
If still refractory: Phenobarbital, Pentobarbital, Midazolam, Propofol
Aura
Present in convulsive/partial
Absent in absence and myclonic
Postictus
period after the seizure, absent in absence
Phenytoin
Mechanism: inhibition of seizure spread, blockade of Ca2+ influx, enhancement of Cl- mediated IPSPs, suppression of epileptic focus, enhanced affinity for inactivated Na+ channels at more depolarized membrane potentials, enhancement of inhibitory surround via stimulation of Cl- mediated IPSPs
Use: drug of choice except in absence epilepsy and atonic seizures, highly effective in Tx of generalized tonic-clonic, partial, and status epilepticus
PO or IV for status epilepticus, IM, protein bound in plasma
Side Effects: Gingival hyperplasia, Hirsutism, Nystagmus, ataxia, vertigo, diplopia, Fetal abnormalities (cleft lip and palate), Cardiovascular collapse
Serious side effects requiring cessation: Rashes (Stevens-Johnson) Hematological reactions (leukopenia, megaloblastic anemia, thrombocytopenia, agranulocytosis, aplastic anemia)
Interactions: enhanced by Carbamazepine, decreased by microsomal enzymes, induces CYP3A4 (reduces levels of digoxin, steroids, and vit K)
Give vit K supplements to prevent prothrombinemia
Fosphenytoin
prodrug of phenytoin, water soluble, IM, better side effect profile
Carbamazepine
unknown mechanism
Use: second line in generalized tonic-clonic, complex partial, and trigeminal neuralgia
Ineffective in absence, not well tolerated in elderly
MAY MAKE MYOCLONIC WORSE
Metabolized to 10,11-epoxide
Autoinduction of metabolism (CYP1A2,2C,3A) Rate of metabolism increase in first 4-6 weeks
Side Effects: GI upset, Vertigo, diplopia, blurred vision, ataxia, heme disorders, hepatotoxicity
Phenobarbital
Mechanism: enhances GABA mediated Cl- flux that causes hyperpolarization, increases threshold for firing and inhibits spread of activity from focus
Use: generalized tonic-clonic, partial seizures, prophylaxis or Tx of febrile
Now typically only used in neonates
Side effects: Sedation, Tolerance, interfere with cognitive function, motor hyperactivity, irritability, decreased attention, mental slowing, addiction, withdrawal seizures, rashes, ataxia, nystagmus
Interactions: induces various CYPs, additive with other CNS depressants, increased by Valproic Acid
Primidone
metabolized in liver to phenobarbital and phenylehtylmalonamide
Side Effects: rashes, leukopenia, thrombocytopenia, SLE, CNS depression, ataxia, dizziness, drowsiness, cognitive impairment, depression of respiration
Valproic Acid
mechanism: interacts with GABA neurons, potentiating inhibitory effects, induces blockage of both Na+ and K+, inhibits T-type calcium channels
Use: absence seizures (refractory to ethosuximide) myoclonic seizures, reflex epilepsies, generalized tonic-clonic (as a combo), complex partial (as a combo), bipolar disorder
Low MW fatty acid, well absorbed from guy, PO, extended release, “sprinkles”
Side Effects: Alopecia, Nausea, Vomiting, CNS behavioral effects, ataxia, tremor, hepatic failure (in patients under 2!)
Avoid in patients with bleeding disorders because can cause a decrease in platelet and clotting function
Interactions: increases lamotrigine, phenobarbital, and primidone by increasing half life
Potentially increases available serum phenytoin levels by displacing phenytoin from plasma proteins and decreasing elimination
Do not use in women of child bearing age because it can cause birth defects (Spina bifida, ASD, cleft palate, Hypospadias Polydactyly, Craniosynostosis
Ethosuximide
Mechanism: blocks T-type Ca2+ channels of thalamic interneurons appears to interrupt neuronal hyper synchrony of thalamocortical pathway
Use: Absence Seizures
Side Effects: Nausea, vomiting, anorexia, drowsiness, lethargy, euphoria, dizziness, headache, hiccups, urticaria, Stevens-Johnson, Blood dyscrasia
Lorazepam (Ativan)
Prototype of Benzo: binds to binding site on GABAa receptor complex leading to allosteric change promoting GABA action, voltage-dependent blockage of Na+ channels, blocks neuronal Ca2+ channels
Clonazepam: inhibits spread - myoclonic and atonic
Clorazepate: metabolized to diazepam
Clonazepam and Diazepam: IV agent status epilepticus
Ethotoin
similar to phenytoin, short half life, fewer side effects, not as effective, rarely used
Use: tonic-clonic, partial seizures
Mephenytoin
only in refractory patients, decreased gingival hyperplasia, hirsutism
greater hepatotoxicity risk, blood disorders
