SEIZURES:

Characterized by: a synchronized, high frequency of neuronal firing. Variety of form.

 Partial seizure: affect one area of the brain, most commonly the mesial temporal lobe. Often preceded by seizures aura; can secondarily generalized.

.Simple Partial: consciousness intact, motor, sensory, autonomic, and psychic.

.Complex Partial: impaired consciousness.

Generalized seizures: Diffuse.

.Absence: petit mal, no postictal confusion, blank stare.

.Myoclonic: quick, repetitive jerks.

.Tonic-Clonic: grand mal, alternating stiffening and movement.

.Tonic: stiffening.

.Atonic: drop seizures, fall to floor; commonly mistaken for fainting.

Epilepsy: a disorder of recurrent seizures.

Febrile seizures are not epilepsy.

Causes of seizure by age:

Children: genetic, infection (febrile), trauma, congenitale, and metabolic.

Adults: tumor, trauma, stroke, and infection.

Elderly: stroke, tumor, trauma, metabolic, and infection.

NEUROLOGY-PHARMACOLOGY.

PHENYTOIN:

Uses: First line in the Tonic-Clonic seizures, use in Partial seizures, and in the prophylaxis for Status convulsive.

Also is a class I B antiarrhythmic.

Mechanism: use-dependent blockade of Na channels; increase of refractory period; inhibition of glutamate release from excitatory presynaptic neuron.

Toxicities: nystagmus, ataxia, diplopia, sedation, SLE-like syndrome, induction of cytochrome P-450. Chronic use produces gingival hyperplasia in children, peripheral neuropathy, hirsutism, megaloblastic anemia due to decrease of folate absorption. Teratogenic= fetal hydantoin syndrome.

Doses: Adults should be given a loading dose of approximately 18mg/kg/24hr IV at a rate no greater than 50mg/min. the loading dose should be continued 24 hrs after a maintenance dose of 5-7 mg/kg/day IV divided into 3 or 4 administrations.

            Infants and young children: loading dose of 15 -20 mg/kg usually produce therapeutic plasma concentrations (10-20mg/ml). The injection speed should be less than 1-3mg/kg/min, does not exceed 50 mg per minute. The maintenance dose will be 5mg/kg/24h.

BARBITURATES: Phenobarbital, Pentobarbital, Thiopental, and Secobarbital.

Uses: Sedative for anxiety, seizures, insomnia, and induction of anesthesia (thiopental).

Phenobarbital-used in the Partial seizures, and Tonic-Clonic Generalized, it is the first line use in pregnant and children.

Mechanism: Facilitate GABA action by increase duration of Cl channel opening, thus decrease neuron firing.

Toxicities: dependence, additive CNS depression effects with alcohol, respiratory or cardiovascular depression, which can lead to death, drug interaction owing to induction of liver microsomal enzymes (cytochrome P-450).

Contraindicated in porphyria.

Doses: Paraenteral: Adults 100-320 mg IM or diluted, slow IV, repeat if necessary to max. 600 mg/24h. Children slow IV diluted: loading single dose 10-20mg/kg, maintenance: 1-6mg/kg/day.

           Oral: 1-3 mg/kg/24h in 2 divided doses, then adapt to individualized maintenance dose. Child 1-6mg/kg/24h in 1-2 doses.

BENZODIAZEPINE: Diazepam, Lorazepam, Triazolam, Temazepam, Oxazepam, Midazolam, Chlordiazepoxide, and Alprazolam.

Uses: Diazepam/Lorazepam used as first line in status convulsive. Also used for seizure s of eclampsia (the first line treat is MgSO4).

   Other uses anxiety, spasticity, detoxification especially alcohol withdrawal-DTs-, night terrors, sleepwalking, general anesthesia (amnesia, muscle relaxation), hypnotic (insomnia).

Mechanism: facilitate GABA action by increase frequency of Cl channel opening. Decrease REM sleep. Most have long half-lives and active metabolites.

Toxicities: Dependence, additive CNS depression effects with alcohol. Less risk of respiratory depression and coma than barbiturates.

Treat overdose with Flumazenil (competitive antagonist at GABA benzodiazepine receptor).

Doses: Diazepam adults oral 2-10 mg, 2-4 times/day, children> 6 months: 0, 1-0,3mg/kg/day. Elderly, IH and IR: 2-2,5mg 1 or 2 times/day increased gradually as needed and tolerated. Febrile seizures in children>1 year, and epileptic seizures: rectal 0.2 to 5 mg/kg/day. Adults 5-10 mg/day. Elderly, debilitated, IH: 5mg/day.

Status epilecticus: paraenteral 0.15 to 0.25 mg/kg IV repeated at intervals of 10-15 min, if necessary. Max 3mg/kg/day.

CARBAMAZEPINE:

Uses: First line use in Tonic-Clonic generalized seizures, used in Partial seizures, and it is the first line in trigeminal neuralgia treatment.

Mechanism: Increase Na channel inactivation.

Toxicities: Diplopia, ataxia, blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of cytochrome P-450, SIADH, Steven-Johnson syndrome.

Doses: Oral Adults: initial 100-200 mg 1 or 2 times/day, increasing slowly up 400mg 2-3 times/day. Oral children <4 years, initially 20-60mg/day increased from 20-60 mg every 2 day, > 4years, initially 100mg/day increasing to 100 mg at weekly intervals, maintenance 10-20mg/kg/day in divided doses.

ETHOSUXIMIDE:

Uses: First line in Absence (generalized seizures).

Mechanism: block thalamic T-type Ca channels.

Toxicities: GI distress, fatigue, headache, Urticaria, SJ syndrome.

Doses: 3-6yrs=250mg/day. >6yrs=500mg/day. Dosage should be increased by small increments (250mg every 4-7 days). Optimal dose is 20mg/kg/day.

VALPROIC ACID:

Uses: first line in Tonic-Clonic seizures, in used in the Partial seizures, and absence. Also used for Myoclonic seizures.

Mechanism: increase Na channel inactivation, and increase GABA concentration.

Toxicities: GI distress, fatigue, headache, Urticaria, and SJ syndrome.

Doses: babies and children: 30mg/kg in 1-2 doses. >12 yrs and adults: 20-30 mg/kg. >65yrs: 15-20mg/kg. Establishment of tto: no treatment with other AEDs, increasing every 4-7 day until optimal doses or every day for crono form, treated with other antiepileptic, 2-8 wks progressively, decreasing 1/3 or ¼ dose of antiepileptic part in use.

IV adults and children >12: with tto oral establishment in perfusate continuous, 4-6h after oral intake. Following the same dosing, regimen established, to the rhythm of 0,5-1mg/kg/h. remaining patients, inj. Slow(3-5min): 15mg/kg continuous after 30 min with perfusate, continuous at 1mg/kg/h up to max. 25mg/kg/h. infants and children: 20-30mg/kg. Elderly: 15-20mg /kg. Switch to oral as soon as possible.

LAMOTRIGINE:

Uses: Partial seizures, and Tonic-Clonic seizures.

Mechanism: block voltage-gated Na channels.

Toxicities: SJ syndrome.

GABAPENTIN:

Uses: Partial and Tonic-Clonic seizures. Also used for peripheral neuropathy and bipolar disorders.

Mechanism: designed as GABA analog, but primarily inhibit HVA Ca channels.

Toxicities: sedation, ataxia.

Doses: ads and children >12 yrs: start with 900mg/day in 3 doses, maintenance, up to 3.600mg/day in 3 doses. In children >6 yrs: in combination therapy in partial seizures with or without secondary generalization, effective dose 25-35mg/kg/day in 3 doses.

TOPIRAMATE:

Uses: Partial and Tonic-Clonic seizures.

Mechanism: block Na channel, increase GABA action.

Toxicities: sedation, mental dulling, kidney stones, and weight loss.

Doses: ads 25 mg/night, 1 week, every 1-2 wk increase dose 25050mg/day in 2 divided doses. Maintenance 100-200mg/day, max 500mg/day divided in 2 doses. Children>6 years 0.5-1 mg/kg/night, 1 wk, every 1-2 wks increase dose by 0.5-1mg/kg/day in 2 doses, maintenance 100mg/day.

References:
First aid for USMLE step 1, 2011
Harrison’ online. Principios de Medicina Interna. 18 ed.
Manual Merck. 10 ed.
Cliniguia. Actualización de Diagnostico y Tratamientos.2007
Guía de Actuación de Urgencias. Vázquez Lima, M.J. Casal Codesio, J.R. 2010. 3ra ed.