Epilepsy and Sleep Flashcards
Topirimate
Use? Mechanism? Side Effects?
- tonic-clonic seizures
- simple and complex partial seizures
- migraine prevention
Mechanism:
- Blocks Na+ channels?
- increases GABA action?
- Blocks AMPA receptors, decreasing glutamic acid’s excitatory effects
- AMPA receptors are non-NMDA type ionotropic glutamate receptors that mediate fast synaptic transmissions in the CNS
- weak carbonic anhydrase inhibitor
Side Effects:
- Sedation
- Mental dulling
- Kidney stones
- Weight loss
- can interfere with OCPs at high doses
- Acute angle glaucoma
Valproic Acid
Use? Mechanism? Side Effects? Metabolism? Formula?
Use:
- tonic-clonic seizures
- absence seizures (2nd or third line)
- both simple and complex partial seizures
- Myoclonic seizures
- Bipolar disorder (mania)
- Migrane prophylaxis
Action:
- prevents the fast Na+ channel influx needed to trigger APs by keeping it in an inactivated state (similar to phenytoin), decreasing neuronal conduction
- Acts as an agonist in the GABAa receptor
- increases the GABA concentration in the CNS by inhibiting GABA transaminase
- blocks T-type Ca2+ channels
Side effects:
- GI distress
- rare but fatal hepatotoxicity (toxic metabolite)
- thrombocytopenia
- pancreatitis
- alopecia
- tremor
- weight gain
- teratogenic (spina bifida)
Contraindications:
- pregnancy = Neural tube defects in fetus\
- POLG mitochondrial disease
- Enzyme INHIBITOR (increases levels of other drugs)
Formula:
(Target total VPA lvl - current total VPA lvl) x(kg/Vd)
Vd: 0.1-0.3 (use 0.2)
Carbamazepine
Use? Mechanism? Side Effects?
Sodium channel blocker
Use:
- first line in treating/preventing both simple and complex partial seizures
- first line for trigeminal neuralgia
Action:
- (identical to phenytoin) prevents the fast Na+ channel influx needed to trigger APs, decreasing neuronal conduction
Side effects:
- CNS depression
- Diplopia
- Ataxia
- Blood discrasias (agranulocytosis, aplastic anemia)
- Liver toxicity
- exfoliative dermatitis
- Teratogenesis (cleft lip, spina bifida)
- Induction of cytochrome P-450
- SIADH and subsequent dilutional hypernatremia
- S-J Syndrome
- osteomalacia
- Can worsen some myoclonic epilepsies
Gabapentin and pregabalin
Use? Mechanism? Side Effects? Metabolism?
GABA Analogue
Use:
- both simple and complex partial seizures
- Can worsen generalized epilepsy and myoclonic seizures
- Peripheral neuropathy
- Postherpetic neuralgia
- migrane prophylaxis
- Bipolar disorder
Action:
- acts as a GABA analogue, inhibiting voltage-gated Ca2+ channels
Side effects:
- Sedation
- Ataxia
Metab
NOT AN INDUCER OR INHIBITOR
Gabapentin: Nonlinear absorption at higher doses, unlike pregabalin which is linear
Excreted without modification via kidneys
Lamotrigine
Use? Mechanism? Side Effects?
Use:
- absence (can rarely worsen)
- GTCs
MoA:
- Na channel antagonist
- Inhibits glutamate release
Side Effects:
- dizziness, blurred vision, diplopia, ataxia
- SJS - needs very long titration
- Can exacerbate some myoclonic epilepsies and rarely absence epilepsies
- Probably the safest in pregnancy but metabolism increases significantly
Metabolism:
- OCPs with estrogen (not progesterone only) increase metabolism, decrease levels
- VPA greatly reduces metabolism, greatly increases levels
- liver metab, renal excretion
GEFS+
- familial, often SCN1A (Na channel mutation)
- FS continue past upper limit of age, afebrile GTCs, otehr seizure types
Progressive Myoclonic Epilepsies (PMEs)
- lysosomal and/or mitochondrial
- progressive cognitive decline, epileptic and nonepileptic myoclonus, seizures, +/- ataxia and movement disorders
- Lafora body disease
- AR, EPM2A for Laforin. Age 12-17, above + transient blindness - Unverrict-Lundborg syndrome (Baltic myoclonic epilepsy)
- AR, EPM1 (codes for an apoptosis protein), mixed epilepsy and stimuli-sensitive myoclonus - neuronal ceroid lipofuscinosis
- myoclonic epilepsy with ragged red fibers (MERRF)
- mitochondrial, with typical co-symptoms. Associated with myopathy - Sialidosis Type 1 and 2
- AR, NEU1. Type 1 in adults, type 2 in kids.
Phenytoin and fosphenytoin
Use? Mechanism? Side effects? Metabolism? Load formula?
Sodium Channel Inactivator
Use:
- tonic-clonic seizures
- both simple and complex partial seizures
- prophylaxis against status epilepticus
Action:
- keeps axonal NA+ channels in inactive state, prevents the fast Na+ channel influx needed to trigger APs, decreasing neuronal conduction
Side effects:
- Nystagmus, diplopia
- CNS depression
- Sedation
- Ataxia
- S-J Syndrome
- Megaloblastic (decreased folate absorption) and aplastic anemia
- Teratogenesis (fetal hydantoin syndrome = cleft lip/palate)
- Hirusitism (chronic use)
- Coarse facial features (chronic use)
- Gingival hyperplasia (chronic use)
- Peripheral neuropathy (chronic use)
- Cerebellar atrophy (chronic use)
- SLE-like syndrome
- Lymphadenopathy (chronic use)
- Osteopenia/osteomalacia (decreased vitamin D)
- fosphey can be infused faster w/ less chance of purple hand syndrome, but is a prodrug so plasma concertation achieved at about same time
Metabolism
- Induction of cytochrome p-450
- Zero-order kinetics. Same amount is eliminated per unit time, regardless of plasma concentration. Can become toxic very quickly above 15microg/mL
- Highly protein bound
Load formula: (Target Total level - current total level) x (kg/Vd)
Vd is usually 0.5-1
Ethosuximide
Use? Mechanism? Side effects? Metabolism?
T-type Calcium Channel Blocker
Use:
- first line treatment for absence seizures
Action
- Blocks thalamic T-type Ca2+ channels in the thalamus
Side effects:
- Fatigue
- GI distress
- Headache
- Itching (urticaria [hives])
- Stevens-Johnson Syndrome (rare) = malaise and fever, followed by rapid onset of erythematous/pruritic macules (oral, ocular, genital) which progress to epidural necrosis and sloughing
Phenobarbital
Use? Mechanism? Side effects? Metabolism?
Barbiturate
Use:
- tonic-clonic seizures
- both simple and complex partial seizures
- first line in neonates
Action:
- increases GABAA action
Side Effects:
- Sedation
- Tolerance and dependence
- Hypnotic effects
- Cardiorespiratory depression
Metabolism:
- Induction of cytochrome P-450
hYPSARRYTHMIA
abnormal interictal high-amplitude slow waves with irregular spikes, with no consistent pattern or rhythm, which disappears ictally or during REM sleep
Vigabatrin
Use? Mechanism? Side effects?
Use:
- both simple and complex partial seizures, especially infantile spasms (first line in tuberous sclerosis). May have value as combo w/ steroids
Mechanism:
- increases [GABA] by irreversibly inhibiting GABA transaminase
Side Effects:
- Permanent peripheral vision loss via retinal toxicity (rare)
Oxcarbazepine
Use? Mechanism? Side effects? Metabolism?
Na channel blocker
Use:
Focal seizures
Mechanism:
Metabolism:
- structural derivative of carbamazepine, is a pro drug but does not become an epoxide like carbamazepine (active metabolite responsible for many side effects)
- less enzyme induction, no autoinduction
Diazepam and Lorazepam
Use? Mechanism? Side effects? Metabolism? Overdose treatment?
Benzodiazepines
Use:
- first line for acute treatment of status epilepticus
- Can also be used for preclampsia seizures (first line is MgSO4)
Mechanism:
- Potentiate GABAA receptor function, increasing frequency of Cl channel opening and encouraging inhibition of CNS neurons
Side effects:
- Sedation
- Tolerance
- Dependence
- Respiratory depression
- Decreased REM sleep
Metabolism:
Liver metabolism, renal excretion
Overdose Treatment:
Flumazenil
- competitive antagonist for GABA benzodiazepine receptor
Lacosamide
Use? Mechanism? Side effects? Metabolism?
Use:
- focal seizures (FDA approved for 17 and over)
MoA:
- selective enhancement of slow inactivation of voltage-dependent Na channels, inhibiting neuronal firing and stabilizing hyperexcitable membranes
- also interferes with CRMP-2, protein involved in neuronal differentiation and axonal guidance
Side effects:
- nausea
- dizziness
Metabolism:
- Renal excretion
- minimal drug interactions
