Anti-Convulsants (4-3-14) Flashcards
what mutations cause tonic-clonic?
Na channels
K channels
N cholinergic receptor
what mutations cause absence?
T-type VGCC
MELAS (Myoclonic seizure)
Mitochondrial Encephalopathy,
Lactic Acidosis,
Stroke
MERRF (Myoclonic seizure)
Myoclonic Epilepsy,
Ragged Red Fibers
involves anything concerning mitochondrial function: oxidative phosphorylation, ETC
Pentylenetetrazol toxicity? MOA?
used as a respiratory stimulant
high doses –> seizure
MOA = inhibit GABAa + opens Ca channels
drugs to counteract Pentylenetetrazol induced seizure?
- Ethosuximide (blocks Ca channels)
- Valproate (increases GABA, block Na channels)
- Benzodiazepines (Clonazepam)** = opens Cl channels
drugs to counteract Electroshock induced seizure (used to treat suicide)
- Phenytoin
- Carbamazepine
- Lamotrigine
note: Benzodiazepines NOT effective
length of Aura in Tonic-Clonic seizure? What happens during this time?
seconds
hallucination, dysmensia (Deja vu, Jamais vu), visceral aura
length of tonic state in Tonic-Clonic seizure?
< 1 min
body rigidity
gasp
length of clonic state in Tonic-Clonic seizure? What happens in this stage?
< 3min
jerking –> tongue biting
Autonomics = incontinence, tachycardia, HTN, hypersalivation, pupillary dilation
length of flaccid coma in Tonic-Clonic seizure?
hours
what seizure are you conscious for?
simple partial
what seizures are you unconscious for?
complex partial
generalized onset epilepsy
what is an interictal spike? What does it mean?
sharp EEG wave during symptom-less period
sign patient has epilepsy
benzodiazepine can block ____-induced seizures but not ____-induced seizures
blocks phenylenetetrazol-induced seizures
cannot block electroshock-induced seizures
what are the 3 major classes of anticonvulsants?
Na channel blockers
Ca channel blockers
GABA agonists
What drugs act on Na channels?
old = carbamazepine, phenytoin, valproic acid new = lamotrigine, topiramate, zonisamide
carbamazepine S/E
Agranulocytosis, aplastic anemia (low WBCs)
hepatoxicitiy
CNS effects: nystagmus, diplopia, tired, vertigo, headache
carbamazepine MOA
Na+-channel inactivation
Phenytoin MOA? What seizure can it NOT be used for?
Na+-channel inactivation
do not give for absence seizures, give ethosuximide
Fosphenytoin sodium. When do you use it?
water soluble, phosphatases convert to phenytoin.
I.V./I.M. administration, no phlebitis
arrhythmias.
Used in status epilepticus
Phenytoin S/E
painful phlebitis lymphadenopathy*** osteomalacia gingival hyperplasia excessive hair growth megaloblastic anemia (low folic acid) double vision increased hepatic degradation of glucocorticoids ataxia/nystagmus
Valproic Acid MOA
a. Prolongation of Na+-channel inactivation
b. more GABA synthesis, less GABA breakdown
c. T-type calcium channel blockade
Valproic Acid S/E
GI distress = Acute pancreatitis, Hepatotoxicity
Thrombocytopenia
Alopecia
Ataxia
Valproic Acid C/I
Pregnancy: folate antagonist –> NTD –> meningocele/spina bifida
Bleeding disorders
Hepatic disease
LAMOTRIGINE S/E
a. Dizziness
b. Diplopia
c. Sedation
d. Ataxia
e. Headache
f. Skin rash
g. Stevens-Johnson syndrome
GABA Agonists
Benzos: LORAZEPAM, DIAZEPAM, CLONAZEPAM
Barbituates: PHENOBARBITAL, PRIMIDONE
TOPIRIMATE
Synthesis of GABA is increased by:
VALPROIC ACID
VIGABATRIN
GABA release increased by:
GABAPENTIN
PREGABALIN
-do not bind to GABA receptors, but increase release
-block membrane insertion of a2d subunit of T-Type Ca channel in glutamatergic neurons
GABA transporter inhibitor
TIAGABINE
topirimate S/E
paresthesia
kidney stones (don’t give w/ CA inhibitors)
weight loss
fatigue, sedation, psychomotor slowing
glaucoma
speech or language problems
hypohidrosis (decreased sweating in response to stimuli)
phenobarbital S/E
sedation
respiratory depression
nystagmus, ataxia
megaloblastic anemia -> Rx = folate
primidone use? S/E?
primidone metabolized to phenobarbital!!!
effective in all seizures EXCEPT ABSENCE
same SE as phenobarbitol = sedation
drug for absence epilepsy
ethosuximide
Block T-type Voltage Gated Ca2+-channels
ethosuximide C/I?
hepatic dx
renal dx
ethosuximide adverse effects?
Bone marrow suppression can’t make as many blood cells = Leukopenia, Thrombocytopenia, Aplastic anemia
Skin reactions, SLE, urticaria, pruritus
Ataxia, lethargy, headache
Step 1 in treatment for status epilepticus
Coma Cocktail
- dextrose
- thiamine
- naloxone
Step 2 in treatment for status epilepticus
1) Benzos: Lorazepam, diazepam (not for longterm Rx)
2) fosphenytoin
3) now refractory status epilepticus –> phenobarbital
4) if still out, give general anesthesia
Rx for focal epilepsy
carbamazepine
lamotrigine
phenytoin
Rx for tonic-clonic
valproic acid
topiramate
lamotrigine
Rx for absence
ethosuximide*
valproic acid
Rx for myoclonic atypical absence atonic
valproic acid
topiramate
lamotrigine
what happens during simple partial seizure?
conscious* Motor signs Somatosensory or special sensory symptoms Autonomic signs Psychic symptoms
what happens during complex partial seizure?
Aura = epigastric, limb numbness, vertigo Automatisms = hand-waving, lip-smacking Other motor (tonic posturing)
