Exam 3 neuro therapeutics -Seizure Flashcards
Which of the following occurs during the hyper-polarization phase of a PDS (Paroxysmal depolarizing shift)?
influx of Cl- ions resulting from GABAa receptor activation
What are the pre and post synaptic targets at the excitatory synapses (glutamatergic)?
Presynaptic- Na and Ca Channels
Postsynapatic- NMDA and AMPA receptors
What are the pre and post synaptic targets at the inhibitory synapses (GABAergic)?
Presynaptic- GABA transporter (GAT-1); GABA transaminase (GABA-T)
Postsynaptic- GABAa receptors; GABAb receptors
What drugs have the mechanism of action to decrease Na influx, prolong inactivation of Na channels?
Phenytoin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine, valproate
-act by binding and stabilizing the inactivated state of Na channels
What are special considerations with PK of phenytoin?
-elimination kinetics are dose-dependent which leads to non-linear pharmacokinetics
-easily displaced by other drugs leading to higher concentrations in the blood
-induces CYP450 enzymes
What medications enhance GABA-mediated neuronal inhibition (targets the GABAa post synaptic target)?
Barbituates (phenobarbital, primidone), benzodiazepines (diazepam, clonazepam)
Which medications enhance GABA-mediated neuronal inhibition (not at GABAa post synaptic target)?
Gabapentin, pregabalin, Vigabatrin (GABA-T), tiagabine (GAT-1)
Which medications antagonize of excitatory transmitters (glutamate): AMPA and NMDA?
Felbamate (NMDA) , topiramate (AMPA)
What is the MOA of ethosuximide?
blocks T-type Ca channels in thalamic neurons
-indicated for absence seizures
What is the MOA of Gabapentin and Pregabalin?
-increases GABA release, decreases presynpatic Ca influx releasing glutamate release
-increases Cl influx in postsynaptic neurons
What is the MOA of lamotrigine and Valproate?
-inhibits Na and voltage-gated Ca channels
What is the MOA of levetiracetam?
-binds the synaptic vesicular protein SV2A which interferes with synaptic vesicle release and neurotransmission & interferes with Ca entry through Ca channels and intraneuronal calcium signaling
What are some medications that can lower the seizure threshold at normal doses?
Bupropion, clozapine, theophylline, varenicline, phenothiazine antipsychotics, CNS stimulants (amphetamines)
What medications are given to patients in status epilepticus?
IV Lorazepam or IV Midazolam
What are second phase treatments for status epilepticus?
IV fosphenytoin, IV valproic acid, IV levetiracetam
*phenobarbital
What are third phase treatments for status epilepticus?
Anesthetic doses of either thiopental, midazolam, phenobarbital, propofol
What is the loading dose for phenytoin/fosphenytoin?
20 mg/kg IV
-up to 50mg/min for phenytoin
-up to 150mg/min for fosphenytoin
cardiac monitoring required -may also cause “purple glove syndrome”
What are the CYP 1A2 + 2C9 inducers?
carbamazepine, phenobarbital, phenytoin
What are the CYP 3A4 inducers?
LAMOTRIGINE, OXCARBAZEPINE, TOPIRAMATE
carbamazepine, phenobarbital, phenytoin
What is the dosing for Lamotrigine?
25 mg once daily x 14 days
50 mg once daily x 14 days
100 mg once daily x 7 days then, 200 mg
-inhibitors 1/2 dose (Valproate)
-inducers double dose (Carbamazepine, Phenytoin)
What is the estrogen and lamotrigine interaction?
-estrogen decreases lamotrigine concentrations by 50% and lamotrigine decreases estrogen concentrations
What electrolyte abnormalities are associated with Topiramate?
decreased sodium bicarbonate–leads to metabolic acidosis
nephrolithiasis
decreased sweating and heat intolerance
What electrolyte abnormalities are associated with Carbamazepine + derivatives?
hyponatremia, SIADH
What electrolyte abnormalities are associated with Phenytoin?
altered Vitamin D metabolism, decreased Ca concentrations–risk for osteoporosis
What labs should be ordered with Valproate?
-can cause thrombocytopenia
-monitor CBC/platelets
-can cause PCOS, weight gain, sedation
