Exam 3 neuro therapeutics -Seizure

Question 1

Which of the following occurs during the hyper-polarization phase of a PDS (Paroxysmal depolarizing shift)?

Answer 1

influx of Cl- ions resulting from GABAa receptor activation

Question 2

What are the pre and post synaptic targets at the excitatory synapses (glutamatergic)?

Answer 2

Presynaptic- Na and Ca Channels
Postsynapatic- NMDA and AMPA receptors

Question 3

What are the pre and post synaptic targets at the inhibitory synapses (GABAergic)?

Answer 3

Presynaptic- GABA transporter (GAT-1); GABA transaminase (GABA-T)
Postsynaptic- GABAa receptors; GABAb receptors

Question 4

What drugs have the mechanism of action to decrease Na influx, prolong inactivation of Na channels?

Answer 4

Phenytoin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine, valproate
-act by binding and stabilizing the inactivated state of Na channels

Question 5

What are special considerations with PK of phenytoin?

Answer 5

-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

Question 6

What medications enhance GABA-mediated neuronal inhibition (targets the GABAa post synaptic target)?

Answer 6

Barbituates (phenobarbital, primidone), benzodiazepines (diazepam, clonazepam)

Question 7

Which medications enhance GABA-mediated neuronal inhibition (not at GABAa post synaptic target)?

Answer 7

Gabapentin, pregabalin, Vigabatrin (GABA-T), tiagabine (GAT-1)

Question 8

Which medications antagonize of excitatory transmitters (glutamate): AMPA and NMDA?

Answer 8

Felbamate (NMDA) , topiramate (AMPA)

Question 9

What is the MOA of ethosuximide?

Answer 9

blocks T-type Ca channels in thalamic neurons
-indicated for absence seizures

Question 10

What is the MOA of Gabapentin and Pregabalin?

Answer 10

-increases GABA release, decreases presynpatic Ca influx releasing glutamate release
-increases Cl influx in postsynaptic neurons

Question 11

What is the MOA of lamotrigine and Valproate?

Answer 11

-inhibits Na and voltage-gated Ca channels

Question 12

What is the MOA of levetiracetam?

Answer 12

-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

Question 13

What are some medications that can lower the seizure threshold at normal doses?

Answer 13

Bupropion, clozapine, theophylline, varenicline, phenothiazine antipsychotics, CNS stimulants (amphetamines)

Question 14

What medications are given to patients in status epilepticus?

Answer 14

IV Lorazepam or IV Midazolam

Question 15

What are second phase treatments for status epilepticus?

Answer 15

IV fosphenytoin, IV valproic acid, IV levetiracetam
*phenobarbital

Question 16

What are third phase treatments for status epilepticus?

Answer 16

Anesthetic doses of either thiopental, midazolam, phenobarbital, propofol

Question 17

What is the loading dose for phenytoin/fosphenytoin?

Answer 17

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”

Question 18

What are the CYP 1A2 + 2C9 inducers?

Answer 18

carbamazepine, phenobarbital, phenytoin

Question 19

What are the CYP 3A4 inducers?

Answer 19

LAMOTRIGINE, OXCARBAZEPINE, TOPIRAMATE
carbamazepine, phenobarbital, phenytoin

Question 20

What is the dosing for Lamotrigine?

Answer 20

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)

Question 21

What is the estrogen and lamotrigine interaction?

Answer 21

-estrogen decreases lamotrigine concentrations by 50% and lamotrigine decreases estrogen concentrations

Question 22

What electrolyte abnormalities are associated with Topiramate?

Answer 22

decreased sodium bicarbonate–leads to metabolic acidosis
nephrolithiasis
decreased sweating and heat intolerance

Question 23

What electrolyte abnormalities are associated with Carbamazepine + derivatives?

Answer 23

hyponatremia, SIADH

Question 24

What electrolyte abnormalities are associated with Phenytoin?

Answer 24

altered Vitamin D metabolism, decreased Ca concentrations–risk for osteoporosis

Question 25

What labs should be ordered with Valproate?

Answer 25

-can cause thrombocytopenia
-monitor CBC/platelets
-can cause PCOS, weight gain, sedation