Antiepileptic drugs Flashcards
What is MOA of Carbamazepine (Oxcarbazepine/Eslicarbazepine)?
Prolong fast inactivation state of Na ion channel on presynaptic glutamate neuron
What is MOA of Lamotrigine?
Prolong fast inactivation state of Na ion channel on presynaptic glutamate neuron
What is MOA of Phenytoin (Fosphenytoin - IV form)?
Prolong fast inactivation state of Na ion channel on presynaptic glutamate neuron
What is MOA of Topiramate?
- Prolong fast inactivation state of Na ion channel on presynaptic glutamate neuron
- Antagonize AMPA receptor in post synaptic glutamate neuron
- Binds post synaptic GABA (A) channel as agonist to promote Cl channel
What is MOA of valproic acid?
- Prolong fast inactivation state of Na ion channel on presynaptic glutamate neuron
- Inhibit GABA-T on presynaptic GABA neuron to promote GABA
- Stimulates GAD to promote the production of GABA from Glutamate
What is MOA of Lacosamide?
- Prolong fast inactivation state of Na ion channel on presynaptic glutamate neuron
- Prolong slow inactivation state of Na ion channel on presynaptic glutamate neuron
What is the action of AMPA receptor?
Ligand gated ion channels on post synaptic vesicle(Na+ and Ca2+). Glutamate binds and causes depolarization
What is the action of the NMDA receptor?
Ligand gated ion channels on post synaptic vesicle(Na+ and Ca2+). Glutamate binds and causes depolarization
What is the action of Perampanel?
AMPA receptor antagonist in postsynaptic glutamate transmission
perAMPAnel
What is the MOA of Felbamate?
NMDA receptor antagonist to prevent glutamate stimulation
What is hallmark of an Absence Seizure?
3Hz spike and wave activity in the thalamus mediated by T-Type Ca2+ channels
How are absence seizures controlled?
T-type Ca2+ channel antagonists:
1. Ethosuximide
- Zonisamide (also has other MOA)
What is the MOA of Levetiracetam?
Inhibition of synaptic vesicle 2A (SV2A) to inhibit glutamate release from vesicles from the presynaptic neuron
What is the MOA of Brivaracetam?
Inhibition of synaptic vesicle 2A (SV2A) to inhibit glutamate release from vesicles from the presynaptic neuron
What is the MOA of Gabapentin?
- Blocks alpha2delta subunit of T-type Ca2+ channels on the presynaptic neuron to reduce excitation and enhance inhibition
- Activate GAD to promote GABA production and enhance inhibition in the presynaptic GABA neuron
GABApentin
What is the action of Pregabalin
- Blocks alpha2delta subunit of T-type Ca2+ channels on the presynaptic Glutamate neuron to reduce excitation
- Activate GAD to promote GABA production and enhance inhibition in the presynaptic GABA neuron
PreGABAlin
What is the action of Ezogabine?
- Open KCNQ K+ channel on the pre and post synaptic glutamate neuron to decrease excitability
High concentrations Binds post synaptic GABA (A) channel as agonist to stabilize Cl channel
What is the action of Tiagabine?
Inhibit reuptake of GABA into the presynaptic neuron via receptor GAT-1
How are Benzodiazepines used as an antiepelectic? (MOA)
Binding causes and allosteric change to potentiate GABA binding to GABA(A) Cl channel and open Cl- channels with greater FREQUENCY
How are Barbituates (PB) used as anti epileptic agents?
bind to distinct sites GABA(A) Cl channel and increases the DURATION of Cl- channel opening
Do barbiturates or benzodiazepines have greater toxicity?
Barbiturates. At high doses barbiturates are GABA independent and have a greater lethality than benzodiazepines
What drug can be used to treat Dravet Syndrome epilepsy?
Cannabidol
What drug can be used to treat Lennox-Gastaut syndrome epilepsy?
Cannabidiol
Pharmacokinetics of Phenytoin?
Zero order meaning it is saturable will not plateau
aspirin is also zero order
What does phenytoin induce?
CYP-450 –> lots of drug-drug interactions
Gingival hyperplasia, hypothyroidism, Hypocalcemia (Vit. D deficiency, Osteoportosis) and CV risk are toxicities of what?
Phenytoin
What anti epileptic drugs are associated with osteopenia/osteoporosis?
Chronic administion is associated with osteopenia/ osteoporosis
- Carbamazepine
- Phenytoin
- Phenobarbital
- Valproic acid
induce CYP450dependant Vitamin D catabolism –> decreased Ca2+ absorption–> PTH-mediated response that demineralize bone
What are the toxicities of carbamazepine?
Leukopenia
Neutropenia
Thrombocytopenia
*always take baseline CBC
Why would Oxcarbazepine be used instead of carbamazepine?
oxcarbazepine is a less potent activator of CYP450 so it has fewer CNS/Hemotological side effects
What are Phenobarbital toxicities?
- CNS depressant
- Hypocalcemia/vit.D deficient
- Osteoporosis
need to monitor serum drug levels because of coma/respiratory depression and fatality risk
What antiepileptic drug can cause permanent, progressive, bilateral, concentric vision loss?
Vigabatrin
- prescribers need to complete REMS risk evaluation program before prescribing
What drugs can induce hepatic CYP450?
- Carbamazepine
- Phenytoin
- Phenobarbital
** can increased clearance of oral hormonal contraceptive and increase risk of unplanned pregnancy***
AED (carbamazepine, phenytoin, Phenobarbital and others) Induces can increases clearance of what drugs?
- Warfarin via CYP isoenzymes–> clotting risk
- Oral contraceptive–> pregnancy risk
- antivirals–> increase clearance of HIV meds and increased risk for replication
Valproic acid and lamotrigine inhibit conjugation of what enzyme?
UGT –> leads to accumulation of parent drug
Phenytoin, Carbamazepine, and Phenobarbital induce conjugation of what enzyme?
UGT–> leads to reduction of the parent drug
What is status epileptics?
Medical emergency of a seizure that persists for a sufficient length of time or very frequent so that there is no recovery between attacks
What causes status epileptics?
abrupt AED withdrawal, benzodiazepines, opioids, alcohol, brain, mass/trauma, infection, fever
What is in the first IV for initial status epileptics therapy
- Lorazepam
2. alternative is diazepam
It there is no IV access, what should be done for status epilepticus?
IM midazolam
What should be in the second IV for status epileptics Tx?
Fosphenytoin OR valproic acid OR levetiracetam OR Phenytoin
