Tuesday, 8-23-Seizures And Epilepsy Pharmacology (Fitzpatrick) Flashcards
Benzodiazepines and Clonazepam are used for the treatment of these seizure disorders
Generalized onset-Myotonic, atonic, clonic
Phenytoin and phenobarbital are used for the tx of these types of seizure disorders
Generalized onset-Tonic/clonic
Can be used to tx partial onset seizure disorders as well
List some anti-epilepsy drugs used to tx partial onset simple and complex seizures
Carbamezapine Gabapentin Pregabalin Oxcarbazepine Lacosamide Tiagabine Vigabatrin Ezogabin
These drugs can be used to treat partial onset seizures of the tonic/clonic variety:
Carbamezepine
Phenytoin
Phenobarbital
These broad spectrum anti-epilepsy drugs can be used alone or in combo with adjuvant agents to treat generalized onset and partial onset seizures
Valproate Lamotrigine Topirimate Levetiracetam Zonisamide
AEDs antagonize excitation by targeting:
1) voltage gated Na ion channels (Nav)
2) Low threshold (T Type) Ca channels
These drugs prolong fast inactivation state of Nav ion channels:
Traditional AED: Phenytoin, carbamazepine
New AEDs: Lamotrigine, Oxcarbazepine
This drug enhances slows inactivation of Nav channels
Lacosamide
In regards to AED’s, the binding site is on the interior site of the Nav channels pore. When can the AED access the pore?
If the activation gate OPENS, AEDs can access pore. If activation gate is CLOSED, cannot access pore
The pharmacological activity of AED Nav blockers is state or use-dependent
Nav blockers act preferentially on the ___
Neurons involved in the disease
The probability of a Nav blockade is proportional to the frequency of Nav channel opening and dose
___ are STATE-DEPENDENT agents that slow the recovery of Nav ion channels from inactivation
Phenytoin and Carbamazepine
___ is a state-dependent agent that is most effective at depolarized membrane potentials and high-frequency action potential firing. The state dependence of this drug causes minimal effects on cognitive functions (low-frequency firing)
Phenytoin
__ is a state-dependent agent that binds Nav less effectively, but with a much faster rate than Phenytoin, making this drug more effective in blocking high-frequency firing. These differences may correlate with different clinical responses
Carbamazepine
The MOA of this drug on Nav ion channels is similar to that of Phenytoin and Carbamazepine (voltage use and dependence). However, this drug also acts on other molecular targets, such as N- and P-type voltage-gated Ca channels in cortical neurons and neocortical K currents.
Lamotrigine
Its anti-epileptic action is not identical to carbamazepin and phenytoin
What drugs and standard protocol is used to manage status epilepticus?
Diazepam or lorazepam with fosphenytoin if needed
___ is a novel AED that effectively treats partial seizures and stabilizes the slow-inactivated state
Lacosamide
How does Lacosamide differ in its MOA on Na channels compared to other AEDs?
It acts on/stabilizes the SLOW-INACTIVATED state whereas other AEDs act primarily on the fast-inactivation state
In a prolonged train of depolarizing stimuli, ___ is more effective at reducing the amplitudes and frequency of sustained repetitive firing spikes when the stimulus was prolonged to tends of seconds as opposed to less than 1 sec
Lacosamide
T-type Ca channels mediate 3 Hz spike and wave activity in the thalamus-the hallmark of ___ seizures
Absence (petit mal) seizures
AEDs that inhibit these T-type Ca channels are particularly useful for controlling absence seizures
This narrow spectrum AED is ONLY used for absence seizures and ONLY limits excitation (Ca channel). It is a non-sedating drug
Ethosuximide
If ethosuximide doesn’t work for an absence seizure, what else can you do?
Some broad spectrum drugs can be used. The most common one used as an alternative is Valproate and then Lamotrigine
Broad spectrum will also affect T-type Ca channels
This drug was the only broad-spectrum agent available and is still considered first line therapy by many for generalized-onset seizures. It does have ‘intolerable’ adverse effects such as weight gain, tremor, hair loss, and lethargy.
Valproate
___ has been associated with neural tube defects in the offspring of women who take it during pregnancy
Valproate
The MOA of ___ on Nav ion channels is similar to that of Phenytoin and Carbamazepine. However, it also acts on other molecular targets such as N- and P-type voltage gated Ca channels in cortical neurons and neocortical K currents. Therefore, its anti-epileptic action is not identical to carbamazepine and phenytoin
Lamotrigine
