A.29

Question 1

Antiepilectics used in partial seizures and generalized tonic-clonic seizures except for the ‘‘broad spectrum’’ agents

Answer 1

Phenytoin,
Carbamazepine,
Phenobarbital,
Pregabalin

Question 2

Phenytoin

Answer 2

MOA: Voltage-gated Na+-channel blocker;
Effect: prevents seizure propagation, but NOT initiation;
IND: Acute seizure management, Tonic-clonic seizures, Trigeminal neuralgia;
SEs: toxic metabolite, Teratogenic, gingiva hyperplasia, proarrhythmic (constant ECG monitoring), extravasation (→tissue necrosis), CNS depression, hirtuism, osteomalacia, megaloblastic anemia;
Extra: CYP-inducer, Hepatic metabolism, non-linear kinetics→ elimination kinetics shift from 1st order (at low doses) to zero-order (at high doses), administration into a large vein in an infusion pump, Fosphenytoin- water soluble pre-drug, less toxic metabolite;
ROA: i.v;
Contra-IND: people with underlying heart problems

Question 3

Carbamazepine

Answer 3

MOA: VG-Na+-channel blocker (bind the inactive form of the channel and ↑ the time spent inactive);
Effect: prevent seizure propagation, but not initiation; Kinetics: BA p.o~80%, hepatic metabolism by CYP3A4, strong CYP-inducer;
ROA: p.o;
IND: Focal onset seizures (prophylaxis), tonic-clonic seizures, bipolar disorders, alcohol withdrawal, trigeminal neuralgia (1st line!);
Extra: have to ↑dose after some time or ask patient to take it with food;
Contra-IND: people with absence seizures (it can cause increase in seizures);
SEs: neuroglial SEs, hyponatremia (→leads to vomiting, nausea, fatigue, dizziness, edema on the skin), Hematologic SEs (leukocytopenia), CNS depression, osteomalacia, aplastic anemia, teratogenic

Question 4

Phenobarbital

Answer 4

MOA: binds to barbiturate site on GABAA-R to enhance GABA activity in opening Cl- ch. (→reduces neuronal excitability & AP frequency), may also block Na+/Ca2+ channels at higher concentrations;
Effect: Anticonvulsant, hypnotic (at ↑dose);
Kinetics: p.o admin., some drug is excreted unchanged but most is oxidized by the liver, T1/2=50-100h
IND: Prevent tonic-clonic or partial seizures (2nd/3rd line due to SEs);
SEs: ↑↑sedative, megaloblastic anemia, hypersensitivity reactions, mental disturbance, in overdose- respiratory and circulatory failure;
Extra: enzyme inducer (ALA-synthase)

Question 5

Pregabaline

Answer 5

MOA: Inhibits N-type Ca2+ ch. (binds α2δ1 subunit)→ ↓Glutamate release; IND: adjuvant treatment for partial seizures, neuropathic pain (1st line); SEs: drowziness, dizziness, Headache, ataxia, tremor; ROA: p.o

Question 6

Categorization of seizures

Answer 6

1. 1.1.Epilepsy syndrome
   1.2. Secondary seizures
2. 2.1. Focal seizures
   2.2. Generalized seizures

Question 7

Epilepsy syndrome

Answer 7

have to be treated prophylactically

Question 8

Secondary seizures

Answer 8

after trauma, stroke, meningitis, encephalitis, alcohol withdrawal, metabolic imbalance. These require finding the origin of the seizure and acute treatment.

Question 9

Focal seizures

Answer 9

the neuronal activity only involves small part of the brain (small part of 1 hemisphere). the conciousness might still be present during a seizure.
1.motor seizures- can involve numbness of 1 organ or seizure of 1 organ
2.Non-motor seizures- weird seizures, can involve almost everything (emotional- patient has a certain emotion and that’s the seizure; ↑BP can be the seizure; can be sensory)

Question 10

Generalized seizures

Answer 10

involve both hemispheres and loss of conciousness
1.motor seizures- “grand-mal”, tonic-clonic movements (common in metabolic and withdrawal causes)
2.Non-motor seizures- absence seizures. Brief and sudden loss of conciousness.

Question 11

Epileptic seizure

Answer 11

abnormally increased brain activity can be general or local area in the brain

Question 12

The neuronal structures can be overly excited by

Answer 12

1. The electric properties on the neurons changes (can be congenital, polymorphism where the VG-Na+-channels work a bit different and this can lead to overactivation; Metabolic changes can also lead to that)
2. The imbalance of neuronal transmission (imbalance btw the excitatory and inhibitory circuits in the CNS, can be caused by alcohol abuse)
3. Structural damage to neuronal circuits (after trauma or stroke neuronal circuits can be damaged; Meningitis/encephalitis can also cause it)
4. Glial abnormalities (seen in many epileptic syndromes; glial cells are not able to keep the EC environment in homeostasis)

Question 13

Pharmacologic targets of antiepileptics

Answer 13

1. VG channels (Na+, Ca2+)
2. Glutamate transmission (AMPA, NMDA) release
3. GABAergic transmission (PAM; GABA metabolism/reuptake inhibition)
4. Others: SV2A (synaptic vesicule 2A protein)