L34. Drugs used in neurological disorders II →↑↓” Anti epileptic

Question 1

Mechanism, Contraindication, S/E of 1.Sodium channel blockers

Answer 1

Phenytoin, Carbamazepine, Lamotrigine

Carbamazepine
MoA: Block sodium channels during rapid,
repetitive, sustained neuronal firing.

Adverse effects: Dizziness, diplopia
(double vision), nausea, ataxia,
blurred vision.

Induces hepatic cytochrome P450
activity (so increases its own & other
AEDs clearance)

Phenytoin: First-line antiepileptic drug.
MoA
→Prevent sodium influx through sodium channels
→Inhibit calcium influx through channels, thereby inhibits voltage-dependent
neurotransmission at the synapse.

S/E
Gingival hyperplasia, coarsening of the facial features in women, drowsiness,
nausea, vomiting, rash, headaches, loss of libido, hormonal dysfunction.

Long-term use - Osteoporosis, ataxia.
During pregnancy – Cleft palate, cleft lip, congenital heart disease, slowed
growth rate, mental deficiency.

Phenytoin is a Strong inducer of hepatic enzymes

Lamotrigine→ Preferred choices for pregnant women. Low incidence of congenital malformations.

MoA
→Block voltage-dependent sodium-
channel conductance.
→ Inhibit depolarization of the
glutaminergic presynaptic membrane, thus inhibiting glutamate release.

Adverse effects:
Allergic skin reactions, headache,
blood dyscrasias, ataxia, GI disturbance, psychosis, tremor, hypersensitivity reaction, insomnia

Question 2

Mechanism, Contraindication, S/E of

Calcium channel blockers

Answer 2

Ethosuxmide
MoA: Calcium channel blocker inhibits depolarization necessary to generate an action potential. also essential for the release of neurotransmitter in the vesicels

Adverse effects:
• Increased risk of suicidal
thoughts or behavior
• Lower bone marrow ability
• Liver or kidney disease
• Concentration problems, speech problems,
drowsiness, and problems with coordination
• Drug interactions
• Not safe for pregnant woman

Question 3

GABA enhancers

Answer 3

MoA 
→When GABA binds to a GABAA receptor,
An influx of chloride will occur.
→→Influx of Cl- increases the negativity
of the cell.
→→→Causing the cell to have greater
difficulty reaching the action potential.

1.GABAA agonist:
MoA : act on receptor
Clobazam, Clonazepam

2.GABA reuptake inhibitor
MoA : Inhibit GABA-transporter-1
(GAT-1) prevent the reuptake of
GABA into the presynatic neuron for
recycle
Tiagabine

3. GABA-transaminase
inhibitor
MoA Inhibit the
breakdown of GABA :
Vigabatrin

4.Glutamic acid decarboxylase
(GAD) modulation: to
enhance GABA concentration
Gabapentin, Valproate

Question 4

Mechanism, Contraindication, S/E of

Glutamate blockers

Answer 4

Topiramate
MoA:
→Inhibit the AMPA and kainate subtype glutamate receptor.
→Inhibits sodium conductance (decrease the duration, bursts, frequency of action potentials)
→Enhances GABA by unknown mechanisms.

Adverse effects:
Ataxia, impairment of concentration, confusion, dizziness, fatigue, anorexia
depression, slowness of speech.
The drug causes weight loss in many patients, due to appetite suppression.
Obesity patients with epilepsy may benefit from this drug.

Question 5

Epilepsy and changing hormones

Answer 5

Progesterone
→Inhibitory hormone
→ Increasing chloride conductance
at GABAA receptors
→ Decrease glutamate excitatory
response.
→ Increase glutamic acid
decarboxylase (GAD) mRNA.

Estrogen
→ Excitatory hormone
→  Reduces chloride conductance
→ Agonist at glutamate receptor
(NMDA)

Question 6

Mechanism, Contraindication, S/E of Synaptic vesicle protein 2A binding agents

Answer 6

Levetriacetam

Exact MoA is unknown.

→ Binds to synaptic vesicle protein 2A
(SV2A)

→ Inhibits presynaptic calcium channels

→ Reduce neurotransmitter release.

Adverse effects:
Asthenia, dizziness, upper respiratory track infection.

Question 7

Mechanism, Contraindication, S/E of Neuronal potassium channel openers

Answer 7

Retigabine

MoA:
→Potassium channel opener.
→→By prolonging the opening of potassium channels
→→→stabilize the membrane potential.

→K+ channels serve as ‘brakes’ that limit neuronal
excitability.