Seizure & Epilepsy Drugs

Question 1

Generalized onset - Absence

Answer 1

Ethosoximide

Question 2

Generalized onset - Myoclonic/atonic/clonic

Answer 2

1. Benzodiazepines

2. Clonazepam

Question 3

Generalized onset - Tonic-clonic

Narrow spectrum

Answer 3

1. Phenytoin
2. Phenobarbital
3. Carbamezepine (partial onset)

Question 4

Partial onset - simple/complex

Narrow spectrum

Answer 4

1. Carbamazepine
2. Gabapentin
3. Pregabalin
4. Oxcarbazepine
5. Locosamide (new)
6. Tiagabine
7. Vigabatrin
8. Ezogabaine

Question 5

Broad spectrum

Answer 5

1. Valproate
2. Lamotrigine
3. Topirimate
4. Levetiracetam
5. Zonisamide

Question 6

Block Na channels

Answer 6

Generalized onset: Tonic-clonic
1. Phenytoin
Partial Onset: Simple/complex
1. Carbamezepine
2. Oxcarbazepine
3. Locosamide
Broad spectrum 
1. Lamotrigine
2. Zonisamide 
3. Valproic acid
4. Topirimate

Question 7

Block T-type Ca channels

Answer 7

Ethosoximide
Also: valproate and zonasimade
- these channel mediate 3Hz spike and wave activity in thalamus

Question 8

Phenytoin

Answer 8

• state dependent
• slow recovery from inactivation
• MOST effective at depolarized membrane potential + high frequency AP firing
• minimum effect on cognition (low frequency firing)
  Adverse effects - 0 order, doubling dose does not double serum level, hepatic CYP450 enz, gingival hyperplasia, hirsutism, hypocalcemia, osteoporosis

Question 9

Carbamazepine

Answer 9

• state dependent
• slow recovery from inactivation
• binds Na with less efficiency but at MUCH FASTER RATE –> high efficiency in blocking high frequency firing (more than phenytoin)
  Adverse effects - hepatic CYP450 enz, induces own metab, loss of efficacy by day 14, aplastic anemia, leukopenia, neutropenia thrombocytopenia, hypocalcemia, osteoporosis, allergic rxn (Stevens-Johnson syndrome)
  If given with oral contraceptives - inc clearance by CYP (pregnancy!)
  If given with warfarin - inc clearance by CYP (inc risk of thrombosis)

Question 10

Lamotrigine

Answer 10

• voltage and use dependent
• similar to phenytoin and carbamazepine
• IN ADDITION acts on N and P-type VG Ca channels (careful: not T)
• can cause S-J syndrome –> rash 12 weeks after, allergic rxn, life threatening (Risk factor - valproate)

Question 11

Locosamide

Answer 11

• enhances slow-inactivated state (vs others will prolong fast inactivated state)
• lowers amplitude and frequency of firing spikes during prolonged stimulation
• longer time scale than other drugs

Question 12

Ethosoximide

Answer 12

• ONLY for absence seizure
• ONLY limits excitation (Ca channel)
• NON-SEDATING drug

Question 13

Zonisamide

Answer 13

Sulfonamide derivative

Adverse effect - rash, renal calculi, hypohidrosis

Question 14

Which drug blocks VG Na channels and T-type VG Ca?

Answer 14

Zonisamide (also Valproic acid)

Note: Lamotrigine blocks VG Ca too but P and N type Ca channels not T-type!!!!!!!!!!!!! Nerd

Question 15

Valproate

Answer 15

• 1st line drug for generalized-onset seizure
• intolerable side effects
• NTD during pregnancy; atrial septal defect, cleft palate, polydactyl

Question 16

Which drugs block GABA reuptake/metabolism?

Answer 16

1. Tiagabine - reuptake (assoc with stupor)

2. Vigabatrin - metabolism

Question 17

Which drugs potentiate GABAa Rc Cl currents?

Answer 17

1. Phenobarbital
2. Primidone
3. Benzodiazepines

Question 18

Phenobarbital

Answer 18

• binds to distinct site
• nonspecific CNS depressant, sedation, LETHAL resp depression
• abuse/addiction potential
• GABA INDEPENDENT
• active metabolite of Primidone

Question 19

Benzodiazepines

Answer 19

• bind to allosteric site
• potential GABA binding –> Cl opened with greater frequency
• GABA DEPENDENT
• treatment of status epilepticus

Question 20

Stopping seizure treatment

Answer 20

Initial IV - Lorazepam/diazepam (5 mins, inc GABA)

If seizure not stopped - Fosphenytoin IV (Na channel block)

Question 21

Valproic acid acts on:

Answer 21

VG Na
T-type Ca
Inc GABA

Question 22

Topirimate acts on:

Answer 22

VG Na
LG Na (AMPA/glut Rc)
Inc GABA
Potentiates GABAa Rc
Adverse effect - nephrolithiasis, open angle glaucoma, hypohidrosis

Question 23

Gabapentin

Answer 23

• binds VG Ca

- no drug interactions

Question 24

Levetiracetam

Answer 24

• binds synaptic vesicle protein (SV2A)
• stop glutamate release
• no CYP interactions

Question 25

Pregabalin

Answer 25

- 100% renal clearance | - multiple mechanisms

Question 26

Ezogabaine

Answer 26

- binds VG K channels | - urinary retention

Question 27

Which drugs induce CYP450 dependent Vit D catabolism?

Answer 27

``` Phenytoin Carbamazepine Phenobarbital Valproic acid (Dec absorption of Ca triggers PTH response - demineralized bone) ```

Question 28

Renal clearance (100%)

Answer 28

1. Gabapentin (VG Ca) | 2. Pregabalin

Question 29

Minimizing drug interactions - renal clearance >50% of total

Answer 29

Topiramate/Oxcarbazepine | Levetiracetam/Zonisamide

Question 30

Oxcarbazepine

Answer 30

- analog of carbamazepine; fewer side effects - lack of formation of active metabolite - metab in liver but min effects by CYP450 Adverse effects: associated with hyponatremia (along with Carbamezepine), rash

Question 31

Drugs inhibiting conjugation of drugs by UGT enzymes

Answer 31

1. Valproate | 2. Lamotrigine

Question 32

Class D teratogens

Answer 32

1. Valproic acid 2. Carbamezepine 3. Phenytoin

Question 33

Topirimate

Answer 33

1. GABAa Rc agonist | 2. Glutamate (AMPA) Rc antagonist

Question 34

Which drugs cause osteoporosis/osteopenia?

Answer 34

1. Phenytoin 2. Carbamazepine 3. Phenobarbital 4. Valproic acid