Pharmacotherapy of Seizure Disorders

Question 1

What ion is sometimes prescribed by neurologists to control seizures and why?

Answer 1

Mg+2 -> sits in the NMDA receptor and blocks it until depolarization is strong enough to displace it

Question 2

For absence seizures, what channel needs to be blocked to most effectively avoid seizures? What drug does that?

Answer 2

T-type thalamic calcium channels

-> as in Ethosuximide for absence seizures

Question 3

Why might a drug other than ethosuximide be used for treating patients with absence seizures?

Answer 3

If you have another seizure type other than absence as well, i.e. generalized tonic-clonic. Ethosuximide is only useful for treatment of absence seizures.

Question 4

At this point you should go in and underline things in first aid.

Answer 4

Based on sketchy

Question 5

What are the mechanisms of action of vigabatrin and tiagabine?

Answer 5

Vigabatrin - irreversibly inhibits GABA transaminase -removal of V-cab transmission

Tiagabine - GABA reuptake inhibitor - Tie stuck in V-cab

Question 6

Why is therapeutic drug monitoring useful? What agents is this easier to do with?

Answer 6

1. Optimizing AED therapy
2. Teasing out drug interactions
3. Detecting noncompliance

Easier to do with older agents which have therapeutic drug monitoring capabiliy

Question 7

What are two important considerations in the dosing of phenytoin?

Answer 7

1. Highly protein bound to albumin >90%

2. Undergoes zero-order (capacity-limited) metabolism when at therapeutic concentrations

Question 8

Other than phenytoin, what other AED is highly protein bound to albumin and what difference does this make?

Answer 8

Valproic acid

Protein binding can change with certain disease states such as nephrotic syndrome or hepatic disease. Loss of albumin during acute illness and these disease states will increase the plasma free drug concentration (reduced binding)

Question 9

What is one important pharmacokinetic consideration for carbamazepine?

Answer 9

Carbamazepine doses need to be increased after 1-3 weeks because it not just induces CYP, but AUTOinduces CYP (increases its own metabolism)

Question 10

Is diazepam or lorazepam better for status epilepticus and why?

Answer 10

Lorazepam is better - not as lipophilic, so has a longer duration of antiseizure activity

Diazepam - slightly faster onset than lorazepam, but highly lipophilic drug makes it redistribute to fat tissues and have a lower duration of action

Question 11

What are the major CYP inducers and inhibitors in the antiepileptic drugs?

Answer 11

Inducers - carbamazepine, phenobarbital, phenytoin

Inhibitors - Valproic acid

Question 12

What are the neurologic and reproductive side effects of phenytoin?

Answer 12

Neurologic: Diplopia, ataxia, sedationn

Reproductive: Teratogen - most common is cleft lip and palate -> think of dude’s cleft baseball cap

Question 13

What are the dermatologic, musculoskeletal, and hematologic side effects of phenytoin?

Answer 13

Dermatologic: hirsutism (guy’s beard), gingival hyperplasia (blowing bubblegum), DRESS syndrome (waitress)

Musculoskeletal: Osteopenia (fracture axle, due to loss of Vitamin D via enzyme induction), SLE-like syndrome (lupus wolf)

Hematologic: Megaloblastic anemia (due to folate wasting, think of tossed salad)

Question 14

What antiepileptic drugs are associated with SJS and why?

Answer 14

Phenytoin, carbamazepine, lamotrigine

->aromatic structure causes an abberant immune response to target self antigens

Especially in asians with a certain HLA-B allele.

Question 15

What are the important side effects of carbamazepine, and what other condition is it first line for?

Answer 15

First line for trigeminal neuralgia (3 gems)

Diplopia, ataxia
Agranulocytosis - hourglass
SIADH - ADH on guy’s head
SJS

Question 16

What are the teratogenic effects of carbamazepine and valproic acid?

Answer 16

Neural tube defects in both

-> think of exhaust pipe tube on side of car

Question 17

What antiepileptic drugs are most associated with weight gain and weight loss?

Answer 17

Weight gain - Valproate - think of the fat incan leader

Weight loss - Topiramate - think of the anorexic cannon boy near Toupee guy

Question 18

What are the important side effects of Valproate?

Answer 18

GI distress - king about to puke
Fetal hepatotoxicity - test LFTs cow with liver pulling cart
Acute pancreatitis
Tremor - think of shaking club
Alopecia

Question 19

What are some other indications for Gabapentin than seizures and what is its mechanism of action?

Answer 19

Calciyumm ice cream truck - Grab a pint! -> Blocks Ca+2 channels

Also used for neuropathic pain and postherpetic neuralgia (think of Zeus)

Question 20

What is the mechanism of action of Topiramate and valproate?

Answer 20

Both are broad spectrum

Topiramate - Blocks Na+ channels, shaking hands with GABA = gaba agonist

Valproic acid - blocks GABA caba, also blocks Na+

Basically they have the same MoA

Question 21

What are the side effects of topiramate?

Answer 21

Sedation - sleep soldier
Mental dulling / slowed cognition - confused soldier
Weight loss - cannon operator
Kidney stones - kidney shaped cannon wheels with cannonballs
Angle-closure glaucoma - they’re holding a literal eyeball tea kettle

Question 22

Why are bone disorders are problem in patients being treated with AEDs?

Answer 22

Increased risk of fractures when falling during seizures

They are really common because of enzyme induction of carbamazepine, phenytoin, and phenobarbital -> leads to vitamin D wasting.

May need to give calcium supplements and bisphosphonates, check bone mineral density every 5 years

Question 23

What is the firstline treatment of neonatal seizures?

Answer 23

Phenobarbital

Question 24

What drugs are most associated with cognitive dysfunction, and why are GABA drugs the worst?

Answer 24

Topiramate and phenobarbital

GABA drugs are the worse because they impair attention / concentration
-> worsened memory

Question 25

What is the recommendation for pregnant women on antiepileptic drugs?

Answer 25

Monotherapy during reproductive years, tapering off the drugs if possible

Folate supplementation

Question 26

How do AEDs affect oral contraceptive efficacy?

Answer 26

Any drug which induces CYP enzymes is likely to decrease oral contraceptive levels (estrogen metabolized by CYP enzymes in the liver)

OCPs can also decrease the drug concentration of lamotrigine