Pharmacotherapy of Seizure Disorders Flashcards
What ion is sometimes prescribed by neurologists to control seizures and why?
Mg+2 -> sits in the NMDA receptor and blocks it until depolarization is strong enough to displace it
For absence seizures, what channel needs to be blocked to most effectively avoid seizures? What drug does that?
T-type thalamic calcium channels
-> as in Ethosuximide for absence seizures
Why might a drug other than ethosuximide be used for treating patients with absence seizures?
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.
At this point you should go in and underline things in first aid.
Based on sketchy
What are the mechanisms of action of vigabatrin and tiagabine?
Vigabatrin - irreversibly inhibits GABA transaminase -removal of V-cab transmission
Tiagabine - GABA reuptake inhibitor - Tie stuck in V-cab
Why is therapeutic drug monitoring useful? What agents is this easier to do with?
- Optimizing AED therapy
- Teasing out drug interactions
- Detecting noncompliance
Easier to do with older agents which have therapeutic drug monitoring capabiliy
What are two important considerations in the dosing of phenytoin?
- Highly protein bound to albumin >90%
2. Undergoes zero-order (capacity-limited) metabolism when at therapeutic concentrations
Other than phenytoin, what other AED is highly protein bound to albumin and what difference does this make?
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)
What is one important pharmacokinetic consideration for carbamazepine?
Carbamazepine doses need to be increased after 1-3 weeks because it not just induces CYP, but AUTOinduces CYP (increases its own metabolism)
Is diazepam or lorazepam better for status epilepticus and why?
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
What are the major CYP inducers and inhibitors in the antiepileptic drugs?
Inducers - carbamazepine, phenobarbital, phenytoin
Inhibitors - Valproic acid
What are the neurologic and reproductive side effects of phenytoin?
Neurologic: Diplopia, ataxia, sedationn
Reproductive: Teratogen - most common is cleft lip and palate -> think of dude’s cleft baseball cap
What are the dermatologic, musculoskeletal, and hematologic side effects of phenytoin?
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)
What antiepileptic drugs are associated with SJS and why?
Phenytoin, carbamazepine, lamotrigine
->aromatic structure causes an abberant immune response to target self antigens
Especially in asians with a certain HLA-B allele.
What are the important side effects of carbamazepine, and what other condition is it first line for?
First line for trigeminal neuralgia (3 gems)
Diplopia, ataxia
Agranulocytosis - hourglass
SIADH - ADH on guy’s head
SJS
What are the teratogenic effects of carbamazepine and valproic acid?
Neural tube defects in both
-> think of exhaust pipe tube on side of car
What antiepileptic drugs are most associated with weight gain and weight loss?
Weight gain - Valproate - think of the fat incan leader
Weight loss - Topiramate - think of the anorexic cannon boy near Toupee guy
What are the important side effects of Valproate?
GI distress - king about to puke Fetal hepatotoxicity - test LFTs cow with liver pulling cart Acute pancreatitis Tremor - think of shaking club Alopecia
What are some other indications for Gabapentin than seizures and what is its mechanism of action?
Calciyumm ice cream truck - Grab a pint! -> Blocks Ca+2 channels
Also used for neuropathic pain and postherpetic neuralgia (think of Zeus)
What is the mechanism of action of Topiramate and valproate?
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
What are the side effects of topiramate?
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
Why are bone disorders are problem in patients being treated with AEDs?
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
What is the firstline treatment of neonatal seizures?
Phenobarbital
What drugs are most associated with cognitive dysfunction, and why are GABA drugs the worst?
Topiramate and phenobarbital
GABA drugs are the worse because they impair attention / concentration
-> worsened memory
