Advanced Pharm Flashcards
What is carbamazepine used for?
Generalized tonic clonic, partial
What is carbamazepine a substrate of and what does it induce?
CYP 3A4
It’s an autoinducer. It induces it’s own metabolism.
What are some of the adverse effects of carbamazepine?
CNS: Blurred vision, unsteadiness, headache, nausea
Black box warnings: Derm reactions, Blood dyscrasias, anticonvulsant hypersensitivity syndrome.
Hyponatremia
What is the target concentration of carbamazepine?
6-8 mcg/mL
When does anticonvulsant hypersensitivity syndrome usually occur?
1-8 weeks after exposure
What are partial seizures?
Limited to one hemisphere. Simple partial (no impaired consciousness). Complex partial (impaired consciousness)
What are the types of Antiepileptic Agents?
Sodium channel blockers
GABAERGIC
Calcium channel blockers
Glutamate blockers
What do sodium channel blockers do?
Reduce sodium influx which slows depolarization. It reduces the ability of neurons to fire at a rapid rate.
By blocking the voltage sensitive sodium channels the inactivation state of the channels is prolonged.
Sodium channel blockers inhibit the release of what?
Excitatory amino acids
What are the black box warnings of carbamazepine?
Dermatologic reactions. Blood dyscrasia. Anticonvulsant hypersensitivity syndrome. Hyponatremia.
What is the patho physiology of anticonvulsant hypersensitivity syndrome?
T-cell activation
What are the symptoms of anticonvulsant hypersensitivity syndrome?
- Fever, malaise
- Rash/skin eruption
- Systemic organ involvement
What is oxcarbazinepine an analog of?
Carbamazepine
How is oxcarbazinepine metabolized and excreted?
MHD is inactivated by glucuronide conjugation and eliminated by kidneys
What is the conversion of carbamazepine to oxcarbazinepine?
Initiate dose 1.5x higher than the carbamazepine dose.
What are the significant adverse effects of oxcarbazinepine?
NO black box warnings
Generally less than carbamazepine
What are the drug interactions of oxcarbazinepine?
Induces 3A4
Reduces oral contraceptive levels
What is eslicarbazepine used for?
Partial onset seizures
What is the metabolism and elimination of eslicarbazepine?
Partial onset seizures.
What is the metabolism and elimination of eslicarbazepine?
Adjust for renal dysfunction
What does the eslicarbazepine induce and what does it inhibit?
Induces CYP 3A4
Inhibits CYP 2C19
Eslicarbazepine decreases concentrations of what?
Oral contraceptives
What are the types of phenytoin?
Phenytoin acid and phenytoin sodium
Phenytoin sodium has how much less than phenytoin?
8% less
What is the dose dependent metabolism of phenytoin?
Michaelis-Mentin or capacity limited
Enzyme system saturable
For phenytoin below the enzyme system saturability, what are the kinetics like?
Linear
For phenytoin, what can small dose increase result in?
Large increase in levels
What is the half life of phenytoin?
7-24 hours
How is the clearance for the elderly with phenytoin?
20% less
What is the target concentration and free concentration of Phenytoin?
Total concentration is 10-20 micrograms
Free concentration is 1-2 micrograms
What are the adverse effects of phenytoin?
Phenytoin hypersensitivity syndrome Nausea, vomiting, constipation Gingival hyperplasia Hirsutism Hypotension Bradycardia QRS prolongation Decreased cognitive ability Leukopenia, thrombocytopenia, anemia
Phenytoin is an inducer of what?
CYP 3A4
What is phenytoin metabolized by?
2C9 and 2C19
What do you have to remember with protein binding when it comes to phenytoin?
There are displacement interactions with other drugs that are highly protein bound.
What must you remember about phenytoin and tube feeding and antacids?
There is a significant reduction in bioavailability
Space dosing by 2 hours
What is the loading and maintenance dose for phenytoin?
Loading is 10-20mg/kg
Maintenance is 4-7 mg/kg/day
What is the maximum infusion rate for phenytoin?
50mg/min
25mg/min in the elderly
What are the pharmacokinetics of zonisamide?
Low protein binding
No active metabolite
How is zonisamide metabolized?
It is hepatically metabolized by carbyoxylestrase.
How is zonisamide excreted?
It is excreted by the kidneys unchanged.
What are some of the adverse effects of zonisamide?
CNS (somnolence, agitation, cognitive impairment)
Renal stones
What are some of the contraindications of zonisamide?
Sulfa allergy
Not recommended inpatients with CLcr of less than 50
How is lamotrigine metabolized?
It is hepatically metabolized through glucoronidation
What are the significant adverse effects of lamotrigine?
Dizziness, blurred vision, headaches
What is the black box warning for lamotrigine?
Skin reactions
Hypersensitivity Syndrome
D/C at first sign
How does oral contraceptives and phenytoin affect lamotrigine?
It induces it thereby decreasing the serum concentration
How much valproic acid is needed to inhibit lamotrigine?
500 mg
Rufinamide is an adjunctive for what?
Lennox-Gastaut
What is the pharmacokinetics of Rufinamade?
Slow absorption
(4-6 hours to peak), increased with food.
How is Rudinamide metabolized?
It is hepatically metabolized to inactive metabolite.
What is the pharmacokinetics of lacosamide?
It is 100% bioavailable
How is lacosamide eliminated?
Eliminated by renal excretion and biotransformation.
What are significant adverse effects of lacosamide?
Prolong PR Interval, heart block
