Anti epileptic Drugs Flashcards
Define status epilepticus**
Generalized tonic-clonic seizures w/ ^^^ frequency (recur before patient returns to normal consciousness from the postictal state)
***MEDICAL EMERGENCY W/ HIGH MORTALITY RATE
(HYPOXIC BRAIN DAMAGE)
Describe treatment for status epilepticus:
First line–> Refractory–> Secondary Refractory
What is important to remember about secondary refractory treatment?
1st: IV BDZ, then IV Phenytonin/Fosphenytoin
(*Admin. to prevent seizure reoccurrence even if seizure has stopped)
Refractory: ^^^Phentonin, ^^^ BDZ
Secondary Refractory: Barbs or Propofol
*Note: secondary refractory treatment may require respiratory support
3 stages of seizure
- Aura (convulsive + partial seizures only)
- Itcus (“seizing”)
- Postictus (hypoglycemic state–not present in absence seizure)
What percentage of patients with uncomplicated tonic/clonic seizures can achieve complete seizure control with treatment?
85%
What are three important things we generally try to avoid when administering anti-convulsive agents?
Alteration in:
- Intellect/alertness
- Physical abilities
- Reproductive ability due to therapy
* Patients generally on tx for life
What are four important issues with compliance to consider when choosing anti convulsive therapy?
- Potential effectiveness
- Adverse problems (i.e. hirsutism in women…)
- Convenience (daily pill)
- $$
Describe two reasons why serum drug levels are important in anti convulsive therapy:
- avoid drug toxicity/ ensure proper dosage
3. check patient compliance
Phenytoin:
MOA (3)
(means = likely to be tested!)
Inhibits seizure spread + Suppresses epileptic foci
- Blocks Ca++ influx
- ^ Cl- influx (GABA tranmission, IPSPs)
- ^ affinity for inactivated Na+ channels
Phenytoin:
Therapeutic Use
**DOC for all seizures EXCEPT absence epilepsy/ atonic seizures
Phenytoin:
ROA (2)
Transport/ Metabolism*
- PO; IV for status epilepticus
- 90% protein bound in plasma
- Metabolized in the liver by saturable enzymes: small dose = ^ in plasma & toxicity
5 most important phenytoin ADRs:
- Gingival hyperplasia (20% kiddos)
- Hirsutism (compliance*)
- vestibular disturbance: nystagmus, ataxia
- Allergic rxn: SJS* rash, hematological
- Cardiotox with ^ IV bolus
CI populations for phenytoin therapy
ALL women of childbearing age; teratogenic
Which vitamin should be supplemented in patients on phenytoin therapy? Why?
Vitamin K; phenytoin = CYP3A4 inducer
**Carbamazepine:
Therapeutic Uses (3)
When should it NOT be used (2)
- Gen tonic-clonic seizures (2nd line)
- Complex partial seizures (2nd line)
- Trigeminal neuraligia (2nd line)
- Not effective for absence seizures
- Makes myoclonic seizures WORSE
Which 2 populations should not take Carbamazepine?
Elderly patients (hepatotoxic) Patients with myoclonic seizures ** ACTUALLY MAKES THESE WORSE**
Describe the unique nature of carbamazepine metabolism
Auto induces its own metabolism via CYP1A2/2C/3A
*Metabolic rate will ^^ within first 4-6 weeks and stabilize within 1mos
**Valparoic Acid:
MOA (3)
Which is a target for treatment of absence epilepsy?
- potentiates GABA
- blocks Na+/K+ channels
- inhibits T-type Ca+ channels (**Tx. absence epilepsy)
2 Important therapeutic uses for Valparoic acid
- Absence seizures refractory to ethosuximide (often 1st line)
- Bipolar disorder
How is it valparoic acid absorbed?
Special method of administration?
Which 4 groups is it CI?
-gut
- can give to kiddos as sprinkles!!! (makes it easy to use)
DO NOT give:
1. kiddos younger than 2
2. elderly
(1 + 2 because hepatotoxic)
3. bleeding disorders
4. Preggos: teratogenic
Most common ADR associated with valparoic acid
1 alopecia- problem with compliance
2 important DD interactions with valproic acid:
- Lamotrigine (^ conc by inhibiting P450)
2. Phenytoin (Displaces from plasma proteins, decreases elimination)
Ethosuximide:
MOA
Therapeutic use
Blocks T type Ca++ channels
Tx: absence seizures only
**Lorazepam and other BDZs:
MOA (3)
Most important use
- Potentiate GABA
- inhibit VGNa++ channels
- block Ca++ channels @ sedating doses
* *IV admin for status epilepticus
Gabapentin:
MOA
Therapeutic use (2)
Advantages to use
- ^ GABA release from central neurons
- Tx: Diabetic neuropathy, occasional adjunct anti epileptic (not very effective for this use)
- *Does not change conc. of other anticonvulsants
**Which antiepileptic drug has the HIGHEST probability of causing SJS
**Lamotrigine
**Lamotrigine: MOA- inhibits what four things?
- Ca Channels
- Na Channels
- Glutamate release
- aspartate release
**Lamotrigine:
Therapeutic use + stipulations*
Used to treat most all seizure disorders in patients >16yo**
Topiramate is abroad spectrum anti epileptic.
What two other conditions are treated with Topiramate?
- migraine
2. IICH
Three important ADRS with Topiramate?
- **Renal stone formation (Its hard “TO” pee”)
- paresthesia (CA inhibitor)
- Loss of mental acuity (“TOPI makes you dopey”)
**Levetiracetam (Keppra): Therapeutic use (2) Most important advantage to use; in which population is it highly indicated?
Unknown MOA
- Adjunct therapy for partial seizures; increasingly used for others
- Migraines
* *Not appreciably metabolized in body; great for patients with hepatic insufficiency (Keppra keeps the liver safe)
Oxcarbazepine:
MOA
Therapeutic use
ADR
Blocks VG Ca++ channels
Tx partial seizures
Causes hyponatremia in first 3 mos
Pregabalin:
Most Common Therapeutic Use
neuropathic pain (esp. diabetics)
Broad Spectrum Antiepileptics (4)
Lamotrigine (>16yo)
Levetiracetam (Keppra keeps the liver safe)
topiramate (“TOPI makes you dopey”)
valproate (No child bearing age ladies!)
Narrow Spectrum anti epileptics (4)
Carbamazepine- makes myoclonics worse; not absence
Oxcarbazepine- partial seizures
Phenobarbital- febrile/ status epilepticus
Phenytoin- not absence/atonic
Drug only for absence seizure (DOC)
Ethosuximide
Why should anticonvulsants be avoided in women of child bearing age despite OCP use?
Anticonvulsants alter hepatic metabolism and plasma protein binding of OCPs–this can lead to unplanned preggos + possible birth defects
Measures to be taken with female on anticonvulsant therapy in planned preggos?
What is the ideal therapy for these patients?
- Best choice: Keep on same drug if possible. Start ladies of this age/in general on safe drug even before desire for pregnancy!!!
- Have to stop barbs, phenytoin, and valproate though if they were taken!!! Switch drug
GOAL: mono therapy with lowest possible dose to
Describe Fetal Hydantoin Syndrome:
Which drug causes this?
Caused by phenytoin:
- Cleft lip/palate
- Congenital heart disease
- slowed growth
- mental deficiency
Describe epilepsy in pregnant patient: does it get better or worse? why? how do we monitor these patients?
Will ^ # seizures during preggos despite medication use
- ^ drug clearance
- ^ maternal volume
* monitor by ^ frequency of labs
What should be avoided in unplanned pregnancy of woman on anticonvulsant therapy (2)
- DON’T COMPLETELY REMOVE ANTICONVULSANT
- DON’T SWITCH ANTICONVULSANT IF PREGNANCY WAS UNPLANNED
**Risk of meds is safer than altering therapy
What happens if a woman with seizure disorder discontinues anti epileptic therapy during preggos?
^ seizure frequency–> anoxic conditions–> birth defects
2 non-pharm therapies for epileptic conditions
- vagal n. stimulation (pulse generator implant )
2. surgical removal of epileptic focus
What seizures generally lack auras?
1) absence
2) myoclonic
3) seizures in kids, because kids may not recognize them
(a true Melissa statement- hahaha)
Post ictus state is caused by?
hypoglycemia
General mechanisms for seizure drugs:
If you forget MOA, guess these:
decrease Na/ Ca/ glutamate/ aspartate
increase Cl-/ GABA
Serious risk assc with all antiepileptics
Steven Johnsons
Role of phenobarbital in anticonvulsive therapy:
-IV administration to stop status epilepticus (2nd refractory)
-severe febrile seizure
(Emergencies, not maintenance)
Two treatments for absence seizures:
valproic acid
ethosuximide
**via T-type Ca+ channels
Felbamate treats?
Lennox Gastaut
Age group Lennox Gastaut is seen in?
under 4 yoa
Infantile spasms:
Age of onset
% idiopathic
under 6 months
15% idiopathic; 85% have identifiable cause
Drugs that are absolutely pregnancy X/ not good for managing seizures in child bearing age women?
- barbs
- phenytoin
- valproate
Drug that requires vitamin K supplementation?
phenytoin- induces CYP3A4
Which seizure drug is safe in hepatic failure patients?
leviteracetam (Keppra)
-no metabolism in the body (“Keppra keeps the liver safe”)
Drug that causes hyponatremia in the first three months?
oxcarbazepine
Drug that auto-induces its own metabolism/ requires dose release during initial 4-6 weeks of treatment?
carbamazepine
Drug that is metabolized by saturable enzymes? What is the consequence?
- phenytoin
- can go rapidly from therapeutic –> toxic levels
- must monitor patient plasma
Drug w/ zero order kinetics?
Phenytoin
