Exam 4 Adv Pharm
anticonvulsatn - hyantoins names - •Ethotoin (Peganone) only available in 250 mg
•Fosphenytoin (Cerebyx) NOT for primary care
•Available only in intramuscular (IM) or intravenous (IV) dosing
•Given only for about 5 days (loading dose), then will start PO drug (Dilantin)
•Phenytoin (Dilantin)
•Oral: 50 mg chewable tablets; oral suspension: 100 mg/4 ml and 125 mg/5 ml
•30, 100 mg capsules, extended release: 100 mg
•Note that generic phenytoin is not interchangeable with Dilantin- caution
anticonv, hydantoins uses, MOA, pharmacokinetics - §Uses: Tonic-clonic (aka grand mal), Focal impaired
awareness (aka Complex Partial) seizures
§MOA
§Works by stabilizing neuronal membranes and decreasing seizure activity by increasing efflux or
decreasing efflux of sodium ions across cell membranes in the motor cortex
§Pharmacokinetics
§Approx 90% plasma bound (be careful with drug-drug interactions & hypoalbuminemia-> seizures or
toxicity)
§Metabolism in liver: strong CYP 2C9 effects
§Onset and duration varies (treatment highly individualized)
drug interactions for hydantoins - •Drug Interactions:
§Effect of drug is increased (high levels; toxicity) when taken with: cimetidine, diazepam, acute alcohol
intake, valproic acid, allopurinol, ETOH (short-term)
§Effect of drug is reduced when taken with (low levels): phenobarbital, carbamazepine, rifampin,
antacids, gingko, ETOH (chronic use), "azole" drugs (Recall Cytochrome P450)
,§May reduce effectiveness of oral contraception pills, corticosteroids, anticoagulants, levodopa, thyroid
hormone, carbamazepine, sulfonylureas, cardiac glycosides
ADRs for hydantoins - §ADRs: many!
§Never give IV or IM in primary-care setting!
§Most common
§Neuro: Nystagmus, diplopia, dizziness, pruritus, paresthesia, headache, sedation (take at night), ataxia,
confusion
§ Mouth/ Face: metallic taste, Gingival hyperplasia, hirsutism
§Allergic reaction: rash [Stevens-Johnson, toxic epidermal necrolysis (TEN) (higher in Asians)], possible
lymphadenopathy, hepatitis
§Cardiovascular effects: hypotension, tachycardia, dysrhythmias (IV; Class III antiarrhythmic), anemia
§Gastrointestinal (GI) effects: n/v, anorexia, constipation
§Genitourinary effects: urinary retention, reddish-brown urine discoloration
§Phenytoin-induced megaloblastic anemia: treated with folic acid (b/c of folic acid deficiency)
•Toxicity/ Elevated Blood levels (10-20 mcg/mL; note that there is still a risk for toxicity at the usual
doses)
•20-30: nystagmus (early sign of toxicity- must not miss)
•30-40: ataxia (early sign of toxicity- must not miss)
•> 40: decr/ LOC!
contraindications for hydantoins - §Contraindication: Pregnancy (Fetal Hydantoin Syndrome; risk-
benefit), CV pts (sinus bradycardia, SA block, 2nd & 3rd degree AV block)
§Warning/ Caution: Diabetics (may increase blood sugar), Pts with renal or hepatic issues (incr. toxicity)
§Rational drug selection
§Nurse practitioner role: working with neurologist who has made diagnosis
§Monitoring
,§Baseline labs and plasma levels (10-20 mcg/mL; narrow therap index -> toxicity)
§Thyroid stimulating hormone (TSH) levels, LFTs, EKG, B/P
§Patient education: discuss risk factors for seizures
§Do not stop abruptly! (Status epilepticus)
§Report hypersensitivity reactions (occur within 3-8 weeks) & suicidality
§Oral hygiene/ Regular dental cleanings
§Females- birth control other than OCPs
iminostilbenes - §Carbamazepine (Tegretol, Tegretol XR, Carbatrol) (Cat D)
§Oxcarbazepine (Trileptal) (Cat C)
§MOA: Unknown; Depresses neuron transmission in the nucleus ventralis anterior of the thalamus
§Uses: Tonic-clonic sz, Focal impaired awareness (aka Complex Partial), Mood stabilizer (mania in BPD),
Trigeminal neuralgia
§Pharmacokinetics
§Highly protein bound: 75-90%
§Induces metabolism of many CYP 450 substrates
§Autoinduction
§Genetic testing of Asians (HLA-A*3101; HLA-B*1502)- hypersensitivity (S-J syndrome, Toxic epidermal
necrolysis)
drug interactions for iminostilbenes - §Drug interactions:
§Drug levels increase with concurrent use of grapefruit juice, propoxyphene (Darvocet), cimetidine,
erythromycin, clarithromycin, verapamil, hydantoins
§Decreases plasma levels of several drugs: OCPs, beta blockers, warfarin, doxycycline, succinimides,
haloperidol
ADRs for iminostilbenes - §Depression of bone marrow/ aplastic anemia (rare; monitor CBC)
, §Liver damage, impairs thyroid function
§Dizziness (44%), nystagmus, ataxia, n/v, dry mouth, diplopia, headache (HA)
§Black Box warning for Rashes including Stevens-Johnson Syndrome & toxic epidermal necrolysis (TEN),
can also cause blood dyscrasias (fever, sore throat, easy bruising)
Contraindications: Carbamazapine- Pregnancy esp. 1st trimester (Fetal Carbamazapine Syndrome
Succinimides - §Use: DOC generalized absence seizures in children and adults
§Ethosuximide (Zarontin), methsuximide (Celontin) (Cat C)
§MOA
§Suppresses seizures by delaying calcium influx into neurons
§Decreases nerve impulses and transmission in the motor cortex
§ADRs
§GI most common (take with food or milk)
§CNS (somnolence, fatigue, ataxia)
§Agranulocytosis, aplastic anemia, granulocytopenia
§Pharmacokinetics: t ½ life: 30 hrs children & 60 hrs adults
Lamotrigine - §Lamotrigine (Lamictal)
§Uses: Adjunctive treatment of Tonic-clonic, Focal impaired awareness (aka Complex Partial), and
Generalized Absence seizures (Cat C)
§Concurrent use with valproic acid, phenytoin
§MOA: Unknown; Na channels
§ADRs: GI: mostly n/v, constipation; CV: chest pain, peripheral edema; CNS: somnolence, fatigue,
dizziness (38%), anxiety insomnia, headache
§BBW: serious skin rashes requiring hospitalization including Stevens-Johnson syndrome (should occur
by 3-8 wks)
anticonvulsatn - hyantoins names - •Ethotoin (Peganone) only available in 250 mg
•Fosphenytoin (Cerebyx) NOT for primary care
•Available only in intramuscular (IM) or intravenous (IV) dosing
•Given only for about 5 days (loading dose), then will start PO drug (Dilantin)
•Phenytoin (Dilantin)
•Oral: 50 mg chewable tablets; oral suspension: 100 mg/4 ml and 125 mg/5 ml
•30, 100 mg capsules, extended release: 100 mg
•Note that generic phenytoin is not interchangeable with Dilantin- caution
anticonv, hydantoins uses, MOA, pharmacokinetics - §Uses: Tonic-clonic (aka grand mal), Focal impaired
awareness (aka Complex Partial) seizures
§MOA
§Works by stabilizing neuronal membranes and decreasing seizure activity by increasing efflux or
decreasing efflux of sodium ions across cell membranes in the motor cortex
§Pharmacokinetics
§Approx 90% plasma bound (be careful with drug-drug interactions & hypoalbuminemia-> seizures or
toxicity)
§Metabolism in liver: strong CYP 2C9 effects
§Onset and duration varies (treatment highly individualized)
drug interactions for hydantoins - •Drug Interactions:
§Effect of drug is increased (high levels; toxicity) when taken with: cimetidine, diazepam, acute alcohol
intake, valproic acid, allopurinol, ETOH (short-term)
§Effect of drug is reduced when taken with (low levels): phenobarbital, carbamazepine, rifampin,
antacids, gingko, ETOH (chronic use), "azole" drugs (Recall Cytochrome P450)
,§May reduce effectiveness of oral contraception pills, corticosteroids, anticoagulants, levodopa, thyroid
hormone, carbamazepine, sulfonylureas, cardiac glycosides
ADRs for hydantoins - §ADRs: many!
§Never give IV or IM in primary-care setting!
§Most common
§Neuro: Nystagmus, diplopia, dizziness, pruritus, paresthesia, headache, sedation (take at night), ataxia,
confusion
§ Mouth/ Face: metallic taste, Gingival hyperplasia, hirsutism
§Allergic reaction: rash [Stevens-Johnson, toxic epidermal necrolysis (TEN) (higher in Asians)], possible
lymphadenopathy, hepatitis
§Cardiovascular effects: hypotension, tachycardia, dysrhythmias (IV; Class III antiarrhythmic), anemia
§Gastrointestinal (GI) effects: n/v, anorexia, constipation
§Genitourinary effects: urinary retention, reddish-brown urine discoloration
§Phenytoin-induced megaloblastic anemia: treated with folic acid (b/c of folic acid deficiency)
•Toxicity/ Elevated Blood levels (10-20 mcg/mL; note that there is still a risk for toxicity at the usual
doses)
•20-30: nystagmus (early sign of toxicity- must not miss)
•30-40: ataxia (early sign of toxicity- must not miss)
•> 40: decr/ LOC!
contraindications for hydantoins - §Contraindication: Pregnancy (Fetal Hydantoin Syndrome; risk-
benefit), CV pts (sinus bradycardia, SA block, 2nd & 3rd degree AV block)
§Warning/ Caution: Diabetics (may increase blood sugar), Pts with renal or hepatic issues (incr. toxicity)
§Rational drug selection
§Nurse practitioner role: working with neurologist who has made diagnosis
§Monitoring
,§Baseline labs and plasma levels (10-20 mcg/mL; narrow therap index -> toxicity)
§Thyroid stimulating hormone (TSH) levels, LFTs, EKG, B/P
§Patient education: discuss risk factors for seizures
§Do not stop abruptly! (Status epilepticus)
§Report hypersensitivity reactions (occur within 3-8 weeks) & suicidality
§Oral hygiene/ Regular dental cleanings
§Females- birth control other than OCPs
iminostilbenes - §Carbamazepine (Tegretol, Tegretol XR, Carbatrol) (Cat D)
§Oxcarbazepine (Trileptal) (Cat C)
§MOA: Unknown; Depresses neuron transmission in the nucleus ventralis anterior of the thalamus
§Uses: Tonic-clonic sz, Focal impaired awareness (aka Complex Partial), Mood stabilizer (mania in BPD),
Trigeminal neuralgia
§Pharmacokinetics
§Highly protein bound: 75-90%
§Induces metabolism of many CYP 450 substrates
§Autoinduction
§Genetic testing of Asians (HLA-A*3101; HLA-B*1502)- hypersensitivity (S-J syndrome, Toxic epidermal
necrolysis)
drug interactions for iminostilbenes - §Drug interactions:
§Drug levels increase with concurrent use of grapefruit juice, propoxyphene (Darvocet), cimetidine,
erythromycin, clarithromycin, verapamil, hydantoins
§Decreases plasma levels of several drugs: OCPs, beta blockers, warfarin, doxycycline, succinimides,
haloperidol
ADRs for iminostilbenes - §Depression of bone marrow/ aplastic anemia (rare; monitor CBC)
, §Liver damage, impairs thyroid function
§Dizziness (44%), nystagmus, ataxia, n/v, dry mouth, diplopia, headache (HA)
§Black Box warning for Rashes including Stevens-Johnson Syndrome & toxic epidermal necrolysis (TEN),
can also cause blood dyscrasias (fever, sore throat, easy bruising)
Contraindications: Carbamazapine- Pregnancy esp. 1st trimester (Fetal Carbamazapine Syndrome
Succinimides - §Use: DOC generalized absence seizures in children and adults
§Ethosuximide (Zarontin), methsuximide (Celontin) (Cat C)
§MOA
§Suppresses seizures by delaying calcium influx into neurons
§Decreases nerve impulses and transmission in the motor cortex
§ADRs
§GI most common (take with food or milk)
§CNS (somnolence, fatigue, ataxia)
§Agranulocytosis, aplastic anemia, granulocytopenia
§Pharmacokinetics: t ½ life: 30 hrs children & 60 hrs adults
Lamotrigine - §Lamotrigine (Lamictal)
§Uses: Adjunctive treatment of Tonic-clonic, Focal impaired awareness (aka Complex Partial), and
Generalized Absence seizures (Cat C)
§Concurrent use with valproic acid, phenytoin
§MOA: Unknown; Na channels
§ADRs: GI: mostly n/v, constipation; CV: chest pain, peripheral edema; CNS: somnolence, fatigue,
dizziness (38%), anxiety insomnia, headache
§BBW: serious skin rashes requiring hospitalization including Stevens-Johnson syndrome (should occur
by 3-8 wks)
