Part 1 Flashcards
Non-pharm
Ketogenic diet
- For REFRACTORY cases
- Primarily in CHILDREN
- Diet contains:
- High fat
- Low carbs/proteins
- 4:1 ratio of fats to combined carbs/proteins - Induces ketosis in the brain, which reduces seizure frequency
- No sugar allowed
- Ketone bodies replace glucose in the brain
Adverse effects:
- Metabolic acidosis
- Ketosis
- Dehydration
- Kidney stones
- Cardiac abnormalities
- Abnormal lipid profile
Non-pharm
Vagal Nerve Stimulator
- For REFRACTORY cases
- You place an implanted electrical generator device and attach electrodes to the LEFT vagus nerve
Complications:
- Cough
- Vocal cord paresis
- Bradycardia/asystole during lead test
- AVOID (vagal nerve) triggers:
- Alcohol
- Lack of sleep
- Prevent fall precautions
- Manage co-morbidities
Resective surgery
- Treatment of choice in REFRACTORY focal epilepsy
- Surgery reduces the risk of epilepsy-related deaths AND may improve depression/anxiety in REFRACTORY epilepsy patients
Common side effects of Anti-epileptic drugs (AEDs)
CNS-related
- Somnolence
- Fatigue
- Cognitive impairment
- Coordination abnormalities (i.e Ataxia, dizziness)
5 Main Mechanisms of Action of Anti-epileptic drugs
1) Na channel blockers
2) Ca channel blockers
3) Glutamate receptor blockers
4) GABA enhancement
5) K+ channel opener
**The main point is that you want to DECREASE excitatory neurotransmission and INCREASE inhibitory neurotransmission (i.e K+ and GABA enhancement)
Carbamazepine
- Tegretol
- Tegretol XR
- Carbatrol
- Epitol
Used for:
- Partial seizures - Generalized tonic clonic seizures - also used in (neuropathic pain, diabetes insipidus, bipolar, trigeminal neuralgia, glossopharyngeal neuralgia)
**may worsen ABSENCE seizures
MOA:
- Blocks Na+ channels - Stimulates ADH
- Tricyclic structure
- Therapeutic levels
- 4 - 12 mcg/mL - Metabolized in the LIVER
- Potent 3A4 INDUCER
- May DECREASE levels of Warfarin and Oral contraceptives - *Auto-induction (metabolizes itself)
- Maximum effect at 4 - 6 weeks
-Pregnancy D – AVOID in pregnancy
Carbamazepine
- Tegretol
- Tegretol XR
- Carbatrol
- Epitol
Black box warning, monitoring, side effects, CI
Black box warning:
- SJS and TEN
- Asians should be tested for HLA-B*1502 allele PRIOR to initiation
- Aplastic anemia
- Agranulocytosis
Monitor:
- Electrolytes - CBC - LFTs - Platelets - Differential and CBZ (carbamazepine) levels
Side effects:
-SIADH
-Vitamin D/calcium deficiency
(CNS, nausea, diplopia, blood dyscrasias, rash, hepatotoxicity)
Contraindications:
- Hx of bone marrow suppression
- MAOi use in the past 2 weeks
- TCA allergy (b/c it has tricyclic structure)
- Concurrent nefazadone, or delavirdine and other NNRT-Is
Carbamazepine
- Tegretol
- Tegretol XR
- Carbatrol
- Epitol
DDIs
1) MAOi
- contraindicated within 2 weeks of taking CBZ
2) May DECREASE levels of Warfarin, oral contraceptives, levothyroxine, other seizure meds, DHP-CCBs
3) Phenytoin, Depakote, and rifampin
- DECREASE CBZ
4) Ketoconazole, Cimetidine, Diltiazem
- INCREASE CBZ
Carbamazepine
- Tegretol
- Tegretol XR
- Carbatrol
- Epitol
Patient education
- Drowsiness
- Take with food
- XR casing is excreted in the stool as a GHOST TABLET
- Don’t crush or chew extended-release formulations
- Decreased efficacy of oral contraceptives, use back up
- Non-hormonal contraception is recommended (i.e condoms, diaphragms, IUDs, etc) - Seek medical attention for:
- Unusual bleeding
- Bruising
- Sore throat
- Mouth ulcer
- Rash
Oxcarbazepine
- Trileptal
- Oxtellar XR
Used for:
- Partial seizures
- Primary and secondary generalized tonic-clonic seizures
MOA:
- Blocks Na+ channels
- Modulates Ca2+ channels
- *PRODRUG of CBZ**
- undergoes reduction to form the pharmacologically active 10-hydroxy-CBZ (10-MHD)
- MHD is metabolized by CYP450 and the metabolite is RENALLY cleared - Weaker CYPP450 INDUCER
- May reduce levels of oral contraceptives - CrCl < 30 ml/min
- Start 300 mg daily - *No auto-induction
- *No plasma level monitoring required
Oxcarbazepine
- Trileptal
- Oxtellar XR
Monitor, side effects, CI
-No BBW
Monitor:
- Sodium levels for the first 3 months
- Thyroid function
- CBC
Side effects:
-Rash (SJS/TEN)
-Contraindicated with known hypersensitivity with CBZ (cross sensitivity with CBZ is 25-30%)
-HYPO-natremia (SIADH)
- Incidence is HIGHER than CBZ
-Occurs within 3 months of initiating treatment
-Sodium levels return to normal when OXC is D/C OR with mild fluid restriction
-Sedation
(ataxia, N/V, diplopia)
Oxcarbazepine
- Trileptal
- Oxtellar XR
Patient education
- Drowsiness
- Decreased efficacy of oral contraceptives, use back up
- DO NOT take if you have experienced hypersensitivity or rash with CBZ
- Take extended-release on EMPTY stomach 1 hour before OR 2 hours after meals
- Supplement with CALCIUM and VITAMIN D
- Trileptal oral suspension:
- once the bottle is open, use WITHIN 7 DAYS
Phenytoin
- Dilantin
- Dilantin Infatabs
- Phenytek
Used for:
- Partial seizures
- General tonic-clonic seizures
- Status epilepticus
- Trigeminal neuralgia
- *Can also be used for digoxin toxicity
MOA:
-Blocks Na+ channels
- *Potent 3A4 INDUCER
- *Therapeutic levels:
- 10 - 20 mcg/mL
**Pregnancy D – AVOID in pregnancy
Phenytoin
- Dilantin
- Dilantin Infatabs
- Phenytek
Black box warning, Monitor, side effects, serum level related toxicities
Black box warning:
- Rate of IV infusion must NOT EXCEED 50 mg/min
- to reduce the risk of HYPO-tension
Monitor:
- CBC
- LFT
- Folate
- Thyroid
- Phenytoin levels
Side effects:
-Chronic:
-Gingival hyperplasia
-Purple glove syndrome
-IV phenytoin is a vesicant and can cause venous irritation. Inject into a LARGE vein SLOWLY and use SALINE FLUSH
-Risk factors for purple glove syndrome:
-Hx of PVD
-Age 60+
-Elderly female
-Hirsutism
-Folate deficiency
(CNS, osteomalacia, rash, hepatoxicity, coarsening of facial features, blood dyscrasias, megaloblastic anemia, GI upset, SJS (rare), peripheral neuropathy, hyperglycemia)
Serum level related toxicities:
- Nystagmus ( >20 mcg/mL)
- Ataxia ( >30 mcg/mL)
- Confusion ( >40 mcg/mL)
Phenytoin
- Dilantin
- Dilantin Infatabs
- Phenytek
Protein binding, DDI, phenytoin characterstics
- 90% protein bound (albumin)
- Free PHT (unbound) levels correlate with pharmacological effect and toxicity
- Altered protein binding in RENAL failure and LOW albumin
DDI: INDUCER
- Reduces levels of:
- CBZ
- VPA
- Oral contraceptives
- Theophylline
- P450 INHIBITORS will INCREASE phenytoin levels
- Cimetidine
- Amiodarone
- Metronidazole
- Alcohol
- Enteral feedings will DECREASE absorption
- must hold feedings 1-2 hours before and after
- proteins in the enteral feed will DECREASE absorption
- *Phenytoin IV is only compatible with Normal saline (NS) because it contains proplyene glycol
- Requires filter and is stable for 4 hours
