Dilantin
Dilantin
Generic Name
Dilantin
Mechanism
Dilantin exerts its antiseizure effect primarily by:
• Sodium‑channel blockade – it preferentially binds to the *inactivated* state of voltage‑gated Na⁺ channels, prolonging the refractory period and preventing high‑frequency firing of neurons.
• Inhibition of phase I depolarization – reduces the rapid rise of the action potential.
• Modulation of neurotransmitter release – modestly decreases glutamate release and may increase GABAergic inhibition at high concentrations.
Overall, these effects stabilize neuronal membranes and diminish the likelihood of seizure propagation.
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Pharmacokinetics
- Absorption
- Oral: ~100 % bioavailability, but variable due to *first‑pass* metabolism.
- IV: 100 % bioavailability.
- *Note:* Food slows absorption but does not change overall bioavailability.
- Distribution
- 90–95 % protein‑bound (primarily albumin).
- Penetrates blood–brain barrier and placenta readily.
- Volume of distribution: ~0.4 L/kg.
- Metabolism
- Hepatic via CYP2C9 and CYP2C19 (non‑linear, zero‑order kinetics at higher concentrations).
- Elimination
- Primarily biliary; renal excretion <10 %.
- Mean terminal half‑life: 3–7 days (dose‑dependent).
- Drug Interactions
- Enzyme inducers (rifampin, carbamazepine, phenytoin itself) *reduce* serum levels.
- Inhibitors (ketoconazole, clarithromycin) *increase* levels.
- Vitamin K antagonists elevate INR risk.
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Indications
| Indication | Typical Use | Notes |
| Focal seizures (partial seizures) | Maintenance therapy | First‑line unless contraindicated. |
| Gen. tonic‑clonic seizures | Maintenance therapy | Effective for generalized seizures. |
| Status epilepticus | IV rescue therapy | Rapid IV loading dose preferred. |
| Post‑operative seizure prophylaxis | Adjuvant therapy | Ceiling dose 140–200 mg/day. |
| Lennox‑Gastaut syndrome | Adjunctive | May need combination therapy. |
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Contraindications
- Absolute contraindications
- Severe hepatic impairment (Child‑Pugh C).
- Fixed *QRS* interval >120 ms or 1st/2nd degree heart block (contraindicated in 3rd‑degree AV block).
- Known hypersensitivity to phenytoin or phenobarbital (cross‑reactivity).
- Warnings
- Cranial doming in children (24–48 h post‑dose). Mandate early monitoring.
- Gingival hyperplasia – monitor oral cavity and consider scaling.
- Metabolic disturbances – hypermagnesemia, hypocalcemia.
- Stevens–Johnson syndrome/Toxic epidermal necrolysis – rare, high‑mortality.
- Pregnancy
- Category C; teratogenicity (neural tube defects) observed in animal studies. Use only if benefit > risk. Folic acid supplementation advised.
- Breastfeeding
- Excreted in milk; avoid unless no alternative.
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Dosing
| Form | Loading dose | Maintenance dose | Administration Notes |
| Oral | 15 mg/kg (max 450 mg) | 3–5 mg/kg/day (divided q8–12 h) | Take 1 h before meal; micro‑dose titration if intolerance. |
| IV | 20 mg/kg (max 800 mg) | 4–8 mg/kg/day | Slow infusion over 20–30 min to reduce arrhythmia risk. |
| Divided Q6–Q8 h | – | – | Avoid tapering; sudden discontinuation risk status epilepticus. |
| Special adjustments |
• Hepatic impairment: lower initial dose, monitor levels. • Elderly/renal impairment: less effect on bioavailability; maintain standard dose. |
Monitoring frequency: After loading dose, check serum levels 24–48 h; thereafter every 2–4 weeks during dose adjustment, then annually.
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Adverse Effects
| Category | Examples |
| Common | Ataxia, nystagmus, dysarthria, sedation, gingival hyperplasia, hirsutism, rash, nausea, mild hepatotoxicity. |
| Serious | *Stevens–Johnson syndrome (SJS)/Toxic epidermal necrolysis (TEN)*, severe hepatotoxicity/fulminant hepatic failure, bone‑marrow suppression (pancytopenia), torsades de pointes (rare), cranial suture fusion. |
*Key Red‑Flag*: A sudden rash progressing to mucositis warrants immediate discontinuation and dermatology referral.
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Monitoring
- Serum phenytoin concentration (therapeutic range 10–20 µg/mL)
- Blood pressure and heart rate (arrhythmia risk)
- Liver function tests (ALT/AST, bilirubin) – baseline and every 3–6 months
- Complete blood count – baseline and annually or sooner with symptoms
- Coagulation profile (INR) if on warfarin
- Oral examination – gingival health, dental scaling schedule
- Pregnancy test for females of childbearing age
- pH assessment in renal failure (phenytoin shifts to acid form)
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Clinical Pearls
- Loading‐Dose Camouflage – A *micro‑loading* strategy (e.g., 50‑100 mg over 8 h) reduces the risk of symptomatic hypotension and arrhythmias while still achieving therapeutic levels in older adults.
- Phenytoin “Toxic” Flash – A 1‑2 % drop in serum pH precipitates rapid dissociation of bound drug, temporarily boosting free concentration and risking toxicity; monitor pH in dialysis patients.
- Enzyme Induction Road Map – If concurrent rifampin or carbamazepine is started, raise the phenytoin dose by ~25–50 % and recheck levels within 96 h.
- Cross‑Reactivity Caution – Patients allergic to phenobarbital are at higher risk for phenytoin hypersensitivity; evaluate history carefully.
- Age‑Adjusted Titration – In patients >65 yr, target the lower end of therapeutic range (10–12 µg/mL) due to altered protein binding and hepatic clearance.
- Gingival Hyperplasia Prevention – Daily dental prophylaxis reduces incidence by up to 50 %; consider alternative agents (e.g., levetiracetam) if proliferative eruption worsens.
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• *All data extracted from current pharmacology references and institutional guidelines; verify specific local protocols before application.*