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Ph Neuro AEDs
Pharma Neuro
| Question | Answer |
|---|---|
| Seizures: preferred mode of tx | monotherapy |
| Polytherapy probs | DI; dose-rel neurotox; minimal improvement in control |
| Rational polytherapy | Consider 2d agent if inadequate control after trials of 2 diff single agents; Diff MOAs, AE, DI’s |
| AED tx planning | Pt ed; confirm compliance; eval tox, DI, serum conc |
| Dilantin/Cerebryx Indications: | Genl tonic-clonic; Simple & complex partial; often for prophylaxis following trauma / neurosurgery |
| Phenytoin dosing | Use adjusted dosing wt for obese pt; adjust levels with LD (IV); start w/ loading dose, then maint dose |
| Phenytoin PK | double dose: more than double fx |
| PHT & Albumin | Low alb (poor renal fn); order Free PHT levels; can adjust PHT conc for low alb if cannot get free PHT level |
| Draw PHT serum conc levels: | LD: 24h postdose; trough prior to next dose; hosp pt: 3-5d post start; O/P: 7d post change & q 2-4 wk til stable; >50 mg/dL take days to return to tx range |
| PHT AE | lethargy, fatigue, drowsiness |
| PHT AE at 40 mg/L | clouded sensorium, coma |
| PHT DI | PHT decreases fx of many drugs (including c’steroids, warfarin, OCP, estrogen, rifampin, doxy, Lasiz, Theophylline) |
| Carbamazepine fx on PHT | decrease PHT conc |
| CBZ indications: | Simple and complex partial seizures; genl tonic-clonic |
| CBZ dosing | No LD; re-assess in 1-2 mos (d/t autoinduction of metabm); maint dose (usu higher in pt <15 yo); max usu <1200 mg/day |
| CBZ AE | Many neuro (lethargy, ataxia, diplopia); N/V; SIADH; cardiac; thyroid hormone clearance; BM suppn (low counts; aplastic anemia), rash; reduce dose or inc interval |
| Oxcarbazepine indications | partial seizure (adult: mono or adjunct; kids: adjunct) |
| Oxcarbazepine AE | cross reactivity w/ CBZ; low blood counts; multi-organ hypersensitivity; erythema multiforme, SJS; toxic epidermal necrolysis |
| Phenobarb / Primidone indications | Genl myoclonic; Partial; Febrile seizures; Sedation; Hypnosis; Preanesthesia |
| Phenobarb loading dose: | (long half life, so:) divide LD into 3-4 doses over several hrs; Primidone no indication for LD |
| Phenobarb injxn: use when: | after failure of benzo & PHT for status epilepticus |
| PB / Primidone AE | CNS depression, impaired cognitive, nystagmus, somnolence, etc; megaloblastic anemia; folate def; dec clot factors; dec vit D; osteomalacia; porphyria; impotence; rash/SJS; resp depn; bradycardia; GI |
| Valpro indications | Genl seizure (atypical, tonic-clonic, myoclonic); febrile; adjunct or 3rd line for partial; less mental impairment, good choice for kids with appropriate seizure type |
| Valpro DI | Most sig: on CBZ & PB |
| Valpro AE | Hepatotox (watch out in kids); pancreatitis; N/V; wt; ataxia/tremor; alopecia; rash; plt dysfn; teratogen |
| Drugs for seizure emergency: | Benzos |
| AED to adj dose for renal: | Gabapentin, pregabalin, zonisamide, Keppra, Sabril |
| Hepatic dosing considerations: | zonisamide, VPA |
| Related to antifolate drugs = | Lamictal |
| Topamax: If CrCl < 70 ml/min: | use one-half usual dose |
| Topamax DI | PHT, CBZ, VPA |
| Tiagabine: dosing | Take with food; works well as add-on for pt w/poor partial seizure control or AEs in partial & tonic-clonic |
| Keppra indication | adjunctive for partial |
| Vigabatrin indications | infantile spasms; refractory complex partial; off-label refractory partial / secondary genl |
| Vigabatrin AE | can cause permanent vision loss; psych disturbances; abnormal infant MRI findings |
| AED titration | Start low * gradually increase; initiate with 1/3-1/4 of anticipated maintenance dose & increase over 3-4 weeks |
| DOC for new onset partial: most common: | CBZ, Lamictal, oxcarb, PHT |
| DOC for partial, refractory | lamictal, oxcarb, Topamax |
| DOC: adjunct: partial, refractory | Gabapentin; Lamotrigine; Keppra; Oxcarb; Topamax; Zonisamide |
| DOC: Genl Seizures, Absence, Newly Dx | Lamotrigine; Ethosuximide; Valpro |
| DOC: Primary Genl (Tonic-Clonic) | Topiramate; Valpro (Alt: Lamotrigine) |
| Status Epilepticus: Tx: | IV Diazepam (slow push x 2 min); IV Lorazepam |
| AED & PG | New gen drugs: most Class C; Class D = PHT, CBZ; Valpro is worst |
| Dilantin/Cerebryx MOA | voltage and time dependent block of sodium channels |
| Topamax MOA | blockade of voltage dependent Na channels, potentiation of GABAergic transmission |
| Clonazepam MOA | Benzo (modulates GABA-related transmission in the brain) |
| Valpro MOA | similar to PB |
| Phenobarb / Primidone MOA | Enhance GABA-ergic inhib; reduce Na & Ca current |
| Zonisamide MOA: | Sulfonamide; may block Na channels and reduce T-type Ca currents |
| Lacosamide MOA | enhances slow inactivation of Na channels & stabilizes hyperexcitable neuronal membranes via this mechanism |
| Vigabatrin MOA | Highly toxic drug; irreversibly inhibits GABA transaminase, which increases GABA levels in the brain |
| d/c AEDs | If onset btw age 2-35 & normal EEG; seizure-free period 2-4 yrs; complete ctrl within 1 yr; very gradual taper over 6 mos; relapse usu within first few mos after withdrawal; f/u in 5 yrs if no probs |
Created by:
Abarnard
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