Antiepileptic Drugs (AEDs)
| Drug | Mechanism | Seizure Types | Key Toxicities / Notes |
|---|---|---|---|
| Valproic acid (Depakote) | Blocks Na+ channels + enhances GABA; multiple mechanisms | Broad spectrum: GTC, absence, myoclonic, partial — most versatile | Hepatotoxicity (monitor LFTs), pancreatitis, neural tube defects (teratogen — avoid in women of childbearing age), weight gain, hair loss, thrombocytopenia, tremor. CONTRAINDICATED in pregnancy (Category D/X). Drug interactions (induces/inhibits CYP enzymes) |
| Levetiracetam (Keppra) | Binds SV2A synaptic vesicle protein → inhibits neurotransmitter release | Broad spectrum: focal, GTC, myoclonic — first-line for many | Behavioral/psychiatric side effects (irritability, aggression, depression — "Keppra rage"); renally cleared (dose adjust in CKD); minimal drug interactions; safe in pregnancy (Category C); available IV for status epilepticus |
| Lamotrigine (Lamictal) | Na+ channel blocker | Focal, GTC, absence, Lennox-Gastaut; also bipolar disorder | Stevens-Johnson syndrome (SJS) risk — MUST titrate slowly (low, slow start), especially with valproate (increases lamotrigine levels 2×). Rash early in therapy requires stopping. Drug of choice in women of reproductive age for epilepsy; lower teratogenic risk. Reduced efficacy by enzyme inducers (carbamazepine, phenytoin) |
| Carbamazepine (Tegretol) | Na+ channel blocker; stabilizes inactivated state | Focal seizures (1st line), GTC, trigeminal neuralgia; NOT for absence or myoclonic | SJS/TEN (especially HLA-B*15:02 — screen Asian patients); aplastic anemia (rare); SIADH (hyponatremia); diplopia, ataxia (dose-related); potent CYP3A4 inducer (induces its own metabolism — autoinduction); many drug interactions; teratogenic (NTDs) |
| Phenytoin (Dilantin) | Na+ channel blocker (use-dependent) | Focal, GTC, status epilepticus (IV fosphenytoin); NOT absence or myoclonic | Gingival hyperplasia, hirsutism, coarsening of facial features (chronic use); nystagmus (first sign of toxicity), ataxia, diplopia; zero-order kinetics (small dose changes cause large level changes); potent CYP inducer; teratogenic (fetal hydantoin syndrome); purple glove syndrome (IV extravasation); infuse slowly IV (<50mg/min) |
| Ethosuximide (Zarontin) | Blocks T-type Ca2+ channels in thalamus | Absence seizures ONLY (first-line, especially childhood absence) | GI side effects (N/V, anorexia); generally well-tolerated; not effective for GTC or focal — use valproate if both absence + GTC |
| Topiramate (Topamax) | Na+ channel blocker + GABA enhancer + AMPA/kainate antagonist + carbonic anhydrase inhibitor | Focal, GTC, Lennox-Gastaut; migraine prophylaxis; weight loss (Qsymia + phentermine) | Cognitive impairment ("Dopamax" — word-finding difficulty), kidney stones, metabolic acidosis, weight loss, paresthesias; teratogenic (cleft palate); angle-closure glaucoma (rare) |
🧠 Mnemonic — AED "Don't use in absence": CLAFPCarbamazepine · Lamotrigine (effective for absence, but start carefully) · AEDs to AVOID in absence: CBZ, phenytoin, tiagabine, vigabatrin (may worsen absence)
Parkinson's Disease Pharmacotherapy
| Drug | Mechanism | Notes / Side Effects |
|---|---|---|
| Levodopa/Carbidopa (Sinemet) | Levodopa = DA precursor → crosses BBB → converted to dopamine. Carbidopa = peripheral dopa decarboxylase inhibitor → prevents peripheral conversion of levodopa → reduces N/V and increases levodopa delivery to brain | Most effective antiparkinsonian drug. Side effects: N/V (early), dyskinesias (peak-dose), wearing-off (end-of-dose), on-off fluctuations (advanced disease), orthostatic hypotension, hallucinations (especially elderly). Give on empty stomach (protein competes with levodopa absorption) |
| Dopamine agonists (pramipexole, ropinirole, rotigotine patch) | Directly stimulate D2/D3 receptors in striatum | Used as initial therapy in younger patients (delay levodopa-related dyskinesias); add-on to levodopa for wearing-off. Side effects: impulse control disorders (gambling, hypersexuality — warn patients), somnolence (sudden sleep attacks), orthostatic hypotension, hallucinations, nausea. Rotigotine: 24-hour transdermal patch |
| MAO-B inhibitors (selegiline, rasagiline) | Inhibit MAO-B → reduce dopamine breakdown in brain | Mild symptomatic benefit; possible neuroprotective effect (unproven). Selegiline metabolized to amphetamine → insomnia; take in morning. Rasagiline: cleaner profile. Avoid with meperidine, SSRIs, TCAs (serotonin syndrome risk) |
| COMT inhibitors (entacapone, tolcapone) | Inhibit COMT enzyme → prevent peripheral degradation of levodopa → extends levodopa effect (reduces wearing-off) | Always used WITH levodopa/carbidopa; entacapone: combined pill (Stalevo = levodopa/carbidopa/entacapone); tolcapone: requires LFT monitoring (hepatotoxicity); entacapone: urine discoloration (orange) |
| Amantadine | NMDA antagonist + dopamine releaser/reuptake inhibitor + anticholinergic | Mild antiparkinsonian effect; most useful for levodopa-induced dyskinesias (reduce peak dose dyskinesias). Side effects: livedo reticularis (mottled skin), ankle edema, hallucinations, confusion (elderly); renally cleared |
| Anticholinergics (benztropine, trihexyphenidyl) | Block muscarinic receptors → reduce relative cholinergic excess in striatum | Mainly for tremor-dominant PD in younger patients; AVOID in elderly (cognitive impairment, confusion, urinary retention, constipation, dry mouth — anticholinergic side effects). Rarely used now |
Stroke Pharmacotherapy
| Drug | Indication | Dose / Time Window | Contraindications / Notes |
|---|---|---|---|
| Alteplase (tPA) | Acute ischemic stroke | 0.9mg/kg IV (max 90mg); 10% bolus, 90% over 1 hour; within 4.5 hours of symptom onset | CI: hemorrhage on CT, BP >185/110 (control first), INR >1.7, platelets <100K, blood glucose <50 or >400, prior stroke within 3 months, major surgery within 10-14 days, intracranial neoplasm, active internal bleeding. Post-tPA: no antiplatelets/anticoagulants × 24 hours; BP <180/105; monitor for angioedema, symptomatic ICH |
| Tenecteplase (TNKase) | Emerging alternative to alteplase for ischemic stroke; also used in ACS | 0.25mg/kg IV (max 25mg) single bolus; easier administration | Same exclusion criteria as alteplase; non-inferior in ATTEST-2 trial; less administration complexity; increasing adoption |
| Aspirin 325mg | Acute ischemic stroke (NOT given within 24 hours of tPA) | 325mg within 24–48 hours of ischemic stroke; long-term 81mg for secondary prevention | Switch to 81mg for long-term secondary prevention. If aspirin allergy: clopidogrel 75mg. For minor stroke/TIA: DAPT (aspirin + clopidogrel) × 21 days (POINT trial), then aspirin alone |
| Anticoagulation for AF-related stroke | DOAC preferred over warfarin for AF stroke prevention (unless mechanical valve or significant MS) | Start 1–4 weeks after moderate-to-large ischemic stroke (bleeding transformation risk); "1-3-6-12" rule — minor: 1 day; moderate: 3-7 days; severe: 12-14 days | Apixaban or rivaroxaban preferred; dabigatran if younger and good renal function; warfarin if mechanical valve or rheumatic mitral stenosis. Do NOT use DOACs if mechanical heart valves (increased stroke risk) |
| Statins | Secondary prevention post-ischemic stroke | High-intensity statin (atorvastatin 80mg) started acutely | SPARCL trial: atorvastatin 80mg reduced recurrent stroke by 16%; however slight increase in hemorrhagic stroke. Still recommended for all ischemic stroke patients with LDL ≥100 |
Multiple Sclerosis Disease-Modifying Therapies
| Efficacy Tier | Drug | Route | Key Points |
|---|---|---|---|
| Moderate (1st line) | Interferon beta-1a (Avonex, Rebif), interferon beta-1b (Betaseron), glatiramer acetate (Copaxone), dimethyl fumarate (Tecfidera), teriflunomide (Aubagio) | SQ/IM/PO | IFN-beta: flu-like symptoms, injection site reactions, liver enzyme elevation, thyroid issues. Glatiramer: injection site reactions, lipoatrophy. Dimethyl fumarate: flushing, GI side effects, lymphopenia (PML risk if lymphocytes very low). Teriflunomide: teratogenic, alopecia |
| High efficacy (escalation) | Natalizumab (Tysabri), ocrelizumab (Ocrevus), ofatumumab (Kesimpta), fingolimod (Gilenya), siponimod (Mayzent), cladribine (Mavenclad) | IV infusion / PO | Natalizumab: IV q4 weeks; risk of PML (JC virus reactivation) — test JC antibody titer; hold if JC+ with high titer. Ocrelizumab: anti-CD20; PPMS approved; PML risk; monitor for infections, HBV reactivation; first-dose reactions. Fingolimod: bradycardia (observe 6 hrs after first dose), macular edema, reactivation of VZV — requires cardiac monitoring at initiation |
| Very high efficacy (highly active MS) | Alemtuzumab (Lemtrada), cladribine, autologous HSCT | IV infusion | Alemtuzumab: yearly infusion × 2 courses; profound lymphodepletion → infusion reactions, autoimmune thyroid disease, ITP, nephropathy — extensive monitoring required; very high efficacy (50–70% relapse reduction) |
🎯 Boards PearlAcute MS relapse: high-dose IV methylprednisolone (1g/day × 3–5 days) speeds recovery but does NOT change long-term disability or affect disease course. All DMTs require pregnancy consideration — most must be stopped before conception. Ocrelizumab (Ocrevus) is the ONLY FDA-approved DMT for PPMS. PML (progressive multifocal leukoencephalopathy) = JC virus reactivation → severe demyelination; associated with natalizumab, dimethyl fumarate (severe lymphopenia), fingolimod.
Dementia Pharmacotherapy
| Drug | Class | Indication | Mechanism & Notes |
|---|---|---|---|
| Donepezil (Aricept) | Acetylcholinesterase inhibitor (AChEI) | Mild-to-moderate and severe AD | Inhibits AChE → increases synaptic ACh → modest cognitive benefit. Side effects: N/D, insomnia, bradycardia (cholinergic). 5mg at bedtime (start low); titrate to 10mg; 23mg dose for severe AD. Available as orally disintegrating tablet |
| Rivastigmine (Exelon) | AChEI + butyrylcholinesterase inhibitor | Mild-moderate AD; Parkinson's disease dementia (PDD) | Patch formulation preferred (fewer GI side effects vs. oral). Preferred agent for DLB and PDD. Applied daily to upper back/arm — rotate sites |
| Galantamine (Razadyne) | AChEI + allosteric nicotinic receptor modulator | Mild-moderate AD | Twice daily or ER once daily; similar efficacy to other AChEIs; GI side effects similar |
| Memantine (Namenda) | NMDA receptor antagonist | Moderate-to-severe AD (alone or combined with AChEI) | Blocks excessive NMDA-glutamate stimulation (excitotoxicity) → neuroprotective. Start 5mg daily; titrate to 10mg BID (20mg/day). Well-tolerated; dizziness, constipation, confusion (rare); reduce dose in renal impairment (CrCl <30) |
| Lecanemab (Leqembi) | Anti-amyloid monoclonal antibody | Early AD (MCI or mild AD) with confirmed amyloid | FDA accelerated approval 2023; traditional approval 2023; IV infusion q2 weeks; reduces amyloid plaques; modest slowing of cognitive decline (27% slower in CLARITY AD trial); risk of ARIA (amyloid-related imaging abnormalities — edema and microhemorrhages); monitor with MRI; very expensive; APOE4 carriers at higher ARIA risk |
Headache / Migraine Pharmacotherapy
| Drug Class | Examples | Use | Notes |
|---|---|---|---|
| Triptans (5-HT1B/1D agonists) | Sumatriptan (Imitrex), rizatriptan, eletriptan, zolmitriptan | Acute moderate-severe migraine (with or without aura) | First-line for acute migraine; vasoconstriction → contraindicated in CVD, uncontrolled HTN, hemiplegic/basilar migraine; do NOT combine with MAOIs or use within 24 hrs of ergotamines |
| CGRP antagonists (gepants) | Rimegepant (Nurtec), ubrogepant (Ubrelvy), atogepant (Qulipta — prevention) | Acute migraine treatment ± prevention | Novel; no vasoconstriction → safe in CVD; available OTC (rimegepant). Atogepant: oral daily for prevention. Also available: erenumab, fremanezumab, galcanezumab (anti-CGRP monoclonal antibodies — monthly SQ for prevention) |
| Prophylaxis | Propranolol, topiramate, amitriptyline, valproate, venlafaxine, candesartan; CGRP inhibitors (erenumab, fremanezumab) | Prevention (≥4 migraine days/month or significantly disabling attacks) | Propranolol and topiramate: most evidence. Amitriptyline: also treats depression/insomnia comorbidities. Topiramate: weight loss benefit. CGRP inhibitors: highly effective, well-tolerated, expensive. Botulinum toxin (Botox): chronic migraine (≥15 days/month) |