Last Minute Review
Pharmacology — Last Minute Review
Rapid Review
A last-minute review of high-yield neuropharmacology facts for the RITE and board exams. Tables, key associations, and must-know one-liners — designed for a quick pass the night before.
Antiepileptic Drugs (ASMs)
| Drug | Mechanism | Key Side Effects | Monitoring | Teratogenicity / Notes |
|---|---|---|---|---|
| Levetiracetam | SV2A binding | Irritability, behavioral changes, depression | None routine | Low teratogenic risk; first-line in pregnancy |
| Valproate | Multiple: ↑ GABA, Na+ channel, T-type Ca2+ block | Weight gain, tremor, alopecia, thrombocytopenia, hepatotoxicity, pancreatitis, hyperammonemia | LFTs, CBC, ammonia, drug level | Most teratogenic ASM — neural tube defects (1–2%), ↓ IQ; avoid in women of childbearing age |
| Carbamazepine | Na+ channel blocker | Diplopia, ataxia, hyponatremia (SIADH), SJS/TEN, aplastic anemia, agranulocytosis | CBC, Na+, LFTs, drug level; HLA-B*1502 in Asian descent | Teratogenic (NTDs); CYP inducer — auto-induces own metabolism |
| Oxcarbazepine | Na+ channel blocker | Hyponatremia (more than CBZ), dizziness, rash | Na+ levels; HLA-B*1502 | Less enzyme induction than CBZ; cross-reactivity rash ~25% |
| Lamotrigine | Na+ channel, glutamate inhibition | SJS/TEN (slow titration required), headache, insomnia | Drug level (pregnancy) | Low teratogenic risk; preferred in pregnancy; valproate doubles lamotrigine levels |
| Phenytoin | Na+ channel blocker | Gingival hyperplasia, hirsutism, cerebellar atrophy, osteoporosis, peripheral neuropathy, SJS, megaloblastic anemia | Drug level (free + total), albumin; zero-order kinetics | CYP inducer; fetal hydantoin syndrome; highly protein-bound |
| Phenobarbital | GABA-A agonist (prolongs Cl− channel opening) | Sedation, cognitive impairment, respiratory depression | Drug level | CYP inducer; teratogenic (cardiac defects) |
| Topiramate | Multiple: Na+ channel, GABA, glutamate, carbonic anhydrase | Cognitive slowing (“Dopamax”), word-finding difficulty, kidney stones, weight loss, metabolic acidosis, angle-closure glaucoma | Bicarb, renal function | Teratogenic (cleft lip/palate); contraceptive failure at high doses |
| Lacosamide | Slow Na+ channel inactivation | PR prolongation, dizziness, diplopia | ECG (baseline) | Low interaction potential; IV formulation available |
| Zonisamide | Na+/Ca2+ channels, carbonic anhydrase | Kidney stones, oligohydrosis (children), weight loss | Renal function | Sulfonamide allergy cross-reactivity |
| Brivaracetam | SV2A (higher affinity than LEV) | Sedation, fatigue, dizziness | None routine | Less behavioral side effects than levetiracetam |
| Clobazam | GABA-A (1,5-benzodiazepine) | Sedation, drooling | CYP2C19 status | Approved for Lennox-Gastaut; less sedating than clonazepam |
| Perampanel | AMPA receptor antagonist | Aggression, dizziness, weight gain | Behavioral monitoring | Boxed warning: serious or life-threatening psychiatric & behavioral reactions (aggression, hostility, irritability, anger, homicidal ideation/threats) |
| Cannabidiol (Epidiolex) | Multiple (unclear primary) | Hepatotoxicity (esp. with VPA), diarrhea, sedation | LFTs | Approved for Dravet, Lennox-Gastaut, TSC; ↑ clobazam levels |
| Vigabatrin | Irreversible GABA transaminase inhibitor | Irreversible bilateral visual field constriction, fatigue | Counseling + periodic ophthalmologic monitoring: visual field testing (perimetry) when feasible; ERG ± OCT when perimetry is unreliable (infants/devo-limited) — OCT NOT a universal REMS test | First-line for infantile spasms (esp. with TSC) |
| Ethosuximide | T-type Ca2+ channel blocker | GI upset, headache, rare SJS | Drug level, CBC | First-line for childhood absence epilepsy; does NOT treat GTCs |
| Felbamate | NMDA antagonist, Na+ channel, GABA | Aplastic anemia, hepatic failure | CBC q2wk, LFTs; REMS program | Reserved for refractory Lennox-Gastaut; black box warnings |
| Rufinamide | Na+ channel (limits repetitive firing) | QT shortening, dizziness, nausea | ECG | Approved for Lennox-Gastaut; contraindicated in familial short QT |
ASM Enzyme Effects
| Category | Drugs | Clinical Impact |
|---|---|---|
| CYP Inducers | Phenytoin, carbamazepine, phenobarbital, primidone, (oxcarbazepine mild) | ↓ Levels of OCP, warfarin, lamotrigine, other ASMs, chemotherapy |
| CYP Inhibitors | Valproate, cannabidiol | ↑ Lamotrigine levels (VPA); ↑ clobazam levels (CBD) |
| Minimal interactions | Levetiracetam, brivaracetam, lacosamide, gabapentin, pregabalin | Preferred when polypharmacy is a concern |
💎 Board Pearl
- Lamotrigine + Valproate: VPA inhibits glucuronidation of LTG → doubles LTG levels → must halve LTG dose when adding VPA; ↑ SJS risk
- HLA-B*1502: Screen patients of Southeast Asian descent before starting carbamazepine, oxcarbazepine, or phenytoin → risk of SJS/TEN
- Phenytoin zero-order kinetics: Small dose changes → large level changes at higher concentrations; always check free level if albumin is low
- Vigabatrin visual fields: Irreversible bilateral concentric constriction — counseling + periodic ophthalmologic monitoring; visual field testing (perimetry) when feasible; ERG ± OCT when perimetry is unreliable (infants/devo-limited)
- Ethosuximide: Works for absence seizures ONLY (T-type Ca2+ channels in thalamus) — does not treat generalized tonic-clonic seizures
Movement Disorder Drugs
| Drug | Mechanism | Indication | Key Side Effect |
|---|---|---|---|
| Levodopa / Carbidopa | DA precursor / peripheral DOPA decarboxylase inhibitor | Parkinson disease (most effective) | Dyskinesias, motor fluctuations (wearing off, on-off), nausea, orthostatic hypotension, hallucinations |
| Pramipexole | D3 > D2 agonist (non-ergot) | PD, RLS | Impulse control disorders (gambling, hypersexuality), EDS, leg edema |
| Ropinirole | D2/D3 agonist (non-ergot) | PD, RLS | Same as pramipexole; augmentation in RLS |
| Selegiline | MAO-B inhibitor (irreversible) | Early PD (mild benefit) | Insomnia (amphetamine metabolite), serotonin syndrome with SSRIs; oral selegiline at PD doses is MAO-B selective (no tyramine reaction); transdermal/high-dose loses selectivity and acts as non-selective MAOI (tyramine reaction risk in psychiatric use) |
| Rasagiline | MAO-B inhibitor (irreversible) | Early PD, adjunct | No amphetamine metabolite; possible neuroprotective effect |
| Safinamide | MAO-B inhibitor + Na+/glutamate modulation | PD adjunct (off episodes) | Dyskinesia, insomnia |
| Entacapone | Peripheral COMT inhibitor | PD (extends levodopa effect) | Orange urine/sweat, diarrhea, ↑ dyskinesias |
| Opicapone | Peripheral COMT inhibitor (once daily) | PD (extends levodopa) | Dyskinesias, dizziness |
| Amantadine | NMDA antagonist, ↑ DA release | PD dyskinesias; also used in early PD, fatigue in MS | Livedo reticularis, ankle edema, hallucinations, anticholinergic effects |
| Trihexyphenidyl | Muscarinic antagonist (central) | PD tremor, dystonia | Cognitive impairment (avoid in elderly), dry mouth, urinary retention, constipation |
| Benztropine | Muscarinic antagonist + DA reuptake inhibitor | Drug-induced dystonia, PD tremor | Same anticholinergic side effects |
| Tetrabenazine | VMAT2 inhibitor (↓ DA) | Huntington chorea | Depression, suicidality (black box), parkinsonism, sedation |
| Deutetrabenazine | VMAT2 inhibitor (deuterated) | Huntington chorea, tardive dyskinesia | Less depression risk; BID dosing; CYP2D6 dependent |
| Valbenazine | VMAT2 inhibitor | Tardive dyskinesia (FDA-approved) | Somnolence, QT prolongation; once daily |
| Botulinum toxin (OnabotulinumtoxinA) | Blocks presynaptic ACh release at NMJ | Cervical dystonia, blepharospasm, limb spasticity, chronic migraine | Excessive weakness, dysphagia (cervical), ptosis (periorbital) |
💎 Board Pearl
- Levodopa response: Best predictor of idiopathic PD; poor levodopa response → think atypical parkinsonism (MSA, PSP, CBD)
- Dopamine agonists in young PD: Used first to delay levodopa dyskinesias, but watch for impulse control disorders
- VMAT2 inhibitors: Deplete presynaptic dopamine — tetrabenazine (chorea), valbenazine/deutetrabenazine (tardive dyskinesia)
- Anticholinergics: Best for tremor-predominant PD in young patients; avoid in elderly (cognitive side effects)
Headache Pharmacology
Acute Treatments
| Drug / Class | Mechanism | Key Point |
|---|---|---|
| Triptans (sumatriptan, rizatriptan, etc.) | 5-HT1B/1D agonist → vasoconstriction + ↓ CGRP release | Contraindicated in CAD, uncontrolled HTN, hemiplegic/basilar migraine, stroke; avoid within 24h of ergots; MOH risk with >10 days/month |
| Gepants (ubrogepant, rimegepant, zavegepant) | CGRP receptor antagonist | No vasoconstriction; no triptan-like CAD/stroke contraindication — useful when triptans are contraindicated; use clinical caution in active/unstable vascular disease (pivotal trials excluded unstable CV disease); rimegepant also approved for prevention (every other day) |
| Lasmiditan | 5-HT1F agonist (ditan) | No vasoconstriction; Schedule V (driving restriction 8h); dizziness, sedation |
| NSAIDs (ibuprofen, naproxen, ketorolac) | COX inhibition → ↓ prostaglandins | First-line for mild–moderate migraine; ketorolac IV/IM for ED; GI/renal risks |
| Ergotamine / DHE | 5-HT1B/1D + D2 + α-adrenergic agonist | DHE IV/nasal for refractory status migrainosus; contraindicated with triptans; vasospasm risk |
Preventive Treatments
| Drug | Class | Mechanism | Key Point |
|---|---|---|---|
| Topiramate | ASM | Multiple (Na+, GABA, glutamate, CA) | FDA-approved; weight loss; cognitive dulling; teratogenic |
| Valproate | ASM | ↑ GABA, Na+ block | FDA-approved; weight gain; teratogenic — avoid in women of childbearing age |
| Propranolol | β-blocker | β1/β2 antagonism | FDA-approved; avoid in asthma, bradycardia, depression |
| Amitriptyline | TCA | NE + 5-HT reuptake inhibition | Best evidence among TCAs; anticholinergic side effects; weight gain |
| Venlafaxine | SNRI | NE + 5-HT reuptake inhibition | Alternative to amitriptyline; fewer anticholinergic effects |
| Erenumab | CGRP mAb | CGRP receptor antagonist | Monthly SC; constipation, HTN (unique to erenumab — receptor Ab). CGRP-targeting therapies (mAbs + oral gepants) are first-line for migraine prevention per AHS 2024 position statement — do NOT require failure of oral preventives as a biologic rule |
| Fremanezumab | CGRP mAb | Anti-CGRP ligand | Monthly or quarterly SC |
| Galcanezumab | CGRP mAb | Anti-CGRP ligand | Monthly SC; also approved for episodic cluster headache |
| Eptinezumab | CGRP mAb | Anti-CGRP ligand | IV infusion quarterly; fastest onset among CGRP mAbs |
| OnabotulinumtoxinA | Neurotoxin | Blocks CGRP & substance P release from trigeminal afferents | FDA-approved for chronic migraine only (≥15 days/month); 31 injection sites q12wk |
💎 Board Pearl
- Erenumab is the only CGRP mAb that targets the receptor; all others target the ligand
- OnabotulinumtoxinA: Only FDA-approved for chronic migraine (≥15 days/month), NOT episodic migraine
- Gepants/lasmiditan: No vasoconstriction; no triptan-like CV contraindication — useful when triptans are contraindicated; use clinical caution in active/unstable vascular disease (limited high-risk data)
- Medication overuse headache: Triptans >10 d/mo, analgesics >15 d/mo, opioids/barbiturates >10 d/mo
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