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
Immunotherapy & MS Drugs
| Drug | Mechanism | Route | Key Risk / Monitoring |
|---|---|---|---|
| Interferon-β (1a, 1b) | Immunomodulatory (↓ T-cell activation, ↓ BBB migration) | IM or SC | Flu-like symptoms, depression, hepatotoxicity, injection site reactions; CBC + LFTs q3–6mo |
| Glatiramer acetate | MBP analog → shifts Th1→Th2 | SC | Injection site reactions, post-injection systemic reaction (flushing, chest tightness — benign); no lab monitoring |
| Dimethyl fumarate | Nrf2 activation, ↓ NF-κB | PO | Flushing, GI, lymphopenia → PML risk if lymphocytes <500 for >6mo; CBC q6mo |
| Teriflunomide | DHODH inhibitor (↓ pyrimidine synthesis → ↓ lymphocyte proliferation) | PO | Contraindicated in pregnancy (boxed warning — teratogenic in animals); requires accelerated elimination with cholestyramine 8 g TID × 11 d or activated charcoal 50 g BID × 11 d, then verify plasma teriflunomide concentration <0.02 mg/L on two tests ≥14 days apart (NOT just "undetectable") before conception; hepatotoxicity; LFTs monthly ×6mo |
| Fingolimod | S1P receptor modulator (traps lymphocytes in lymph nodes) | PO | First-dose bradycardia (6h monitoring), macular edema, ↑ infections, PML; CBC, OCT, ECG, VZV status |
| Siponimod | S1P1,5 receptor modulator | PO | Approved for active SPMS; CYP2C9 genotyping required; bradycardia, macular edema |
| Ozanimod | S1P1,5 receptor modulator | PO | Titration reduces cardiac effects; avoid with MAOIs (active metabolite inhibits MAO-B) |
| Natalizumab | Anti-α4 integrin → blocks lymphocyte CNS entry | IV q4wk | PML risk — stratify by JCV Ab index; JCV+ & index >1.5 & >2yr → highest risk; REMS program |
| Ocrelizumab | Anti-CD20 (humanized) → B-cell depletion | IV (initial 300 mg × 2 doses 2 weeks apart, then 600 mg q6 mo) | Infusion reactions, ↑ infections, ↓ IgG over time, hepatitis B reactivation; screen HBV |
| Ofatumumab | Anti-CD20 (fully human) | SC monthly | Similar to ocrelizumab; self-administered; injection site reactions |
| Alemtuzumab | Anti-CD52 → pan-lymphocyte depletion | IV (2 courses) | Secondary autoimmunity (thyroid 30–40%, ITP, anti-GBM disease); monthly CBC, creatinine, TSH, urinalysis ×48 mo after last dose (detects anti-GBM glomerulonephritis); REMS |
| Cladribine | Purine analog → lymphocyte apoptosis | PO (2 courses, years 1 & 2) | Lymphopenia, herpes zoster, malignancy concern; CBC |
| Rituximab | Anti-CD20 (chimeric) → B-cell depletion | IV q6mo | Off-label for MS/NMOSD; infusion reactions; HBV screening; ↓ IgG monitoring |
PML Risk Stratification (Natalizumab)
| JCV Ab Status | JCV Index | Duration | Prior Immunosuppression | PML Risk |
|---|---|---|---|---|
| Negative | N/A | Any | Any | ~0.1/1000 |
| Positive | ≤0.9 | ≤2 yr | No | ~0.1/1000 |
| Positive | ≤0.9 | >2 yr | No | ~0.7/1000 (further ↑ with prior IS) |
| Positive | 0.9–1.5 | >2 yr | No | ~3/1000 |
| Positive | >1.5 | >2 yr | Yes (prior IS) | Highest (~10/1000) |
💎 Board Pearl
- Natalizumab PML: JCV Ab index >1.5 + >2 years of therapy → highest risk; consider extended interval dosing (EID, q6wk) to reduce risk
- Fingolimod first dose: Requires 6-hour cardiac monitoring for bradycardia; check VZV titer and vaccinate if negative before starting
- Alemtuzumab autoimmunity: Monitor thyroid (TSH monthly), CBC, creatinine for 4 years after last infusion
- Teriflunomide washout: Cholestyramine or activated charcoal needed before pregnancy (long half-life); endpoint = plasma teriflunomide concentration <0.02 mg/L on two tests ≥14 days apart (NOT just "undetectable")
- Anti-CD20 agents: Deplete B cells but NOT plasma cells → IgG may decline over years; check immunoglobulin levels
Neuromuscular Pharmacology
| Drug | Mechanism | Use |
|---|---|---|
| Myasthenia Gravis | ||
| Pyridostigmine | AChE inhibitor → ↑ ACh at NMJ | First-line symptomatic MG treatment; muscarinic side effects (SLUDGE) |
| IVIg | Immunomodulatory (multiple mechanisms: Fc receptor blockade, anti-idiotypic Ab) | MG exacerbation, crisis; also GBS, CIDP; headache, aseptic meningitis, thrombosis, renal failure |
| PLEX | Removes circulating antibodies | MG crisis, rapid pre-thymectomy; coagulopathy, hypotension, line infections |
| Azathioprine | Purine synthesis inhibitor | MG steroid-sparing; check TPMT before starting; hepatotoxicity, myelosuppression; onset 3–6mo |
| Mycophenolate | IMPDH inhibitor (↓ purine synthesis) | MG steroid-sparing; GI side effects, teratogenic; onset 3–6mo |
| Eculizumab | Anti-C5 complement → blocks MAC formation | Refractory generalized AChR+ MG; IV q2 weeks maintenance (after 5-week induction); requires meningococcal vaccination; ↑ Neisseria risk |
| Ravulizumab | Anti-C5 (long-acting eculizumab) | AChR+ gMG; IV q8 weeks maintenance (contrast with eculizumab q2wk); same meningococcal risk |
| Zilucoplan (Zilbrysq) | Macrocyclic peptide C5 inhibitor (blocks MAC formation + C5a) | AChR+ gMG; SC daily (self-administered); meningococcal vaccination required |
| Efgartigimod | FcRn inhibitor → ↓ IgG (including pathogenic Ab) | AChR+ gMG; IV or SC; cyclical dosing based on symptoms |
| Rozanolixizumab | FcRn inhibitor | AChR+ gMG; SC weekly; headache common |
| ALS | ||
| Riluzole | Glutamate release inhibitor + Na+ channel | ALS — extends survival ~2–3 months; LFTs monitoring |
| Edaravone | Free radical scavenger | ALS — may slow functional decline in select patients; IV or PO |
| Tofersen | Antisense oligonucleotide (ASO) targeting SOD1 mRNA | SOD1-ALS only; intrathecal; ↓ neurofilament levels |
| SMA | ||
| Nusinersen | ASO → modifies SMN2 splicing → ↑ SMN protein | SMA (all types); intrathecal q4mo; thrombocytopenia, renal toxicity |
| Onasemnogene abeparvovec | AAV9 gene therapy delivering SMN1 | SMA type 1 (<2 years); one-time IV; hepatotoxicity (monitor LFTs, give steroids) |
| Risdiplam | SMN2 splicing modifier (oral) | SMA (all types, ≥2mo); daily PO; fever, rash |
| hATTR Amyloidosis | ||
| Patisiran | siRNA → ↓ TTR mRNA | hATTR polyneuropathy; IV q3wk; infusion reactions |
| Inotersen | ASO → ↓ TTR mRNA | hATTR polyneuropathy; SC weekly; thrombocytopenia, glomerulonephritis (REMS) |
| Tafamidis | TTR tetramer stabilizer | ATTR cardiomyopathy; PO daily |
💎 Board Pearl
- Pyridostigmine overdose: Cholinergic crisis mimics myasthenic crisis — both cause weakness; cholinergic crisis has ↑ secretions, miosis, bradycardia
- Eculizumab: Meningococcal vaccination required ≥2 weeks before; covers MenACWY + MenB
- TPMT testing: Required before azathioprine — deficiency → fatal myelosuppression
- Drugs that worsen MG: Aminoglycosides, fluoroquinolones, magnesium, beta-blockers, botulinum toxin, D-penicillamine, checkpoint inhibitors
Psychopharmacology
| Class | Key Drugs | Mechanism | Key Side Effects |
|---|---|---|---|
| SSRIs | Fluoxetine, sertraline, paroxetine, citalopram, escitalopram | Selective 5-HT reuptake inhibition | GI upset, sexual dysfunction, SIADH (hyponatremia), ↑ bleeding risk, serotonin syndrome; paroxetine most anticholinergic; citalopram → QT prolongation |
| SNRIs | Venlafaxine, duloxetine, milnacipran | 5-HT + NE reuptake inhibition | HTN (venlafaxine), nausea, serotonin syndrome; duloxetine for neuropathic pain & fibromyalgia |
| TCAs | Amitriptyline, nortriptyline, desipramine, imipramine | 5-HT + NE reuptake inhibition + anticholinergic + antihistaminic | Anticholinergic (dry mouth, urinary retention, constipation), cardiac conduction delay (QRS widening), sedation, weight gain, seizures in overdose; fatal in overdose |
| MAOIs | Phenelzine, tranylcypromine, selegiline (transdermal) | Irreversible MAO-A/B inhibition | Tyramine crisis (hypertensive emergency with aged cheese, wine); serotonin syndrome with SSRIs/meperidine; 2-week washout required |
| Typical antipsychotics | Haloperidol, chlorpromazine, fluphenazine | D2 receptor blockade | EPS (acute dystonia, akathisia, parkinsonism, tardive dyskinesia), NMS, QT prolongation, prolactin elevation |
| Atypical antipsychotics | Quetiapine, olanzapine, risperidone, clozapine, aripiprazole | 5-HT2A + D2 blockade | Metabolic syndrome (weight, DM, lipids — worst with olanzapine/clozapine); clozapine → agranulocytosis (weekly CBC ×6mo); quetiapine = sedation |
| Lithium | Multiple (GSK-3 inhibition, inositol depletion) | Bipolar (gold standard for mania prophylaxis) | Tremor, hypothyroidism, nephrogenic DI, renal impairment, teratogenic (Ebstein anomaly); narrow therapeutic index — level 0.6–1.2 mEq/L |
| Benzodiazepines | Diazepam, lorazepam, clonazepam, midazolam | GABA-A positive allosteric modulator (↑ Cl− channel frequency) | Sedation, respiratory depression, dependence, paradoxical agitation (elderly); reversal = flumazenil |
Serotonin Syndrome vs Neuroleptic Malignant Syndrome
| Feature | Serotonin Syndrome | NMS |
|---|---|---|
| Cause | Serotonergic drugs (SSRIs, MAOIs, triptans, tramadol, linezolid) | Dopamine antagonists (antipsychotics) or sudden DA withdrawal |
| Onset | Rapid (hours) | Gradual (days–weeks) |
| Neuromuscular | Clonus, hyperreflexia, myoclonus (lower > upper extremity) | Lead-pipe rigidity, bradyreflexia |
| Pupils | Dilated (mydriasis) | Normal |
| Bowel sounds | ↑ (hyperactive) | ↓ (hypoactive) |
| Fever | Present | Very high (>40°C) |
| CK | Mild elevation | Markedly elevated (>1000) |
| Treatment | Stop offending agent, cyproheptadine, benzodiazepines, cooling | Stop offending agent, dantrolene, bromocriptine, cooling, ICU |
| Resolution | 24–72 hours | Days–weeks |
💎 Board Pearl
- Serotonin syndrome key triad: Mental status changes + autonomic instability + neuromuscular hyperactivity (clonus is the hallmark)
- NMS key triad: Hyperthermia + rigidity + altered mental status (CK massively elevated)
- Clozapine: Most effective antipsychotic for treatment-resistant schizophrenia; requires REMS due to agranulocytosis risk
- MAOI washout: 2 weeks before starting SSRI (5 weeks for fluoxetine due to long half-life of norfluoxetine)
- TCA overdose: QRS widening on ECG → treat with sodium bicarbonate
Pain & Anesthesia Pharmacology
| Drug / Class | Mechanism | Use | Key Point |
|---|---|---|---|
| Gabapentin | α2δ Ca2+ channel subunit binding → ↓ excitatory NT release | Neuropathic pain, PHN, RLS | Sedation, dizziness, edema; renal dosing; no hepatic metabolism |
| Pregabalin | α2δ Ca2+ channel subunit binding | Neuropathic pain, fibromyalgia, PHN | Schedule V; more predictable pharmacokinetics than gabapentin; linear absorption |
| Duloxetine | SNRI (5-HT + NE) | Diabetic neuropathy, fibromyalgia, chronic pain | Avoid in severe hepatic/renal impairment; nausea most common SE |
| Carbamazepine | Na+ channel blocker | First-line for trigeminal neuralgia | Check HLA-B*1502; enzyme inducer; monitor Na+, CBC |
| Oxcarbazepine | Na+ channel blocker | Second-line for trigeminal neuralgia | More hyponatremia than CBZ; fewer drug interactions |
Opioid Receptors
| Receptor | Effects | Key Agonists |
|---|---|---|
| Mu (μ) | Analgesia, euphoria, respiratory depression, miosis, constipation, dependence | Morphine, fentanyl, methadone, oxycodone |
| Kappa (κ) | Analgesia (spinal), dysphoria, sedation, diuresis | Pentazocine, butorphanol (mixed agonist-antagonists — kappa agonist, mu partial agonist/antagonist) |
| Delta (δ) | Analgesia, antidepressant effects | Enkephalins |
Neuromuscular Blockers & Local Anesthetics
| Category | Examples | Mechanism | Key Point |
|---|---|---|---|
| Depolarizing NMB | Succinylcholine | ACh receptor agonist → sustained depolarization → Phase I then Phase II block | Malignant hyperthermia (with volatile anesthetics); hyperkalemia (avoid in burns, denervation, spinal cord injury >24h); fasciculations before paralysis |
| Non-depolarizing NMB | Rocuronium, vecuronium, cisatracurium, pancuronium | Competitive ACh receptor antagonist | Reversed by neostigmine + glycopyrrolate or sugammadex (rocuronium/vecuronium) |
| Local anesthetics | Lidocaine, bupivacaine, ropivacaine | Na+ channel blockade → blocks nerve conduction | Small myelinated fibers blocked first (pain/temp before motor); bupivacaine = most cardiotoxic; treat toxicity with lipid emulsion (Intralipid) |
💎 Board Pearl
- Malignant hyperthermia: Succinylcholine + volatile anesthetics → RYR1 mutation → uncontrolled Ca2+ release → rigidity, hyperthermia, rhabdomyolysis; treat with dantrolene
- Succinylcholine contraindications: Burns/crush >24h, denervation injury, prolonged immobilization, hyperkalemia, personal/family history of MH
- Carbamazepine for TN: First-line; if ineffective → oxcarbazepine or add baclofen; surgical options for refractory
- Local anesthetic order of blockade: Autonomic (small unmyelinated C) → pain/temp (small myelinated Aδ) → proprioception → motor (large myelinated Aα)
Antimicrobials for CNS Infections
Bacterial Meningitis Empiric Therapy by Age
| Age Group | Common Organisms | Empiric Regimen |
|---|---|---|
| <1 month | GBS, E. coli, Listeria | Ampicillin + gentamicin and/or cefotaxime (3rd-gen ceph) depending on age/severity/local resistance/meningitis concern; AVOID ceftriaxone (bilirubin displacement → kernicterus) |
| 1–23 months | S. pneumoniae, N. meningitidis, H. influenzae, E. coli | Vancomycin + ceftriaxone (or cefotaxime) |
| 2–50 years | S. pneumoniae, N. meningitidis | Vancomycin + ceftriaxone + dexamethasone |
| >50 years | S. pneumoniae, N. meningitidis, Listeria, gram-negatives | Vancomycin + ceftriaxone + ampicillin (for Listeria) + dexamethasone |
| Immunocompromised | Above + Listeria, Pseudomonas, fungi | Vancomycin + cefepime (or meropenem) + ampicillin |
Specific CNS Infections
| Organism / Condition | First-Line Treatment | Key Point |
|---|---|---|
| HSV encephalitis | IV acyclovir (21 days for neonates, 14–21 days for adults) | Start empirically if suspected — do NOT wait for PCR; temporal lobe predilection |
| VZV vasculopathy / encephalitis | IV acyclovir | Can cause large vessel or small vessel CNS vasculopathy; CSF may show VZV IgG (PCR less sensitive late) |
| CMV encephalitis / radiculitis | Ganciclovir + foscarnet | Immunocompromised; CMV polyradiculopathy presents with rapidly progressive cauda equina syndrome |
| TB meningitis | RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) + dexamethasone | Steroids reduce mortality; basilar meningitis, CN palsies, hydrocephalus; isoniazid → peripheral neuropathy (give B6) |
| Cryptococcal meningitis | Amphotericin B + flucytosine (induction) → fluconazole (consolidation/maintenance) | Immunocompromised (CD4 <100); India ink, CrAg; ↑ ICP management critical (serial LPs) |
| Toxoplasma encephalitis | Pyrimethamine + sulfadiazine + leucovorin | Ring-enhancing lesions in AIDS (CD4 <100); empiric treatment if serologies positive; biopsy if no response in 2wk |
| PML (JC virus) | No proven antiviral; restore immune function (ART for HIV, remove immunosuppression) | Asymmetric white matter lesions, no mass effect, no enhancement; JCV PCR in CSF; associated with natalizumab, rituximab |
| Neurosyphilis | IV penicillin G (10–14 days) | Tabes dorsalis (dorsal columns), Argyll Robertson pupil (accommodates but doesn’t react), general paresis; CSF VDRL specific, FTA-ABS sensitive |
| Neurocysticercosis | Albendazole (+ praziquantel if heavy burden) + dexamethasone + ASMs | Most common cause of epilepsy worldwide; treat with steroids before/during antiparasitics to prevent inflammatory surge |
| Brain abscess | Ceftriaxone + metronidazole ± vancomycin | Ring-enhancing with restricted diffusion on MRI (vs tumor: restricted diffusion in abscess cavity); surgical drainage if >2.5 cm |
| Fungal meningitis (Coccidioides) | Fluconazole (lifelong) | Southwest US; eosinophilic meningitis; basilar meningitis with hydrocephalus |
💎 Board Pearl
- Dexamethasone in bacterial meningitis: Give BEFORE or WITH first antibiotic dose; proven benefit for S. pneumoniae (↓ hearing loss, mortality); not useful if antibiotics already started
- Ampicillin for Listeria: Add in neonates, age >50, immunocompromised, and pregnancy; Listeria is NOT covered by cephalosporins
- HSV encephalitis: Do NOT wait for PCR results — start acyclovir immediately if clinical suspicion
- Brain abscess vs tumor on MRI: Abscess → restricted diffusion (bright DWI, dark ADC) within the cavity; tumor necrosis does NOT restrict
Drug Interactions & CYP450 Enzyme Effects
CYP450 Inducers (↓ drug levels of substrates)
| Inducer | Clinically Important Interactions |
|---|---|
| Phenytoin | ↓ Warfarin, OCPs, lamotrigine, valproate, corticosteroids, cyclosporine, methadone |
| Carbamazepine | ↓ OCPs, lamotrigine, valproate, warfarin, haloperidol, clonazepam; auto-induces own metabolism |
| Phenobarbital | ↓ OCPs, warfarin, lamotrigine, theophylline, corticosteroids |
| Rifampin | Most potent inducer; ↓ virtually all CYP substrates (warfarin, OCPs, antiretrovirals, azole antifungals, immunosuppressants) |
| St. John’s Wort | ↓ SSRIs, OCPs, cyclosporine, warfarin, digoxin |
CYP450 Inhibitors (↑ drug levels of substrates)
| Inhibitor | Clinically Important Interactions |
|---|---|
| Valproate | ↑ Lamotrigine (2×), phenobarbital, free phenytoin; inhibits glucuronidation & epoxide hydrolase |
| Fluoxetine / Fluvoxamine | ↑ TCAs, benzodiazepines, warfarin, phenytoin (CYP2D6/2C19/3A4) |
| Cimetidine | ↑ Warfarin, phenytoin, theophylline, benzodiazepines (non-selective CYP inhibitor) |
| Ketoconazole / Itraconazole | ↑ Benzodiazepines, statins, cyclosporine, tacrolimus (potent CYP3A4 inhibitors) |
| Erythromycin / Clarithromycin | ↑ Carbamazepine, statins, warfarin, theophylline (CYP3A4) |
| Grapefruit juice | ↑ CYP3A4 substrates (statins, Ca2+ channel blockers, carbamazepine, cyclosporine) |
Commonly Affected Drug Levels
| Drug Affected | Increased By | Decreased By |
|---|---|---|
| Lamotrigine | Valproate (×2) | CBZ, PHT, PB, OCPs (estrogen) |
| Phenytoin | Valproate (free level), fluoxetine, cimetidine, isoniazid | CBZ, rifampin, chronic alcohol |
| Carbamazepine | Erythromycin, ketoconazole, grapefruit, valproate | Self-induction, phenytoin, phenobarbital |
| Warfarin | Valproate, fluoxetine, cimetidine, amiodarone, metronidazole | PHT, CBZ, PB, rifampin, St. John’s Wort |
| OCPs (estrogen) | — | PHT, CBZ, PB, topiramate (≥200mg), rifampin, St. John’s Wort |
💎 Board Pearl
- Mnemonic for CYP inducers — “CRAP-GPS”: Carbamazepine, Rifampin, Alcohol (chronic), Phenytoin, Griseofulvin, Phenobarbital, Sulfonylureas
- Valproate + lamotrigine: Most commonly tested drug interaction in neurology — VPA doubles LTG levels, increasing SJS risk
- Pregnancy + ASMs: Enzyme inducers ↓ OCP efficacy; lamotrigine clearance ↑ 50–100% during pregnancy (estrogen induces glucuronidation) — monitor levels monthly
- Phenytoin protein binding: ~90% protein-bound; in hypoalbuminemia, measure free phenytoin level; total level can be falsely “normal”
Neurocritical Care & Stroke Pharmacology
Status Epilepticus Algorithm
| Step | Agent | Dose | Notes |
|---|---|---|---|
| 1st line (5–20 min) | Lorazepam IV OR midazolam IM OR diazepam IV/PR | LZP 4 mg IV (max 0.1 mg/kg) MDZ 10 mg IM DZP 0.15–0.2 mg/kg | Midazolam IM = preferred no-IV (RAMPART); LZP preferred when IV access |
| 2nd line (20–40 min) | Fosphenytoin OR levetiracetam OR valproate | fPHT 20 PE/kg LEV 60 mg/kg (max 4500 mg) VPA 40 mg/kg | ESETT (2019) showed equivalence — ~45–47% seizure cessation for all three |
| 3rd line (refractory) | Midazolam infusion OR propofol OR pentobarbital | Titrate to seizure suppression / burst suppression | cEEG monitoring required; treat non-convulsive SE |
Stroke Thrombolytics & Window
| Drug / Strategy | Dose | Window / Evidence |
|---|---|---|
| Alteplase (tPA) | 0.9 mg/kg (max 90 mg); 10% IV bolus, remainder over 60 min | 0–4.5 h (NINDS, ECASS-III) |
| Tenecteplase (TNK) | 0.25 mg/kg single IV bolus (max 25 mg) — NOT 0.4 mg/kg for AIS | 2026 AHA/ASA AIS guideline endorses either alteplase 0.9 mg/kg OR tenecteplase 0.25 mg/kg (max 25 mg) for IVT-eligible adult AIS within 4.5 h; AcT (2022), TRACE-2 (2023) non-inferiority |
| Extended window | Alteplase | 4.5–9 h with perfusion mismatch (EXTEND); wake-up stroke with FLAIR-DWI mismatch (WAKE-UP) |
Antiplatelets & DAPT in Stroke/TIA
| Regimen | Indication / Trial | Duration |
|---|---|---|
| Aspirin 81–325 mg | Standard secondary prevention | Indefinite |
| Clopidogrel 75 mg | Alternative; CYP2C19 LOF carriers — FDA boxed warning, reduced efficacy | Indefinite |
| ASA + clopidogrel (DAPT) | Minor stroke (NIHSS ≤3) / high-risk TIA (ABCD² ≥4) — default 21 d (CHANCE); 90 d reserved for severe symptomatic intracranial stenosis (SAMMPRIS-like); then single antiplatelet (ASA OR clopidogrel) | 21 d default; 90 d only for specific contexts (severe symptomatic intracranial stenosis) |
| ASA + ticagrelor | THALES — minor stroke / high-risk TIA | 30 d |
| ASA + clopidogrel (CHANCE-2) | For CYP2C19 LOF carriers — ticagrelor preferred | 21 d |
DOAC Reversal
| Anticoagulant | Mechanism | Reversal |
|---|---|---|
| Dabigatran | Direct thrombin inhibitor | Idarucizumab (Praxbind) |
| Apixaban / Rivaroxaban | Factor Xa inhibitor | Andexanet alfa OR 4F-PCC; ANNEXA-I (2024) showed andexanet ↑ thrombotic events |
| Edoxaban | Factor Xa inhibitor | 4F-PCC; NOT for CrCl >95 (reduced efficacy) |
| Warfarin | Vitamin K antagonist | Vitamin K + 4F-PCC (Kcentra) |
ICH Blood Pressure Management
| Target SBP (mild-moderate spontaneous ICH, SBP 150–220) | Smooth lowering to target ~140; maintain SBP 130–150; AVOID acute SBP <130 (2022 AHA/ASA — INTERACT2/ATACH-2/INTERACT-3) |
| Preferred agents | Nicardipine, clevidipine, labetalol |
| Avoid | Nitroglycerin, hydralazine (↑ ICP, unpredictable) |
TBI / Elevated ICP
- Hyperosmolar therapy: 3% hypertonic saline; mannitol 0.25–1 g/kg
- Hyperventilation: acute/temporizing only (target PaCO&sub2; 30–35)
- Head-of-bed 30°, sedation/paralytic, CSF drainage via EVD
- Decompressive craniectomy for refractory ICP
AED Therapeutic Ranges
| Drug | Range |
|---|---|
| Phenytoin | 10–20 mcg/mL (free: 1–2) |
| Valproate | 50–100 mcg/mL |
| Carbamazepine | 4–12 mcg/mL |
| Phenobarbital | 15–40 mcg/mL |
| Lithium | 0.6–1.2 mEq/L |
Local Anesthetic Systemic Toxicity (LAST)
- Presentation: CNS excitation (perioral numbness, tinnitus, agitation) → seizures → CNS depression → cardiac arrhythmia / cardiac arrest
- Rescue: Intralipid 20% — 1.5 mL/kg bolus + 0.25 mL/kg/min infusion
- Bupivacaine = most cardiotoxic
PRES (Posterior Reversible Encephalopathy Syndrome)
- Common offenders: tacrolimus, cyclosporine, cisplatin, bevacizumab, other VEGF/TKI agents
- Triggers: hypertensive emergency, eclampsia, sepsis
- Management: remove offending agent + BP control + AED for seizures
New & Emerging Neuro Therapeutics
Parkinson Disease — New Agents
| Drug | Mechanism | Indication / Notes |
|---|---|---|
| Foslevodopa-foscarbidopa (Vyalev) | Prodrug of levodopa-carbidopa | 24-h continuous SC pump for advanced PD; FDA Oct 2024 |
| Pimavanserin (Nuplazid) | 5-HT&sub2;A inverse agonist (no D2 activity) | Only FDA-approved drug for PD psychosis; QT prolongation |
| MRgFUS (MR-guided focused ultrasound) | Thermal lesion | Vim → essential tremor / tremor-predominant PD; GPi → dyskinesia |
Alzheimer Disease — New Agents
| Drug | Mechanism | Key Point |
|---|---|---|
| Lecanemab (Leqembi) | Anti-amyloid (protofibril) mAb | FDA-approved early AD; ARIA-E (edema) and ARIA-H (hemorrhage) on MRI; ApoE4 homozygotes higher risk; avoid concurrent anticoagulation |
| Donanemab (Kisunla) | Anti-amyloid (plaque) mAb | FDA 2024; same ARIA monitoring; can be stopped after plaque clearance |
| Brexpiprazole (Rexulti) | Atypical antipsychotic (D2 partial agonist + 5-HT&sub2;A) | FDA 2023 for Alzheimer agitation — first approved for this indication |
Other Recent Neuro Approvals
| Drug | Mechanism | Indication |
|---|---|---|
| Omaveloxolone (Skyclarys) | Nrf2 activator | First FDA-approved Rx for Friedreich ataxia (Feb 2023) |
| Vorasidenib (Voranigo) | IDH1/2 inhibitor | Grade 2 IDH-mutant gliomas after surgery (FDA Aug 2024) |
| Arimoclomol (Miplyffa) | Heat shock protein co-inducer | Niemann-Pick C (FDA Sept 2024) |
| Suzetrigine (Journavx) | NaV1.8 inhibitor (peripheral, non-opioid) | Acute moderate-to-severe pain (FDA Jan 2025) |
| 3,4-Diaminopyridine (Amifampridine, Firdapse) | K+ channel blocker → ↑ presynaptic ACh release | LEMS (FDA 2018) |
| Relyvrio (AMX0035) — WITHDRAWN April 2024 | Sodium phenylbutyrate + taurursodiol | Withdrawn from US market after PHOENIX trial failure in ALS |
Duchenne Muscular Dystrophy — Therapeutic Landscape
| Class / Drug | Mechanism | Notes |
|---|---|---|
| Corticosteroids (prednisone, deflazacort) | Anti-inflammatory; preserve muscle | Standard of care; growth suppression, weight gain |
| Vamorolone (Agamree) | Dissociative steroid (membrane stabilizer) | Fewer growth/bone side effects than prednisone |
| Exon-skipping ASOs | Restore reading frame → partial dystrophin | Eteplirsen (exon 51), golodirsen (53), viltolarsen (53), casimersen (45) |
| Elevidys (delandistrogene moxeparvovec) | AAVrh74 micro-dystrophin gene therapy | For AMBULATORY DMD ONLY (confirmed DMD mutation); FDA action Nov 14, 2025 added boxed warning for acute serious liver injury / acute liver failure and revised indication to ambulatory-only; the prior "ambulatory + non-ambulatory" wording is outdated |
| Givinostat (Duvyzat) | HDAC inhibitor | FDA March 2024; oral, mutation-agnostic |
Classic Board Traps
High-Yield Board Traps — Pharmacology
- Phenytoin zero-order kinetics: A small dose increase at therapeutic levels causes a disproportionately large rise in serum level → toxicity (nystagmus → ataxia → lethargy). This is the #1 tested pharmacokinetic concept.
- Valproate in women of childbearing age: If the answer choice is valproate for a young woman — it is almost always WRONG. Highest teratogenicity among ASMs (NTDs, ↓ IQ). Preferred: lamotrigine or levetiracetam.
- Carbamazepine hyponatremia: Can mimic or worsen seizures. If a patient on CBZ has new seizures, check Na+ before escalating the dose.
- Lamotrigine rash: Must titrate slowly (especially with VPA). Any rash while titrating → stop drug, evaluate for SJS/TEN.
- Topiramate kidney stones + glaucoma: Carbonic anhydrase inhibition causes metabolic acidosis AND acute angle-closure glaucoma (NOT open-angle) — common distractor.
- Vigabatrin visual loss is IRREVERSIBLE: Not just a side effect to monitor — it does not reverse after discontinuation.
- Serotonin syndrome vs NMS: Clonus = serotonin syndrome. Lead-pipe rigidity = NMS. Both have fever. Boards test onset speed (SS = hours, NMS = days) and treatment (SS = cyproheptadine, NMS = dantrolene).
- Succinylcholine hyperkalemia: Contraindicated >24 hours after burns, crush injury, spinal cord injury, denervation — upregulated ACh receptors cause massive K+ efflux.
- Aminoglycosides + MG: Aminoglycosides worsen myasthenia gravis by blocking presynaptic Ca2+ channels at the NMJ — classic board trap when choosing antibiotics for a MG patient with infection.
- Dexamethasone timing in meningitis: Must be given BEFORE or WITH the first antibiotic dose. Given after antibiotics → no proven benefit.
- Listeria and cephalosporins: Cephalosporins do NOT cover Listeria. Always add ampicillin in neonates, elderly (>50), immunocompromised, and pregnant patients.
- Natalizumab PML risk: JCV Ab positive + index >1.5 + >2 years on drug = highest risk. JCV-negative patients have very low PML risk, NOT zero (false negatives + later seroconversion possible) — continue periodic JCV Ab monitoring.
- Clozapine agranulocytosis: Requires weekly CBC for first 6 months, then biweekly, then monthly. Most effective antipsychotic but rarely first-line due to monitoring burden.
- Riluzole in ALS: Only extends survival by ~2–3 months. It does NOT improve strength or function — a common distractor.
- TPMT before azathioprine: Missing this step on boards = wrong answer. Deficiency causes fatal myelosuppression.
- TCA overdose → QRS widening: Treat with IV sodium bicarbonate (NOT magnesium, NOT lidocaine as first-line). Seizures with benzodiazepines.
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