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I now have comprehensive information from multiple authoritative textbooks. Here is a complete overview of the drugs used in stroke management with their mechanisms of action and doses.
Drugs Used in Stroke — Mechanism of Action & Doses
Stroke treatment is divided into: (1) Acute Ischemic Stroke and (2) Secondary Prevention.
🔴 ACUTE ISCHEMIC STROKE
1. Alteplase (rt-PA) — IV Thrombolytic
| Parameter | Detail |
|---|---|
| Drug class | Recombinant tissue plasminogen activator (rt-PA) |
| MOA | Binds to fibrin in a thrombus and converts plasminogen → plasmin, which breaks down the fibrin clot, restoring blood flow to ischemic brain |
| Dose | 0.9 mg/kg IV (max 90 mg total): 10% as IV bolus over 1 min → remaining 90% as infusion over 60 min |
| Window | Within 3 hours of symptom onset (up to 4.5 hours in selected patients) |
| Low-dose alternative | 0.6 mg/kg (evaluated in ENCHANTED trial; noninferior with less hemorrhage) |
2. Tenecteplase (TNK) — IV Thrombolytic
| Parameter | Detail |
|---|---|
| MOA | Modified rt-PA with longer half-life and higher fibrin specificity than alteplase; converts plasminogen → plasmin |
| Dose | 0.25 mg/kg IV single bolus (max 25 mg) — preferred when treating within 4.5 hours of onset; also used as bridge before thrombectomy |
| Advantage | Single bolus (vs alteplase's infusion); higher fibrin specificity |
3. Mechanical Thrombectomy (device-based, not pharmacological)
- Used for large vessel occlusion (LVO) up to 16–24 hours from onset (DAWN & DEFUSE-3 criteria)
- Can be combined with IV thrombolytics
🟡 BLOOD PRESSURE MANAGEMENT (During Acute Stroke / Post-tPA)
Labetalol (IV)
| Scenario | Dose |
|---|---|
| SBP 180–230 or DBP 105–120 mmHg | 10 mg IV over 1–2 min; repeat q10–20 min; max 300 mg or infusion at 2–8 mg/min |
| SBP >230 or DBP 121–140 mmHg | Same as above, or add nicardipine |
| MOA | Alpha + beta adrenergic blocker → reduces systemic vascular resistance and heart rate |
Nicardipine (IV)
| Parameter | Detail |
|---|---|
| Dose | 5 mg/h IV infusion; titrate up by 2.5 mg/h every 5 min → max 15 mg/h |
| MOA | Dihydropyridine calcium channel blocker → vasodilation → lowers BP |
Sodium Nitroprusside
- Reserved for refractory hypertension
- MOA: Releases nitric oxide → direct vasodilation of arteries and veins
🟢 SECONDARY PREVENTION (After Ischemic Stroke / TIA)
4. Aspirin — Antiplatelet
| Parameter | Detail |
|---|---|
| MOA | Irreversibly inhibits COX-1 and COX-2 → ↓ thromboxane A2 synthesis → ↓ platelet aggregation |
| Dose | 50–325 mg/day orally (commonly 81–100 mg/day for long-term prevention) |
| Note | First-line antiplatelet; given within 48 h of stroke onset |
5. Clopidogrel — Antiplatelet
| Parameter | Detail |
|---|---|
| MOA | Irreversibly blocks P2Y12 ADP receptor on platelets → inhibits ADP-mediated platelet activation and aggregation |
| Dose | 75 mg/day orally |
| Use | First-line alternative to aspirin; reasonable for secondary stroke prevention |
6. Aspirin + Extended-Release Dipyridamole (Aggrenox) — Dual Antiplatelet
| Parameter | Detail |
|---|---|
| MOA | Aspirin: COX inhibitor; Dipyridamole: inhibits phosphodiesterase → ↑ cAMP → ↓ platelet aggregation; also inhibits adenosine uptake → vasodilation |
| Dose | Aspirin 25 mg + dipyridamole 200 mg extended-release — twice daily |
| Evidence | Shown equivalent or superior to aspirin alone for secondary stroke prevention |
7. Ticagrelor — Antiplatelet
| Parameter | Detail |
|---|---|
| MOA | Reversible P2Y12 receptor antagonist → inhibits ADP-mediated platelet activation |
| Dose | 180 mg loading dose on day 1, then 90 mg twice daily |
| Note | Used in dual antiplatelet therapy (with aspirin) for short-term secondary prevention; alone is not superior to aspirin |
8. Anticoagulants — For Cardioembolic Stroke (esp. Atrial Fibrillation)
| Drug | MOA | Dose |
|---|---|---|
| Warfarin | Inhibits Vitamin K-dependent clotting factors (II, VII, IX, X) | Adjusted to INR 2–3 |
| Apixaban | Factor Xa inhibitor | 5 mg twice daily (or 2.5 mg BID if dose-reduction criteria met) |
| Rivaroxaban | Factor Xa inhibitor | 20 mg once daily with evening meal (15 mg if reduced) |
| Dabigatran | Direct thrombin (IIa) inhibitor | 150 mg twice daily (75 mg BID if reduced) |
| Edoxaban | Factor Xa inhibitor | 60 mg once daily (30 mg if reduced) |
Anticoagulants are preferred over antiplatelets when stroke is due to atrial fibrillation or prosthetic heart valve.
9. Statins — Lipid-Lowering (Secondary Prevention)
| Parameter | Detail |
|---|---|
| MOA | Inhibit HMG-CoA reductase → ↓ hepatic cholesterol synthesis → ↓ LDL; also have pleiotropic anti-inflammatory and plaque-stabilizing effects |
| Drugs & Doses | Atorvastatin 40–80 mg/day or Rosuvastatin 20–40 mg/day (high-intensity statins) |
| Target | LDL < 70 mg/dL |
| Note | Stopping statins acutely during ischemic stroke increases morbidity and mortality |
Summary Table
| Drug | Class | MOA | Dose |
|---|---|---|---|
| Alteplase | Thrombolytic | Converts plasminogen → plasmin | 0.9 mg/kg IV (max 90 mg) |
| Tenecteplase | Thrombolytic | Fibrin-specific plasminogen activator | 0.25 mg/kg IV bolus (max 25 mg) |
| Aspirin | Antiplatelet | COX-1/2 inhibitor → ↓ TXA2 | 50–325 mg/day |
| Clopidogrel | Antiplatelet | P2Y12 ADP receptor blocker | 75 mg/day |
| Aspirin/Dipyridamole | Dual antiplatelet | COX inhibitor + PDE inhibitor | 25/200 mg twice daily |
| Ticagrelor | Antiplatelet | Reversible P2Y12 blocker | 180 mg load → 90 mg BID |
| Warfarin | Anticoagulant | Vitamin K antagonist | INR-adjusted (target 2–3) |
| Apixaban | Anticoagulant | Factor Xa inhibitor | 5 mg BID |
| Dabigatran | Anticoagulant | Direct thrombin inhibitor | 150 mg BID |
| Rivaroxaban | Anticoagulant | Factor Xa inhibitor | 20 mg OD |
| Atorvastatin | Statin | HMG-CoA reductase inhibitor | 40–80 mg/day |
| Labetalol | Antihypertensive | α+β blocker | 10 mg IV bolus, max 300 mg |
| Nicardipine | Antihypertensive | CCB (dihydropyridine) | 5–15 mg/h IV infusion |
Sources: ROSEN's Emergency Medicine; Goldman-Cecil Medicine; Adams & Victor's Neurology, 12th Ed; Harrison's Principles of Internal Medicine 22E
Adverse efffe
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I now have solid textbook data for all drug classes. Here is a complete breakdown of adverse effects for all stroke drugs:
Adverse Effects of Stroke Drugs
1. Alteplase / Tenecteplase (Thrombolytics)
| Adverse Effect | Details |
|---|---|
| Symptomatic Intracranial Hemorrhage (sICH) | Most feared complication; incidence 2–7% after IV thrombolysis. Usually large-volume lobar bleeds, often multiple, with intraventricular/subarachnoid extension |
| Asymptomatic ICH | Higher rate — 30–45% of patients experience cerebral microbleeds |
| Systemic bleeding | Gingival bleeding, ecchymosis, hematoma at puncture sites, GI/urinary tract bleeding |
| Orolingual angioedema | Rare but serious; can cause airway obstruction |
| Reperfusion injury | Paradoxical worsening after recanalization |
| Hypotension | Especially with rapid infusion |
Risk factors for post-thrombolysis ICH:
- Older age, severe stroke (high NIHSS), hypertension
- Diabetes, atrial fibrillation, congestive heart failure
- Visible acute infarct on imaging, baseline antiplatelet use, leukoaraiosis
2. Aspirin (Antiplatelet)
| Adverse Effect | Details |
|---|---|
| GI upset / ulcers | Most common — gastric and duodenal ulcers, dyspepsia, nausea |
| GI bleeding | Especially with long-term use; risk ↑ in diabetic patients |
| Bronchospasm / Asthma | Aspirin-exacerbated respiratory disease (AERD) |
| Angioedema | Rare |
| Reye's syndrome | In children with viral illness — avoid in children |
| Stevens-Johnson Syndrome (SJS) | Very rare |
| Bleeding | Increased bleeding time due to irreversible platelet inhibition |
| Drug interactions | Anticoagulants, NSAIDs, P2Y12 inhibitors → ↑ bleeding risk |
3. Clopidogrel (P2Y12 Blocker)
| Adverse Effect | Details |
|---|---|
| Bleeding | Most significant; GI bleeding, intracranial hemorrhage (especially in combination with aspirin) |
| Stevens-Johnson Syndrome | Rare |
| Drug interaction | Strong CYP2C19 inhibitors (e.g., omeprazole) reduce conversion to active metabolite → reduced antiplatelet effect |
| TTP (rare) | Thrombotic thrombocytopenic purpura — rare but life-threatening |
4. Aspirin + Dipyridamole (Aggrenox)
| Drug | Adverse Effect |
|---|---|
| Dipyridamole | Headache (very common, due to vasodilation), dizziness, GI discomfort, flushing, rash, bleeding |
| Aspirin component | GI upset, bleeding |
| Combined | Increased bleeding risk when combined with thrombolytics or anticoagulants |
5. Ticagrelor (Reversible P2Y12 Blocker)
| Adverse Effect | Details |
|---|---|
| Bleeding | Major risk, especially with dual antiplatelet therapy |
| Dyspnea | Common (~14%); mechanism unclear, not bronchospasm — often self-limiting |
| Headache | Common |
| ↑ Serum creatinine | Mild renal impairment |
| Bradycardia | Ventricular pauses, especially in first week |
| Drug interactions | Strong CYP3A4 inhibitors (e.g., ketoconazole) → ↑ bleeding; CYP3A4 inducers (e.g., rifampin) → ↓ efficacy |
6. Anticoagulants
Warfarin (Vitamin K Antagonist)
| Adverse Effect | Details |
|---|---|
| Hemorrhage | Major and minor bleeding — most common and serious; risk ↑ with supratherapeutic INR |
| Skin necrosis | Early in therapy (days 3–8); due to transient hypercoagulability from protein C/S depletion |
| Teratogenicity | Crosses placenta → fetal warfarin syndrome (nasal hypoplasia, stippled epiphyses) — contraindicated in pregnancy |
| Drug & food interactions | Extensive — vitamin K-rich foods ↓ effect; many drugs alter INR |
| Purple toe syndrome | Cholesterol microemboli — rare |
| Requires INR monitoring | Narrow therapeutic index |
Dabigatran (Direct Thrombin Inhibitor)
| Adverse Effect | Details |
|---|---|
| Bleeding | Major and minor (GI, intracranial) |
| GI side effects | Dyspepsia, GI irritation — most common reason for discontinuation |
| No routine monitoring | But hard to reverse (idarucizumab is reversal agent) |
| Contraindicated | Severe renal impairment (renally cleared) |
Apixaban / Rivaroxaban / Edoxaban (Factor Xa Inhibitors)
| Adverse Effect | Details |
|---|---|
| Bleeding | GI, urogenital, intracranial hemorrhage |
| Fewer drug interactions | Compared to warfarin |
| No routine monitoring | But reversal agent (andexanet alfa) needed for major bleeds |
| GI bleeding | Rivaroxaban/edoxaban have slightly higher GI bleeding risk vs warfarin |
7. Statins (Atorvastatin / Rosuvastatin)
| Adverse Effect | Details |
|---|---|
| Myopathy / Myalgia | Most common — muscle pain, weakness, fatigue |
| Rhabdomyolysis | Rare but life-threatening; elevated CK, myoglobinuria, acute kidney injury |
| Hepatotoxicity | Elevated liver enzymes (transaminases); rare liver failure |
| New-onset diabetes | Slight increased risk with high-intensity statin therapy |
| Mechanism of muscle toxicity | Inhibition of heme A and ubiquinone (CoQ10) synthesis, which are essential for mitochondrial oxidative phosphorylation |
8. Antihypertensives (Used in Acute Stroke)
Labetalol (IV)
| Adverse Effect | Details |
|---|---|
| Bradycardia / heart block | Due to β-blockade |
| Bronchospasm | Contraindicated in asthma/COPD |
| Hypotension | If BP lowered too aggressively |
| Fatigue, dizziness | Common |
Nicardipine (IV)
| Adverse Effect | Details |
|---|---|
| Hypotension | If infused too rapidly |
| Reflex tachycardia | Due to peripheral vasodilation |
| Headache, flushing | Vasodilatory effects |
| Phlebitis | At IV infusion site |
Quick Reference Summary Table
| Drug | Key Adverse Effects |
|---|---|
| Alteplase | sICH (2–7%), systemic bleeding, angioedema |
| Aspirin | GI ulcers/bleeding, bronchospasm, Reye's (children) |
| Clopidogrel | Bleeding, SJS, omeprazole interaction, TTP (rare) |
| Aspirin + Dipyridamole | Headache (dipyridamole), GI upset, bleeding |
| Ticagrelor | Bleeding, dyspnea, bradycardia, ↑ creatinine |
| Warfarin | Hemorrhage, skin necrosis, teratogenic, drug interactions |
| Dabigatran | Bleeding, GI upset/dyspepsia, renal-dependent |
| Apixaban/Rivaroxaban | Bleeding, GI hemorrhage |
| Statins | Myopathy, rhabdomyolysis, hepatotoxicity, new-onset DM |
| Labetalol | Bradycardia, bronchospasm, hypotension |
| Nicardipine | Hypotension, reflex tachycardia, headache |
Sources: Katzung's Basic & Clinical Pharmacology 16e; Lippincott Illustrated Reviews: Pharmacology; ROSEN's Emergency Medicine; Lippincott Biochemistry 8e
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