Antihypertensive & Coagulation-Altering Drugs plus Blood Products – Comprehensive Study Notes

Antihypertensive Medications (focus of this week)

Context: First-line choices for primary hypertension—thiazide diuretics and ACE-inhibitors—are NOT on this week’s list (they come next week). Everything below is typically used when those first-line agents are contraindicated, not tolerated, or a comorbidity makes an alternate drug attractive.

Renin–Angiotensin System Modifier

• Aliskiren
  • Direct renin inhibitor (acts “upstream” of ACE-I)
  • Single indication: hypertension
  • Rarely selected ("last-ditch" choice; nephrology may see it more)
  • No multiple cardiovascular benefits the way ACE-I/ARB often provide

Central α₂-Agonist

• Clonidine
  • Mechanism: stimulates presynaptic α₂ → negative feedback → ↓ sympathetic outflow → ↓ BP
  • Rapid on/off → handy for transient, surge-type hypertension (e.g., alcohol-withdrawal HTN)
  • Key adverse effects (review from previous module):
  • Sedation & fatigue
  • Dry mouth (xerostomia)
  • Bradycardia → hypotension
  • Rebound hypertension if abruptly stopped—always taper

Aldosterone Antagonist

• Eplerenone (cousin of spironolactone)
  • Blocks aldosterone receptors → ↓ Na⁺/H₂O retention, ↓ K⁺ wasting
  • Main niche here: HTN in setting of heart-failure–related fluid overload
  • Compared with spironolactone, less endocrine AE (e.g., gynecomastia)

Direct Vasodilator

• Hydralazine
  • Arteriolar smooth-muscle relaxation → ↓ SVR → ↓ BP
  • Adverse-effect profile predicted from vasodilation:
  • Marked hypotension
  • Reflex sympathetic drive → palpitations/tachycardia
  • Peripheral edema (gravity-dependent; ankles/legs)
  • Facial flushing
  • Not first-line for chronic HTN; occasionally in refractory cases or specific populations (e.g., pregnancy + hydralazine IV in HTN emergency)

β-Blockers (review of receptor selectivity)

• Metoprolol – β₁-selective ("cardio-selective")

• Propranolol – non-selective (β₁ + β₂)

  Clinical relevance

  • Migraine prophylaxis → often propranolol (needs β₂-block for effect)
  • COPD/asthma → prefer metoprolol to avoid bronchoconstriction
  • Arrhythmia rate-control → either, but metoprolol’s β₁ selectivity favorable

  Place in HTN algorithm

  • After thiazide/ACE/ARB ± calcium-channel blockers (CCB)
  • Move higher if compelling indication (post-MI, HF-rEF, tachy-arrhythmia)

Nitroprusside (IV HTN emergency)

• Potent arterial & venous dilator → rapid ↓ BP
• Special monitoring: cyanide toxicity (metabolic by-product); check cyanide/thiocyanate levels with prolonged or high-dose infusions + routine BP monitoring

α₁-Blockers

• Prazosin, Doxazosin
  • Dual indications: HTN & Benign Prostatic Hyperplasia (BPH)
  • Main AE: orthostatic hypotension (first-dose phenomenon) → counsel slow position change, bedtime dosing

Blood Products – Know Each Indication Only

• Albumin
  • Oncotic "fluid-shifter" (ascites in liver cirrhosis; volume expansion when blood refused for religious/personal reasons)
• Granulocytes – rescue for profound neutropenia
• Erythropoietin (EPO) – stimulates RBC production; use is now conservative due to thrombotic and mortality concerns
• Filgrastim (G-CSF) – ↑ neutrophils in severe neutropenia (chemo, marrow failure)
• Fresh-Frozen Plasma (FFP) – immediate warfarin reversal & multiple coag-factor deficiencies
• Oprelvekin – recombinant IL-11 → raises platelets in severe thrombocytopenia (supply often limited)
• Packed RBCs (PRBCs) – symptomatic or severe anemia / acute blood loss

Drugs That Alter Coagulation (“Blood Thinners”)

Shared themes

• Universal adverse-effect: bleeding
• Almost all prevent clot formation by prolonging coagulation time; one (alteplase) dissolves existing clots
• Major indications: atrial fibrillation, prior DVT/PE, mechanical valves, pro-thrombotic disorders, ischemic events, catheter patency, etc.

Thrombolytic (Clot-Buster)

• Alteplase (tPA)
  • Converts plasminogen → plasmin → lyses fibrin
  • Uses: ischemic stroke, massive PE, MI (when PCI unavailable), occluded central line
  • Dissolves all clots → strict contraindications (recent surgery/trauma, active bleed, severe HTN, thrombocytopenia <100 000, recent tPA, etc.)
  • Monitor neuro status, coagulation labs, BP; anticipate emergent reversal with cryoprecipitate/fibrinogen if catastrophic bleed

Antiplatelet Agents

• Aspirin – irreversible COX-1 inhibition → ↓ TXA₂ synthesis → platelets less “sticky” for lifespan (≈7 days)
• Clopidogrel – ADP-receptor (P2Y₁₂) blocker → prevents platelet aggregation; high affinity for coronary stents ("Sephora" metaphor: stents attract platelets like teens to a store; clopidogrel keeps them walking single-file)
  • NOT always lifelong: duration depends on stent type (e.g., bare-metal vs drug-eluting)

Parenteral Anticoagulants (Heparin Family)

Other facts

• Onset = immediate (IV UFH) or within hours (SC)
• HIT (Heparin-Induced Thrombocytopenia): ≥50 % platelet drop ≈ day 2; mandates permanent heparin avoidance → switch to argatroban/other non-heparin anticoagulant
• Outpatient self-injection feasible for enoxaparin/fondaparinux (e.g., DVT bridge)

Oral Direct Anticoagulants (DOACs)

• Dabigatran – direct thrombin (IIa) inhibitor

• Rivaroxaban – direct Xa inhibitor

  Clinical pearls

  • Rapid onset ≈ parenteral LMWH; no routine lab monitoring
  • Lifestyle-friendly vs warfarin, but silent under-/over-dosing risk (no lab to warn us)
  • Reversal agents now available (idarucizumab for dabigatran; andexanet alfa for rivaroxaban/apixaban)

Vitamin K Antagonist

• Warfarin (Coumadin)
  • Blocks hepatic synthesis of vitamin-K-dependent factors II, VII, IX, X & proteins C/S
  • Delayed onset: must wait for existing factors to clear (≈3–4 days; Factor II longest t½)
  • INR monitoring – goal 2!\text{–}3 for AFib, 2.5!\text{–}3.5 for mechanical valves; baseline (no anticoag) ≈ 0.9!–!1.1
  • Bridging: start with enoxaparin until first therapeutic INR (≥2 on two consecutive days)
  • Dosing is individualized (pharmacogenomics, diet, drug interactions)
  • Vitamin K intake rule: consistency, not abstinence (leafy greens, spinach, multivitamins). Abrupt diet swings → INR chaos.

Warfarin Reversal Algorithm (without/with bleeding)

• If INR >10 and no active bleed → give PO/IV vitamin K
• If INR 5!–!10 and no bleed → hold dose, re-check in 24–48 h
• Any active major bleed at any INR → administer vitamin K plus FFP (provides ready-made clotting factors)

Reversal Summary Table

Patient-Teaching: Detecting Bleeding Early

• Unexpected bruises, persistent gum bleed when brushing teeth
• Melena (black tarry stool) > bright-red external blood
• Fatigue, pallor, feeling unusually cold (possible anemia)
• Hematuria, heavy/prolonged menses, prolonged nosebleeds
• Always inform dentist/surgeon of therapy; avoid contact sports, use soft-bristle toothbrush & electric razor

Integrative & Practical Points

• Risk–Benefit Balance: All anticoagulants juggle risk of thrombosis vs hemorrhage; dosing/choice tailored to patient comorbidities, lifestyle, cost, and monitoring bandwidth.

• Ethical/Religious Considerations: Albumin as compromise when blood refusal; informed consent required for thrombolytics given high bleed risk.

• Pharmacy Logistics: Oprelvekin shortage, high cost of argatroban & DOAC reversal agents → stewardship considerations.

• Connections to Prior Modules:

  • Clonidine sedation/dry mouth (Autonomics module)
  • Spironolactone vs eplerenone (Dermatology & Endocrine cross-talk)
  • Beta-blocker receptor discussion (Adrenergic pharmacology week)

• Metaphors & Memory Aids:

  • Platelets = teenage girls at the mall; aspirin/clopidogrel turn them into boys walking single-file
  • Stent = "Sephora"—the platelet magnet that clopidogrel keeps them away from
  • INR seesaw: