Classification of Drugs for Peripheral Vascular Diseases

Peripheral vascular diseases (PVDs) refer to disorders that affect blood circulation outside of the heart and brain, commonly involving the arteries and veins of the limbs. These conditions can result from atherosclerosis, vasospasm, thrombosis, or inflammatory vascular diseases. Treatment includes lifestyle modification, surgical intervention, and pharmacological therapy.

This blog from Pharmacy Freak focuses on the classification, clinical uses, drug of choice, adverse effects, and updated treatment strategies for peripheral vascular conditions.

What is Peripheral Vascular Diseases

Peripheral vascular disease is a broad term for conditions causing obstruction, constriction, or inflammation in peripheral blood vessels, leading to impaired blood flow to the limbs or other organs. It includes conditions like atherosclerotic peripheral arterial disease, thromboangiitis obliterans (Buerger’s disease), Raynaud’s phenomenon, and venous insufficiency.

Classification of Drugs for Peripheral Vascular Diseases ( Tripathi)

• Rheological agent: Pentoxiphylline (Oxpentifylline)
• Phosphodiesterase-3 inhibitor: Cilostazol
• Antiplatelet drugs: Aspirin, Clopidogrel, Ticlopidine
• Antioxidants: Vitamin E

• Vasodilators –
  • Direct acting: Cyclandelate, Xanthinol nicotinate
  • β-adrenergic agonists: Isoxsuprine
  • α-adrenergic blockers: Prazosin, Phenoxybenzamine
  • Calcium channel blockers: Nifedipine, Nitrendipine
  • Prostacyclin (PGI₂)

Classification (General)

Drugs used in PVDs are classified based on the mechanism and condition they target:

1. Antiplatelet Drugs
   Mechanism: Inhibit platelet aggregation to prevent arterial thrombosis
   Examples: Aspirin, Clopidogrel, Cilostazol, Ticlopidine
   Use: Atherosclerotic peripheral arterial disease, intermittent claudication
   Note: Aspirin and Clopidogrel reduce the risk of cardiovascular events in PVD
2. Vasodilators
   • a. Nitrates
     Mechanism: Release nitric oxide, relax vascular smooth muscle
     Example: Nitroglycerin
     Use: Raynaud’s phenomenon, ischemic symptoms
   • b. Calcium Channel Blockers
     Mechanism: Block calcium entry into vascular smooth muscle
     Examples: Nifedipine, Amlodipine
     Use: Raynaud’s disease and systemic sclerosis-related vasospasm
   • c. Phosphodiesterase III Inhibitors
     Mechanism: Increase intracellular cAMP, vasodilation, and inhibition of platelet aggregation
     Examples: Cilostazol
     Use: Intermittent claudication in PAD
     Note: Also has antiplatelet effects
     

3. Hemorheological Agents
   Mechanism: Improve red blood cell flexibility and decrease blood viscosity
   Examples: Pentoxifylline
   Use: Intermittent claudication
   Note: Less effective than Cilostazol
4. Anticoagulants
   Mechanism: Inhibit clot formation by interfering with coagulation pathways
   Examples: Heparin, Low Molecular Weight Heparins (Enoxaparin), Warfarin
   Use: Acute limb ischemia, deep vein thrombosis (DVT), prevention of embolism
5. Fibrinolytics (Thrombolytics)
   Mechanism: Promote dissolution of fibrin clots
   Examples: Streptokinase, Urokinase, Alteplase (tPA)
   Use: Acute arterial occlusion, pulmonary embolism
6. Endothelin Receptor Antagonists
   Mechanism: Block endothelin-1, a potent vasoconstrictor
   Example: Bosentan
   Use: Pulmonary arterial hypertension, systemic sclerosis-associated Raynaud’s
7. Prostaglandin Analogues
   Mechanism: Vasodilation and inhibition of platelet aggregation
   Examples: Alprostadil, Iloprost
   Use: Critical limb ischemia, Raynaud’s disease (intravenous use)
8. Statins
   Mechanism: HMG-CoA reductase inhibitors; improve endothelial function and reduce atherosclerotic progression
   Examples: Atorvastatin, Rosuvastatin
   Use: PAD with coexisting dyslipidemia
   Note: Improve walking distance in PAD patients

Uses

Drugs are used in PVD to achieve the following clinical goals:

• Relieve symptoms like claudication or vasospasm
• Prevent thrombosis and embolism
• Improve walking distance and quality of life
• Prevent progression to gangrene or ulceration
• Treat underlying conditions like atherosclerosis and hypertension

Drug of Choice Highlights

1. Intermittent claudication – Cilostazol
2. Buerger’s disease – Smoking cessation is essential; symptomatic relief with vasodilators
3. Raynaud’s phenomenon – Nifedipine
4. Critical limb ischemia – Prostaglandin analogues like Iloprost
5. Acute arterial occlusion – Heparin (initial), followed by thrombolysis or surgery
6. Pulmonary hypertension – Bosentan
7. DVT prophylaxis – LMWH or Warfarin depending on setting

Side Effects

• Aspirin – Gastric irritation, bleeding, hypersensitivity
• Clopidogrel – Diarrhea, rash, neutropenia (rare)
• Cilostazol – Headache, palpitations, contraindicated in heart failure
• Pentoxifylline – Nausea, dizziness, flushing
• Calcium channel blockers – Edema, hypotension, headache
• Heparin – Bleeding, heparin-induced thrombocytopenia
• Warfarin – Bleeding, skin necrosis, teratogenicity
• Statins – Myopathy, elevated liver enzymes
• Bosentan – Hepatotoxicity, anemia
• Iloprost – Flushing, jaw pain, hypotension

Updated Clinical Pearls

• Cilostazol is more effective than Pentoxifylline in improving walking distance in intermittent claudication.
• Statins are indicated in all patients with peripheral artery disease, even if cholesterol is normal.
• Smoking cessation is the most critical intervention in thromboangiitis obliterans.
• In Raynaud’s phenomenon, cold avoidance and CCBs are the mainstay.
• In acute arterial occlusion, immediate anticoagulation with heparin is crucial to prevent thrombus propagation.
• Combination therapy with antiplatelet and vasodilators may be required in resistant cases.

References

1. Tripathi KD. Essentials of Medical Pharmacology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 2013. p. 875–877
2. Gupta S, Garg A. Review of Pharmacology. 15th ed. New Delhi: Jaypee Brothers Medical Publishers; 2023. p. 308–310
3. Brunton LL, Chabner BA, Knollmann BC, editors. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 12th ed. New York: McGraw-Hill Education; 2011. p. 1047–1052

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