Cardiovascular System Disorder Drugs: Angina, Thromboembolics, and PVD

Antineoplastic and Cardiovascular Lecture: Angina Pectoris and Thromboembolic Disorders

  • Overview of Lecture Objectives:
    • Identify drugs used to treat angina pectoris and thromboembolic disorders.
    • Understand nursing implications for patients receiving these medications.
    • Determine laboratory values to monitor for anticoagulant therapy.
    • Identify antidotes for specific pharmacological agents where applicable.
    • Learn assessment techniques for monitoring bleeding and subsequent nursing interventions.

Pathophysiology of Angina Pectoris

  • Definition: Angina pectoris is chest pain resulting from partial occlusion of the blood vessels in the heart, leading to tissue ischemia.
  • Anatomical Considerations:
    • Normal Blood Vessels: Patent and open, allowing for the unobstructed transport of blood and delivery of oxygen (O2O_2) to cardiac cells.
    • Occluded Blood Vessels: Characterized by a narrowed lumen which obstructs blood flow and limits oxygen diffusion into the tissue.
  • Progression of Disease:
    • Hyperlipidemia: Elevated cholesterol levels lead to the buildup of plaque in the arterial walls (atherosclerosis).
    • Plaque and Injury: Injury to the endothelial lining results in platelet aggregation and thrombus (clot) formation.
    • Ischemia vs. Infarction:
      • Ischemia: Partial occlusion causes a deprivation of blood flow and oxygen, manifesting as angina (chest pain).
      • Myocardial Infarction (MI): Prolonged oxygen deprivation leads to necrotic (dead) tissue. Necrotic tissue cannot facilitate the heart's pumping mechanism effectively.
  • Oxygen Supply and Demand Balance:
    • Economics Analogy: A deficit occurs when there is increased demand for oxygen but decreased supply.
    • Deficit Management: Patients must take action to either increase supply (difficult due to narrowed vessels) or decrease demand to achieve equilibrium.
    • Activity and Rest: Patients must balance activity and rest. If chest pain occurs during exercise, the patient must stop immediately as the heart's demand for oxygen has exceeded the available supply.

Pharmacotherapy for Angina Pectoris

  • Comprehensive Treatment Regimen:
    1. Dyslipidemia Management: Cholesterol-lowering agents are used to address the root cause of plaque formation.
    2. Daily Aspirin: Low-dose aspirin is used to prevent platelet aggregation and subsequent clot formation.
    3. Vasodilators (Nitroglycerin): Used during acute angina episodes to open vessels and relieve ischemia.
    4. Beta-Blockers: Used routinely to slow the heart rate and decrease the overall workload of the heart.
    5. Calcium Channel Blockers: Used to decrease the heart's workload.
  • Nitrates (The First-Line Treatment):
    • Examples: Nitroglycerin (the most common), Isosorbide dinitrate, and Isosorbide mononitrate.
    • Mechanism of Action: Causes vasodilation to open narrowed arteries, increasing blood flow and oxygen distribution to relieve ischemia.
    • Adverse Effects:
      • Hypotension (due to systemic vasodilation).
      • Reflex tachycardia.
      • Headaches (can be treated with non-opioid analgesics like Acetaminophen).
      • Tolerance: Can develop if the drug is present continuously.
  • Nitroglycerin Administration Routes:
    • Transdermal Patch:
      • Application: Place on a non-hairy area of the chest; rotate sites.
      • Frequency: Typically placed for 12−1412-14 hours and removed for 10−1210-12 hours (often on at 06:0006:00, off at 18:0018:00).
      • Purpose of Off-time: To prevent the development of drug tolerance.
    • Sublingual (SL) Tablet:
      • Administration: Place under the tongue; do not swallow. Absorbed systemically via sublingual blood vessels.
      • Protocol for Acute Pain: Take a maximum of 33 tablets, 55 minutes apart.
      • Step 1: Stop activity and rest.
      • Step 2: Take the first tablet at the onset of pain. Wait 55 minutes.
      • Step 3: If pain persists, take a second tablet and consider calling 911911. Wait 55 minutes.
      • Step 4: If pain persists, take the third and final tablet. If pain remains, it suggests a complete occlusion (MI), and emergency care is mandatory.
      • Storage: Must stay in its original dark glass bottle to prevent degradation. Discard 66 months after opening.
    • Topical Ointment: Applied to calibrated paper, measured in inches, and taped to the skin.
    • Intravenous (IV): Given as a titrated drip for unstable angina; requires close monitoring.

Adjuvant Medications for Angina

  • Beta-Blockers:
    • Examples: Atenolol, Metoprolol, Propranolol, Nadolol.
    • Action: Suppresses the sympathetic nervous system to decrease heart rate and blood pressure, thereby reducing oxygen demand.
    • Adverse Effects: Bradycardia, hypotension, constipation, and hypoglycemia masking (monitor glucose levels).
    • Contraindication: Non-selective beta-blockers like Propranolol can cause bronchoconstriction. Do not give to patients with COPD or Asthma. Selective beta-blockers like Metoprolol (Beta-1 specific) are safer for these patients.
  • Calcium Channel Blockers (CCBs):
    • Examples: Amlodipine, Diltiazem, Nicardipine, Nifedipine, Verapamil.
    • Action: Decreases cardiac workload for routine angina management.
    • Adverse Effects: Hypotension, constipation, nausea, flushing, and dizziness.
  • Angiotensin-Converting Enzyme (ACE) Inhibitors:
    • Examples: Captopril, Enalapril, Lisinopril.
    • Action: Blocks Angiotensin II production, decreasing blood pressure and fluid retention to reduce cardiac workload.
    • Adverse Effects: Dry irritating cough, orthostatic hypotension (advise rising slowly).
  • Sodium Channel Blockers:
    • Example: Ranolazine.
    • Action: Mechanism not fully known but produces myocardial relaxation and reduces angina symptoms.
    • Adverse Effects: Dizziness, headache, nausea, and constipation.

Thromboembolic Disorders and Clot Formation

  • Clotting Factors:
    • Platelets: Produced by bone marrow to promote clotting.
    • Vitamin K Dependent Factors: Essential for the coagulation cascade.
  • Pathological Consequences of Clotting:
    • Deep Vein Thrombosis (DVT): Clots in the calves causing swelling, redness, and pain.
    • Pulmonary Embolism (PE): Clot dislodges and occludes lung vessels.
    • Myocardial Infarction (MI): Clot occludes coronary arteries.
    • Stroke: Clot occludes cerebral vessels, depriving the brain of oxygen.
  • Conditions Requiring Anticoagulation:
    • History of stroke or MI.
    • Atrial Fibrillation (AFib): Quivering atria cause blood stasis, leading to high clot risk.
    • Mechanical Heart Valves.
    • Peripheral Arterial Disease (PAD).

Anticoagulant and Antiplatelet Medications

  • Antiplatelets:
    • Action: Inhibit platelet aggregation.
    • Examples: Aspirin, Clopidogrel (Plavix), Prasugrel, Ticagrelor.
    • Usage: Secondary prevention for stroke and MI (arterial clots).
    • Adverse Effects: GI bleeding, nausea, vomiting, neutropenia. Contraindicated for patients with active gastric ulcers.
  • Factor Xa Inhibitors:
    • Examples: Apixaban, Betrixaban, Rivaroxaban.
    • Action: Inhibits only clotting factor 1010.
    • Advantage: Low bleeding risk compared to multi-factor inhibitors; does not require frequent lab monitoring.
  • Heparin (Unfractionated):
    • Formulations: IV (emergency for PE) or Subcutaneous (DVT prophylaxis/treatment).
    • Adverse Effects: Bleeding, hematoma at injection site (use abdomen/adipose tissue), and Heparin-Induced Thrombocytopenia (HIT).
    • HIT: Body uses up platelets to form micro-clots, leading to paradoxical bleeding due to platelet depletion. Treated with antithrombin.
    • Monitoring: PTT (Partial Thromboplastin Time) or aPTT.
      • Normal PTT: 25−35 s25-35\,s.
      • Therapeutic PTT: 1.51.5 to 2.5×normal2.5 \times \text{normal}, which is approximately 45−75 s45-75\,s.
      • Critical Value: If PTT is >100 s> 100\,s, stop the drug and notify the physician.
    • Antidote: Protamine Sulfate.
  • Low Molecular Weight Heparins (LMWH):
    • Examples: Enoxaparin (Lovenox), Dalteparin.
    • Usage: Primarily for prevention and treatment of venous clots (DVT).
  • Warfarin (Coumadin):
    • Route: PO (oral).
    • Action: Alters Vitamin K dependent clotting factors.
    • Monitoring: PT (Prothrombin Time) and INR (International Normalized Ratio).
      • Therapeutic INR: Goal of 2−32-3 (or up to 3.53.5 for mechanical valves).
      • Therapeutic PT: Goal is approximately 18 s18\,s (range 13.5−26 s13.5-26\,s).
      • Interpretation: If INR <2< 2, the dose is sub-therapeutic (risk of clot). If INR >3> 3, risk for bleeding is high.
    • Antidote: Vitamin K.
  • Thrombin Inhibitors:
    • Example: Dabigatran.
    • Action: Inhibits clotting factor II (thrombin) to prevent fibrinogen conversion to fibrin.
  • Thrombolytics (Fibrinolytics):
    • Examples: Alteplase (TPA), Reteplase, Tenecteplase.
    • Action: Dissolves and disintegrates existing clots. Most potent class.
    • Indications: Acute MI, acute ischemic stroke, severe PE.
    • Adverse Effects: Severe bleeding, including intracranial/cerebral bleeding (monitor Level of Consciousness/LOC).
    • Antidote: Aminocaproic acid.

General Nursing Implications for Coagulation Modifiers

  • Assessment for Bleeding:
    • Obvious signs: Epistaxis (nosebleed), hematuria (blood in urine), ecchymosis (bruising).
    • Non-obvious signs: Internal abdominal bleeding (distended abdomen, dropping blood pressure), occult blood in stool.
  • Safety Precautions:
    • Refrain from intramuscular (IM) injections.
    • Limit venipuncture sticks; coordinate lab draws to single access points if possible.
    • Monitor LOC for potential brain bleeds.
  • Herbal Interactions:
    • Patients must avoid herbal remedies that potentiate bleeding: Ginger, Ginkgo, and Feverfew.

Drugs for Peripheral Vascular Disease (PVD)

  • Pentoxifylline:
    • Indication: Peripheral Arterial Disease (PAD) causing intermittent claudication (leg pain during walking that resolves at rest).
    • Action: Decreases blood viscosity and inhibits platelet aggregation to improve blood flow to extremities.
    • Adverse Effects: Dizziness, dysrhythmias, dyspepsia, and shortness of breath.
  • Cilostazol:
    • Indication: Peripheral vascular disease.
    • Action: Platelet aggregation inhibitor.
    • Adverse Effects: Palpitations, diarrhea, and dyspepsia. Monitor for peptic ulcers.