Cardiovascular Medications Study Guide week 5

Cardiovascular Medications

Chapter 9: Drug Therapy for Coagulation Disorders

Terms to Know
  • Anticoagulants: Drugs that prevent the formation of new clots and the extension of existing clots, but do NOT dissolve formed clots.
  • Antiplatelets: Drugs that prevent one or more steps in the prothrombotic activity of platelets.
  • Embolus: An object (thrombus, fat, air, amniotic fluid, tissue, or bacterial debris) that migrates through the circulation and lodges in a vessel, causing occlusion.
  • Heparin-Induced Thrombocytopenia (HIT): An immune-mediated adverse effect that leads to thrombosis, characterized by a decrease in platelet count related to heparin administration in patients with detectable HIT antibodies.
  • Thrombolytics: Drugs that dissolve blood clots.
  • Thrombus: A blood clot.

Anticoagulant Drugs

Prototype: Heparin
  • Pharmacokinetics:
    • Administered intravenously (IV) or subcutaneously (Subcut). Not absorbed in the GI tract.
    • IV administration provides immediate action. Subcut administration onset is 20-30 minutes.
    • Not removed through hemodialysis.
  • Action: Inactivates clotting factors, preventing thrombus formation.
  • Uses:
    • Prophylactic use for major illnesses.
    • History of DVT (deep vein thrombosis) or PE (pulmonary embolism).
    • Major abdominal or thoracic surgery.
    • Gynecological surgeries.
    • Patients with mobility restrictions.
  • Adverse Effects (AE): HIT, bleeding.
  • Contraindications: (Unspecified in the provided text).
  • Patient Education (Pt Ed): (Unspecified in the provided text).
Nursing Implications (Heparin)
  • Be aware of herbs and foods that increase the effects of heparin:
    • Chamomile, garlic, ginger, ginkgo, ginseng, high-dose vitamin E.
  • Administration:
    • Narrow Therapeutic Index (TI).
    • Monitor aPTT (activated partial thromboplastin time).
    • Therapeutic range: 1.5 to 2.5 times the normal range (25 to 35 seconds).
    • Therapeutic aPTT: 45 to 70 seconds.
    • Short duration of action.

LMWH – Synthetic Heparins

  • Smaller molecular structures compared to heparin.
  • Inactivate factor Xa.
  • As effective as IV heparin.
  • Do not cross the placenta.
  • Examples:
    • enoxaparin (Lovenox)
    • dalteparin (Fragmin)
  • Administered subcutaneously.

Vitamin K Antagonists: Warfarin (Coumadin)

  • Pharmacokinetics:
    • Oral administration (ok to take with food).
    • Highly bound to plasma proteins (albumin).
  • Action: Prevents the synthesis of vitamin K-dependent clotting factors.
    • Takes 3 to 5 days to become effective.
  • Uses: Long-term management of thromboembolic disorders.
  • Adverse Effects (AE): Hemorrhage, nausea/vomiting (n/v), abdominal pain, alopecia, dizziness, urticaria, and joint or muscle pain.
  • Contraindications: Same as heparin (unspecified in the provided text).
  • Black Box Warning: Major or fatal bleeding.
  • Patient Education (Pt Ed): PT/INR lab monitoring, signs and symptoms of bleeding prevention.
Nursing Implications (Warfarin)
  • Herbs & Foods that Increase Warfarin Effects:
    • Chamomile, chondroitin, cranberry juice, feverfew, garlic, ginkgo, grape seed extract, green tea, psyllium, turmeric.
  • Herbs & Foods that Decrease Warfarin Effects:
    • Ginseng, St. John’s wort, Vitamin K, foods high in vitamin K (broccoli, Brussel sprouts, cabbage, cauliflower, chives, collard greens, kale, lettuce, mustard greens, peppers, spinach, tomatoes, turnips, and watercress).
  • Therapeutic Effect: Monitored via PT/INR (prothrombin time/international normalized ratio).

Direct Thrombin Inhibitors: Dabigatran Etexilate (Pradaxa)

  • Pharmacokinetics:
    • Half-life of 12 to 17 hours.
    • May be prolonged in the elderly and those with renal failure.
    • Oral administration.
  • Action: Peaks in 1 hour, no known antagonists (antidote).
  • Uses:
    • Prevent stroke.
    • Embolization due to atrial fibrillation (a-fib).
    • Treatment of DVT/PE.
  • Adverse Effects (AE): Bleeding, dyspepsia (indigestion), abdominal pain, gastritis, and anemia.
  • Contraindications: Active pathological bleeding, mechanical prosthetic heart valve, pregnancy & lactation.
  • Patient Education (Pt Ed): Same as warfarin.
Nursing Implications (Dabigatran)
  • High-alert drug.
  • Give on an empty stomach.
  • Drug-Drug interactions that increase dabigatran effects:
    • Aspirin, NSAIDs, anticoagulants, antiplatelets (clopidogrel).
  • Drug-Drug interactions that decrease dabigatran effects:
    • Antacids, atorvastatin, proton pump inhibitors (PPI), estrogen, progestins.

Direct Factor Xa Inhibitors: Rivaroxaban

  • Pharmacokinetics:
    • Rapidly absorbed and highly protein bound.
  • Action:
    • Peak 2 to 4 hours, half-life 5 to 9 hours.
    • Inhibits platelet activation.
  • Uses: Prevention of DVT & stroke in patients with atrial fibrillation.
  • Adverse Effects (AE): Bleeding.
  • Contraindications: Pregnancy category X.
  • Patient Education (Pt Ed): (Unspecified in the provided text).
Nursing Implications (Rivaroxaban)
  • 15 to 20 mg dose should be given with food.
  • Give in the evening.
  • No routine lab monitoring required.
  • Drug-Drug interactions that increase rivaroxaban effects:
    • Aspirin, NSAIDs, vitamin E.
  • Drug-Drug interactions that decrease rivaroxaban effects:
    • Estrogen, progestins.
  • Herbs & Foods that increase rivaroxaban effects:
    • Alfalfa, anise, bilberry, grapefruit juice.
  • Herbs & Foods that decrease rivaroxaban effects:
    • St. John’s wort.

Other Direct Factor Xa Inhibitors

  • Apixaban (Eliquis)
  • Edoxaban (Savaysa)

Antiplatelets: Clopidogrel (Plavix)

  • Pharmacokinetics:
    • Oral administration.
    • Extensive first-pass metabolism.
    • Slow onset – requires a loading dose.
    • Half-life of 8 hours.
  • Action: Prevents platelet aggregation.
  • Uses:
    • Myocardial infarction (MI).
    • Post-coronary stent placement.
    • Patients unable to take warfarin.
  • Adverse Effects (AE):
    • Common: Pruritus (severe itching), rash, purpura, diarrhea.
    • Severe: Thrombotic thrombocytopenic purpura (TTP), hemorrhage, and severe neutropenia.
  • Contraindications: Active bleeding.
  • Patient Education (Pt Ed): (Unspecified in the provided text).
Nursing Implications (Clopidogrel)
  • Drugs increasing clopidogrel effect:
    • Aspirin, NSAIDs, atorvastatin.
  • Drugs decreasing clopidogrel effect:
    • Amiodarone, diltiazem, erythromycin, omeprazole, SSRIs.
  • Take once daily without regard to food.
  • Monitor Hematocrit & Hemoglobin.

Thrombolytic: Alteplase (rtPA)

  • Pharmacokinetics:
    • Administered IV.
    • Clears quickly – 80% within 10 minutes of discontinuation.
    • Unknown if crosses the placenta or is excreted into breast milk.
  • Action: Clot buster – dissolves formed clots.
  • Uses: First-line treatment of acute ischemic stroke (specific criteria must be met).
  • Adverse Effects (AE): (Unspecified in the provided text).
  • Contraindications: (Unspecified in the provided text).
  • Patient Education (Pt Ed): (Unspecified in the provided text).
Nursing Implications (Alteplase)
  • Prior to administering:
    • Check coagulation labs and platelet count.
    • Assess for any active bleeding or risks for bleeding.
    • Must be given within 3 hours of symptom onset.
  • During administration:
    • Monitor labs and signs/symptoms of bleeding.

Reversal Agents (Antidotes)

  • Heparin & LMWH: Protamine sulfate
    • Black box warning: severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension.
    • Given as a slow IV infusion over at least 10 minutes.
    • Duration approximately 2 hours; may require a second dose.
  • Vitamin K Antagonists (Warfarin): Vitamin K
    • Urgent reversal – PCC (Prothrombin Complex Concentrate) Kcentra or Fresh Frozen Plasma (FFP).
    • Black box warning: thromboembolic complications.
  • Direct Thrombin Inhibitors: Idarucizumab (Praxbind)
    • Used for uncontrolled or life-threatening bleeding or emergency surgery.
    • Administered IV in 2 doses, no more than 15 minutes apart.
    • Half-life of 45 minutes (normal renal function).
  • Thrombolytic: Aminocaproic acid (Amicar) and tranexamic acid (Cyklokapron)
    • Amicar – IV infusion.
    • Cyklokapron – oral or IV.

Medications for Hypertension (Chapter 26)

Clinical Guidelines of American College of Cardiology/American Heart Association

  • Classification of Blood Pressure (BP):
    • Normal: <120/80 mmHg
    • Elevated: 120-129/<80 mmHg
    • Stage 1 Hypertension: 130-139/80-89 mmHg
    • Stage 2 Hypertension: >140/90 mmHg

Nonpharmacologic Interventions for Elevated BP or Hypertension

  • Weight loss in overweight or obese adults (Class I recommendation; Level of Evidence: A).
  • A heart-healthy diet (e.g., DASH) to reduce BP (Class I recommendation; Level of Evidence: A).
  • Sodium reduction (Class I recommendation; Level of Evidence: A).
  • Potassium supplementation, preferably by dietary modification (Class I recommendation; Level of Evidence: A).
  • Increased physical activity with a structured exercise program (Class I recommendation; Level of Evidence: A).
  • Abstinence from or moderation in alcohol consumption (women, ≤1 standard drink per day; men, <2 standard drinks per day) (Class I recommendation; Level of Evidence: A).

Drugs that Act on the RAAS System

  • Angiotensin-Converting Enzyme (ACE) inhibitor: captopril (-prils).
  • Angiotensin II Receptor Blocker (ARB): losartan (-sartans).
  • Direct Renin Inhibitor: aliskiren.
  • Aldosterone Antagonist: eplerenone.

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) – captopril

  • Pharmacokinetics:
    • Absorption reduced by food.
    • Onset 1 to 1.5 hours, prolonged half-life with renal impairment.
    • Excreted in urine (and breast milk).
  • Action: Blocks the conversion of angiotensin I to angiotensin II.
  • Uses: Heart Failure & Hypertension.
  • Adverse Effects (AE): Angioedema, persistent cough, acute hypotension.
  • Contraindications: Pregnancy.
  • Patient Education (Pt Ed): Refer to Box 26.4, pg 521.
Drug-Drug Interactions (ACE Inhibitors)
  • Diuretics: May intensify first-dose hypotension.
  • Antihypertensive agents: Additive effect.
  • Drugs that raise potassium levels: Increased risk of hyperkalemia.
  • Lithium: May accumulate to toxic levels.
  • NSAIDs: May reduce anti-hypertensive effect.
Nursing Implications (ACE Inhibitors)
  • Increases serum concentration of digoxin and lithium; increase risk of toxicity.
  • Take 1 hour before or 2 hours after food.
  • May crush tablets.
  • Monitor BP and K+ level (hyperkalemia).

Angiotensin II Receptor Blockers – losartan

  • Pharmacokinetics: Extensive first-pass effect.
  • Action: Block access to angiotensin II receptors in blood vessels, adrenals, and other tissues.
  • Uses: (Unspecified in provided text)
  • Adverse Effects (AE): Angioedema.
  • Contraindications: Fetal harm (2nd or 3rd trimester), Renal Failure.
  • Patient Education (Pt Ed): Refer to Box 26.4, pg 521.
Nursing Implications (ARBs)
  • Evaluate (Unspecified in the provided text).
  • Monitor for elevated (Unspecified in the provided text).
  • Before (Unspecified in the provided text).

Calcium Channel Blockers - amlodipine

  • Pharmacokinetics:
    • Peak 6-12 hours
    • Significant initial reduction in BP 24-48 hours
    • Therapeutic levels reached 7 days of consistent daily dosing
  • Action: Block influx of Ca++Ca^{++}, causing relaxation and vasodilation.
  • Uses: Hypertension (alone or with other antihypertensives), Angina pectoris, Cardiac dysrhythmias.
  • Adverse Effects (AE): Peripheral edema (in HF patients), generally well tolerated, headache, drowsiness, fatigue, dizziness, nausea.
  • Contraindications: Heart Failure.
  • Patient Education (Pt Ed): Refer to Box 26.4 pg 521.

Classification of CCB

  • Dihydropyridines: nifedipine
  • Phenylalkylamine: verapamil
  • Benzothiazepine: diltiazem

CCB Verapamil

  • Indications: Angina pectoris, Hypertension, Cardiac dysrhythmias.
  • Hemodynamic effects: Vasodilation, ↓arterial pressure, ↑coronary perfusion.

Nifedipine

  • Indications: Angina pectoris, Hypertension.
  • Effects: Lowers blood pressure, reflexive (Transient) ↑HR; ↑ contractile force.
Nursing Implications (CCBs)
  • Assess BP (SBP <90) & P; renal & liver function labs.
  • Identify high-risk patients.
  • Contraindications: Hypotension; heart block; sick sinus syndrome.
  • Minimize adverse effects:
    • Cardiosuppression: Notify MD if slow heartbeat, SOB or weight gain.
    • Peripheral edema: notify MD if noted.
    • Constipation: ↑ fluid, ↑ fiber.

Direct Renin Inhibitors (DRI) - Aliskiren (Tekturna)

  • Treatment of HTN, used as monotherapy or in combination.
  • Less cough and angioedema.
  • Adverse Effects (AE): Diarrhea; hyperkalemia if taken with other drugs that ↑K.
  • Caution: Fetal risk, drug-drug interactions.
  • Take 1 hour before meals.

Beta1, Beta2, and Alpha1 Blockers (Beta Blockers with Vasodilating Actions)

  • Carvedilol: Hypertension, Heart failure.
  • Labetalol: Hypertension.
  • Nebivolol: Hypertension.

Prototype: Nonselective Beta Blockers: Propranolol

  • Blocks beta1 AND beta2 receptors.
  • Uses: HTN, Angina, Cardiac dysrhythmias, MI, Migraine headache.
  • Precautions/Contraindications: Severe allergy, Diabetes, Asthma, Depression, Heart failure, AV heart block, sinus bradycardia.

Prototype: Selective Beta Blockers: Metoprolol

  • Cardioselective: metoprolol (Lopressor); Blocks Beta1 receptors.
  • Preferred for patients with asthma or diabetes.
  • Uses: HTN, angina pectoris, HF, MI.
  • Avoid abrupt withdrawal: Exacerbation of angina, Ventricular dysrhythmias, MI.

Beta Antagonists

  • Non-selective (beta1, beta2):
    • Propranolol (prototype)
    • Carteolol
    • Nadolol
    • Pindolol
    • Sotalol
    • Timolol
  • Beta1- selective:
    • Metoprolol (prototype)
    • Atenolol
    • Bisoprolol
    • Esmolol
    • Acebutolol
    • Nebivolol
Nursing Implications (Beta Blockers)
  • Monitor heart rate, BP.
  • Count pulse, report if <50.
  • Observe for drug interactions.
  • Identify high-risk patients.
  • Warn patients against abrupt discontinuation.
  • Inform patients about early signs of heart failure.
  • Inform patients about signs/symptoms of postural hypotension.
  • Diabetic precautions.

Drug Classification Practice

  • ACE: Captopril
  • ARB: Losartan
  • CCB: Verapamil
  • Beta Blocker: Metoprolol

Drug Therapy for Fluid Volume Excess (Chapter 34)

Terms to Know

  • Anasarca: Generalized massive edema.
  • Anuria: No urine output.
  • Ascites: Accumulation of fluid in the abdominal cavity.
  • Edema: Excessive accumulation of fluid in body tissue.
  • Dependent edema: Localized edema in feet and ankles.

Kidney Functions and Diuretics

  • Diuretics act on different parts of the nephron to affect reabsorption.

Diuretics - Action

  • Blockade of sodium and chloride reabsorption.
  • Increased osmotic pressure in the nephron prevents passive reabsorption of water.
  • Increase in urine flow is directly related to the amount of sodium and chloride reabsorption that the diuretic blocks.

Signs and Symptoms of Hypokalemia

  • Alkalosis
  • Shallow Respirations
  • Irritability
  • Confusion and drowsiness
  • Weakness and fatigue
  • Arrhythmias
  • Lethargy
  • Thready Pulse

Impact of Diuretics on Fluid and Electrolyte Balance

  • Adverse impact includes:
    • Extracellular Fluid Volume depletion (Hypovolemia)
    • Acid-base imbalance
    • Altered electrolyte levels

Loop Diuretics: Furosemide (Lasix)

  • Site of action: ascending loop of Henle.
  • Most effective diuretics, high ceiling diuretics
Pharmacokinetics (Furosemide)
  • Oral or IV administration.
  • PO: Onset: 30-60 min | Peak: 1 to 2 hours | Duration: 6 to 8 hours.
  • IV: Onset: 5 min | Peak: 30 min | Duration: 2 hours.
Action (Furosemide)
  • Inhibits Na+Na^+ & Cl−Cl^- reabsorption in the ascending loop of Henle.
  • 10x the sodium-losing effect of thiazides.
Uses (Furosemide)
  • HTN, Acute Pulmonary Edema, HF, Hepatic & Renal disease.
Adverse Effects (Furosemide)
  • Fluid & Electrolyte imbalance, Ototoxicity.
Contraindications (Furosemide)
  • Chronic Renal Failure (CRF), allergy to sulfonamides, pregnancy.
Patient Education (Furosemide)
  • Refer to Box 34.4 pg 685.
Drug-Drug Interactions (Furosemide)
  • Digoxin & Corticosteroids: Monitor potassium levels.
  • Nephrotoxic & Ototoxic drugs (Aminoglycosides, cephalosporins).
  • Lithium: May reach toxic levels – monitor carefully.
  • Potassium-sparing diuretics: Minimize hypokalemia.

Thiazide Diuretics: Hydrochlorothiazide (HCTZ)

  • Site of Action: Early Distal Convoluted Tubule.
Pharmacokinetics (HCTZ)
  • Oral and is highly bound to plasma proteins.
  • Onset: 2 hours | Peak: 4 to 6 hours | Duration 6 to 24 hours.
Action (HCTZ)
  • Acts to decrease reabsorption of sodium, water, chloride, and bicarbonate in the distal convoluted tubule.
Uses (HCTZ)
  • HTN, Edema – HF and Nephrotic syndrome.
Adverse Effects (HCTZ)
  • (Unspecified in the provided text)
Contraindications (HCTZ)
  • Allergy to sulfonamide-derived agents, Anuria, Pregnancy.
Patient Education (HCTZ)
  • Refer to Box 34.4 pg 685.
Specific Considerations (HCTZ)
  • Ceiling threshold - increasing the dose beyond a certain point does not produce a greater diuretic effect
  • Risk of Ototoxicity
    • High serum drug levels
    • Renal impairment
    • Concurrent use of other ototoxic drugs (e.g., aminoglycoside antibiotics).

Potassium-Sparing Diuretics

Aldosterone Antagonist: Spironolactone (Aldactone)
Non-Aldosterone Antagonist: triamterene
Pharmacokinetics (Spironolactone)
  • Requires several days for a full therapeutic effect (6 weeks for max effect).
  • Onset – 24-48 hours; duration 48-72 hours.
  • With food for best absorption.
Action (Spironolactone)
  • Blocks the action of aldosterone in the distal nephron.
Uses (Spironolactone)
  • HTN, HF, ascites, hypokalemia, hyperaldosteronism.
Adverse Effects (Spironolactone)
  • Dizziness, HA, abd cramping, diarrhea.
  • Deepening of voice, gynecomastia, menstrual irregularities, testicular atrophy.
  • Hyperkalemia, Risk of GI bleeding.
Contraindications (Spironolactone)
  • Renal insufficiency, 1st trimester of pregnancy.
Patient Education (Spironolactone)
  • Take in the morning at the same time each day.

Triamterene (K+- Sparing)

Action (Triamterene)
  • Directly inhibits the exchange of K+K^+ and Na+Na^+ in the distal nephron.
Pharmacokinetics (Triamterene)
  • Onset – 2-4 hours; duration 12-16 hours.
  • Scanty diuresis.
Uses (Triamterene)
  • HTN, Edema, Counteract K+K^+ loss.
Adverse Effects (Triamterene)
  • Hyperkalemia, n/v, leg cramps, dizziness.

Symptoms of Hyperkalemia (High Potassium)

  • Many times, there are no symptoms, but when there are, symptoms can include:
    • Nausea
    • Slow, weak, or irregular pulse
    • Sudden collapse
    • Irritability
    • Numbness (usually felt in the hands, arms, legs, or feet)
    • Muscle weakness
    • Diarrhea or abdominal cramping

Combinations (Diuretics)

  • Decreases likelihood of hypokalemia.
  • Example: Dyazide (Triamterene/HCTZ).

Osmotic Diuretics: Mannitol (Osmitrol)

  • Site of Action: Proximal Convoluted Tubule.
Pharmacokinetics (Mannitol)
  • Given IV (typically in ICU).
  • Onset: 30 to 60 min | Peak: 1 hours | Duration: 6-8 hours.
  • Half-life 1 to 1.6 hours.
Action (Mannitol)
  • Creates osmotic force within the lumen of the nephron - Inhibits passive reabsorption of water.
Uses (Mannitol)
  • Prophylaxis of renal failure, reduces ICP (intracranial pressure), reduces IOP (intraocular pressure).
Adverse Effects (Mannitol)
  • Edema, may precipitate CHF (congestive heart failure) and Pulmonary Edema in patients with heart disease, Coma, hypotension.
Contraindications (Mannitol)
  • Anuria, severe hypovolemia, severe pulmonary edema, active intracranial bleeding.