Cardiovascular Drugs Study Notes

Anti-hypertensive Drugs

• Hypertension Defined (JNC-8):
  • 60 years or older: Systolic blood pressure (SBP) > 150 mm Hg or diastolic blood pressure (DBP) > 90 mm Hg.
  • Younger than 60 years and those with chronic kidney disease or diabetes: SBP > 140 and DBP > 90.
  • Hypertension is a major risk factor for coronary artery disease (CAD) and cardiovascular disease (CVD).
• Blood Pressure (BP) Calculation:
  • BP = CO \, \times \, SVR, where CO is cardiac output and SVR is systemic vascular resistance.

Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8)

• Initial Antihypertensive Treatment:
  • General non-African American population: Thiazide diuretic, calcium channel blocker, ACE inhibitor, or ARB.
  • General African American population: Thiazide diuretic or calcium channel blocker.
• If Target BP Not Reached:
  • Increase the dosage of the initial medication or add a second medication if the target blood pressure is not reached within one month after initiating therapy.

Drug Therapy for Hypertension

• Must be individualized.
• Seven Main Categories of Drugs:
  • Angiotensin-converting enzyme (ACE) inhibitors
  • Angiotensin II receptor blockers (ARBs)
  • Beta blockers
  • Calcium channel blockers (CCBs)
  • Diuretics – first line of treatment
  • Vasodilators
  • Adrenergic drugs
  • Direct renin inhibitors
• African-American considerations: CCB + Diuretic

Angiotensin-Converting Enzyme (ACE) Inhibitors

• Large group of safe and effective drugs; currently, there are 10 ACE inhibitors.
• Often used as first-line drugs for HF and hypertension.
• May be combined with a thiazide diuretic or CCB.
• MOA: Inhibit Angiotensin converting enzyme (ACE).
• Suffix “PRIL”.

Renin-Angiotensin-Aldosterone System (RAAS)

• Renin converts angiotensinogen to angiotensin I.
• ACE converts angiotensin I to angiotensin II.
• Angiotensin II causes systemic vasoconstriction, aldosterone release, ADH release, and stimulates thirst.
• Aldosterone leads to sodium/water retention and reduced baroreflex sensitivity.

Angiotensin-Converting Enzyme (ACE) Inhibitors (Cont.)

• Examples: Captopril (Capoten), Benazepril (Lotensin), Enalapril (Vasotec), Fosinopril (Monopril), Lisinopril (Prinivil), Perindopril (Aceon), Quinapril (Accupril), Ramipril (Altace), Trandolapril (Mavik).

Primary Effects of the ACE Inhibitors

• Cardiovascular and renal benefits:
  • Reduces BP by decreasing SVR.
  • HF: Prevents sodium and water resorption by inhibiting aldosterone secretion, leading to diuresis, decreased blood volume, and reduced preload.

Cardioprotective Effects of the ACE Inhibitors

• ACE inhibitors decrease SVR (afterload) and preload.
• Used to prevent complications after MI, including ventricular remodeling (left ventricular hypertrophy).
• Decreases morbidity and mortality in patients with HF.
• Drugs of choice for hypertensive patients with HF.

Renal Protective Effects of the ACE Inhibitors

• ACE inhibitors reduce glomerular filtration pressure.
• Cardiovascular drugs of choice for patients with diabetes.
• Reduce proteinuria.
• Standard therapy for diabetic patients to prevent the progression of diabetic nephropathy.

ACE Inhibitors: Indications

• Hypertension
• HF (either alone or in combination with diuretics or other drugs)
• Slow progression of left ventricular hypertrophy after myocardial infarction (MI) (cardioprotective)
• Renal protective effects in patients with diabetes

ACE Inhibitors: Adverse Effects

• First dose- orthostatic hypotension
  • If client is taking a diuretic, stop the medication temporarily for 2 to 3 days prior to start of ACE inhibitor
  • Monitor blood pressure for 2 hours after initiation of medication
• Rash
• Mood changes
• Impaired taste - dysgeusia
• Hyperkalemia
• Dry, nonproductive cough, which reverses when therapy is stopped
• Angioedema: rare but potentially fatal
• NOTE: First-dose hypotensive effect may occur.

ACE Inhibitors: Specific Drugs

• Captopril (Capoten):
  • Uses: Prevention of ventricular remodeling after MI; reduce the risk of HF after MI.
  • Shortest half-life - administered multiple times throughout the day.
  • Not a prodrug; therefore, it does not need to be metabolized by the liver to be effective. This is an advantage in patients with liver disease.
• Enalapril (Vasotec):
  • Only ACE inhibitor available in both oral and parenteral preparations.
  • Oral enalapril: prodrug.
  • Improves patient’s chances of survival after an MI.

ACE Inhibitors and Laboratory Values

• ACE inhibitors can cause renal impairment, which can be identified with serum creatinine.
• ACE inhibitors can also cause hyperkalemia, so potassium levels need to be monitored.

Angiotensin II Receptor Blockers (ARBs)

• Also referred to as angiotensin II blockers
• Well tolerated
• Do not cause a dry cough that is common with ACE inhibitors
• Suffix “sartan”

Angiotensin II Receptor Blockers: Mechanism of Action

• ARBs affect primarily vascular smooth muscle and the adrenal gland.
• Selectively block the binding of Angiotensin II to the type 1 Angiotensin II receptors in these tissues
• ARBs block vasoconstriction and the secretion of aldosterone.
  • Potent vasodilators - decrease systemic vascular resistance (afterload)
    • Helps with heart failure

Angiotensin II Receptor Blockers

• Examples: Losartan (Cozaar), Eprosartan (Teveten), Valsartan (Diovan), Irbesartan (Avapro), Candesartan (Atacand), Olmesartan (Benicar), Telmisartan (Micardis), Azilsartan (Edarbi).

Comparison of ACE Inhibitors and Angiotensin II Receptor Blockers

• ACE inhibitors and ARBs appear to be equally effective for the treatment of hypertension.
• Both are well tolerated.
• ARBs are less likely to cause dry cough and hyperkalemia
• Evidence that ARBs are better tolerated and are associated with lower mortality after MI than ACE inhibitors

Angiotensin II Receptor Blockers: Indications

• Hypertension
• Adjunctive drugs for the treatment of HF
• May be used alone or with other drugs such as diuretics

Angiotensin II Receptor Blockers: Adverse Effects

• Hypotension
• Hyperkalemia and cough are less likely to occur than with the ACE inhibitors.
• Angioedema – swelling of tongue and pharynx (throat)
  • Treated with epinephrine
  • Discontinue medication and notify provider immediately

Angiotensin II Receptor Blockers: Specific Drugs

• Losartan (Cozaar)
  • Beneficial in patients with hypertension and HF
  • Used with caution in patients with renal or hepatic dysfunction and in patients with renal artery stenosis
  • Not safe for breastfeeding women and should not be used in pregnancy

Beta Blockers: Mechanism of Action

• Block beta1 receptors on the heart
• Decrease heart rate, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heart
• Decrease myocardial contractility, helping to conserve energy or decrease demand
• Propranolol, metoprolol, and atenolol

Beta Blockers: Indications

• Angina
• Antihypertensive
• Cardiac dysrhythmias
• Cardioprotective effects, especially after MI
• Some used for migraine headaches, essential tremors, and stage fright

Beta Blockers: Contraindications

• Systolic HF
• Serious conduction disturbances
• Caution: bronchial asthma because any level of blockade of beta2 receptors can promote bronchoconstriction
• Diabetes mellitus: can mask hypoglycemia-induced tachycardia
• Peripheral vascular disease: may further compromise cerebral or peripheral blood flow

Beta Blockers: Adverse Effects

• Hypotension
• Bradycardia
  • Reduction of the heart rate through beta1 receptor blockade
• Bronchospasm - wheezing
• Cause reduced secretion of renin
• Mask signs of hypoglycemia
• May cause hyperlipidemia
• Impotence
• Long-term use causes reduced peripheral vascular resistance.

Beta Blockers: Specific Drugs

• Nebivolol (Bystolic)
• Uses: hypertension and HF
• Less sexual dysfunction
• Do not stop abruptly; must be tapered over 1 to 2 weeks

Dual-Action Alpha1 and Beta Receptor Blockers

• Labetalol and carvedilol
  • Dual antihypertensive effects of reduction in heart rate (beta1 receptor blockade) and vasodilation (alpha1 receptor blockade)

Dual-Action Alpha1 and Beta Receptor Blockers: Carvedilol (Coreg)

• Widely used drug that is well tolerated
• Uses: hypertension, mild to moderate HF in conjunction with digoxin, diuretics, and ACE inhibitors
• Contraindications: known drug allergy, cardiogenic shock, severe bradycardia or HF, bronchospastic conditions such as asthma, and various cardiac problems involving the conduction system

Calcium Channel Blockers: Mechanism of Action

• Cause coronary artery vasodilation
• Cause peripheral arterial vasodilation, thus decreasing systemic vascular resistance
• Reduce the workload of the heart
• Dysrhythmias: depression of the automaticity of and conduction through the sinoatrial and AV nodes
• Results in:
  • Decreased peripheral smooth muscle tone
  • Arteries/Arterioles
  • Decreased SVR
  • Decreased BP
  • Decreased myocardial oxygen demand

Calcium Channel Blockers

• Nifedipine
• Verapamil
• Diltiazem
• Amlodipine
• Felodipine
• Nimodipine
• Nicardipine

Calcium Channel Blockers: Indications

• Angina
• Hypertension: amlodipine (Norvasc)
• Dysrhythmias
• Migraine headaches
• Preterm labor: nifedipine
• Raynaud’s disease
• Prevent the cerebral artery spasms after subarachnoid hemorrhage: nimodipine

Calcium Channel Blockers: Contraindications

• Known drug allergy
• Acute MI
• Second- or third-degree AV block (unless the patient has a pacemaker)
• Hypotension

Calcium Channel Blockers: Adverse Effects

• Constipation – primarily verapamil
• Reflex tachycardia
• Orthostatic hypotension
• Peripheral edema
• Suppression of cardiac function (verapamil, diltiazem)
• Interactions:
  • Grapefruit juice can lead to toxicity
• Acute toxicity - hypotension, bradycardia, AV block and dysrhythmia

Diuretics

• First-line antihypertensives in the JNC 8 guidelines for the treatment of hypertension
• Decrease plasma and extracellular fluid volumes
• Results
  • Decreased preload
  • Decreased CO
  • Decreased total peripheral resistance
• Overall effect
  • Decreased workload of the heart and decreased BP
• Thiazide diuretics are the most commonly used diuretics for hypertension.

Diuretics: Loop Diuretics (Furosemide)

• Adverse effects: electrolyte imbalance, ototoxicity, hypotension, dehydration, increase LDL and triglycerides
• Drug Interactions:
  • Digoxin
  • Lithium
  • Aminoglycosides - ototoxicity
  • NSAID’s
• If potassium drops below normal – monitor ECG and notify provider
• Take medication first thing in the morning

Diuretics: Thiazide Diuretics

• Adverse effects: electrolyte imbalance, dehydration, hypotension
  • Hyperuricemia, hyperglycemia
• First line of treatment for hypertension
• Take medication first thing in the morning

Diuretics: Potassium-sparing Diuretics (Aldosterone antagonists)

• Spironolactone
• Eplerenone
• Adverse effects: hyperkalemia, endocrine effects (hirsutism, irregular menstrual cycle, gynecomastia, deepened voice), drowsiness and metabolic acidosis
• Avoid salt substitutes that contain potassium

Vasodilators

• Diazoxide (Hyperstat)
• Hydralazine (Apresoline)
  • BiDil: (isosorbide dinitrate/hydralazine) specifically indicated as an adjunct for treatment of HF in African-American patients
  • Injectable: hypertensive emergencies
• Minoxidil (Rogaine)
  • For hair regrowth
• Nitroprusside (Nitropress)

Vasodilators: Mechanism of Action

• Directly relax arteriolar or venous smooth muscle (or both)
  • Results in:
    • Decreased SVR
    • Decreased afterload
    • Peripheral vasodilation
• Indications
  • Treatment of hypertension
  • May be used in combination with other drugs
  • Sodium nitroprusside and IV diazoxide are reserved for the management of hypertensive emergencies.

Vasodilators: Adverse Effects

• Hydralazine: dizziness, headache, anxiety, tachycardia, edema, dyspnea, nausea, vomiting, diarrhea, hepatitis, systemic lupus erythematosus, vitamin B6 deficiency, and rash
• Minoxidil: T-wave electrocardiographic changes, pericardial effusion or tamponade, angina, breast tenderness, rash, and thrombocytopenia
• Sodium nitroprusside: bradycardia, decreased platelet aggregation, rash, hypothyroidism, hypotension, methemoglobinemia, and (rarely) cyanide toxicity

Centrally Acting Adrenergic Drugs

• Clonidine and methyldopa
  • Stimulate alpha2-adrenergic receptors in the brain
  • Decrease sympathetic outflow from the central nervous system because of decrease norepinephrine production - Result in decreased BP
  • Not typically prescribed as first-line antihypertensive drugs
  • High incidence of unwanted adverse effects: orthostatic hypotension, fatigue, and dizziness
  • Adjunct drugs to treat hypertension after other drugs have failed. Used in conjunction with other antihypertensives such as diuretics

Centrally Acting Adrenergic Drugs: Clonidine

• Used primarily for its ability to decrease blood pressure
• Also used for management of opioid withdrawal
• Oral and topical patch
• Do not stop abruptly
  • May lead to rebound hypertension

Peripherally Acting Alpha1 Blockers

• Doxazosin, prazosin, and terazosin
  • Block alpha1-adrenergic receptors
  • When alpha1-adrenergic receptors are blocked, BP is decreased.
  • Dilate arteries and veins
  • Alpha1 blockers also increase urinary flow rates and decrease outflow obstruction by preventing smooth muscle contractions in the bladder neck and urethra.
  • Use: benign prostatic hyperplasia (BPH)
• Tamsulosin (Flomax) – indicated solely for BPH

Miscellaneous Antihypertensive Drugs: Eplerenone (Inspra)

• Newer class of drugs called selective aldosterone blockers
• Reduces BP by blocking the actions of aldosterone at its corresponding receptors in the kidney, heart, blood vessels, and brain
• Indications: routine treatment of hypertension and for post-MI HF
• Contraindicated if serum potassium levels are high (above 5.6 mEq/L)

Nursing Implications

• Before beginning therapy, obtain a thorough health history and head-to-toe physical examination.
• Assess for contraindications to specific antihypertensive drugs.
• Assess for conditions that require cautious use of these drugs.
• Educate patients about the importance of not missing a dose and taking the medications exactly as prescribed.
• Monitor BP during therapy; instruct patients to keep a journal of regular BP checks.
• Instruct patients that these drugs should not be stopped abruptly because this may cause a rebound hypertensive crisis and perhaps lead to stroke.
• Oral forms should be given with meals so that absorption is more gradual and effective.
• Encourage patients to watch their diet, stress level, weight, and alcohol intake.
• Instruct patients to avoid smoking and eating foods high in sodium.
• Encourage supervised exercise.
• Teach patients to change positions slowly to avoid syncope from postural hypotension.
• Instruct patients to report unusual shortness of breath; difficulty breathing; swelling of the feet, ankles, face, or around the eyes; weight gain or loss; chest pain; palpitations; and excessive fatigue.
• Male patients who take these drugs may not be aware that impotence is an expected effect, and this may influence compliance with drug therapy.
• If patients are experiencing serious adverse effects or if they believe the dose or medication needs to be changed, they should contact their physicians immediately.
• Hot tubs, showers, or baths; hot weather; prolonged sitting or standing; physical exercise; and alcohol ingestion may aggravate low BP, leading to fainting and injury; patients should sit or lie down until symptoms subside.
• Patients should not take any other medications, including over-the-counter drugs, without first getting the approval of their physicians.
• Educate patients about lifestyle changes that may be needed.
  • Weight loss
  • Stress management
  • Supervised exercise
  • Dietary measures
• Monitor for adverse effects (dizziness, orthostatic hypotension, fatigue) and for toxic effects.
• Monitor for therapeutic effects.

Angina Pectoris (Chest Pain)

• When the supply of oxygen and nutrients in the blood is insufficient to meet the demands of the heart, the heart muscle “aches.”
  • The heart requires a large supply of oxygen to meet the demands placed on it.
• Ischemic heart disease
  • Poor blood supply to the heart muscle
  • Atherosclerosis
  • Coronary artery disease
• Myocardial infarction (MI)
  • Necrosis, or death, of cardiac tissue
  • Disabling or fatal

Types of Angina

• Chronic stable angina (also called classic or effort angina); Predictable
• Unstable angina (also called preinfarction or crescendo angina); Unpredictable
• Vasospastic angina (also called Prinzmetal or variant angina)

Therapeutic Objectives

• Minimize the frequency of attacks and decrease the duration and intensity of anginal pain.
• Improve the patient’s functional capacity with as few adverse effects as possible.
• Prevent or delay the worst possible outcome: MI.

Drugs for Angina

• Nitrates or nitrites
• Beta blockers
• Calcium channel blockers (CCBs)

Nitrates and Nitrites

• Available forms
  • Sublingual*
  • Chewable tablets
  • Oral capsules/tablets
  • Intravenous (IV) solutions*
  • Transdermal patches*
  • Ointments
  • Translingual sprays*
    • *Bypass the liver and the first-pass effect.

Nitrates and Nitrites (Cont.)

• Nitroglycerin (both rapid and long acting)
• Isosorbide dinitrate (both rapid and long acting)
• Isosorbide mononitrate (primarily long acting)

Nitrates and Nitrites: Mechanism of Action and Drug Effects

• Cause vasodilation because of relaxation of smooth muscles
• Potent dilating effect on coronary arteries
• Result: oxygen to ischemic myocardial tissue
• Used for prevention and treatment of angina

Nitrates and Nitrites: Indications

• Treat stable, unstable, and vasospastic angina
• Rapid-acting forms
  • Used to TREAT ACUTE anginal attacks
    • Sublingual tablets, IV infusion
• Long-acting forms
  • Used to PREVENT anginal episodes

Nitrates: Contraindications

• Known drug allergy
• Severe anemia
• Closed-angle glaucoma
• Hypotension
• Severe head injury
• Use of the erectile dysfunction drugs sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra)

Nitrates: Adverse Effects

• Headaches
  • Usually diminish in intensity and frequency with continued use
• Reflex tachycardia
• Postural hypotension
• Skin irritation with topical application
• Tolerance may develop
  • Occurs in patients taking nitrates around the clock or with long-acting forms
  • Prevented by allowing a regular nitrate-free period to allow enzyme pathways to replenish
    • Transdermal forms: remove patch at bedtime for 8 hours, then apply a new patch in the morning

Isosorbide dinitrate (Isordil)

• Organic nitrate
• Available in rapid-acting sublingual tablets, immediate-release tablets, and long-acting oral dosage forms
• Produces more consistent, steady, therapeutic response

Nitroglycerin

• Prototypical nitrate
• The most important drug used in the symptomatic treatment of ischemic heart conditions such as angina
• Large first-pass effect with oral forms
• Routes—PO, SL, metered-dose aerosol that is sprayed under the tongue, IV, and topical
• IV form used for BP control in perioperative hypertension, treatment of heart failure (HF), ischemic pain, pulmonary edema associated with acute MI, and hypertensive emergencies

Beta Blockers

• Mainstay in the treatment of several cardiovascular diseases
  • Angina
  • MI
  • Hypertension
  • Dysrhythmias
• Reduces mortality rate in patients after MI and in treating angina

Beta Blockers:

• After an MI, a high level of circulating catecholamines irritates the heart, causing an imbalance in supply and demand ratio and even leading to life-threatening dysrhythmias.
• Beta blockers block the harmful effects of catecholamines, thus improving survival after an MI.

Calcium Channel Blockers for Chronic Stable Angina

• Amlodipine
• Nicardipine
• Nifedipine
• Verapamil
• Diltiazem

Miscellaneous Antianginal Drug: Ranolazine (Ranexa)

• Mechanism of action is unknown – lower myocardial oxygen demand
• Known to prolong the QT interval on the electrocardiogram
• Reserved for patients who have failed to benefit from other antianginal drug therapy
• Contraindications: pre-existing QT prolongation or hepatic impairment, in those taking other QT-prolonging drugs
• Drug interactions
  • Grapefruit juice, macrolide antibiotics, azole antifungals, some CCB’s – increase levels of ranolazine which may lead to torsades de pointes
  • Quinidine and Sotalol– prolong QT interval
  • Can cause increased levels of digoxin and simvastatin

Nursing Implications

• Patients should be encouraged to limit caffeine intake.
• Patients should report:
  • Blurred vision
  • Persistent headache
  • Dry mouth
  • Edema
  • Fainting episodes
  • Weight gain of 2 lb in 1 day or 5 lb in 1 week
  • Pulse rate less than 60 beats/min
  • Dyspnea
• Teach patients to change positions slowly to avoid postural BP changes.
• Encourage patients to keep a record of their anginal attacks, including precipitating factors, number of pills taken, and therapeutic effects.

Nursing Implications: Nitroglycerin

• Instruct patients in proper technique and guidelines for taking sublingual nitroglycerin for anginal pain.
• Instruct patients never to chew or swallow the sublingual form.
• Instruct patients that a burning sensation felt with sublingual forms indicates that the drug is still potent.
• Instruct patients to keep a fresh supply of sublingual medication on hand; potency is lost in about 3 months after the bottle has been opened.
• To preserve potency, medications should be stored in an airtight, dark glass bottle with a metal cap and no cotton filler.

Nursing Implications: Nitroglycerin (Cont.)

• Instruct patients in the proper application of nitrate topical ointments and transdermal forms, including site rotation and removal of old medication.
• To reduce tolerance, the patient may be instructed to remove topical forms at bedtime and apply new doses in the morning, allowing for a nitrate-free period.
• Instruct patients to take as-needed nitrates at the first hint of anginal pain.
• Monitor vital signs frequently during acute exacerbations of angina and during IV administration.
• If experiencing chest pain, the patient taking sublingual nitroglycerin should lie down to prevent or decrease dizziness and fainting that may occur because of hypotension.
• If anginal pain occurs:
  • Stop activity and sit or lie down and take a sublingual tablet.
  • If there is no relief in 5 minutes, call 911 or emergency services immediately and take a second sublingual tablet.
  • If there is no relief in 5 minutes, take a third sublingual tablet.
  • Do not try to drive to the hospital.
• IV forms of nitroglycerin must be given with special non-PVC tubing and bags.
• Discard parenteral solution that is blue, green, or dark red.

Nursing Implications: Beta blockers

• Patients taking beta blockers should monitor their pulse rates daily and report any rate lower than 60 beats/min or symptoms of relative bradycardia.
• Instruct patients to report dizziness or fainting.
• Inform patients that these medications should never be abruptly discontinued.
• Inform patients that these medications are for long-term prevention of angina, not for immediate relief.

Nursing Implications: CCBs & Antianginal drugs

• Constipation is a common problem; instruct patients to take in adequate fluids and eat high-fiber foods.
• Monitor for adverse reactions: allergic reactions, headache, lightheadedness, hypotension, dizziness.
• Monitor for therapeutic effects: relief of angina, decreased BP, or both.

Heart Failure

• Not a specific disease
• The heart is unable to pump blood in sufficient amounts from the ventricles to meet the body’s metabolic needs.
• Symptoms depend on the cardiac area affected
  • Common symptoms: dyspnea, fatigue, fluid retention and/or pulmonary edema
  • “Left-sided” heart failure (HF): pulmonary edema, coughing, shortness of breath, and dyspnea
  • “Right-sided” HF: systemic venous congestion, pedal edema, jugular venous distension, ascites, and hepatic congestion

Heart Failure: Causes

• Myocardial infarction (MI)
• Coronary artery disease
• Cardiomyopathy
• Valvular insufficiency
• Atrial fibrillation
• Infection
• Tamponade
• Ischemia
• Pulmonary hypertension
• Systemic hypertension
• Outflow obstruction
• Hypervolemia
• Congenital abnormalities
• Anemia
• Thyroid disease
• Infection
• Diabetes

Drug Therapy for Heart Failure

• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin receptor blockers (ARBs)
• Angiotensin receptor-neprilysin inhibitors(ARNI)
• Beta blockers
• Aldosterone Antagonists
• Diuretics
• Sinoatrial modulators
• Phosphodiesterase Inhibitors (PDIs)
• Cardiac glycosides

Drugs of Choice for Early Treatment of Heart Failure

• Focus on reducing effects of the renin- angiotensin-aldosterone system and the sympathetic nervous system
  • ACE inhibitors (lisinopril, enalapril, captopril)
  • ARBs (valsartan, candesartan, losartan)
• Certain beta blockers (metoprolol, a cardioselective beta blocker; carvedilol, a nonspecific beta blocker)

Drugs of Choice for Early Treatment of Heart Failure (Cont.)

• Loop diuretics (furosemide) are used to reduce the symptoms of HF secondary to fluid overload.
• Aldosterone inhibitors (spironolactone, eplerenone) are added as the HF progresses.
• Only after these drugs are used is digoxin added.

Drugs of Choice for Early Treatment of Heart Failure (Cont.)

• Dobutamine: positive inotropic drug
• Hydralazine and isosorbide dinitrate became the first drug approved for a specific ethnic group. Hydralazine/isosorbide dinitrate (BiDil) was approved specifically for use in Blacks.

Angiotensin Receptor-Neprilysin Inhibitors (ARNI)

• Combination drug: ARB and neprilysin inhibitor
  • Valsartan/sacubitril (Entresto)
• New class used for management of heart failure with reduced ejection fraction
• Common adverse effects: hypotension, hyperkalemia, increased serum creatinine
• Not for use in pregnancy
• Several drug interactions, including ACEIs and NSAIDs

Aldosterone Antagonists

• Useful in severe stages of HF
• Action: activation of the renin-angiotensin- aldosterone system causes increased levels of aldosterone, which causes retention of sodium and water, leading to edema that can worsen HF.

Aldosterone Antagonists (Cont.)

• Spironolactone (Aldactone): potassium- sparing diuretic and aldosterone antagonist shown to reduce the symptoms of HF
• Eplerenone (Inspra): selective aldosterone blocker, blocking aldosterone at its receptors in the kidney, heart, blood vessels, and brain

Ivabradine (Corlanor)

• Sinoatrial node modulator - results in reduced heart rate
• Used in stable, symptomatic HF with ejection fraction of 35% or less
• Increase risk of atrial fibrillation, bradycardia, and conduction disturbances
• Avoid grapefruit juice

Phosphodiesterase Inhibitors (PDIs)

• Work by inhibiting the enzyme phosphodiesterase
  • Increase in calcium for myocardial muscle contraction.
• Inodilators (inotropics and dilators)
• Short-term management of HF for patients in the intensive care unit (ICU)
• Milrinone - injectable form
  • Only available phosphodiesterase inhibitor
  • Adverse effects: cardiac dysrhythmias, headache, hypokalemia, tremor, thrombocytopenia, and elevated liver enzyme levels
  • Interactions: diuretics (additive hypotensive effects) and digoxin (additive inotropic effects)

Cardiac Glycosides

• One of the oldest groups of cardiac drugs
• No longer used as first-line treatment
• Not been shown to reduce mortality in HF patients
• Originally obtained from Digitalis plant, foxglove
• Digoxin is the prototype.
• Used in HF and to control ventricular response to atrial fibrillation

Cardiac Glycosides: Mechanism of Action

• Increase myocardial contractility
  • Positive inotropic effect
    • Increased force and velocity of myocardial contraction (without an increase in oxygen consumption)
• Negative chronotropic effect
  • Reduced heart rate
• Negative dromotropic effect
  • Decreased automaticity at SA node, decreased AV nodal conduction, and other effects

Cardiac Glycosides: Adverse Effects/Digoxin (Lanoxin)

• Very narrow therapeutic window
• Drug levels must be monitored.
  • Therapeutic level - 0.5 to 2 ng/mL
• Low potassium levels increase its toxicity.
  • Low magnesium and high calcium can also increase risk of toxicity
• Electrolyte levels must be monitored.
• Cardiovascular: dysrhythmias, including bradycardia or tachycardia
• Central nervous system: headaches, fatigue, malaise, confusion, convulsions
• Eyes: colored vision (seeing green, yellow, purple), halo vision, flickering lights
• Gastrointestinal: anorexia, nausea, vomiting, diarrhea

Digoxin Toxicity

• Digoxin immune Fab (Digibind) therapy
• Hyperkalemia (serum potassium greater than 5 mEq/L) in a digitalis-toxic patient
• Life-threatening cardiac dysrhythmias
• Life-threatening digoxin overdose

Conditions That Predispose to Digoxin Toxicity

• Hypokalemia
• Hypercalcemia
• Hypomagnesemia
• Use of cardiac pacemaker
• Hepatic dysfunction
• Dysrhythmias
• Hypothyroid, respiratory, or renal disease
• Advanced age

Heart Failure Drugs: Nursing Implications

• Assess history, drug allergies, and contraindications.
• Assess clinical parameters, including:
  • BP
  • Apical pulse for 1 full minute
  • Heart sounds, breath sounds
  • Weight, input and output measures
  • Electrocardiogram
  • Serum labs: potassium, sodium, magnesium, calcium, renal, and liver function studies
• Before giving any dose of digoxin and beta blockers, count apical pulse for 1 full minute.
• For an apical pulse less than 60 or greater than 100 beats/min:
  • Hold dose.
  • Notify prescriber.
• Hold dose and notify prescriber if the patient experiences signs or symptoms of digoxin toxicity.
  • Anorexia, nausea, vomiting, diarrhea
  • Visual disturbances (blurred vision, seeing green or yellow halos around objects)
• Avoid giving digoxin with high-fiber foods (fiber binds with digitalis).
• Patients should immediately report a weight gain of 2 lb or more in 1 day or 5 lb or more in 1 week.
• Nesiritide or milrinone
  • Use an infusion pump.
  • Monitor input and output, heart rate and rhythm, BP, daily weights, respirations, and so on.
• Monitor for therapeutic effects:
  • Increased