Cardiovascular I PDF

For more information:  Chapter 22: Antihypertensive Drugs  Chapter 23: Antianginal Drugs  Chapter 24: Heart Failure Drugs Terms  Preload=volume of blood in ventricles at the end of diastole  Afterload=pressure required to pump against (open aortic valve)  Cardiac output=amount of blood ejected...

For more information:  Chapter 22: Antihypertensive Drugs  Chapter 23: Antianginal Drugs  Chapter 24: Heart Failure Drugs Terms  Preload=volume of blood in ventricles at the end of diastole  Afterload=pressure required to pump against (open aortic valve)  Cardiac output=amount of blood ejected from left ventricle  Ejection Fraction=proportion of blood that is ejected during each ventricular contraction, compared to the total ventricular filling volume Normal EF is about 65%  Stroke Volume (SV)=amount of blood ejected from heart to body Blood Pressure  Blood pressure (BP) = CO × SVR  CO = cardiac output  CO = Stroke volume x Heart Rate  SVR = systemic vascular resistance  If you decrease SVR, you will see a change in cardiac output  Hypertension = high BP  Hypertension is currently one of the most common disease states.  Hypertension is major risk factor for coronary artery disease (CAD), cardiovascular disease (CVD). Copyright © 2020 Elsevier Inc. All Rights Reserved. 4 Hypertension Defined  60 years or older: systolic blood pressure (SBP) of greater than 150 mm Hg or diastolic blood pressure (DBP) greater than 90 mm Hg  Younger than 60 years and those who have chronic kidney disease or diabetes: SBP greater than 140 and DBP greater than 90 Copyright © 2020 Elsevier Inc. All Rights Reserved. 5 Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8)* Four stages based on BP measurements 1. Normal 2. Prehypertension 3. Stage 1 hypertension 4. Stage 2 hypertension *Released December 2013. Copyright © 2020 Elsevier Inc. All Rights Reserved. 6 Eighth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-8)* (Cont.)  According to the JNC 8: -- Treat if BP is >150/90 (for patients older than 60 years) --Treat if BP >140/90 for patients younger than 60 and those who have chronic kidney disease or diabetes. *Released December 2013. Copyright © 2020 Elsevier Inc. All Rights Reserved. 7 Classification of Blood Pressure  Hypertension can also be defined by its cause.  Unknown cause  Essential, idiopathic, or primary hypertension  90% of cases  Known cause  Secondary hypertension  10% of cases Copyright © 2020 Elsevier Inc. All Rights Reserved. 8 Pharmacology Overview  Drug therapy for hypertension must be individualized.  Seven main categories of drugs to treat hypertension  A: ACE inhibitors and ARBs  B: Beta Blockers  C: Calcium Channel Blockers  D: Diuretics  D: Dilators (Vasodilators)  Direct renin inhibitors Copyright © 2020 Elsevier Inc. All Rights Reserved. 9 Review of Autonomic Neurotransmission  Two divisions of autonomic nervous system (ANS)  Parasympathetic nervous system (PNS): stimulates smooth muscles, cardiac muscles, glands  Sympathetic nervous system (SNS): stimulates heart, blood vessels, skeletal muscles  Stimulation is controlled by neurotransmitters.  Acetylcholine(PNS)  Norepinephrine(SNS)  Receptors located throughout the body Copyright © 2020 Elsevier Inc. All Rights Reserved. 10 Adrenergic Drugs: Five Subcategories  Adrenergic neuron blockers (central and peripheral)  Alpha2 receptor agonists (central)  Alpha1 receptor blockers (peripheral)  Beta receptor blockers (peripheral)  Combination alpha1 and beta receptor blockers (peripheral) Copyright © 2020 Elsevier Inc. All Rights Reserved. 11 Centrally Acting Adrenergic Drugs  Clonidine and methyldopa  Stimulate alpha2-adrenergic receptors in the brain  Decrease sympathetic outflow from the central nervous system  Decrease norepinephrine production  Stimulate alpha2-adrenergic receptors, thus reducing renin activity in the kidneys  Result in decreased BP Copyright © 2020 Elsevier Inc. All Rights Reserved. 12 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) Copyright © 2020 Elsevier Inc. All Rights Reserved. 13 Beta Blockers  Propranolol, metoprolol, and atenolol  Reduction of the heart rate through beta1 receptor blockade  Cause reduced secretion of renin  Long-term use causes reduced peripheral vascular resistance. Copyright © 2020 Elsevier Inc. All Rights Reserved. 14 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) Copyright © 2020 Elsevier Inc. All Rights Reserved. 15 Adrenergic Drugs: Indications/Contraindications All used to treat hypertension Glaucoma BPH: doxazosin, prazosin, and terazosin Management of severe heart failure (HF) when used with cardiac glycosides and diuretics  Contraindications:          Acute HF MOAIs Peptic ulcers Severe liver/kidney disease Asthma (with beta blockers) Copyright © 2020 Elsevier Inc. All Rights Reserved. 16 Adrenergic Drugs: Adverse Effects  High incidence of orthostatic hypotension  First-dose syncope  Most common        Bradycardia with reflex tachycardia Dry mouth Drowsiness, sedation Constipation Depression Edema Sexual dysfunction Copyright © 2020 Elsevier Inc. All Rights Reserved. 17 Adrenergic Drugs: Adverse Effects (Cont.)  Other  Headaches  Sleep disturbances  Nausea  Rash  Rebound hypertension with abrupt discontinuation Copyright © 2020 Elsevier Inc. All Rights Reserved. 18 Adrenergic Drugs: Interactions  Can cause additive CNS depression with alcohol, benzodiazepines, opioids  Always check for specific drug interactions Copyright © 2020 Elsevier Inc. All Rights Reserved. 19 Alpha2-Adrenergic Receptor Stimulators (Agonists)  Clonidine and methyldopa  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 20 Clonidine (Catapres)  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 21 Alpha1 Blockers  Doxazosin (Cardura)—patient teaching:  Take at bedtime  Call the nurse before getting up  Prazosin (Minipress)  Tamsulosin (Flomax)*  Terazosin (Hytrin) *Tamsulosin is not used to control BP but is indicated solely for symptomatic control of BPH. Copyright © 2020 Elsevier Inc. All Rights Reserved. 22 Doxazosin (Cardura)  Commonly used alpha1 blocker  Reduces peripheral vascular resistance and BP by dilating both arterial and venous blood vessels Copyright © 2020 Elsevier Inc. All Rights Reserved. 23 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  Do not give the medication if heart rate and blood pressure are already low (must assess VS before giving) Copyright © 2020 Elsevier Inc. All Rights Reserved. 24 Beta Receptor Blocker  Nebivolol (Bystolic)  Uses: hypertension and HF  Action: blocks beta1 receptors and produces vasodilatation, which results in a decrease in SVR  Less sexual dysfunction  Do not stop abruptly; must be tapered over 1 to 2 weeks Copyright © 2020 Elsevier Inc. All Rights Reserved. 25 Angiotensin-Converting Enzyme (ACE) Inhibitors  Large group of safe and effective drugs  Currently are 10 ACE inhibitors  Often used as first-line drugs for HF and hypertension  May be combined with a thiazide diuretic or CCB Copyright © 2020 Elsevier Inc. All Rights Reserved. 26 Angiotensin-Converting Enzyme (ACE) Inhibitors (Cont.)           Captopril (Capoten) Benazepril (Lotensin) Enalapril (Vasotec) Fosinopril (Monopril) Lisinopril (Prinivil) Moexipril (Univasc) Perindopril (Aceon) Quinapril (Accupril) Ramipril (Altace) Trandolapril (Mavik) Copyright © 2020 Elsevier Inc. All Rights Reserved. 27 ACE Inhibitors: Mechanism of Action  Inhibit ACE  ACE: converts angiotensin I (AI) (formed through the     action of renin) to angiotensin II (AII) AII: potent vasoconstrictors that induce aldosterone secretion by the adrenal glands Aldosterone: stimulates sodium and water resorption, which can raise BP Renin-angiotensin-aldosterone system ACE inhibitors thus lower BP. Copyright © 2020 Elsevier Inc. All Rights Reserved. 28 Primary Effects of the ACE Inhibitors  Cardiovascular and renal  BP: reduce BP by decreasing SVR  HF  Prevent sodium and water resorption by inhibiting aldosterone secretion  Diuresis: decreases blood volume and return to the heart  Decreases preload, or the left ventricular end-diastolic volume  Decreases work required of the heart Copyright © 2020 Elsevier Inc. All Rights Reserved. 29 Cardioprotective Effects of the ACE Inhibitors  ACE inhibitors decrease SVR (a measure of     afterload) and preload. Used to prevent complications after MI Ventricular remodeling: left ventricular hypertrophy, which is sometimes seen after MI ACE inhibitors have been shown to decrease morbidity and mortality in patients with HF. Drugs of choice for hypertensive patients with HF Copyright © 2020 Elsevier Inc. All Rights Reserved. 30 Renal Protective Effects of the ACE Inhibitors  ACE inhibitors: reduce glomerular filtration pressure  Cardiovascular drugs of choice for patients with diabetes  ACE inhibitors reduce proteinuria.  Standard therapy for diabetic patients to prevent the progression of diabetic nephropathy Copyright © 2020 Elsevier Inc. All Rights Reserved. 31 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 32 ACE Inhibitors: Adverse Effects Fatigue Dizziness Headache Mood changes Impaired taste Possible hyperkalemia Dry, nonproductive cough, which reverses when therapy is stopped  Angioedema (laryngeal swelling): rare but potentially fatal        NOTE: First-dose hypotensive effect may occur. Copyright © 2020 Elsevier Inc. All Rights Reserved. 33 Captopril (Capoten)  Uses: prevention of ventricular remodeling after MI; reduce the risk of HF after MI  Shortest half-life  Must be administered multiple times throughout the day Copyright © 2020 Elsevier Inc. All Rights Reserved. 34 Enalapril (Vasotec)  Only ACE inhibitor available in both oral and parenteral preparations  Enalapril intravenous (IV) does not require cardiac monitoring.  Oral enalapril: prodrug  Improves patient’s chances of survival after an MI  Reduces the incidence of HF Copyright © 2020 Elsevier Inc. All Rights Reserved. 35 Angiotensin II Receptor Blockers  Also referred to as angiotensin II blockers or ARBs  Well tolerated  Do not cause a dry cough that is common with ACE inhibitors Copyright © 2020 Elsevier Inc. All Rights Reserved. 36 Angiotensin II Receptor Blockers (Cont.)         Losartan (Cozaar) Eprosartan (Teveten) Valsartan (Diovan) Irbesartan (Avapro) Candesartan (Atacand) Olmesartan (Benicar) Telmisartan (Micardis) Azilsartan (Edarbi) Copyright © 2020 Elsevier Inc. All Rights Reserved. 37 Angiotensin II Receptor Blockers: Mechanism of Action  ARBs affect primarily vascular smooth muscle and the adrenal gland.  Selectively block the binding of AII to the type 1 AII receptors in these tissues  ARBs block vasoconstriction and the secretion of aldosterone. Copyright © 2020 Elsevier Inc. All Rights Reserved. 38 Comparison of ACE Inhibitors and Angiotensin II Receptor Blockers ACE Inhibitors ARBs Equally effective in treatment of hypertension Both are well tolerated Cause cough Do not cause cough Better tolerated after MI than ACE Inh Not clear if these treat HF as well as ACE Inh or if they protect kidneys as well as ACE Inh Copyright © 2020 Elsevier Inc. All Rights Reserved. 39 Angiotensin II Receptor Blockers: Indications  Hypertension  Adjunctive drugs for the treatment of HF  May be used alone or with other drugs such as diuretics Copyright © 2020 Elsevier Inc. All Rights Reserved. 40 Angiotensin II Receptor Blockers: Adverse Effects  Most common adverse effects of ARBs  Chest pain  Fatigue  Hypoglycemia  Diarrhea  Urinary tract infection  Anemia  Weakness  Hyperkalemia and cough are less likely to occur than with the ACE inhibitors. Copyright © 2020 Elsevier Inc. All Rights Reserved. 41 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 42 Calcium Channel Blockers (CCBs): Mechanism of Action  Primary use: HTN and angina  Cause smooth muscle relaxation by blocking the binding of calcium to its receptors, preventing muscle contraction  Results in:  Decreased peripheral smooth muscle tone  Decreased SVR  Decreased BP Copyright © 2020 Elsevier Inc. All Rights Reserved. 43 Calcium Channel Blockers: Indications  Angina  Hypertension: amlodipine (Norvasc)  Dysrhythmias  Migraine headaches  Raynaud’s disease  Prevent the cerebral artery spasms after subarachnoid hemorrhage: nimodipine Copyright © 2020 Elsevier Inc. All Rights Reserved. 44 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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 45 Vasodilators  Diazoxide (Hyperstat)  Hydralazine (Apresoline)  Minoxidil (Rogaine)  For hair regrowth  Nitroprusside (Nitropress) Copyright © 2020 Elsevier Inc. All Rights Reserved. 46 Vasodilators: Mechanism of Action  Directly relax arteriolar or venous smooth muscle (or both)  Results in:  Decreased SVR  Decreased afterload  Peripheral vasodilation Copyright © 2020 Elsevier Inc. All Rights Reserved. 47 Vasodilators: 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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 48 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 49 Vasodilators: Adverse Effects (Cont.)  Sodium nitroprusside: bradycardia, decreased platelet aggregation, rash, hypothyroidism, hypotension, methemoglobinemia, and (rarely) cyanide toxicity Copyright © 2020 Elsevier Inc. All Rights Reserved. 50 Vasodilators: Hydralazine (Apresoline)  Orally: routine cases of essential hypertension  Injectable: hypertensive emergencies  BiDil: specifically indicated as an adjunct for treatment of HF in African-American patients Copyright © 2020 Elsevier Inc. All Rights Reserved. 51 Vasodilators: Sodium Nitroprusside (Nitropress)  Used in the intensive care setting for severe hypertensive emergencies; titrated to effect by IV infusion  Contraindications: known hypersensitivity to the drug, severe HF, and known inadequate cerebral perfusion (especially during neurosurgical procedures) Copyright © 2020 Elsevier Inc. All Rights Reserved. 52 Miscellaneous Antihypertensive Drugs  Eplerenone (Inspra)  New 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 53 Break Questions Antianginal Drugs Copyright © 2020 Elsevier Inc. All Rights Reserved. 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.  There is a fine balance between oxygen supply and demand. Copyright © 2020 Elsevier Inc. All Rights Reserved. 56 Ischemia  Ischemia  Poor blood supply to an organ  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 57 Types of Angina  Chronic stable angina (also called classic or effort angina)  Unstable angina (also called preinfarction or crescendo angina)  Vasospastic angina (also called Prinzmetal or variant angina) Drugs for Angina  Nitrates or nitrites  Beta blockers  Calcium channel blockers (CCBs) Copyright © 2020 Elsevier Inc. All Rights Reserved. 58 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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 59 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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 60 Nitrates and Nitrites (Cont.)  Nitroglycerin (both rapid and long acting)  Isosorbide dinitrate (both rapid and long acting)  Isosorbide mononitrate (primarily long acting) Copyright © 2020 Elsevier Inc. All Rights Reserved. 61 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  Most effective medication for decreasing preload and afterload Copyright © 2020 Elsevier Inc. All Rights Reserved. 62 Nitrates and Nitrites: Indications  Treat stable, unstable, and vasospastic angina  Rapid-acting forms  Used to treat acute anginal attacks  Sublingual tablets (may feel stinging sensation under tongue)  IV infusion  Long-acting forms  Used to PREVENT anginal episodes Copyright © 2020 Elsevier Inc. All Rights Reserved. 63 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) Copyright © 2020 Elsevier Inc. All Rights Reserved. 64 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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 65 Tolerance  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 66 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 67 Nitroglycerin  Prototypical nitrate  The most important drug used in the symptomatic treatment of ischemic heart conditions such as angina  Routes—PO, SL, metered-dose aerosol that is sprayed under the tongue, IV, and topical Copyright © 2020 Elsevier Inc. All Rights Reserved. 68 Nitrates  Nitroglycerin  Large first-pass effect with oral forms  Used for symptomatic treatment of ischemic heart conditions (angina)  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 69 Beta Blockers  Mainstay in the treatment of several cardiovascular diseases  Angina  MI  Hypertension  Dysrhythmias Copyright © 2020 Elsevier Inc. All Rights Reserved. 70 Antianginal Beta Blockers  Atenolol  Metoprolol  Propranolol  Nadolol Copyright © 2020 Elsevier Inc. All Rights Reserved. 71 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/workload on heart Copyright © 2020 Elsevier Inc. All Rights Reserved. 72 Beta Blockers: Mechanism of Action (Cont.)  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 73 Beta Blockers: Indications  Angina  Antihypertensive  Cardiac dysrhythmias  Cardioprotective effects, especially after MI  Some used for migraine headaches, essential tremors, and stage fright Copyright © 2020 Elsevier Inc. All Rights Reserved. 74 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 75 Beta Blockers: Adverse Effects Body system Adverse effects Cardiovascular Bradycardia, hypotension, atrioventricular (AV) block Metabolic Hyperglycemia, hypoglycemia, hyperlipidemia Copyright © 2020 Elsevier Inc. All Rights Reserved. 76 Beta Blockers: Adverse Effects (Cont.) Body system Adverse effects Central nervous system Dizziness, fatigue, depression, lethargy Other Impotence, wheezing, dyspnea (Advise patient to discuss treatments for impotence with physician) Copyright © 2020 Elsevier Inc. All Rights Reserved. 77 Atenolol (Tenormin)  Cardioselective beta1-adrenergic receptor blocker  Indication: prophylactic treatment of angina pectoris  Use of atenolol after MI has been shown to decrease mortality. Copyright © 2020 Elsevier Inc. All Rights Reserved. 78 Metoprolol (Lopressor, Toprol-XL)  Cardioselective beta1-adrenergic receptor blocker  Indication: prophylactic treatment of angina  Many of the same characteristics as atenolol  Reduces mortality rate in patients after MI and in treating angina  Forms: oral (immediate release and long acting) and parenteral (injectable) forms  IV metoprolol is commonly administered to hospitalized patients after an MI and is used for treatment of hypertension in patients unable to take oral medicine. Copyright © 2020 Elsevier Inc. All Rights Reserved. 79 Calcium Channel Blockers for Chronic Stable Angina  Amlodipine  Diltiazem  Nicardipine  Nifedipine  Verapamil Copyright © 2020 Elsevier Inc. All Rights Reserved. 80 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  Result: decreased myocardial oxygen demand  Dysrhythmias: depression of the automaticity of and conduction through the sinoatrial and AV nodes  Negative inotrope Copyright © 2020 Elsevier Inc. All Rights Reserved. 81 Calcium Channel Blockers: Indications  Angina  Hypertension  Supraventricular tachycardia  Coronary artery spasms (Prinzmetal angina)  Short-term management of atrial fibrillation and flutter  Migraine headaches  Raynaud’s disease  Nimodipine: cerebral artery spasms associated with aneurysm rupture Copyright © 2020 Elsevier Inc. All Rights Reserved. 82 Calcium Channel Blockers: Contraindications  Known drug allergy  Acute MI  Second- or third-degree AV block (unless the patient has a pacemaker)  Hypotension Copyright © 2020 Elsevier Inc. All Rights Reserved. 83 Calcium Channel Blockers: Adverse Effects  Limited  Primarily relate to overexpression of their therapeutic effects  May cause hypotension, palpitations, tachycardia or bradycardia, constipation, nausea, dyspnea, other adverse effects Copyright © 2020 Elsevier Inc. All Rights Reserved. 84 Diltiazem (Cardizem, Dilacor, Tiazac)  Very effective for the treatment of angina pectoris resulting from coronary insufficiency and hypertension  Used in the treatment of atrial fibrillation and flutter along with paroxysmal supraventricular tachycardia Copyright © 2020 Elsevier Inc. All Rights Reserved. 85 Amlodipine (Norvasc)  Indicated for both angina and hypertension  Available only for oral use Copyright © 2020 Elsevier Inc. All Rights Reserved. 86 Miscellaneous Antianginal Drug  Ranolazine (Ranexa)  Mechanism of action is unknown.  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 QTprolonging drugs  Drug interactions Copyright © 2020 Elsevier Inc. All Rights Reserved. 87 Nursing Implications  Before administering, perform a complete health history to determine presence of conditions that may be contraindications for use or those that may call for cautious use.  Obtain baseline vital signs, including respiratory patterns and rate.  Assess for drug interactions. Copyright © 2020 Elsevier Inc. All Rights Reserved. 88 Nursing Implications (Cont.)  Patients should not take any medications, including over-thecounter medications, without checking with their physicians.  Patients should be encouraged to limit caffeine intake. Copyright © 2020 Elsevier Inc. All Rights Reserved. 89 Nursing Implications (Cont.)  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 90 Nursing Implications (Cont.)  Alcohol consumption and spending time in hot baths or whirlpools, hot tubs, or saunas will result in vasodilation, hypotension, and the possibility of fainting.  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 91 Nursing Implications (Cont.)  Nitroglycerin—part 1  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 92 Nursing Implications (Cont.)  Nitroglycerin—part 2  To preserve potency, medications should be stored in an airtight, dark glass bottle with a metal cap and no cotton filler.  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 93 Nursing Implications (Cont.)  Nitroglycerin—part 3  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 94 Nursing Implications (Cont.)  Nitroglycerin—part 4  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.  Follow specific manufacturer’s instructions for IV administration. Copyright © 2020 Elsevier Inc. All Rights Reserved. 95 Nursing Implications (Cont.)  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 96 Nursing Implications (Cont.)  CCBs  Constipation is a common problem; instruct patients to take in adequate fluids and eat high-fiber foods.  Antianginal drugs  Monitor for adverse reactions: allergic reactions, headache, lightheadedness, hypotension, dizziness.  Monitor for therapeutic effects: relief of angina, decreased BP, or both.  Increase supply and decrease demand to the heart. Copyright © 2020 Elsevier Inc. All Rights Reserved. 97 Break Questions Heart Failure Drugs Copyright © 2020 Elsevier Inc. All Rights Reserved. Heart Failure  Not a specific disease  Complex clinical syndrome resulting from any functional or structural impairment to the heart, specifically ejection of blood or ventricular filling  The heart is unable to pump blood in sufficient amounts from the ventricles to meet the body’s metabolic needs. Copyright © 2020 Elsevier Inc. All Rights Reserved. 100 Heart Failure (Cont.)  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 101 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 102 American College of Cardiology Foundation/American Heart Association (ACCF/AHA) Stages of Heart Failure  Stage A: At high risk for heart failure but no symptoms or structural heart disease  Stage B: Structural heart disease but no symptoms  Stage C: Structural heart disease with symptoms  Stage D: Refractory HF requiring interventions Copyright © 2020 Elsevier Inc. All Rights Reserved. 103 Definitions  Positive inotropic drugs: increase the force of myocardial contraction  Positive chronotropic drugs: increase heart rate  Positive dromotropic drugs: accelerate cardiac conduction Copyright © 2020 Elsevier Inc. All Rights Reserved. 104 Drug Therapy for Heart Failure(Cont.)          Positive inotropic drugs Phosphodiesterase inhibitors (PDI)-(example: Milrinone) Cardiac glycosides (example: Digoxin) Sinoatrial modulators Angiotensin receptor-neprilysin inhibitors (ARNI) Angiotensin-converting enzyme (ACE) inhibitors Angiotensin receptor blockers (ARBs) Beta blockers Diuretics –how do you know if a diuretic is working? Copyright © 2020 Elsevier Inc. All Rights Reserved. 105 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, and others)  ARBs (valsartan, candesartan, losartan, and others)  Certain beta blockers (metoprolol, a cardioselective beta blocker; carvedilol, a nonspecific beta blocker) Copyright © 2020 Elsevier Inc. All Rights Reserved. 106 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 (these are potassium sparing)  Only after these drugs are used is digoxin added. Copyright © 2020 Elsevier Inc. All Rights Reserved. 107 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 the AfricanAmerican population. Copyright © 2020 Elsevier Inc. All Rights Reserved. 108 ACE Inhibitors  Inhibit angiotensin-converting enzyme.  Responsible for converting angiotensin I to angiotensin II  Prevent sodium and water resorption by inhibiting aldosterone secretion.  Diuresis results, which decreases preload, or the left ventricular end-volume, and the work of the heart.  Examples: lisinopril, enalapril, fosinopril, quinapril, captopril, ramipril, trandolapril, and perindopril Copyright © 2020 Elsevier Inc. All Rights Reserved. 109 Lisinopril (Prinivil, Zestril)  Uses: hypertension, HF, and acute MI  Hyperkalemia—don’t give if patient’s potassium level is already high  Common adverse effect: dry cough, hyperkalemia, decreased renal function Copyright © 2020 Elsevier Inc. All Rights Reserved. 110 Angiotensin II Receptor Blockers (ARBs)  Potent vasodilators; decrease systemic vascular resistance (afterload)  Used alone or in combination with other drugs such as diuretics in the treatment of hypertension or HF  Examples: valsartan (Diovan), candesartan (Atacand), eprosartan (Teveten), irbesartan (Avapro), telmisartan (Micardis), olmesartan (Benicar), and losartan (Cozaar) Copyright © 2020 Elsevier Inc. All Rights Reserved. 111 Valsartan (Diovan)  Valsartan shares many of the same adverse effects as lisinopril.  ARBs are not as likely to cause the cough associated with the ACE inhibitors.  ARBs are not as likely to cause hyperkalemia. Copyright © 2020 Elsevier Inc. All Rights Reserved. 112 Angiotensin Receptor-Neprilysin Inhibitors (ARNI)  Newer class of drugs  Valsartan/sacubitril (Entresto)  Blocks the degradation of vasoactive peptides by inhibiting the neprilysin enzyme  The first ingredient, valsartan, has been used for years to treat HF (reduces blood vessel tightening and the buildup of sodium and fluid)  The second ingredient, sacubitril, works differently than other HF treatment; it helps relax blood vessels and decrease sodium and fluid in the body.  Common adverse effects: hypotension, hyperkalemia, increased serum creatinine Copyright © 2020 Elsevier Inc. All Rights Reserved. 113 Beta Blockers  Cardioprotective quality of beta blockers: prevent catecholaminemediated actions on the heart by reducing or blocking sympathetic nervous system stimulation to the heart and the heart’s conduction system  Intended effects: reduced heart rate, delayed AV node conduction, reduced myocardial contractility, less shortness of breath, decreased myocardial automaticity  Metoprolol  Carvedilol (Coreg) Copyright © 2020 Elsevier Inc. All Rights Reserved. 114 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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 115 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 116 Group activity Miscellaneous Drugs to Treat Heart Failure  Hydralazine/isosorbide dinitrate (BiDil)  First drug approved for a specific ethnic group, namely African Americans  Dobutamine  Beta1-selective vasoactive adrenergic drug  Structurally similar to dopamine Copyright © 2020 Elsevier Inc. All Rights Reserved. 118 Ivabradine (Corlanor)  Sinoatrial node modulator  Inhibits f-channels within the SA node which ultimately results in reduced heart rate  Used in stable, symptomatic HF with ejection fraction of =/< 35%  Increase risk of atrial fibrillation, bradycardia, and conduction disturbances  Avoid grapefruit juice Copyright © 2020 Elsevier Inc. All Rights Reserved. 119 B-Type Natriuretic Peptides  Nesiritide (Natrecor)  Synthetic version of human B-type natriuretic peptide  Vasodilating effects on both arteries and veins  Effects of nesiritide  Diuresis (urinary fluid loss)  Natriuresis (urinary sodium loss)  Vasodilation  Indirect increase in cardiac output and suppression of neurohormonal systems such as the renin-angiotensin system Copyright © 2020 Elsevier Inc. All Rights Reserved. 120 B-Type Natriuretic Peptides: Adverse Effects  Nesiritide is used in the intensive care setting as a final effort to treat      severe, life-threatening HF, often in combination with several other cardiostimulatory medications. Hypotension Dysrhythmia Headache Abdominal pain Insomnia Copyright © 2020 Elsevier Inc. All Rights Reserved. 121 Phosphodiesterase Inhibitors (PDIs)  Work by inhibiting the enzyme phosphodiesterase  Result in  Intracellular increase in cAMP  Positive inotropic response  Vasodilation  Increase in calcium for myocardial muscle contraction.  Inodilators (inotropics and dilators)  Example: Milrinone Copyright © 2020 Elsevier Inc. All Rights Reserved. 122 Phosphodiesterase Inhibitors: Indications  Short-term management of HF for patients in the intensive care unit (ICU)  AHA and ACC advise against long-term infusions. Copyright © 2020 Elsevier Inc. All Rights Reserved. 123 Milrinone  Only available phosphodiesterase inhibitor  Milrinone is available only in injectable form.  Increases contractility and vasodilation  Adverse effects: cardiac dysrhythmias, headache, hypokalemia, tremor, thrombocytopenia, and elevated liver enzyme levels  Interactions: diuretics (additive hypotensive effects) and digoxin (additive inotropic effects) Copyright © 2020 Elsevier Inc. All Rights Reserved. 124 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 125 Cardiac Glycosides: Mechanism of Action  Increase myocardial contractility  Change electrical conduction properties of the heart  Decrease rate of electrical conduction  Prolong the refractory period  Area between sinoatrial (SA) node and atrioventricular (AV) node Copyright © 2020 Elsevier Inc. All Rights Reserved. 126 Cardiac Glycosides: Drug Effects  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 127 Cardiac Glycosides: Drug Effects (Cont.)      Increased stroke volume Reduction in heart size during diastole Decrease in venous BP and vein engorgement Increase in coronary circulation Decrease in exertional and paroxysmal nocturnal dyspnea, cough, and cyanosis  Improved symptom control, quality of life, and exercise tolerance  No apparent reduction in mortality  Promotion of tissue perfusion and diuresis as a result of improved circulation Copyright © 2020 Elsevier Inc. All Rights Reserved. 128 Cardiac Glycosides: Adverse Effects  Digoxin (Lanoxin)  Very narrow therapeutic window  Drug levels must be monitored.  0.5 to 2 ng/mL  Low potassium levels increase its toxicity.  Electrolyte levels must be monitored.  Positive inotropic effect/negative chronotropic effect Copyright © 2020 Elsevier Inc. All Rights Reserved. 129 Cardiac Glycosides: Adverse Effects (Cont.)  Digoxin (Lanoxin)  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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 130 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 131 Conditions That Predispose to Digoxin Toxicity  Hypokalemia  Use of cardiac pacemaker  Hepatic dysfunction  Hypercalcemia  Dysrhythmias  Hypothyroid, respiratory, or renal disease  Advanced age Copyright © 2020 Elsevier Inc. All Rights Reserved. 132 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 Copyright © 2020 Elsevier Inc. All Rights Reserved. 133 Heart Failure Drugs: Nursing Implications (Cont.)  Assess clinical parameters (Cont.)  Weight, input, and output measures  Electrocardiogram  Serum labs: potassium, sodium, magnesium, calcium, renal, and liver function studies Copyright © 2020 Elsevier Inc. All Rights Reserved. 134 Heart Failure Drugs: Nursing Implications (Cont.)  Before giving any dose, count apical pulse for 1 full minute.  For an apical pulse less than 60 or greater than 100 beats/min:  Hold dose.  Notify prescriber. Copyright © 2020 Elsevier Inc. All Rights Reserved. 135 Heart Failure Drugs: Nursing Implications (Cont.)  Hold dose and notify prescriber if the patient experiences signs or symptoms of toxicity.  Anorexia, nausea, vomiting, diarrhea  Visual disturbances (blurred vision, seeing green or yellow halos around objects) Copyright © 2020 Elsevier Inc. All Rights Reserved. 136 Heart Failure Drugs: Nursing Implications (Cont.)  Check dosage forms carefully and follow instructions for administering.  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. Copyright © 2020 Elsevier Inc. All Rights Reserved. 137 Heart Failure Drugs: Nursing Implications (Cont.)  Nesiritide or milrinone  Use an infusion pump.  Monitor input and output, heart rate and rhythm, BP, daily weights, respirations, and so on. Copyright © 2020 Elsevier Inc. All Rights Reserved. 138 Heart Failure Drugs: Nursing Implications (Cont.)  Monitor for therapeutic effects:  Increased urinary output  Decreased edema, shortness of breath, dyspnea, crackles, fatigue  Resolution of paroxysmal nocturnal dyspnea  Improved peripheral pulses, skin color, temperature  Monitor for adverse effects. Copyright © 2020 Elsevier Inc. All Rights Reserved. 139 Questions? Have a great week!