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Focus on PHARMACOLOGY ESSENTIALS FOR HEALTH PROFESSIONALS CHAPTER 22 Drugs Used to Treat Vascular Conditions Vascular System • • • • Arterial pressure Capillary pressure Venous pressure Blood pressure (BP): created by pumping action of heart; in arteries, BP rises during ventricular systole and falls during ventricular diastole Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Factors That Affect BP • Cardiac output: volume of blood pumped per minute (determined by heart rate and stroke volume—amount of blood pumped by ventricle in one contraction) • Peripheral resistance: friction in arteries as blood flows through • Blood volume: amount of blood in vascular system Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Figure 22-1 The structure of an artery, showing the outer protective layer, muscle layer, elastic layer, and inner lining. © Dorling Kindersley. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-1 Classification of Blood Pressure in Adults Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Hypertension • Primary: 90% of cases • Secondary: such as nephrosclerosis, hyperaldosteronism, or pheochromocytoma • Hypertensive crisis: severe elevation • Major cause of CVA Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antihypertensive Agents • Diuretics: reduce blood volume • Beta-blockers: slow heart rate and dilate vessels • Vasodilators: dilate vessels • Calcium channel blockers: slow heart rate, reduce conduction irritability, dilate vessels Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Antihypertensive Agents • ACE inhibitors: vasodilate and increase renal blood flow • Angiotensin-receptor blockers (ARBs): block vasoconstriction Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 (continued) Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 (continued) Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 (continued) Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 (continued) Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 (continued) Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-2 (continued) Most Commonly Prescribed Antihypertensive Agents Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alpha- and Beta-Blockers: Uses • Used to treat mild, moderate, and severe hypertension • Used alone or in combination with other antihypertensive agents, especially thiazide diuretics Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alpha- and Beta-Blockers: Adverse Effects • • • • • Postural hypotension Dizziness or vertigo Headache Bronchospasm Dyspnea Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alpha- and Beta-Blockers: Contraindications • Contraindicated in bronchial asthma, uncontrolled cardiac failure, cardiogenic shock, severe bradycardia • Safe use during pregnancy and lactation, or in children not established. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alpha- and Beta-Blockers: Patient Information • Advise patients to change positions slowly to avoid dizziness and to avoid driving or hazardous activities until response to drug is known. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Alpha- and Beta-Blockers: Use in Older Adults • Older adults are especially sensitive to hypotensive effects of these drugs. • Warn patients to avoid hazardous activities. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Centrally Acting Adrenergic Blockers: Uses • Work by reducing hyperactivity in medulla oblongata in brain to reduce vascular resistance and cardiac output • Used to manage hypertension and usually combined with diuretics Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Centrally Acting Adrenergic Blockers: Adverse Effects • • • • • • Drowsiness or sedation Headache Nightmares Anxiety Hypotension Congestive heart failure Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Centrally Acting Adrenergic Blockers: Contraindications • Contraindicated in pregnancy, lactation, hepatitis, cirrhosis, blood dyscrasias • Use cautiously in kidney disease, angina, and mental depression Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Centrally Acting Adrenergic Blockers: Patient Information • Advise patients to avoid hazardous activities until response to drug is known. • Instruct patients to check with physician before taking OTC medications. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Peripherally Acting Adrenergic Blockers: Uses • Inhibit norepinephrine release to reduce vascular tone in veins and arteries • Used for severe hypertension or as adjunctive therapy in severe hypertension Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Peripherally Acting Adrenergic Blockers: Adverse Effects • • • • • • • • Drowsiness Fatigue Headache Confusion Palpitation Dry mouth Dyspnea Nausea and vomiting Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Peripherally Acting Adrenergic Blockers: Contraindications • Contraindications include mental depression, acute peptic ulcer, and ulcerative colitis • Use cautiously in diabetes mellitus, impaired renal or hepatic function, coronary disease with insufficiency, recent MI. • Interact with alcohol, reserpine, norepinephrine, and antidepressants Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Peripherally Acting Adrenergic Blockers: Patient Information • Advise patients to change positions carefully and slowly to avoid dizziness. • Instruct patients to take at same time each day. • Advise patients to check with their physician before taking OTC drugs. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ACE Inhibitors: Uses • Decrease formation of angiotensin II, which lowers blood volume and BP • Used to treat severe hypertension and CHF; drug of choice for primary hypertension Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Figure 22-2 The renin–angiotensin system. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ACE Inhibitors: Adverse Effects • • • • • • • • Loss of taste Photosensitivity Severe hypotension Hyperkalemia Renal impairment Blood dyscrasias Dizziness Angioedema Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ACE Inhibitors: Contraindications • Contraindicated in angioedema, CHF, pregnancy and lactation, renal impairment, scleroderma, lupus erythematosus, hypovolemia • Interact with potassium-sparing diuretics, aspirin and NSAIDs, lithium Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ACE Inhibitors: Patient Information • Instruct patients to report vomiting or diarrhea and to check with physician before taking OTC drugs. • Advise patients to inform surgeons or dentists of ACE inhibitor use. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ACE Inhibitors and Diabetes • ACE inhibitors can produce hypoglycemia in diabetic patients. • Advise patients to monitor blood glucose levels during first few weeks of ACE inhibitor therapy. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ARBs: Uses • Inhibit binding of angiotensin II to angiotensin I receptor in vascular smooth muscle, thereby blocking vasoconstriction and aldosterone secretion • Used to manage hypertension and treat CHF Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ARBs: Adverse Effects • Common: similar to those of ACE inhibitors Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ARBs: Contraindications • Contraindicated in bilateral artery stenosis, overt cardiac failure, cardiogenic shock, pregnancy, lactation Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ARBs: Contraindications • Use cautiously in asthma, COPRD, peripheral vascular disease, diabetes, hyperthyroidism, renal and hepatic insufficiency. • Interact with amiodarone and betablockers Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini ARBs: Patient Information • Advise patients to report dizziness. • Advise female patients to immediately report pregnancy and to avoid breastfeeding. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Vasodilators: Uses • Produce direct relaxation of vascular smooth muscle, resulting in vasodilation • Used with beta-blockers and diuretics to treat hypertension Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Vasodilators: Adverse Effects • • • • Headache Dizziness Tachycardia Nausea and vomiting Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Vasodilators: Contraindications • Use of fenoldopam and beta-blockers is contraindicated. • Use of hydralazine is contraindicated in CAD, mitral valvular rheumatic heart disease, and MI. • Use cautiously in CVA, renal impairment, CAD. • Interact with epinephrine, norepinephrine, guanethidine Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Congestive Heart Failure (CHF) • Heart pumps at insufficient rate • Kidneys retain sodium and water • Fluid accumulates in interstitial space Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Figure 22-3 Human heart with atrium and ventricles highlighted to illustrate the flow of blood through the chambers and pulmonary blood vessels. Arrows depict the path of blood through the open valves. © Dorling Kindersley. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Figure 22-4 Signs of congestive heart failure with pulmonary congestion. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-4 Main Classes of Drugs Used for Congestive Heart Failure Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-4 (continued) Main Classes of Drugs Used for Congestive Heart Failure Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Figure 22-5 Mechanisms of action of drugs used for congestive heart failure, including cardiac glycosides. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Cardiac Glycosides: Uses • Work by increasing cell calcium concentration to enhance contractility of cardiac muscle • Include cardiac glycosides and betaadrenergic agonists • Used to relieve CHF symptoms; do not reverse CHF Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Cardiac Glycosides: Adverse Effects • • • • • • • • Fatigue Muscle weakness Headache Mental depression Visual disturbances Anorexia Nausea and vomiting Diarrhea Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Cardiac Glycosides: Contraindications • Contraindicated in ventricular fibrillation, ventricular tachycardia • Use cautiously in renal insufficiency, hypokalemia, advanced heart disease, acute MI, hypothyroidism, pregnancy, lactation, and in older adults. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Cardiac Glycosides: Patient Information • Advise patients to report any of the following: – Anorexia – Nausea and vomiting – Diarrhea – Visual disturbances (which may be signs of toxicity) Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Digoxin and Foxglove • Digoxin is derived from foxglove, a purple flowering plant. • Oleander and lily of the valley also have cardiac glycoside properties. • Patient must not take digoxin along with oleander or lily of the valley. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Other Agents for CHF • Beta-agonists: improve cardiac performance by positive inotropic effects and vasodilation • Phosphodiesterase inhibitors (amrinone and milrinone): increase force of heart contraction and cause vasodilation • Diuretics: relieve pulmonary congestion and peripheral edema by decreasing plasma volume Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Hyperlipidemia • • • • • High-density lipoproteins (HDL) Low-density lipoproteins (LDL) Very-low-density lipoproteins (VLDL) Triglycerides (TG) Hypercholesterolemia: several types Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-5 Antihyperlipidemic Drugs Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Table 22-5 (continued) Antihyperlipidemic Drugs Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Bile Acid Sequestrants: Uses • Increase binding of cholesterol to bile acids that are excreted in feces; lowers levels of circulating LDL and cholesterol • Used to treat primary hyperlipidemias Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Bile Acid Sequestrants: Adverse Effects • • • • Constipation Nausea Flatulence Impaired absorption of fat-soluble vitamins Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Bile Acid Sequestrants: Contraindications • Contraindicated in bowel obstruction, dysphagia, swallowing disorders, major GI tract surgery • Safety in pregnancy and lactation or in children not known. • Interact with intestinal absorption of many drugs Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Bile Acid Sequestrants: Patient Information • Advise patients to report severe gastric distress. • Inform patients to increase fluid intake to avoid constipation. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Statins: Uses • Reduce LDL and total triglyceride production • Used to treat hyperlipidemia • Often given with other antihyperlipidemic drugs Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Statins: Adverse Effects • Common: abdominal pain, flatulence, constipation, dyspepsia, headache, cramping • Serious: rhabdomyolysis Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Statins: Contraindications • Contraindicated in myopathy, active liver disease, unexplained persistent transaminase elevations, or during pregnancy and lactation • Interact with digoxin, norethindrone, ethinyl estradiol Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Statins: Patient Information • Instruct patients to follow dosing instructions of physician. • Advise patients to report muscle tenderness or pain, especially if accompanied by fever or malaise. • Advise patients to avoid alcohol. • Warn female patients to avoid if pregnant or lactating. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Grapefruit and Statins • Advise patients to avoid grapefruit/grapefruit juice when taking simvastatin. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Statins in Children • The safety of statins in children and adolescents is not established . • These drugs should not be prescribed for this age group. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Nicotinic Acid: Uses • Appears to reduce levels of VLDL, LDL, and total cholesterol by decreasing liver triacylglycerol synthesis • Used as adjuvant treatment of hypercholesterolemia in patient who do not respond to diet or weight loss Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Nicotinic Acid: Adverse Effects • Common: cutaneous flush and pruritus, nausea and abdominal pain, syncope, nervousness, blurred vision • Serious: hepatotoxicity Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Nicotinic Acid: Contraindications • Avoid in hepatic impairment, severe hypotension, active peptic ulcer, pregnancy, lactation, and in children younger than 16. • Use cautiously in patients with history of gallbladder disease, liver disease, peptic ulcer, glaucoma, CAD, and diabetes. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Nicotinic Acid: Patient Information • Warn patients of cutaneous flush that may occur within 2 hours of oral ingestion and last for several hours. • Relief can be obtained by reducing the dosage and then increasing dose in small increments over time. Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Fibric Acid Derivatives: Uses • Block lipolysis of stored triglycerides in adipose tissues and inhibit liver uptake of fatty acids • Used to treat hypertriglyceridemia and severe familial hypercholesterolemia Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Fibric Acid Derivatives: Adverse Effects • Common: GI disturbances, dizziness, blurred vision • Serious: cancer (clofibrate) Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Fibric Acid Derivatives: Contraindications • Contraindicated in gallbladder disease, biliary cirrhosis, hepatic or severe renal dysfunction, and during pregnancy and lactation • Safe use in children younger than 18 not established. • May increase hypoprothrombinemic effects of anticoagulants Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini Fibric Acid Derivatives: Patient Information • Instruct patients to report unexplained bleeding, including: – Easy bruising – Epistaxis – Hematuria Focus on Pharmacology: Essentials for Health Professionals, Second Edition Jahangir Moini