1. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Focus on Pharmacology Essentials for Health Professionals Chapter 18, 19 & 20 Effects of Drugs on the Cardiovascular & Vascular System and Anticoagulants Jahangir Moini, MD, MPH

2. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Cardiac Drugs Broadly classified according to effects on heart: –Rate of heartbeat –Rhythm of heartbeat –Amount of blood output –Strength of contraction

3. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heart Muscular pump with three layers: –Endocardium (thin inner lining) –Myocardium (heart muscle) –Epicardium: (thin outer lining)

4. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Figure 18-1 Anatomy of the heart.

5. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Figure 18-2 Electrical conduction system of the heart.

6. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Nitroglycerin (Nitrostat): Uses Dilates blood vessels in vascular smooth muscles to decrease cardiac oxygen demand; also relaxes spasms of variant angina Used to treat stable and variant angina Most effective, inexspensive & fast acting

7. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Nitroglycerin (Nitrostat): How it works: Directly affects vascular smooth muscle to dilate blood vessels Administered a variety of routes: Sublingual: effective rapidly, last about 1 hour, ideal for acute anginal pain, if one does is not effective can take 1-2 additional doses in 5 minute intervals, bottle should not be opened unless it is needed (light decreases shelf life) Transdermal: patch applied once a day to a hairless site, patches should be rotated daily to prevent irritation, worn for no more than 10-12 hours Topical Ointment: must be measures on a paper provided with drug to ensure proper dosage

8. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Nitroglycerin: Adverse Effects Headache Hypotension Tachycardia

9. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Nitroglycerin: Contraindications Hypertrophic cardiomyopathy ( heart muscle (myocardium) becomes abnormally thick ), pronounced hypovolemia ( decrease in volume of circulating blood ), MI, raised intracranial pressure, and cardiac tamponade ( compression of the heart that occurs when blood or fluid builds up ) Contraindicated in pregnancy and lactation

10. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Nitroglycerin: Patient Information Advise patients to avoid carrying nitroglycerin close to body and to store in cool, dark place. Advise patients to avoid alcohol. Instruct patients to seek emergency medical attention if pain continues after 3 tablets. Discard unused tablets after 6 months.

11. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Beta-Adrenergic Blockers Beta-blockers (propranolol, atenolol) reduce heart’s oxygen demand by decreasing heart rate Prevent development of myocardial ischemia and pain

12. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Calcium Channel Blockers Interfere with movement of calcium ions through cell membranes Can affect heart or peripheral vasculature Used to treat pain of angina and to lower blood pressure

13. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Myocardial Infarction Caused by severe, prolonged lack of oxygen, which kills an area of heart muscle Leading cause of death in industrialized nations CAD, clot formation in the coronary artery, spasm of arteries, heavy exertion, abrupt increase in blood pressure can all cause MI

14. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Therapeutic Agents for MI Goal is to limit damage to myocardium IV fluids Nitroglycerin Aspirin and thrombolytic drugs Morphine sulfate Beta-blockers and calcium channel blockers Oxygen

15. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Dysrhythmias Can occur from heart disease of chronic drug therapy

16. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Quinidine (Quinidex): Uses Depresses myocardium and conduction system to decrease contractile force of heart and slow heart rate Used to treat atrial fibrillation and flutter and ventricular tachycardia

17. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Quinidine: Adverse Effects Common: diarrhea, flatulence, abdominal pain, fever, reduced platelet, liver function abnormalities Serious: sudden ventricular fibrillation

18. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Quinidine: Contraindications Contraindicated in pregnancy, lactation, bacterial endocarditis, myasthenia gravis Interacts with digoxin, amiodarone, verapamil

19. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Quinidine: Patient Information Instruct patients to immediately report chest pain or a change in heart rhythm Advise patients to take with food and to report diarrhea to health-care provider.

20. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Propranolol (Inderal): Uses Affects beta receptors to slow heart rate and lower blood pressure Used to treat tachycardia, hypertension, angina, and to prevent MI

21. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Propranolol: Adverse Effects Hypotension and bradycardia Diminished sex drive Impotence

22. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Propranolol: Contraindications Contraindicated in bronchial asthma, severe chronic obstructive airway disease, allergic rhinitis, pregnancy Interacts with Catapres, Tagamet, epinephrine, insulin

23. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Warn patients not to discontinue abruptly. Tell patients to monitor pulse and report a rate less than 60 bpm. Advise patients to rise slowly from a lying or sitting position to avoid dizziness. Propranolol: Patient Information

24. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Blocks potassium and sodium ion channels to prolong heart’s resting stage Used to treat atrial dysrhythmias in patients with heart failure Amiodarone: Uses

25. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Common: dizziness, nausea, vomiting, anorexia, bitter taste, weight loss, numbness of fingers and toes Serious: pulmonary fibrosis ( formation or development of excess fibrous connective tissue (fibrosis) in the lungs ) with long-term use Amiodarone: Adverse Effects

26. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Contraindicated in severe liver disease, pregnancy, severe sinus bradycardia, and in children Interacts with many drugs including digoxin and phenytoin Amiodarone: Contraindications

27. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Advise patients to immediate report shortness of breath, cough, change in heart rate and rhythm, or vision changes. Advise patients to protect skin and eyes from sun. Instruct patients to change positions slowly to avoid dizziness. Amiodarone: Patient Information

28. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Acts primarily on AV node to slow conduction, causing depression of myocardial contractibility and dilation of coronary arteries Used to stabilize dysrhythmias and to treat angina and hypertension Verapamil (Calan, Isoptin): Uses

29. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Dizziness or vertigo Emotional depression Sleepiness Headache Peripheral edema Hypotension Nausea Constipation Verapamil: Adverse Effects

30. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Contraindicated in patients with hypotension and CHF and in pregnancy and lactation Interacts with lithium, cyclosporine, digoxin, calcium salts Verapamil: Contraindications

31. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Instruct patients to monitor blood pressure and report if less than 90/60 mm Hg. Advise patients to report breathing difficulty or change in heart rhythm. Instruct patients to take with food and to increase fiber intake. Verapamil: Patient Information

32. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini 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

33. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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

34. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini

35. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Hypertension Primary: 90% of cases Hypertensive crisis: severe elevation in BP Major cause of CVA (stroke)

36. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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 ACE inhibitors: vasodilate and increase renal blood flow Angiotensin-receptor blockers (ARBs): block vasoconstriction

37. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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 diuretics

38. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Alpha- and Beta-Blockers: Adverse Effects Postural hypotension (Low blood pressure on standing up, AKA -orthostatic hypotension) Dizziness or vertigo Headache Bronchospasm (spasmodic contraction of the smooth muscle of the bronchi, as in asthma.) Dyspnea

39. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Alpha- and Beta-Blockers: Contraindications Contraindicated in bronchial asthma, uncontrolled cardiac failure, severe bradycardia Safe use during pregnancy and lactation, or in children not established

40. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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.

41. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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

42. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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

43. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Centrally Acting Adrenergic Blockers: Adverse Effects Drowsiness or sedation Headache Nightmares Anxiety Hypotension Congestive heart failure

44. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Centrally Acting Adrenergic Blockers: Contraindications Contraindicated in pregnancy, lactation, hepatitis, cirrhosis, blood dyscrasias Use cautiously in kidney disease, angina, and a history of mental depression

45. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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.

46. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Peripherally Acting Adrenergic Blockers: Uses Inhibit norepinephrine release to reduce vascular tone (relating to, or containing blood vessels) in veins and arteries Used for severe hypertension or as adjunctive therapy in severe hypertension

47. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Peripherally Acting Adrenergic Blockers: Adverse Effects Drowsiness Fatigue Headache Confusion Palpitation Dry mouth Dyspnea Nausea and vomiting

48. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Peripherally Acting Adrenergic Blockers: Contraindications Contraindications include mental depression, acute peptic ulcer, and ulcerative colitis (a type of inflammatory bowel disease) Use cautiously in diabetes mellitus, impaired renal or hepatic function, coronary disease, recent MI. Interact with alcohol, norepinephrine, and antidepressants

49. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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.

50. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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

51. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini ACE Inhibitors: Adverse Effects Loss of taste Photosensitivity Severe hypotension Hyperkalemia (a condition caused by abnormally high levels of potassium in the blood) Renal impairment Blood dyscrasias (A diseased state of the blood) Dizziness Angioedema

52. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini ACE Inhibitors: Contraindications Contraindicated in angioedema, CHF, pregnancy and lactation, renal impairment, scleroderma, lupus, hypovolemia (a state of decreased blood volume) Interact with potassium-sparing diuretics, aspirin and NSAIDs, lithium

53. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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.

54. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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.

55. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini 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 ARBs: Uses

56. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Common: similar to those of ACE inhibitors Loss of taste Photosensitivity Severe hypotension Hyperkalemia (a condition caused by abnormally high levels of potassium in the blood) Renal impairment Blood dyscrasias (A diseased state of the blood) Dizziness Angioedema ARBs: Adverse Effects

57. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Contraindicated in bilateral artery stenosis, cardiac failure, pregnancy, lactation Use cautiously in asthma, COPD, peripheral vascular disease, diabetes, hyperthyroidism, renal and hepatic insufficiency Interact with amiodarone and beta-blockers ARBs: Contraindications

58. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Advise patients to report dizziness. Advise female patients to immediately report pregnancy and to avoid breastfeeding. ARBs: Patient Information

59. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Produce direct relaxation of vascular smooth muscle, resulting in vasodilation Used with beta-blockers and diuretics to treat hypertension Vasodilators: Uses

60. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Headache Dizziness Tachycardia Nausea and vomiting Vasodilators: Adverse Effects

61. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Use of corlopam and beta-blockers is contraindicated. Use of hydralazine is contraindicated in CAD, mitral valvular rheumatic heart disease, and MI. Use cautiously in CVA (stroke), renal impairment, CAD Interact with epinephrine, norepinephrine Vasodilators: Contraindications

62. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heart pumps at insufficient rate Kidneys retain sodium and water Fluid accumulates in interstitial space Congestive Heart Failure (CHF)

63. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Work by increasing cell calcium concentration to enhance contractility of cardiac muscle Include cardiac glycosides and beta- adrenergic agonists Used to relieve CHF symptoms; do not reverse CHF Cardiac Glycosides: Uses

64. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Fatigue Muscle weakness Headache Mental depression Visual disturbances Anorexia Nausea and vomiting Diarrhea Cardiac Glycosides: Adverse Effects

65. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Contraindicated in ventricular fibrillation, ventricular tachycardia Use cautiously in renal insufficiency, advanced heart disease, acute MI, hypothyroidism, pregnancy, lactation, and in older adults Cardiac Glycosides: Contraindications

66. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Advise patients to report any of the following: –Anorexia –Nausea and vomiting –Diarrhea –Visual disturbances (which may be signs of toxicity) Cardiac Glycosides: Patient Information

67. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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

68. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Beta-agonists: improve cardiac performance vasodilation Phosphodiesterase inhibitors (amrinone and Primacor): increase force of heart contraction and cause vasodilation Diuretics: relieve pulmonary congestion and peripheral edema by decreasing plasma volume Other Agents for CHF

69. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini High-density lipoproteins (HDL) Low-density lipoproteins (LDL) Very-low-density lipoproteins (VLDL) Triglycerides (TG) Hypercholesterolemia: several types Hyperlipidemia

70. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Increase binding of cholesterol to bile acids that are excreted in feces; lowers levels of circulating LDL and cholesterol Used to treat primary hyperlipidemias Bile Acid Sequestrants: Uses

71. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Constipation Nausea Flatulence Impaired absorption of fat-soluble vitamins Bile Acid Sequestrants: Adverse Effects

72. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini 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 Bile Acid Sequestrants: Contraindications

73. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Advise patients to report severe gastric distress Inform patients to increase fluid intake to avoid constipation. Bile Acid Sequestrants: Patient Information

74. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Reduce LDL and total triglyceride production Used to treat hyperlipidemia Often given with other antihyperlipidemic drugs Zocor, Lescol, Pravachol Statins: Uses

75. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Common: abdominal pain, flatulence, constipation, dyspepsia, headache, cramping Serious: rhabdomyolysis (the breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream) Statins: Adverse Effects

76. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Contraindicated in myopathy (muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness), active liver disease, or during pregnancy and lactation Interact with digoxin,ethinyl estradiol (an oral contraceptive) Statins: Contraindications

77. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini 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. Statins: Patient Information

78. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Grapefruit and Statins Advise patients to avoid grapefruit/grapefruit juice when taking simvastatin. Regular consumption of the fruit or the juice can lead to higher levels of the drug in the blood.

79. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By 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

80. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Appears to reduce levels of VLDL, LDL, and total cholesterol Used as adjuvant treatment of hypercholesterolemia in patient who do not respond to diet or weight loss Nicotinic Acid: Uses

81. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Common: cutaneous flush, pruritus, nausea and abdominal pain, syncope (fainting), nervousness, blurred vision Serious: hepatotoxicity Nicotinic Acid: Adverse Effects

82. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini 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. Nicotinic Acid: Contraindications

83. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Warn patients of cutaneous flush (reddness of the skin) 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 Nicotinic Acid: Patient Information

84. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Block lipolysis of stored triglycerides in adipose tissues and inhibit liver uptake of fatty acids Used to treat hypertriglyceridemia and severe familial hypercholesterolemia Fibric Acid Derivatives: Uses

85. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Common: GI disturbances, dizziness, blurred vision Serious: cancer Fibric Acid Derivatives: Adverse Effects

86. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini 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 Fibric Acid Derivatives: Contraindications

87. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Instruct patients to report unexplained bleeding, including: –Easy bruising –Epistaxis –Hematuria. Fibric Acid Derivatives: Patient Information

88. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Hemostasis: Three Events After Injury 1.Vascular spasms: Platelets release serotonin, which causes blood vessel to spasm and decrease blood loss until clotting occurs 2.Platelet plug: Platelets become sticky and adhere to vessel lining and each other, forming platelet plug, which is invaded by clotting factors 3.Coagulation: clot forms through chemical reactions that create netlike structure of fibrin, sealing off opening in injured vessel

89. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Anticoagulants Medications that prolong bleeding time Do not dissolve clots already formed, but may prevent clots from becoming larger Used to treat MI, venous thrombosis, pulmonary emboli Primarily used for thrombosis in veins

90. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heparin: Uses Works by increasing length of coagulation; inhibits thrombi from forming or growing larger Treat emboli, thrombi, MI, and to prevent clotting during open-heart surgery, coronary artery bypass graft, and dialysis

91. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heparin: Adverse Effects Hemorrhage in urinary or GI tracts, subdural hematomas, hemorrhagic pancreatitis, hemarthrosis (Bleeding into a joint), ecchymosis (escape of blood into the tissues from ruptured blood vessels)

92. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heparin: Contraindications Contraindicated in serious and intracranial bleeding, severe liver or kidney disease, malignant hypertension Interacts with aspirin, NSAIDs, anesthetics, valproic acid, thrombolytics, and other drugs

93. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heparin: Patient Information Teach patients how to administer heparin subcutaneously. Advise patients to protect themselves from injury (e.g., use electric shaver). Warn patients to avoid aspirin and other OTC drugs. Instruct patients to report signs of bleeding.

94. Copyright ©2008 by Pearson Education, Inc. Upper Saddle River, New Jersey 07458 All rights reserved. Focus on Pharmacology, First Edition By Jahangir Moini Heparin in Older Adults Older adults are more susceptible to effects of anticoagulants. Signs of overdose include epistaxis (nasal bleding), blood in stool or urine, excessive bruising, and prolonged bleeding. Overdose can be treated by slow infusion of 1% protamine sulfate.