1. Chapter 44 ANTIHYPERTENSIVE DRUGS http://www.medcomrn.com/dev/flash/flvplayer/movie.php?movie=http:// ss1.medcomrn.com/flv/78586r_sec02_300k.flv&title=&detectflash=false http://www.youtube.com/watch?v=t7wmPWTnDbE

2. Hypertension Selected regulators of blood pressure Kidneys via renin- angiotensin system (RAS) Vasodilation = hypotension (dec. BP) Vasoconstriction = hypertension (inc. BP) http://www.youtube.com/watc h?v=M0vpn6YVwiI

3. Hypertension (cont’d) Baroreceptors in the aorta and carotid sinus Vasomotor center in the medulla Hormones: antidiuretic hormone (ADH) atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP)

4. Hypertension Physiologic risk factors Excess fat and carbohydrate intake Alcohol increases renin secretions Obesity affects cardiovascular system Cultural responses Asian Americans twice as sensitive as whites to beta blockers & other hypertensives American Indians reduced/lower response to beta blockers African Americans decreased response to beta blockers and ACE inhibitors (use calcium channel blockers)

5. Hypertension Nonpharmacologic control of hypertension Stress reduction techniques Exercise Salt restriction Decreased ETOH Weight reduction

6. Guidelines for Determining Hypertension Category Systolic Pressure Diastolic Pressure Normal <120 mm Hg <80 mm Hg Prehypertension 120-139 mm Hg 80-89 mm Hg Stage 1 hypertension 140-159 mm H g 90-99 mm Hg Stage 2 hypertension >160 mm Hg >100 mm Hg

7. Antihypertensive Drugs Diuretics Thiazides : hydrochlorothiazide (HydroDiuril) Loop (high-ceiling) diuretics (Lasix) Combinations of hydrochlorothiazide with potassium-sparing diuretics and other antihypertensive drugs, i.e., ACE inhibitors, etc. Side effects Potassium loss/hypokalemia, electrolyte imbalances, hypovolemia/dehydration, hypotension (orthostatic)

8. Sympatholytics (Sympathetic Depressants) Beta-adrenergic blockers Centrally acting alpha 2 agonists Alpha-adrenergic blockers Adrenergic neuron blockers (peripherally acting sympatholytics) Alpha 1 - and beta 1 -adrenergic blockers

9. Beta-Adrenergic Blockers Noncardioselective beta blockers (beta 1 and beta 2) Action: Slows HR thereby reducing BP Caution : may cause bronchoconstriction Contraindications : chronic obstructive pulmonary disease (COPD) propanolol (Inderal)

10. Beta-Adrenergic Blockers Cardioselective beta blockers (beta 1) Action: works mainly on the heart and not the lungs (Preferred over non-selective) Caution: clients with diabetes mellitus, pulmonary disease Examples: metoprolol (Lopressor) Atenolol (Tenormin) May be given as a combo drug with a thiazide diuretic

11. Beta-Adrenergic Blockers Nursing Considerations Monitor VS-especially HR and BP Teach patient to stand slowly Teach patient non-pharmacological methods to reduce BP Teach patient about long term effects of HTN Side/adverse effects Decreased pulse rate markedly decreased BP Rebound hypertension with abrupt discontinuation Insomnia, depression, nightmares, sexual dysfunction

13. Centrally Acting Alpha 2 Agonists Multiple actions results in reduced peripheral vascular resistance and increased vasodilation Contraindications: impaired liver function Side effects: sodium and water retention, dry mouth, bradycardia Diuretics are frequently prescribed to avoid fluid retention Avoid abruptly stopping drug, rebound hypertension may result

14. Alpha-adrenergic blockers Prototype: prazosin (Minipress) Function Vasodilation  decreased BP Also helps with lipid abnormalities (decrease VLDL) Does not affect glucose or respiratory function Side effects: orthostatic hypotension, nausea, drowsiness, nasal congestion, impotence, urinary frequency, edema

15. Alpha-adrenergic blockers Nursing considerations Client needs to report edema that is present in the morning. Daily BP record should be kept Do not take OTC cough and cold meds without contacting MD

16. Other Antihypertensive Drugs Direct-acting arteriolar vasodilators VERY potent! Nitroprusside and Diazoxide only used for acute HTN emergency! Side effects : reflex tachycardia, palpitations, restlessness, agitation, confusion, hyperglycemia (diazoxide- inhibits insulin release from the pancreas)

17. Angiotensin-Converting Enzyme (ACE) Inhibitors Function Inhibits formation of angiotensin II Lack of aldosterone  sodium excretion, potassium retained Little change in CO, HR Cultural effects: not for African Americans, older adults

18. Angiotensin-Converting Enzyme (ACE) Inhibitors Side effects: irritating cough, insomnia, hyperkalemia, GI distress, first dose hypotension lisinopril (Prinivil) pg 665 Remember the “pril”

19. Angiotensin II Receptor Blockers (ARBs) Function Block angiotensin II at receptor Cause vasodilation and decreased peripheral resistance Cultural effects : Do not use with African Americans losartan potassium (Cozaar) pg 666 Remember “sartan”

20. Calcium Channel Blockers for Hypertension Block calcium channel promoting vasodilation Coronary and peripheral vessels sensitive  peripheral edema Use this class for African Americans amlopidine (Norvasc) Remember “pidine”

22. Calcium Channel Blockers for Hypertension Herbal Interactions with all hypertensives Ephedra: counteracts antihypertensives Black cohosh : increase hypotensive effect Licorice : antagonize antihypertensives Parsley : increase hypotensive effect

23. Practice Question #1 CB’s diuretic was changed to an angiotensin II receptor blocker (ARB). An example of an ARB is: A. losartan (Cozaar). B. amlodipine (Norvasc). C. captopril (Capoten). D. metoprolol (Lopressor).

24. Practice Question #2 CB’s diuretic was changed to an angiotensin II receptor blocker (ARB). An example of an ARB is: A. losartan (Cozaar). B. amlodipine (Norvasc). C. captopril (Capoten). D. metoprolol (Lopressor).

25. Practice Question #3 A common side effect of ACE is: A. irritating cough. B. nervousness (tremors). C. asthmatic attacks. D. dizziness.

26. Practice Question #3 A common side effect of ACE is: A. irritating cough. B. nervousness (tremors). C. asthmatic attacks. D. dizziness.

27. Chapter 45 ANTICOAGULANTS, ANTIPLATELETS, AND THROMBOLYTICS

28. Anticoagulants

29. Heparin Purposes: DVT, PE, open heart surgery, DIC Contraindications : stroke, peptic ulcer, blood anomalies Administration of heparins : SubQ, IV Monitoring heparin doses : PTT, aPTT Side effects : bleeding Antidote : protamine sulfate (only when heparin present)

30. Low Molecular Weight Heparin Prevent venous thrombus with decreased bleeding risk enoxaparin sodium (Lovenox) Monitor platelet count: must be >100 (PTT not monitored)

31. Oral Anticoagulants Monitoring warfarin (Coumadin) doses: therapeutic INR (2-4) depending on diagnosis or PT Drug interaction (highly protein-bound) Herbal interaction Increased effect: dong quai, feverfew, garlic, ginger, gingko, bilberry Decreased: ginseng, alfalfa, golden seal Side effects: bleeding warfarin (Coumadin) pg 675 Oral antidote: Vitamin K (IM)

32. Anticoagulants New drug: daabigatran etexilate (Pradaxa) Use for atrial fibrillation only No labs required New research found increased bleeding risk

33. Antiplatelets Prophylactic use only!!! Functions: inhibits platelet aggregation Antiplatelet drugs clopidogrel (Plavix), ticlopidine (Ticlid), dipyridamole (Persantine), and others Side effects : flu-like symptoms, dizzness, headaches, fatigue Herbal products : dong quai, feverfew, garlic, gingko

34. Thrombolytics “Clot Busters” Purposes : MI, thrombolic stroke, PE Contraindications : hemorrhagic stroke, contusion Thrombolytic drugs : altepase(tPA/Activase), streptokinase, and others Adverse effects : hemorrhage, vascular collapse Should be administered within 3 hrs of CVA/ 4hrs of MI

35. Practice Question #1 PQ had a major stroke. Following his stroke he was prescribed aspirin 81 mg and clopidogrel (Plavix). Classification of clopidogrel is: A. anticoagulant. B. intravenous anticoagulant. C. antiplatelet. D. thrombolytic.

36. Practice Question #1 PQ had a major stroke. Following his stroke he was prescribed aspirin 81 mg and clopidogrel (Plavix). Classification of clopidogrel is: A. anticoagulant. B. intravenous anticoagulant. C. antiplatelet. D. thrombolytic.

37. Practice Question #2 PQ arrived in the emergency department 2 hours following his stroke. He was given an intravenous (IV) injection of tPA. This drug is a(n): A. anticoagulant. B. intravenous anticoagulant. C. antiplatelet. D. thrombolytic.

38. Practice Question #2 PQ arrived in the emergency department 2 hours following his stroke. He was given an intravenous (IV) injection of t-PA. This drug is a(n): A. anticoagulant. B. intravenous anticoagulant. C. antiplatelet. D. thrombolytic.

39. ANTIHYPERLIPIDEMICS AND PERIPHERAL VASODILATORS

40. Antihyperlipidemics HDL – Highly desired lipoproteins LDL – Least desired lipoproteins Nonpharmacologic methods for cholesterol reduction Decrease saturate fats and cholesterol 75% to 85% cholesterol endogenous Exercise program (increases HDL) Stop smoking (increases LDL, decreases HDL)

41. Antihyperlipidemics Lipoprotein classification: VLDL, LDL, HDL Serum lipids values Cholesterol: 150-200 mg/dl Triglycerides: 40-150 mg/dl LDL: less than 100 mg/dl HDL: 45-60 mg/dl

42. Antihyperlipidemics (cont’d) Types of antilipidemics Bile-acid sequestrants : cholestyramine (Questran) Fibrates (fibric acid): gemfibrozil (Lopid) Nicotinic acid (niacin) – watch for flushing Cholesterol absorption inhibitors : ezetimibe (Zetia) Hepatic 3-hydroxy-3-methyglutaryl-coenzyme A (HMG-CoA) - statins

43. HMG-CoA / Statins Function inhibit cholesterol synthesis in liver Decrease serum cholesterol, LDL, VLDL, triglyceride Slightly increase HDL atorvastatin calcium (Lipitor) pg 689 Side/adverse effects Very rare Rhabdomyolysis: muscle tenderness/weakness, fever, malaise

44. Peripheral Vasodilators Function : increase blood flow to extremities Uses: Raynaud’s (vasospasm), arteriosclerosis Classifications Beta-adrenergic antagonists isoxsuprine HCl (Vasodilan) Side/adverse effects : lightheadedness, dizziness, orthostatic hypotension, tachycardia, palpitations, flush, GI distress

45. Peripheral Vasodilators Hemorrheologic : pentoxifylline (Trental) Works by increasing the microcirulation and enhances tissue oxygenation Others: i.e., antiplatelets, certain antihypertensives

46. Practice Question #1 AL’s serum lipids were as follows: cholesterol 197 mg/dL, low-density lipoprotein (LDL) 110 mg/dL, and high- density lipoprotein (HDL) 35 mg/dL. Which of the following is a correct statement? A. Serum lipids are within desirable values. B. Cholesterol is within desirable value, but not LDL and HDL. C. Cholesterol is not within desirable value, though LDL and HDL are. D. Cholesterol, LDL, and HDL are not within desirable values.

47. Practice Question #1 AL’s serum lipids were as follows: cholesterol 197 mg/dL, low-density lipoprotein (LDL) 110 mg/dL, and high- density lipoprotein (HDL) 35 mg/dL. Which of the following is a correct statement? A. Serum lipids are within desirable values. B. Cholesterol is within desirable value, but not LDL and HDL. C. Cholesterol is not within desirable value, though LDL and HDL are. D. Cholesterol, LDL, and HDL are not within desirable values.

48. Practice Question #2 AL was prescribed atorvastatin (Lipitor) 10 mg to prevent coronary artery disease (CAD). The drug classification of atorvastatin is a: A. fibrate. B. bile-acid sequestrant. C. combination of anticholesterol drugs. D. statin.

49. Practice Question #2 AL was prescribed atorvastatin (Lipitor) 10 mg to prevent coronary artery disease (CAD). The drug classification of atorvastatin is a: A. fibrate. B. bile-acid sequestrant. C. combination of anticholesterol drugs. D. statin.

50. Practice Question #3 A serious adverse reaction of atorvastatin (Lipitor) is: A. pharyngitis. B. rash/pruritus. C. rhabdomyolysis. D. agranulocytosis.

51. Practice Question #3 A serious adverse reaction of Lipitor is: A. pharyngitis. B. rash/pruritus. C. rhabdomyolysis. D. agranulocytosis.