1. Cardiology Review: HTN Julia Akaah M.D.

2. Of the estimated 50 million Americans that have HTN (average BP>140/90): Of the estimated 50 million Americans that have HTN (average BP>140/90): 90% have essential HTN 90% have essential HTN Remainder have secondary HTN Remainder have secondary HTN Renal parenchymal disease Renal parenchymal disease Renovascular disease Renovascular disease Pheochromocytoma Pheochromocytoma Cushing’s syndrome Cushing’s syndrome Primary hyperaldosteronism Primary hyperaldosteronism Coarctation of the aorta Coarctation of the aorta Autosomal dominant or recessive diseases of the adrenal-renal axis that result in salt retention Autosomal dominant or recessive diseases of the adrenal-renal axis that result in salt retention

6. Laboratory Evaluation Help identify patient’s baseline and any evidence of organ damage Help identify patient’s baseline and any evidence of organ damage Urinalysis Urinalysis Hematocrit Hematocrit Electrolytes, BUN, Cr, glucose, Ca Electrolytes, BUN, Cr, glucose, Ca Uric acid Uric acid Fasting lipid profile Fasting lipid profile CXR CXR ECG ECG echocardiogram echocardiogram

7. Initial Management Goal of treatment is to prevent long term sequelae Goal of treatment is to prevent long term sequelae Most patients should be given a 3-6 month opportunity to reduce BP by nonpharmacologic means Most patients should be given a 3-6 month opportunity to reduce BP by nonpharmacologic means

8. Pharmacologic therapy Diuretics Diuretics Beta Blockers Beta Blockers Alpha1-receptor blockers Alpha1-receptor blockers Centrally acting Adrenergic Antagonists Centrally acting Adrenergic Antagonists Calcium channel blockers Calcium channel blockers ACE-I/ARBs ACE-I/ARBs Vasodilators Vasodilators

10. Diuretics: Mechanism of Action Initiate natriuresis and decrease intravascular volume Initiate natriuresis and decrease intravascular volume May initially increase peripheral resistance and decrease cardiac output May initially increase peripheral resistance and decrease cardiac output May produce mild vasodilation by inhibiting Na entry into vascular smooth muscle cells May produce mild vasodilation by inhibiting Na entry into vascular smooth muscle cells

11. Thiazide diuretics HCTZ, chlorthalidone, metolazone Block sodium reabsorption in distal convoluted tubule by inhibition of the thiazide sensitive Na/Cl co transporter Block sodium reabsorption in distal convoluted tubule by inhibition of the thiazide sensitive Na/Cl co transporter Usually ineffective when creatinine >2.0mg/dl Usually ineffective when creatinine >2.0mg/dl

12. Side effects: Side effects: Weakness Weakness ms. Cramps ms. Cramps Impotence Impotence Hypokalemia Hypokalemia Hypomagnesemia Hypomagnesemia increased LDL and TG increased LDL and TG Hypercalcemia Hyperglycemia Hyperuricemia Hyponatremia thiazide induced pancreatitis

13. Loop diuretics furosemide, torsemide, bumetanide Block Na reabsorption in the thick ascending loop of Henle by inhibiting the Na/K/2Cl cotransporter Block Na reabsorption in the thick ascending loop of Henle by inhibiting the Na/K/2Cl cotransporter Most effective in patients with associated renal insufficiency Most effective in patients with associated renal insufficiency Can cause hypomagnesemia, hypocalcemia, hypokalemia, increase fasting glucose, postural hypotension and reversible ototoxicity (dose related) Can cause hypomagnesemia, hypocalcemia, hypokalemia, increase fasting glucose, postural hypotension and reversible ototoxicity (dose related)

14. Spironolactone competitively inhibits the action of aldosterone Spironolactone competitively inhibits the action of aldosterone Triamterene and amiloride inhibit the reabsorption of Na and secretion of K Triamterene and amiloride inhibit the reabsorption of Na and secretion of K Weak agents when used alone therefore combined with thiazide for added potency Weak agents when used alone therefore combined with thiazide for added potency Hyperkalemia, gynecomastia, renal tubular damage and renal calculi with combination of triamterene and HCTZ Hyperkalemia, gynecomastia, renal tubular damage and renal calculi with combination of triamterene and HCTZ Potassium sparing diuretics spironolactone, amiloride, triamterene

15. Beta Blockers Competitive inhibition of catecholamines at B- adrenergic receptors which decreases heart rate, cardiac output, and decreases plasma renin Competitive inhibition of catecholamines at B- adrenergic receptors which decreases heart rate, cardiac output, and decreases plasma renin Advantageous in patients with increased adrenergic drive, LVH and previous MI and stable HF Advantageous in patients with increased adrenergic drive, LVH and previous MI and stable HF

16. Cardioselective beta blockers have primarily beta-1 blocking effects (atenolol, metoprolol, bisoprolol, etc.) Cardioselective beta blockers have primarily beta-1 blocking effects (atenolol, metoprolol, bisoprolol, etc.) therefore can be given at low doses, with caution in mild COPD, DM and peripheral vascular disease therefore can be given at low doses, with caution in mild COPD, DM and peripheral vascular disease At higher doses, selectivity is lost At higher doses, selectivity is lost Nonselective (nadolol, propranolol, timolol) Nonselective (nadolol, propranolol, timolol) Alpha and beta antagonists (labetolol, carvedilol) Alpha and beta antagonists (labetolol, carvedilol)

17. As lipid solubility increases, the liver metabolizes more of the drug and more enters the brain, and therefore duration of action is shorter As lipid solubility increases, the liver metabolizes more of the drug and more enters the brain, and therefore duration of action is shorter Very lipid soluble: propranolol, metoprolol, timolol Very lipid soluble: propranolol, metoprolol, timolol As lipid solubility decreases the drug is renally eliminated and less drug enters the brain and therefore duration of action is longer As lipid solubility decreases the drug is renally eliminated and less drug enters the brain and therefore duration of action is longer Least-lipid soluble: atenolol, betaxolol, nadolol Least-lipid soluble: atenolol, betaxolol, nadolol Side effects: high degree AV block, HF, Raynauds, impotence, insomnia, depression, contraindicated in asthma, severe COPD, and DM Side effects: high degree AV block, HF, Raynauds, impotence, insomnia, depression, contraindicated in asthma, severe COPD, and DM

18. Alpha1-receptor blockers prazosin, terazosin, doxazosin Block alpha receptors, producing arterial and venous vasodilation Block alpha receptors, producing arterial and venous vasodilation Side effects Side effects First dose effect First dose effect Hypotension Hypotension Syncope Syncope May decrease total cholesterol and TG levels and increase HDL May decrease total cholesterol and TG levels and increase HDL

19. Centrally acting Adrenergic Antagonists methyldopa, clonidine Stimulate presynaptic alpha 2-adrenergic receptors leading to decrease in peripheral sympathetic tone and systemic vascular resistance Stimulate presynaptic alpha 2-adrenergic receptors leading to decrease in peripheral sympathetic tone and systemic vascular resistance Side effects: bradycardia, drowsiness, dry mouth, orthostatic hypotension, galactorrhea and sexual dysfunction Side effects: bradycardia, drowsiness, dry mouth, orthostatic hypotension, galactorrhea and sexual dysfunction acute withdrawal of clonidine can cause rebound HTN acute withdrawal of clonidine can cause rebound HTN

20. Calcium channel antagonists Effective in both blacks and whites Effective in both blacks and whites Dihydropyridines (nifedipine, felodipine, amlodipine etc.) Dihydropyridines (nifedipine, felodipine, amlodipine etc.) Nondihydropyridines (verapamil, diltiazem) Nondihydropyridines (verapamil, diltiazem)

21. Cause arteriolar vasodilation by selective blockade of the slow inward calcium channels in vascular smooth muscle cells. May cause initial natriureses Cause arteriolar vasodilation by selective blockade of the slow inward calcium channels in vascular smooth muscle cells. May cause initial natriureses Side effects: constipation, nausea, HA, orthostatic hypotension, lower extremity edema Side effects: constipation, nausea, HA, orthostatic hypotension, lower extremity edema

23. Inhibitors of the renin-angiotensin system: ACE-I Inhibition of ACE leads to arteriolar and venous vasodilation and to natriuresis Inhibition of ACE leads to arteriolar and venous vasodilation and to natriuresis beneficial in pts. with associated heart failure or kidney disease beneficial in pts. with associated heart failure or kidney disease Retard progression of nephropathy and proteinuria Retard progression of nephropathy and proteinuria

24. ACE-I prevent recurrent MI and the development of CHF in persons who have had an MI complicated by reduced LV function ACE-I prevent recurrent MI and the development of CHF in persons who have had an MI complicated by reduced LV function Dose reduction in renal insufficiency and contraindicated in pregnancy Dose reduction in renal insufficiency and contraindicated in pregnancy Side effects: orthostatic hypotension, hyperkalemia, cough, angioedema, and loss of renal function Side effects: orthostatic hypotension, hyperkalemia, cough, angioedema, and loss of renal function

25. Angiotensin II receptor blockers losartan, valsartan, candesartan Cause decreased peripheral resistance by by inhibiting the actions of angiotensin II at its cell surface receptor Cause decreased peripheral resistance by by inhibiting the actions of angiotensin II at its cell surface receptor Side effect profile similar to ACE-I but decreased likelihood of cough Side effect profile similar to ACE-I but decreased likelihood of cough Avoid in pregnancy Avoid in pregnancy

26. Vasodilators hydralazine, minoxidil Direct dilatation of arterioles Direct dilatation of arterioles Dose should not exceed 200mg/d because of the increased risk of lupus like syndrome Dose should not exceed 200mg/d because of the increased risk of lupus like syndrome Side effects: headache, palpitations, tachycardia, fluid retention, lupus like syndrome, and peripheral neuropathy with hydralazine Side effects: headache, palpitations, tachycardia, fluid retention, lupus like syndrome, and peripheral neuropathy with hydralazine

27. Side effects: weight gain, hirsutism and pericardial effusions with minoxidil Side effects: weight gain, hirsutism and pericardial effusions with minoxidil Don’t use in ischemic heart disease, dissecting aneurysm, or cerebral hemorrhage because it can increase cardiac output and cerebral blood flow Don’t use in ischemic heart disease, dissecting aneurysm, or cerebral hemorrhage because it can increase cardiac output and cerebral blood flow

29. Drugs for monotherapy: diuretics, B blockers, CCBs, ACEI, alpha-beta blockers, and ARBs Drugs for monotherapy: diuretics, B blockers, CCBs, ACEI, alpha-beta blockers, and ARBs Diuretics and calcium antagonists are more effective in blacks and elderly Diuretics and calcium antagonists are more effective in blacks and elderly Centrally acting alpha agonists are not used as monotherapy but are appropriate in combination with diuretics Centrally acting alpha agonists are not used as monotherapy but are appropriate in combination with diuretics Vasodilators are best used as third drug in combination with diuretics and adrenergic inhibitors Vasodilators are best used as third drug in combination with diuretics and adrenergic inhibitors

30. Hypertensive crisis Hypertensive Urgency Hypertensive Urgency DBP >120-130mmHg DBP >120-130mmHg BP reduction within several hours BP reduction within several hours Hypertensive Emergency Hypertensive Emergency SBP >210, DBP >130 SBP >210, DBP >130 Manifestations of acute organ disease Manifestations of acute organ disease Immediate BP reduction by 20-25% Immediate BP reduction by 20-25%

31. Inservice topics related to HTN: Antihypertensive monotherapy for elderly black patient Antihypertensive monotherapy for elderly black patient Rebound hypertension with clonidine Rebound hypertension with clonidine Identify drugs that can unmask hyporeninemic hypoaldosteronism Identify drugs that can unmask hyporeninemic hypoaldosteronism Hypertension in DM with proteinuria Hypertension in DM with proteinuria Hypertensive crisis Hypertensive crisis

34. In several office visits, a 33 yr old woman has an average BP of 150/105 mmHg. She has a strong family history of HTN. She is asymptomatic. Except for mild obesity, the physical examination is normal. The results of routine laboratory studies are also normal. She is a nonsmoker. She states that she recently married and is trying to get pregnant. In addition to lifestyle recommendations, what is the most appropriate drug to consider for BP reduction? In several office visits, a 33 yr old woman has an average BP of 150/105 mmHg. She has a strong family history of HTN. She is asymptomatic. Except for mild obesity, the physical examination is normal. The results of routine laboratory studies are also normal. She is a nonsmoker. She states that she recently married and is trying to get pregnant. In addition to lifestyle recommendations, what is the most appropriate drug to consider for BP reduction? a. Atenolol b. Methyldopa c. Lisinopril d. HCTZ e. Losartan