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Pharmacologic Therapy

Pharmacologic Therapy

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Pharmacologic Therapy

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  1. Pharmacologic Therapy • Drug therapy is recommended for individuals with blood pressures 140/90 mmHg. The degree of benefit derived from antihypertensive agents is related to the magnitude of the blood pressure reduction. Lowering systolic blood pressure by 10–12 mmHg and diastolic blood pressure by 5–6 mmHg confers relative risk reductions of 35–40% for stroke and 12–16% for CHD within 5 years of initiating treatment. • Risk of heart failure is reduced by >50%.

  2. Without Compelling Indications With Compelling Indications Drug(s) for the compelling indications Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. Stage 1 HTN (SBP 140–159 or DBP 90–99 mmHg) Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. Stage 2 HTN (SBP >160 or DBP >100 mmHg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB) Not at Goal Blood Pressure Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist. Algorithm for Treatment of Hypertension Lifestyle Modifications Not at Goal Blood Pressure (<140/90 mmHg) (<130/80 mmHg for those with diabetes or chronic kidney disease) Initial Drug Choices JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314

  3. Diuretics • Low-dose thiazide diuretics are often used as first-line agents, alone or in combination with other antihypertensive drugs. increase sodium excretion. Long term, they may also act as vasodilators. • They provide additive blood pressure–lowering effects when combined with beta blockers, ACE inhibitors, or angiotensin receptor blockers. • In contrast, addition of a diuretic to a calcium channel blocker is less effective. • Usual doses of hydrochlorothiazide range from 6.25–50 mg/d.

  4. Diuretics • Owing to an increased incidence of metabolic side effects (hypokalemia, insulin resistance, increased cholesterol), higher doses are generally not recommended. • Loop diuretics are generally reserved for hypertensive patients with reduced glomerular filtration rates [reflected in serum creatinine > 220 mol/L (>2.5 mg/dL)], CHF, or sodium retention and edema for some other reason such as treatment with a potent vasodilator, e.g., minoxidil.

  5. Diuretics • Owing to an increased incidence of metabolic side effects (hypokalemia, insulin resistance, increased cholesterol), higher doses are generally not recommended. • Loop diuretics are generally reserved for hypertensive patients with reduced glomerular filtration rates [reflected in serum creatinine > 220 mol/L (>2.5 mg/dL)], CHF, or sodium retention and edema for some other reason such as treatment with a potent vasodilator, e.g., minoxidil.

  6. Blockers of the Renin-Angiotensin System • ACE inhibitors : -Decrease the production of angiotensin II -Increase bradykinin levels -Reduce sympathetic nervous system activity. • Side effects of ACE inhibitors and angiotensin receptor blockers include functional renal insufficiency due to efferent renal arteriolar dilatation in a kidney with a stenotic lesion of the renal artery. Additional predisposing conditions to renal insufficiency induced by these agents include dehydration, CHF, and use of nonsteroidal anti-inflammatory drugs.

  7. Less effective in older pepole and blacks due to low renin level • Dry cough occurs in ~15% of patients, and • angioedema occurs in <1% of patients taking ACE inhibitors. • Hyperkalemia due to hypoaldosteronism is an occasional side effect of both ACE inhibitors and angiotensin receptor blockers.

  8. Aldosterone Antagonists • Spironolactone is a nonselective aldosterone antagonist . • It may be a particularly effective agent in patients with low-renin essential hypertension, resistant hypertension, and primary aldosteronism. In patients with CHF, low-dose spironolactone reduces mortality and hospitalizations for heart failure when given in addition to conventional therapy with ACE inhibitors, digoxin, and loop diuretics. • side effects may include gynecomastia, impotence, and menstrual abnormalities.

  9. Beta Blockers • ß Adrenergic receptor blockers lower blood pressure by decreasing cardiac output, due to a reduction of heart rate and contractility. • Mechanisms by which beta blockers lower blood pressure include a central nervous system effect, and inhibition of renin release. • Beta blockers are particularly effective in hypertensive patients with tachycardia, and their hypotensive potency is enhanced by coadministration with a diuretic.

  10. In lower doses, some beta blockers selectively inhibit cardiac ß 1 receptors and have less influence on ß 2 receptors on bronchial and vascular smooth muscle cells; however, there seems to be no difference in the antihypertensive potencies of cardio-selective and non-selective beta blockers. • In patients with CHF, beta blockers have been shown to reduce the risks of hospitalization and mortality.

  11. Beta Blockers • Mechanism: Competitively inhibit the binding of catecholamines to beta-adrenergic receptors • Examples: • Atenolol 25-100 mg PO daily • Metoprolol 25 -100 mg PO daily or BID • Carvedilol 6.25-25 mg PO BID • Monitor: HR, Blood Glucose in DM • Not contraindicated in asthma or COPD but use caution • Compelling indications: HF, post-MI, High CAD risk, Diabetes Heart

  12. Calcium Channel Blockers • Calcium antagonists reduce vascular resistance through L-channel blockade, which reduces intracellular calcium and blunts vasoconstriction. • Phenylalkylamines (verapamil), benzothiazepines (diltiazem), and 1,4-dihydropyridines (nifedipine-like). Used alone and in combination with other agents (ACE inhibitors, beta blockers, 1-adrenergic blockers), calcium antagonists effectively lower blood pressure. • Side effects of flushing, headache, and edema with dihydropyridine use are related to their potencies as arteriolar dilators; edema is due to an increase in transcapillary pressure gradients, not to net salt and water retention

  13. Dihydropyridine Calcium Channel Blockers • Mechanism: Decrease calcium influx into cells of vascular smooth muscle • Examples: • Amlodipine 2.5-10 mg PO daily • Felodipine2.5-10 mg PO daily • Do not use immediate release nifedipine • Monitor: Peripheral edema, HR (can cause reflex tachycardia) • Good add on agent if cost is not an issue Arteries

  14. Blood Pressure Goals of Antihypertensive Therapy • The maximum protection against combined cardiovascular endpoints is achieved with pressures <135–140 mmHg for systolic blood pressure and <80–85 mmHg for diastolic blood pressure; however, treatment has not reduced cardiovascular disease risk to the level in nonhypertensive individuals.

  15. More aggressive blood pressure targets for blood pressure control (e.g., office or clinic blood pressure < 130/80 mmHg) may be appropriate for patients with: - Diabetes - CHD - Chronic kidney disease - Additional cardiovascular disease risk factors

  16. The term resistant hypertension refers to patients with blood pressures persistently >140/90 mmHg despite taking three or more antihypertensive agents, including a diuretic, • Resistant or difficult-to-control hypertension is more common in patients >60 years than in younger patients. Resistant hypertension may be related to "pseudoresistance" (high office blood pressures and lower home blood pressures), nonadherence to therapy, identifiable causes of hypertension (including obesity and excessive alcohol intake).

  17. In older patients, pseudohypertension may be related to the inability to measure blood pressure accurately in severely sclerotic arteries. • The actual blood pressure can be determined by direct intraarterial measurement. • Evaluation of patients with resistant hypertension might include home blood pressure monitoring to determine if office blood pressures are representative of the usual blood pressure. A more extensive evaluation for a secondary form of hypertension should be undertaken if no other explanation for hypertension resistance becomes apparent.

  18. Hypertensive Emergencies • Most patients who present with severe hypertension are chronically hypertensive, and in the absence of acute, end-organ damage, precipitous lowering of blood pressure may be associated with significant morbidity and should be avoided. • The key to successful management of severe hypertension is to differentiate hypertensive crises from hypertensive urgencies. The degree of target organ damage, rather than the level of blood pressure alone, determines the rapidity with which blood pressure should be lowered.

  19. Malignant hypertension is a syndrome associated with an abrupt increase of blood pressure in a patient with underlying hypertension or related to the sudden onset of hypertension in a previously normotensive individual. The absolute level of blood pressure is not as important as its rate of rise. • Pathologically, the syndrome is associated with diffuse necrotizing vasculitis, arteriolar thrombi, and fibrin deposition in arteriolar walls. Fibrinoid necrosis has been observed in arterioles of kidney, brain, retina, and other organs

  20. . Clinically, the syndrome is recognized by progressive retinopathy (arteriolar spasm, hemorrhages, exudates, and papilledema), deteriorating renal function with proteinuria, microangiopathic hemolytic anemia, and encephalopathy. In these patients, historic inquiry should include questions about the use of monamine oxidase inhibitors and recreational drugs (e.g., cocaine, amphetamines).

  21. Although blood pressure should be lowered rapidly in patients with hypertensive encephalopathy, there are inherent risks of overly aggressive therapy. In hypertensive individuals, the upper and lower limits of autoregulation of cerebral blood flow are shifted to higher levels of arterial pressure, and rapid lowering of blood pressure to below the lower limit of autoregulation may precipitate cerebral ischemia or infarction as a consequence of decreased cerebral blood flow. • Renal and coronary blood flows may also decrease with overly aggressive acute therapy

  22. Initial goal of therapy is to reduce mean arterial blood pressure by no more than 25% within minutes to 2 h or to a blood pressure in the range of 160/100–110 mmHg. • In patients with malignant hypertension without encephalopathy or some other catastrophic event, it is preferable to reduce blood pressure over hours or longer rather than minutes. This goal may effectively be achieved initially with frequent dosing of short-acting oral agents, such as captopril, clonidine, or labetalol.

  23. Currently, in the absence of other indications for acute therapy, for patients with cerebral infarction who are not candidates for thrombolytic therapy, one recommended guideline is to institute antihypertensive therapy only for those patients with a systolic blood pressure > 220 mmHg or a diastolic blood pressure > 130 mmHg. • If thrombolytic therapy is to be used, the recommended goal blood pressure is <185 mmHg systolic pressure and <110 mmHg diastolic pressure.

  24. In patients with hemorrhagic stroke, suggested guidelines for initiating antihypertensive therapy are systolic > 180 mmHg or diastolic pressure > 130 mmHg. The management of hypertension after subarachnoid hemorrhage is controversial. Cautious reduction of blood pressure is indicated if mean arterial pressure is >130 mmHg. • In addition to pheochromocytoma, an adrenergic crisis due to catecholamine excess may be related to cocaine or amphetamine overdose, clonidine withdrawal, acute spinal cord injuries, and an interaction of tyramine-containing compounds with monamine oxidase inhibitors. These patients may be treated with phentolamine or nitroprusside.