книга / 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Chapter 1 λ Diuretics

Chapter Summary

λDiuretics are used to treat HTN, heart failure, edema, renal dysfunction, hypercalcemia, renal stones, glaucoma, and mountain sickness. In addition to their diuretic action, the loop and thiazide diuretics also cause vasodilation.

λFigure III-1-1 illustrates the water and ion exchange occurring in the various segments of a renal tubule and the site of action of the different classes of diuretics.

λThe positive and negative effects of IV mannitol, an osmotic diuretic, are discussed.

λCarbonic anhydrase inhibitors (e.g., acetazolamide) act in the proximal tubule to decrease absorption of Na+ and bicarbonate. The mechanisms involved are summarized in Figure III-1-2. The clinical uses and adverse affects are listed.

λLoop diuretics (e.g., furosemide) inhibit the Na+/K+/2Cl– cotransporter on the luminal membrane of the thick ascending loop. The mechanisms causing their diuretic actions (Figure III-1-3) and their clinical uses and adverse effects are discussed.

λThe thiazides (e.g., hydrochlorothiazide) inhibit the Na+/Cl– cotransporter on the luminal membrane of the distal convoluted tubule. The mechanisms leading to their diuretic actions (Figure III-1-4) and their clinical uses and adverse effects are discussed.

λSpironolactone, amiloride, and triamterene are K+-sparing, weak diuretics that act at the collecting tubule and duct level. The mechanisms leading to their diuretic actions (Figure III-1-5) and their clinical uses and adverse effects are discussed.

λTable III-1-1 summarizes the mechanisms of action, the urinary electrolyte patterns, and the resultant blood pH associated with administration of the various classes of diuretics.

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Section III λ Cardiac and Renal Pharmacology

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS (ACEIs)

AND ANGIOTENSIN-RECEPTOR BLOCKERS (ARBs)

λDrugs:

−ACEIs: captopril, lisinopril (and other “−prils”)

ºBlock formation of angiotensin II

ºResulting in prevention of AT1-receptor stimulation

º↓ aldosterone, vasodilation

ºACEIs prevent bradykinin degradation

−ARBs: losartan (and other “−sartans”)

ºBlock AT1 receptors

ºSame results as ACEIs on BP mechanisms

ºARBs do not interfere with bradykinin degradation

−Renin inhibitor: Aliskiren

ºBlocks formation of angiotensin I

ºSame results as ACEIs on BP mechanisms

ºAliskiren does not interfere with bradykinin degradation

λUses:

−Mild-to-moderate hypertension (all)

−Protective of diabetic nephropathy (ACEI/ARBs)

−CHF (ACEI/ARBs)

λSide effects:

−Dry cough (ACEIs)

−Hyperkalemia

−Acute renal failure in renal artery stenosis

−Angioedema

λContraindication: pregnancy

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Section III λ Cardiac and Renal Pharmacology

Chapter Summary

λHypertension (HTN) is a major risk factor for stroke, heart failure, renal disease, peripheral vascular disease, and coronary artery disease. Factors inducing HTN include decreased vagal tone, increased sympathetic tone, increased renin-angiotensin activity, and excess water retention.

λTreatments for HTN aim to reduce sympathetic tone and blood volume and/ or relax vascular smooth muscle. However, homeostatic mechanisms may lead to compensatory increases in heart rate and/or salt and water retention.

λThe metabolic characteristics, clinical uses, and potential adverse effects of various hypertensives are discussed. Examples of each class are provided.

λThiazide diuretics are used to treat HTN. The diuretics are discussed in more detail elsewhere.

λDrugs that act via the renin-angiotensin system are the angiotensinconverting enzyme (ACE) inhibitors (e.g., captopril) and the angiotensin-II (AT-1) blockers (ARBs; e.g., losartan). Figure III-2-1 illustrates the angiotensin system and the pharmacologic effects of these drugs. Their clinical uses and adverse affects are discussed.

λCalcium channel blockers (CCBs) enhance vasodilation by blocking L-type Ca2+ channels in cardiac and vascular tissues. Drugs considered are verapamil, diltiazem, and dihydropyriodines.

λBeta blockers, alpha-1 blockers, and alpha-2 agonists alter sympathetic tone to lower blood pressure.

λDirect-acting vasodilators lower the peripheral vascular resistance mainly by causing arteriolar dilation. Drugs discussed are nitroprusside, hydralazine, minoxidil, and diazoxide.

λTable III-2-1 summarizes the use of antihypertensives in comorbid conditions.

λBosentan, epoprostenol, and sildenafil are used in pulmonary hypertension.

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Section III λ Cardiac and Renal Pharmacology

Pharmacotherapy aimed at:

λ↓ preload: diuretics, ACEIs, ARBs, and venodilators

λ↓ afterload: ACEIs, ARBs, and arteriodilators

λ↑ contractility: digoxin, beta agonists, PDE III inhibitors

λ↓ remodeling of cardiac muscle: ACEIs, ARBs, spironolactone, beta blockers

Whereas digoxin does not improve survival, ACEIs, ARBs, beta blockers, and spironolactone have been proven beneficial in CHF. ACEIs and ARBs are currently drugs of choice for the chronic management of CHF. Inotropes are more beneficial in management of acute CHF.

PRIMARY TREATMENTS FOR CHF

λACEI (ARB as an alternative)

λBeta blockers (metoprolol, bisoprolol, carvedilol)

−Provide antiarrhythmic effect and also ↓ remodeling

λDiuretics

−Loop or thiazide diuretics to decrease preload

−Spironolactone or eplerenone to block aldosterone receptors and ↓ remodeling (used in advanced CHF)

λHydralazine + isosorbide dinitrate

−Preferred for chronic therapy in patients who cannot tolerate an ACEI or ARB

β1 receptor

DOBUTAMINE

Figure III-3-2. Mechanism of Action of Inotropes

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