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Flashcards in Antihypertension Drugs Deck (15)
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1

hypertension

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rationale for the treatment of hypertension

•Effective long-term antihypertensive therapy is associated with reduced risks for all major cardiovascular outcomes, including stroke, coronary heart disease, heart failure and total mortality.

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classes of first line antihypertensive drugs

1. thiazide type diuretics

2. drugs acting on the renin angiotensin aldosterone system (RAAS)

-ACE inhibitor

-angiotensin II receptor antaonists (ARBs)

3. Ca++ channel blockers

4. beta adrenergic receptor blockers

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alternative for first line antihypertensive drugs

•hydralazine

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drug for hypertensive emergencies

•sodium nitroprusside

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chlorthalidone

•thiazide type diurectic

•inhibit Na+/Cl- reabsorption in the distal tubule

•hypertension, HF, diabets insipidus, kidney stones due to hypercalciuria

•side effects: hypokalemia, hypoatremia, hypergylcemia, hyperurecemia, metabolic alkalosis

•Production of negative salt and water balance by blocking the Na⁺-Cl⁻ cotransporter of the proximal portion of the distal convoluted tubule of the kidney. This action is characterized by an initial increased excretion of sodium and water.

Hemodynamic response*

a. The initial drop in blood pressure with diuretic therapy is due to a reduction in plasma volume and cardiac output.

b. After a month of therapy the cardiac output and extracellular fluid volume return to nearpre-treatment values due to compensatory activation of the renin angiotensin aldosterone system (RAAS). The long-term hypotensive response to diuretics is maintained by a decrease in peripheral vascular resistance. The mechanism of this vasodilation is unknown.

*Reason for the blood pressure decline.

•Antihypertensive therapy with chlorthalidone uses doses that are lower than those used for diuretic effects. The drug is more potent than hydrochlorothiazide thus the doses will be different than for hydrochlorothiazide

•Chlorthalidone has a long half-life compared to hydrochlorothiazide, 60 hours vs. 9 hours respectively.

•side effects: Hypokalemia requiring treatment occurs in 7-8% of patients receiving chlorthalidone. Paradoxically hyponatremia may occur when there is relatively more sodium than water lost or there is water retention. A low salt diet will contribute to blood pressure lowering and reduce the risk of hypokalemia. The fluid and electrolyte abnormalities caused by diuretics occur in the first month of use if they are going to occur at all.

7

hydrochlorothiazide

•thiazide type diurectic

•thiazide type diurectic

•inhibit Na+/Cl- reabsorption in the distal tubule

•hypertension, HF, diabets insipidus, kidney stones due to hypercalciuria

•side effects: hypokalemia, hypoatremia, hypergylcemia, hyperurecemia, metabolic alkalosis

 

•Production of negative salt and water balance by blocking the Na⁺-Cl⁻ cotransporter of the proximal portion of the distal convoluted tubule of the kidney. This action is characterized by an initial increased excretion of sodium and water.

Hemodynamic response*

a. The initial drop in blood pressure with diuretic therapy is due to a reduction in plasma volume and cardiac output.

b. After a month of therapy the cardiac output and extracellular fluid volume return to nearpre-treatment values due to compensatory activation of the renin angiotensin aldosterone system (RAAS). The long-term hypotensive response to diuretics is maintained by a decrease in peripheral vascular resistance. The mechanism of this vasodilation is unknown.

*Reason for the blood pressure decline.

•There is little if any evidence that hydrochlorothiazide alone in low doses reduces cardiovascular events and because of its short half-life the blood pressure may not be well controlled over night.

•The above being said, hydrochlorothiazide remains the most commonly employed thiazide type diuretic for the treatment of hypertension in the U.S.

•side effects: Hypokalemia requiring treatment occurs in 7-8% of patients receiving chlorthalidone. Paradoxically hyponatremia may occur when there is relatively more sodium than water lost or there is water retention. A low salt diet will contribute to blood pressure lowering and reduce the risk of hypokalemia. The fluid and electrolyte abnormalities caused by diuretics occur in the first month of use if they are going to occur at all.

8

benazepril

•angiotensin converting enzyme inhibitor (ACEI), decrease aldosterone secretion

•hypertension, heart failure, diabetic neuropathy

•side effects: angioedema, cough, hyperkalemia, teratogenicity

 

•Inhibition of the enzyme that converts angiotensin I to angiotensin II lowers systemic vascular resistance and mean, diastolic, and systolic blood pressures in various hypertensive states except when high blood pressure is due to primary aldosteronism. The same enzyme is also responsible for the inactivation of bradykinin, which mediates the production of the vasodilators: nitric oxide and prostaglandin E2. The effect of angiotensin II on blood vessels and the heart (and other tissues) is blocked

•Hemodynamic response

1. Reduction in systemic vascular resistance (afterload and preload reduced).

2. Not much change in pulse rate.

•side effects:

1. Hypotension with the first dose

2. Cough in 5% - 20% of patients. May be due to increased kinin concentration. The cough abates within days of discontinuation of the ACEI.

3. Renal insufficiency may occur especially in a person with bilateral renal artery stenosis or a single kidney with renal artery stenosis. There should be assessment of kidney function before and after initiation of ACE inhibitor therapy.

4. Hyperkalemia may occur in patients with: Renal insufficiency Hypoaldosteronism Concurrent therapy using a K+ sparing diuretic or dietary K+ supplementation. Dual renin-angiotensin system blockade with ARBs, ACE inhibitors and direct renin inhibitors is of concern because of the possibility of hyperkalemia, low blood pressure and kidney failure.

5. Angioedema in 0.1%-0.5% of patients due to increased kinin (onset maybe days to years). There is rapid swelling in the nose, throat, mouth, glottis, larynx, lips, or tongue. Once ACE inhibitors are discontinued the angioedema abates within hours. It may be necessary to protect the patient’s airway. African Americans have a 4.5 times greater risk of ACE inhibitor –induced angioedema than Caucasians.

6. Should not be given to pregnant women because the is the risk of birth defects

7. Drug Interactions Nonsteroidal antiinflammatory drugs (NSAIDs) may reduce the antihypertensive response by causing Na+/water retention.

•Use

1. ACEI first-line drug class used in the management of hypertension of all degrees of blood pressure elevation.

2. Also used in the management of heart failure and post- myocardial infarction to prolong survival. (See section on Heart Failure) 3. This class of drugs will delay the development of renal insufficiency in persons with type 1 and 2 diabetes mellitus with proteinuria.

9

losartan

•angiotensin II receptor antagonist (ARB)

•Blocks the binding of angiotensin II to its receptors in blood vessels and other tissues inhibit most of the biological effects of AngII.

•hypertension, HF, diabetic neuropathy

•side effects: teratogenicity, hyperkalemia

•Hemodynamic response Vasodilation with decrease preload and afterload

•Use

-As with the ACE inhibitors In type 2 DM the ARBs have a greater renoprotective effect than the ACEIs

•side effects:

1. As with angiotensin converting enzyme inhibitors, the drug should not be given to pregnant women or those women desiring to become pregnant.

2. Cough is less frequent

3. Hyperkalemia

10

amlodipine

•Ca++ channel blocker, dihydropyridine CCB

•The drugs bind to voltage-dependent L type calcium channels to decrease the amount of calcium available for vascular smooth muscle and cardiac muscle contraction.

•Hemodynamic response There is vasodilation with decrease in systemic vascular resistance.

•side effects:

1. Constipation

2. Non-cardiogenic peripheral edema due to precapillary dilation and reflex postcapillary constriction.

3. Negative inotropic action (verapamil & diltiazem), which may aggravate heart failure.

4. Action on A-V node (verapamil & diltiazem) also may cause bradycardia or A-V block especially in the presence of other drugs acting on the A-V node (digoxin or βblockers)

5. Headache

•Uses. There are no absolute indications for the use of calcium channel blockers in the treatment of hypertension. The long-acting dihydropyridine, amlodipine may be used in combination with other antihypertensive drugs. Verapamil and diltiazem are also used as antiarrhythmic agents and in the management of angina pectoris.

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metoprolol

•beta adrenergic receptor blocker (BB)

•cardioselective

1. β- adrenergic receptor blockade.

2. Cardioselective drugs act primarily on cardiac, i.e. β1 receptors.

•Hemodynamic response

-Decrease in heart rate and contractility and cardiac output

-Decrease in renin release from the juxtaglomerular complex and the subsequent reduced production of angiotensin II, a vasoconstrictor.

-Selective and nonselective β-blockers are equally efficacious as antihypertensive drugs.

•side effects:

1. CNS- Bad dreams Depression

2. Cardiovascular Aggravation of severe, unstable heart failure Aggravation of occlusive peripheral vascular disease (unopposed α activity)

3. Pulmonary Bronchospasm in severe asthma or chronic obstructive pulmonary disease (COPD) with reactive airways

•Drug interactions:

1. Beta-blockers may interact with other drugs (calcium channel blockers or digoxin) that also depress atrioventricular (A-V) conduction to cause A-V block.

Beta -blockers are not used as the initial treatment of hypertension because of data from a single study that shows their use results in a higher rate of the primary composite outcome of cardiovascular death, myocardial infarction or stroke compared to use of an ARB. The betablockers are indicated for the treatment after an acute myocardial infarction, in the management of stable heart failure, for rate control in atrial fibrillation and control of angina. In the absence of such indications in the hypertensive patient it is suggested that beta-blockers should not be used for initial antihypertensive therapy.

β -blockers should not be given to persons with asthma, COPD with reactive airways, severe unstable heart failure, occlusive peripheral vascular disease or high degree A-V block.

12

hydralazine

•When “first-line “drugs fail or cannot be used the vasodilator hydralazine may be used.

•Direct relaxation of vascular smooth muscle by actions that are not understood.

•alters intracellular Ca2++, relaxes arteriolar smooth muscle, decreases cardiac afterload

•moderate to severe hypertension, heart failure

•side effects: edema, lupus syndrome, reflex tachycardia and ischemia

•Hemodynamic response

1. Blood pressure lowering is due to decrease in systemic vascular resistance

•side effects:

1. Immunologic. Slow acetylators may develop a lupus-like syndrome.

2. Cardiovascular. Vasodilation triggers baroreceptor reflexes with increase in heart rate and myocardial oxygen consumption. β-blockers will blunt these responses.

•Uses:

 Not a first-line antihypertensive but hydralazine is used when first-line drugs fail or cannot be used. Hydralazine is also used to reduce afterload in the treatment of heart failure when angiotensin converting enzyme inhibitors or angiotensin receptor blockers cannot be used.

13

sodium nitroprusside

•drug for hypertensive emergencies

•relaxes venous and arteriolar smooth muscle

•hypertensive crisis, acute HF

•side effects: cyanide toxicity, hypotension, headache

•An iron-cyanide complex that releases nitric oxide (NO) thereby activating guanylcyclase to stimulate the production of cGMP that leads to vascular smooth muscle relaxation.

•Hemodynamic response to i.v. infusion

1. Relaxation of venous and arteriolar smooth muscle with decrease in cardiac preload and afterload. Cardiac output and SVR are decreased to lower the blood pressure.

•side effects:

1. Hypotension

2. Possible cyanide and thiocyanate intoxication with prolonged use. It is for this reason that the drug is contraindicated in pregnancy.

•Use:

 This drug is used I.V. in the management of hypertensive emergencies. Concern about cyanide/thiocyanate toxicity is overstated as the drug is used over short intervals during which oral therapy is instituted.

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labetolol

•beta blocker

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carvedilol

•beta blocker

•also for heart failure