Pharmacology of ACE Inhibitors and ARBs

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Questions and Answers

What is a potential adverse effect of captopril, especially at high doses in renal patients?

Angioedema

Hyperkalemia

Neutropenia (correct)

Dysgeusia

Which medication class can lead to reduced bioavailability when taken together with antacids?

Angiotensin receptor blockers

ACE inhibitors (correct)

Potassium-sparing diuretics

Nonsteroidal anti-inflammatory drugs

What is a key distinguishing factor between ACE inhibitors and angiotensin receptor blockers (ARBs) regarding adverse effects?

ACE inhibitors have a higher incidence of angioedema (correct)

ACE inhibitors have fewer gastrointestinal manifestations

ARBs cause more dry cough

ARBs are less likely to cause renal failure

In which trimester is the use of ACE inhibitors especially concerning due to teratogenicity?

First trimester Signup and view all the answers

What mechanism do angiotensin receptor blockers primarily employ to produce their effects?

Blocking AT1 receptors Signup and view all the answers

What cardiovascular effect do ARBs NOT induce?

Increased heart rate Signup and view all the answers

What condition may potentially be exacerbated in patients taking potassium supplements along with certain medications?

Hyperkalemia Signup and view all the answers

Which aspect of the pharmacodynamics of angiotensin receptor blockers contributes to decreased platelet aggregation?

Inhibition of thromboxane A2 activity Signup and view all the answers

What is the primary mechanism by which Sacubitril exerts its effects in heart failure?

Inhibiting neprilysin, leading to increased levels of natriuretic peptides Signup and view all the answers

Which adverse reaction is most commonly associated with the use of Sacubitril/Valsartan?

Hyperkalemia Signup and view all the answers

How should β-blockers like Metoprolol be administered to patients with compensated heart failure?

Administered in a staggered approach with gradually increasing doses Signup and view all the answers

When might thiazide diuretics be beneficial in heart failure management?

When combined with loop diuretics in refractory cases Signup and view all the answers

What is the potential consequence of excessive diuresis in heart failure patients?

Reduced cardiac output leading to complications Signup and view all the answers

Which of the following statements is true regarding the combination of hydralazine and isosorbide dinitrate?

This combination is useful in treating chronic heart failure Signup and view all the answers

What is the role of aldosterone antagonists in heart failure treatment?

To reduce mortality in severe heart failure by preventing myocardial fibrosis Signup and view all the answers

What is the primary effect of ACE inhibitors on angiotensin II levels?

Inhibits conversion of Angiotensin I to Angiotensin II Signup and view all the answers

What is a key effect of neprilysin inhibition in heart failure management?

Increased vasodilating peptides and reduced vasoconstrictors Signup and view all the answers

Which of the following is NOT one of the therapeutic uses of ACE inhibitors?

Asthma management Signup and view all the answers

What is a significant pharmacological effect of ACE inhibitors?

Has a vasodilatory effect Signup and view all the answers

Which ACE inhibitor is uniquely cleared by both bile and urine?

Fosinopril Signup and view all the answers

What is the consequence of ACE inhibitors on bradykinin levels?

Inhibits degradation of bradykinin Signup and view all the answers

First-dose hypotension related to ACE inhibitors is most likely to occur in which population?

Hypovolemic patients Signup and view all the answers

What is a common gastrointestinal effect caused by digoxin?

Diarrhea Signup and view all the answers

How do ACE inhibitors provide cardioprotective effects in chronic heart failure (CHF)?

By inhibiting degradation of substance P Signup and view all the answers

Which of the following outcomes is NOT associated with the use of ACE inhibitors?

Increase in sodium retention Signup and view all the answers

Which therapeutic use of digoxin is indicated for patients with normal sinus rhythm who remain symptomatic?

Congestive heart failure Signup and view all the answers

What condition contraindicates the use of digoxin?

Wolf-Parkinson-White syndrome Signup and view all the answers

What is a potential severe adverse effect of digoxin treatment?

Visual disturbances Signup and view all the answers

Which drug may increase digoxin levels by inhibiting P-glycoprotein?

Amiodarone Signup and view all the answers

What is the mechanism of action of phosphodiesterase inhibitors like Milrinone?

Increase cAMP levels Signup and view all the answers

Which of the following interactions can decrease the effect of digoxin?

Antacids Signup and view all the answers

What is the specific antidote used for treating digoxin toxicity?

Digoxin immune fab Signup and view all the answers

What is the mechanism by which digoxin exerts its positive inotropic effect?

Binds and inhibits Na+/K+ ATPase Signup and view all the answers

How long does it take to achieve steady state after initiating the maintenance dose of digoxin?

7 days Signup and view all the answers

Which electrolyte can enhance the effect of digoxin on Na+/K+ ATPase?

Calcium (Ca+) Signup and view all the answers

What is the typical half-life of digoxin in normal renal function?

36-40 hours Signup and view all the answers

Which of the following conditions can result from high concentrations of digoxin?

Self-sustained tachycardia Signup and view all the answers

What percentage of oral bioavailability does digoxin typically achieve?

65-80% Signup and view all the answers

What is the therapeutic range for digoxin concentrations in the blood?

0.8-2.0 ng/ml Signup and view all the answers

What effect does digoxin have at low therapeutic doses on the cardiac electrical conduction system?

Decreased conduction through the AV node Signup and view all the answers

Study Notes

ACE Inhibitors (ACEIs)

ACEIs are primarily cleared by the kidneys, except for fosinopril, which also uses bile elimination. Dosage adjustment is necessary in patients with renal impairment.

Pharmacodynamics of ACEIs

Mode of Action: ACEIs competitively inhibit ACE (kininase II), leading to several effects:
- Inhibition of Angiotensin I to Angiotensin II conversion, reducing the vasoconstrictor and aldosterone-releasing effects of Angiotensin II. This also increases renin release as a compensatory mechanism.
- Increasing bradykinin levels due to inhibition of its degradation, which has a vasodilating effect.
- Inhibiting the degradation of substance P and stem cell regulator peptides, which contributes to the cardioprotective effects in heart failure (CHF)
Pharmacological Effects:
- Lowering blood pressure by reducing peripheral resistance
- Reduced salt and water retention due to decreased aldosterone release and increased sodium excretion.
- No significant effect on heart rate or cardiac output.
- No reflex sympathetic activation (safe for ischemic heart disease)
- Reduced intraglomerular capillary pressure, potentially decreasing proteinuria.

Therapeutic Uses of ACEIs

Hypertension (alone or combined with other agents like calcium channel blockers, beta-blockers, or diuretics)
Left ventricular systolic dysfunction
Acute myocardial infarction, especially in hypertensive or diabetic patients.
Patients at high risk for cardiovascular events (reducing myocardial infarction and stroke).
Diabetic nephropathy (via reduction of increased glomerular pressures and mesangial cell growth)
Scleroderma crisis (Angiotensin II plays a role in this, and ACE inhibitors can be life-saving)

Adverse Effects of ACEIs

First-dose hypotension, especially in patients with hypovolemia, multiple antihypertensives, or heart failure.
Dry cough due to increased bradykinin levels.
Hyperkalemia (increased potassium levels), especially in renal impairment or diabetes
Acute renal failure, particularly in bilateral renal artery stenosis or stenosis of solitary kidney.
Angioedema (swelling of the face, tongue, and throat).

Drug Interactions with ACEIs

Antacids: reduced bioavailability
NSAIDs: impaired hypotensive effect (by blocking bradykinin).
Potassium supplements, beta-blockers, and potassium-sparing diuretics: potential for hyperkalemia.

Angiotensin Receptor Blockers (ARBs)

Pharmacokinetics: Oral bioavailability ranges from <50% to 70%, with plasma protein binding above 90%.
Mode of Action: Competitive antagonists for AT1 receptors, resulting in:
- Vasodilation
- Reduced sympathetic stimulation
- Decreased aldosterone release and increase potassium levels
- Reduced salt and water retention
- Inhibited cardiac hypertrophy and remodeling
- Blocking of thromboxane A2 receptors, which is antiplatelet
- Vasodilation due to activation of the unblocked AT2 receptors, followed by inhibition of hypertrophy and remodeling
Adverse Effects: Similar to ACEIs but typically with less incidence of cough and angioedema.
Therapeutic Uses: Similar to ACEIs.

Sacubitril/Valsartan (Neprilysin Inhibitor)

Inhibition of neprilysin prevents the degradation of natriuretic peptides (ANP, BNP), promoting vasodilation, natriuresis, and diuresis.
This results in a decrease in vasoconstriction via reduced breakdown of angiotensin II.
Adverse effects are similar to ACE inhibitors.

Diuretics

Loop diuretics (e.g., furosemide) are important but can cause salt and water loss; the dose should thus be minimal to maintain euvolemia (normal blood fluid levels.)
Thiazide (e.g., hydrochlorothiazide) diuretics have limited use in heart failure. They may be combined with loop diuretics in refractory cases.
Avoid diuretics in asymptomatic left ventricular dysfunction.
Aldosterone blockers (e.g., spironolactone) reduce mortality in severe heart failure, reducing myocardial and vascular fibrosis.

Beta-Blockers

Used with low dose and slow titration in compensated heart failure to counteract harmful sympathetic activation.
Examples: metoprolol, carvedilol, bisoprolol.

Vasodilators

Hydralazine (arterial vasodilation) and isosorbide dinitrate (venodilation) are beneficial in chronic heart failure. Combinations are often used.

Other Positive Inotropic Drugs

Digoxin
- Chemistry: Plant-derived steroid, linked to a lactone ring and a sugar moiety.
- Pharmacokinetics: Oral absorption, with 65-80% bioavailability; widely distributed; excreted unchanged by kidneys; half-life of 36-40 hours in normal renal function. Dose must be reduced in renal dysfunction and elderly persons.
- Pharmacodynamics: Inhibits Na+/K+ ATPase in cardiac myocytes, causing increased intracellular calcium and thereby enhancing contractility.
Phosphodiesterase inhibitors: Examples include milrinone.
Dobutamine: IV used for rapid response in acute decompensated heart failure to increase contractility and cardiac output, with minimal effect on heart rate; recent beta-blocker therapy can cause resistance to the effects.

Additional Information

Other adverse effects of various antihypertensive drugs are mentioned, including gastrointestinal disturbances, visual disturbances, and arrhythmias, along with possible drug-drug interactions.

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Description

Test your knowledge on the pharmacological effects, side effects, and mechanisms of action of ACE inhibitors and angiotensin receptor blockers (ARBs). This quiz covers important concepts related to their use, especially in renal patients, and highlights critical distinctions between the two medication classes. Perfect for medical students and healthcare professionals.