PHARMACOLOGY OF HEART FAILURE

By Rutendo Ganyani and Sarah Folkerts

What are the signs & symptoms of heart failure?

Signs and Symptoms of heart failureSymptoms:

- Dyspnoea- Orthopnoea- Paroxysmal nocturnal

dyspnoea- Fatigue- Cough (pink, frothy

sputum)- Nocturia

Signs:

- Resting tachycardia- JVP elevation- Lung crackles- Wheezing- 3rd heart sound- Peripheral oedema- Ascites

What are the NICE guidelines for treatment of LV heart failure?

NICE Guidelines

Diuretic for symptom relief…..thenACEi + Beta blockers

Consider adding an Aldosterone antagonist or an ARB or hydralazine + nitrate

Consider ARB if patient can’t tolerate ACEi

Consider hydralazine + nitrate if patient can’t tolerate ACEi and ARBs

Digoxin

Implantable devices

TransplantationWhen other heart pathologies or risk factors are present, consider treatment for these. e.g. aspirin, Ca-channel blockers

◦Describe the mechanism of action of ACE inhibitors!

◦ Side effects?

◦ Example?

ACEi pharmacology

◦ stop the conversion of angiotensin I to angiotensin II thus stopping all the downstream effects. (vasodilation)

◦ Side effects:◦ Dry cough ◦ Hyperkalaemia◦ Other side effects include:

◦ Teratogenic

◦ Hypotension

◦ Renal impairment (do not use w/ renal artery stenosis!)

◦ Examples: • Ramipril

◦Describe the mechanism of action of ARBs!

◦ Side effects?

◦ Example?

Angiotensin receptor blocker (ARB) pharmacology

◦ Inhibit action of Angiotensin II

• Reduce vascular resistance

• Restore tissue perfusion

• Reduce afterload

• Reduce aldosterone production

→Reduced sodium reabsorption

→Water loss

Side effects:

Hypotension

Renal impairment

Hyperkalaemia

Examples: Losartan

Control of renin release and formation and action of angiotensin II (RAAS system)

◦Describe the mechanism of action of beta blockers!

◦ Side effects?

◦ Example?

Beta blocker pharmacology◦ block beta-1 adrenergic receptors (Gs coupled receptors which cause

an increase in cAMP -> increase in PK-A -> increase of intracellular Ca in cardiac myocytes) in the heart.

◦ Reduced heart rate

◦ Decrease cardiac contractility

◦ Reduce arterial pressure

◦ Attenuate ventricular remodelling: fibrosis, apoptosis and arrythmogenesis

Side effects:

- Bronchoconstriction

- Cardiac depression

- Bradycardia

- Hypoglycaemia

- Fatigue

- Cold extremities

- Examples: Bisoprolol, metoprolol

◦Describe the mechanism of action of Aldosterone antagonists!

◦ Side effects?

◦ Example?

Aldosterone receptor blocker pharmacology

◦ Blocks action of aldosterone at DCT (block mineralocorticoid receptors)

→ Reduced expression of ENac

→ Reduced Na+ reabsorption

→ Increased water excretion

• K+-sparing

◦ Side effects:

◦ Hyperkalaemia, ◦ Hypotension

Mainly w/ spironolactone◦ Gynaecomastia, ◦ Impotence

◦ Examples: Eplerenone, spironolactone

◦Describe the mechanism of action of Nitrates!

◦ Side effects?

◦ Example?

Pharmacology of nitrates

• Metabolised to NO activate guanylate cyclase increase in cGMP activates protein kinase G vascular relaxation

• Side effect– Headache (due to dilatation of intracranial

arteries)– Postural hypotension– Dizziness

• Also problem with quickly developing tolerance that can lead to abnormal constriction of coronary arteries following withdrawal

………….and the others◦Digoxin (in particular for heart failure w/

established atrial fibrillation or if symptomatic despite diuretics and ACEi) -> increases inotropy (=pos. inotrope)

◦Hydralazine - Unknown mechanism of action, however it dilates arteries & arterioles -> reducing the afterload. (= vasodilator)• Side effects:

• Tachycardia

• Headache

◦We will not be looking at transplantation or implantable devices….. Don’t worry about this at this stage. Just know the options exist.

Digoxin

Summary of site of action of different drugs used to treat heart failure

Any Questions?