S2W5 Pharmacology- Lecture 4 Cardiac blood flow, angina and MI JF

What is Cardiac Pharmacology?

Cardiac Pharmacology focuses on the pharmacological treatment of various cardiac conditions, including arrhythmias, hypertension, angina, myocardial infarction, and heart failure.

What are the learning outcomes?

Students will understand pharmacological treatments for:

• Arrhythmias

• Hypertension

• Angina

• Myocardial Infarction

• Heart Failure

What are the details regarding cardiac blood flow and treatment approaches?

• Atherosclerotic narrowing of coronary arteries causing reduced myocardium perfusion.

• Angina pectoris is pain from ischaemic muscle releasing chemicals, classified into:

  • Stable Angina: Exercise-induced.

  • Unstable Angina: Occurs at rest due to plaque rupture or thrombus formation, leading to myocardial infarction (MI).

  • Myocardial Infarction (MI): Complete blockage of an artery resulting in tissue death and necrosis.

What are the treatment aims?

The aims of treatment include:

• Reducing cardiac work

• Increasing perfusion of heart muscle

• Preventing Myocardial Infarction (MI)

What are the NICE guidelines for treatment?

NICE guidelines focus on treatment for:

• Acute attacks

• Long term prevention strategies

• Antianginal therapy

What is the antianginal therapy approach?

What about acute and long-term treatments?

• Acute attacks: Use sublingual glyceryl trinitrate.

• Long-term prevention:

  • Rate limiting calcium channel blockers

  • Beta-blockers like Atenolol, Bisoprolol, Metoprolol.

  • A combination of CCB and BB may be considered.

  • NICE CG126 suggests considering long-acting nitrates, ivabradine, nicorandil, or ranolazine as additions.

What are nitrates and their mechanism of action?

• Examples of nitrates: Glyceryl trinitrate (short-acting) and Isosorbide mononitrate (long-acting).

• Mechanism: Metabolised to Nitric Oxide (NO), causing dilation of veins and arteries, decreased preload and afterload, reduced cardiac work and O2 demand, increased coronary blood supply, and enhanced rate of cardiac muscle relaxation (lusitropy).

What are the side effects and pharmacokinetics of nitrates?

• Tolerance: Due to depletion of sulfhydryl groups (tissue thiols).

• Side Effects: Headache (vasodilation), postural hypotension (venodilation leads to venous pooling).

• Pharmacokinetics: Rapidly inactivated by hepatic metabolism, administration via sublingual routes (effects in minutes for ~30 mins) or transdermal patches (effects last ~24h).

What are preventive strategies for cardiovascular diseases?

What about primary and secondary prevention?

• Primary Prevention: Antihypertensive therapies and cholesterol lowering.

• Secondary Prevention: Antiplatelet therapy (aspirin), antihypertensive medications (ACE inhibitors/ARBs or BB), cholesterol lowering with statins, and aldosterone antagonists for reduced left ventricular ejection fraction in heart failure treatments.

How does aspirin work as antianginal therapy?

What is its mechanism of action and side effects?

• Mechanism: Inhibits cyclooxygenase enzyme, decreasing thromboxane A2 formation from arachidonic acid, which reduces platelet activation and clot formation.

• Side Effects: GI disturbances and bleeding, with caution in asthmatic patients.

What are potassium-sparing diuretics' mechanisms and side effects?

What is their mechanism of action?

• Mechanism: Binds to mineralocorticoid receptors, blocking aldosterone, inhibiting sodium reabsorption, leading to retention of K+ and H+ in circulation.

• Side Effects: Hyperkalemia and antiandrogenic effects such as gynecomastia in men and menstrual irregularities in women. Examples include Eplerenone and Spironolactone.

What are the components of cardiac rehabilitation and secondary prevention?

What are the rehabilitation program components?

• Initiate before hospital discharge with an assessment within 10 days post-discharge.

• Components include tailored physical activity, lifestyle advice (driving, flying, sexual activity), stress management techniques, and health education.

What about the drug therapy for secondary prevention?

• Long-term ACE inhibitor or ARB.

• Dual antiplatelet therapy (aspirin plus another antiplatelet) for up to 12 months.

• Consider beta-blockers for patients with reduced left ventricular ejection fraction.

• Promote lifestyle changes like diet, exercise, smoking cessation, and weight management.

What are the drug titration guidelines?

• Monitor and gradually titrate ACE inhibitors, beta-blockers, and antiplatelet therapies post-MI.

What guidelines do NICE provide for acute coronary syndromes?

• NICE Guidelines (NG185) provide guidance for the treatment and management of acute coronary syndromes.