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Antihypertensives / hypertension Vasodilators / angina Inotropic agents / heart failure Antiarrhythmic agents Lipid lowering drugs Diuretics Anticoagulant drugs
Professor Robert Widdop Department of Pharmacology Monash University robert.widdop@monash.edu
Symptoms: Pain, severe, crushing, sub-sternal, may radiate + Shortness of breath lasts a few minutes (usually relieved by rest &/or sublingual nitrate) Causes: Coronary artery disease, coronary vasospasm due to insufficient O2 supply to heart i.e. imbalance: myocardial O2 demand >> O2 supply Urgent medical attention required for: worsening angina (unstable angina) chest pain lasting more than a few minutes
Angina pectoris
Types
Chronic, stable angina (atherosclerosis +/++)
caused by exercise, coronary artery disease
Risk factors: Hypertension, cholesterol, smoking etc Precipitated by: Exertion, cold, stress, large meals
Treatment of angina
Modification of risk factors: smoking, obesity, hypertension, hyperlipidemia, diabetes Surgery/angioplasty/stents Drug treatment
ST depression during angina: indicates myocardial ischaemia, as might occur on exercise testing
Balloon angioplasty
Venodilatation CO oxygen consumption Arterial dilatation peripheral resistance oxygen consumption coronary dilatation increase oxygen supply
Nitrates
Result in release of nitric oxide in vascular smooth muscle with consequent vasodilatation, particularly in veins (smooth muscle relaxants) They have no effect on cardiac or skeletal muscle
NO NO
guanylate cyclase
cGMP
Ca2+
RELAXATION
NO
Glyceryl trinitrate (GTN) nitrates
NO
cGMP
Ca2+
RELAXATION
Nitrates - metabolism
Large hepatic first pass metabolism (eg. > 90%) Nitroglycerin inactive orally (give sublingually or transdermally)
Examples of nitrates
Nitroglycerin (glyceryl trinitrate): sub-lingual (tablet or spray, lasts<30 min) transdermal (patch or ointment, < 24 hr) Isosorbide dinitrate: sub-lingual (lasts < 2 hr) oral (lasts < 6 hr)
Nitrates tolerance:
Develops after continual exposure A nitrate-free period (e.g. for 8 hours per 24 hours when using transdermal patches) reduces tolerance
Sildenafil (VIAGRA)
PDE5 inhibitor (many isoforms) Potentiate NO donours BP Contraindicated with nitrates
Deaths Associated with Sildenafil Therapy in the United States. From: Lue: N Engl J Med, Volume 342(24).June 15, 2000.1802-1813
Ca channel blockers
Cause: Vasodilatation (arterial > venous) Reduced cardiac contractility & reduced atrioventricular conduction (verapamil > diltiazem > nifedipine) Indications: Angina, hypertension, tachyarrhythmias (SVT) Angina: TPR & cardiac work reduce cardiac oxygen demand coronary vasodilation can help variant angina (angina due to vessel spasm, not fixed block)
Uses of -blockers
e.g. propranolol- nonselective 1 & 2 antag atenolol, metoprolol- 1 selective antag
angina hypertension arrhythmias clinically stable heart failure (carvedilol- blocker)
Variant angina
Nitrates and calcium antagonists also reduce coronary artery spasm in variant angina (not due to fixed block) In addition, beta blockers, by slowing heart rate, can increase coronary artery perfusion time Variant angina: beware -blockers
Angina: cardiac oxygen demand heart rate increases coronary artery perfusion time during diastole (relaxation phase) oxygen supply to the heart
Unstable angina
Dipyridamol : adenosine- vasodilator (variant) - antiplatelet (unstable) Aspirin - antiplatelet