Anti Angina 2024 Lecture PDF

Pharmacology of anti-Angina drugs Being a lecture presentation to MBBS Class 2024-2027 on 09232024 By Dr A.A Alli Oluwafuyi As part of the lecture series in Intro B posting Summary Angina (or angina pectoris) is chest pain or discomfort caused by...

Pharmacology of anti-Angina drugs Being a lecture presentation to MBBS Class 2024-2027 on 09232024 By Dr A.A Alli Oluwafuyi As part of the lecture series in Intro B posting Summary Angina (or angina pectoris) is chest pain or discomfort caused by reduced blood flow through the coronary arteries to the myocardium Increased oxygen demand due to exertion (and therefore insufficient oxygen consumption) Vasospasms Drugs used to prevent or treat angina include Drugs that reduce cardiac contractility (and thus oxygen demand) Reduce preload via venodilation eg organic nitrates such as nitroglycerin Reduce contractility eg beta adrenoceptor antagonists Drugs that increase coronary blood supply Arterial vasodilators eg calcium channel blockers such as amlodipine Drugs that prevent likelihood of clot formation Antiplatelets such as aspirin Anticoagulants such as heparin HMG-COA reductase inhibitors, statins such as atorvastatin Ranolazine Angina Organic nitrates: MOA CVS effect of Nitrates (Net effect = reduced 02 consumption) Vasodilation Preferably of veins (at low concentrations) Venous return Right and left ventricular chamber size and end-diastolic pressure Little change in systemic vascular resistance Heart rate Systemic arterial pressure may fall slightly Low conc may cause arteriolar dilation in face and neck Facial flush Meningeal arterial vessels dilation headaches CVS At higher doses of nitrates Significant venous pooling Decreased preload Decreased cardiac output Decreased diastolic pressure Decreased oxygen consumption Decreased arteriolar resistance Decreased systemic blood pressure Decreased afterload Decreased oxygen consumption Weakness Palor Dizziness Activation of compensatory sympathetic reflexes Reflex tachycardia Increased peripheral arteriolar vasoconstriction CVS effect Coronary blood flow Increases due to coronary vasodilation Can further increase myocardial ischemia-induced vasodilation Especially useful in significant coronary stenoses when demand (eg exercise) increases However, it might decrease if cardiac output and blood pressure reduces significantly Nitrates also increase cGMP in platelets Inhibits platelets deposition in vessel walls Clinical effects Patients feel relief from pain Patients can exercise longer after nitrates administration Nitrates Nitroglycerin Sublingual Peaks in 4 minutes 1-3 minutes half-life No effect seen after 1 hour Oral sustained-release Effects peak at 60-90 mins Last 3-6 hrs Skin ointment Effecst within 30-60 mins Last 4-6 hrs Useful in nocturnal angina Transdermal Trasnmucosal Effecst seen within 2-5 mins Isosorbide dinitrate Oral Sublingual Onset 6 minutes Half life 45 mins Metabolites have long half lives ~ 3-6 hours  Isosorbide-5-mononitrate Oral Chronic angina Inhaled NO: Selective pulmonary vasodilation Used in pulmonary hypertension Therapeutic uses Angina Unstable angina (in addition to other agents) Acute myocardial infarction Calcium channel blockers CCBs Decrease coronary vascular resistance and increase coronary blood flow Dihydropyridines are more potent than verapamil Preferentially (especially the dihydropyridines) preferentially dilate arterial resistance vessels Decrease in arterial pressure Elicits reflex sympathetic tachycardia and positive inotropy Negative inotropy (though at much higher concentrations than needed for smooth muscle dilation) Therapeutic uses Variant angina Occurs due to reduced blood flow CCBs can increase coronary blood flow Exertional angina Increased coronary arterial dilation Decreased myocardial oxygen demand (due to decreased blood pressure) Unstable angina May be useful (for vasospasms) Β-adrenergic receptor antagonists Decrease myocardial oxygen consumption due to negative chronotropy, inotropy and reduced arterial pressure Useful in exertional angina and unstable angina Not useful in vasospastic angina