吉林大学：《药理学》课程PPT教学课件（七年制）Antianginal Drugs

Antianginal Drugs

Antianginal Drugs

OVERVIEW Angina pectoris is a characteristic chest pain caused by coronary blood flow that is insufficient to meet the oxygen demands of the myocardium

OVERVIEW ◼ Angina pectoris is a characteristic chest pain caused by coronary blood flow that is insufficient to meet the oxygen demands of the myocardium

ORGANIC NITRATES Organic nitrates are simple nitric and nitrous acid esters of alcohols.These compounds cause a rapid reduction in myocardial oxygen demand followed by rapid relief of symptoms.They are effective in stable and unstable angina, as well as Prinzmetal's or variant angina pectoris

ORGANIC NITRATES ◼ Organic nitrates are simple nitric and nitrous acid esters of alcohols. These compounds cause a rapid reduction in myocardial oxygen demand followed by rapid relief of symptoms. They are effective in stable and unstable angina, as well as Prinzmetal's or variant angina pectoris

Nitroglycerin Nitrates,beta-blockers,and calcium channel blockers are equally effective for relief of anginal symptoms.However, for prompt relief of an ongoing attack of angina precipitated by exercise or emotional stress,sublingual (or spray form)nitroglycerin is the drug of choice

Nitroglycerin ◼ Nitrates, beta-blockers, and calcium channel blockers are equally effective for relief of anginal symptoms. However, for prompt relief of an ongoing attack of angina precipitated by exercise or emotional stress, sublingual (or spray form) nitroglycerin is the drug of choice

Mechanisms of action nitroglycerin are thought to relax vascular smooth muscle by their intracellular conversion to nitrite ions and then to nitric oxide(NO),which in turn activates guanylate cyclase and increases the cells'cyclic GMP. Elevated cGMP ultimately leads to dephosphorylation of the myosin light chain, resulting in vascular smooth muscle relaxation

Mechanisms of action ◼ nitroglycerin are thought to relax vascular smooth muscle by their intracellular conversion to nitrite ions and then to nitric oxide (NO), which in turn activates guanylate cyclase and increases the cells' cyclic GMP. Elevated cGMP ultimately leads to dephosphorylation of the myosin light chain, resulting in vascular smooth muscle relaxation

Effects on cardiovascular system First,it causes dilation of the large veins, resulting in pooling of blood in the veins.This diminishes preload (venous return to the heart),and reduces the work of the heart. Second,nitroglycerin dilates the coronary vasculature,providing increased blood supply to the heart muscle.Nitroglycerin causes a decrease in myocardial oxygen consumption because of decreased cardiac work

Effects on cardiovascular system ◼ First, it causes dilation of the large veins, resulting in pooling of blood in the veins. This diminishes preload (venous return to the heart), and reduces the work of the heart. ◼ Second, nitroglycerin dilates the coronary vasculature, providing increased blood supply to the heart muscle. Nitroglycerin causes a decrease in myocardial oxygen consumption because of decreased cardiac work

Pharmacokinetics The time to onset of action varies from one minute for nitroglycerin to more than one hour for isosorbide mononitrate. Significant first-pass metabolism of nitroglycerin occurs in the liver. either sublingually or via a transdermal

Pharmacokinetics ◼ The time to onset of action varies from one minute for nitroglycerin to more than one hour for isosorbide mononitrate. ◼ Significant first-pass metabolism of nitroglycerin occurs in the liver. ◼ either sublingually or via a transdermal

Adverse effects The most common adverse effect of nitroglycerin,as well as the other nitrates,is headache.Thirty to sixty percent of patients receiving intermittent nitrate therapy with long- acting agents develop headaches.High doses of organic nitrates can also cause postural hypotension,facial flushing, and tachycardia

Adverse effects ◼ The most common adverse effect of nitroglycerin, as well as the other nitrates, is headache. Thirty to sixty percent of patients receiving intermittent nitrate therapy with long￾acting agents develop headaches. High doses of organic nitrates can also cause postural hypotension, facial flushing, and tachycardia

Tolerance Tolerance to the actions of nitrates develops rapidly.It can be overcome by provision of a daily "nitrate-free interval"to restore sensitivity to the drug.This interval is typically 6 to 8 hours,usually at night because there is decreased demand on the heart at that time

Tolerance ◼ Tolerance to the actions of nitrates develops rapidly. It can be overcome by provision of a daily "nitrate-free interval" to restore sensitivity to the drug. This interval is typically 6 to 8 hours, usually at night because there is decreased demand on the heart at that time

beta-ADRENERGIC BLOCKERS beta-adrenergic blocking agents suppress the activation of the heart by blocking [beta-receptors They also reduce the work of the heart by decreasing cardiac output and causing a slight decrease in blood pressure. Propranolol is the prototype of this class of compounds

beta-ADRENERGIC BLOCKERS ◼ •beta-adrenergic blocking agents suppress the activation of the heart by blocking •beta-receptors .They also reduce the work of the heart by decreasing cardiac output and causing a slight decrease in blood pressure. Propranolol is the prototype of this class of compounds