CARDIOVASCULAR AGENTS
Contents
➢ Description of Cardiovascular agents
➢ Anti-angina agents – Coronary artery diseases
➢ Intermediary myocardial metabolism
➢ Ischemic glucose metabolism
➢ Nitrovasodilators – Smooth muscle Contraction/relaxation
➢ Mode of action of nitrovasodilators
➢ Metabolism of nitrovasodilators
➢ Study of individual compounds
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Learning Objectives
At the end of this lecture, student will be able to
➢ Describe various of cardiovascular diseases
➢ Discuss intermediary myocardial metabolism and ischemic glucose
metabolism
➢ Explain the mode of action of nitrovasodilators
➢ Discuss the metabolism of nitrovasodilators
➢ Emphasize the utility of nitrovasodilators in curing angina pectoris
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Cardiovascular Agents
➢ Cardiovascular agents (drugs) are used for their action on the heart
or other parts of the vascular system, to modify the total output of
the heart or the distribution of blood to the circulatory system
➢ These drugs are employed in the treatment of
❖ Angina
❖ Cardiac arrhythmias
❖ Hypertension
❖ Hyperlipidemias and
❖ Disorders of blood coagulation
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THERAPY FOR ANGINA
• Pharmacological therapy to prevent myocardial infarction and
death is with antiplatelet agents (aspirin, clopidogrel) and lipid
lowering agents. Recently, angiotensin-converting enzyme (ACE)
inhibitors have also reported to reduce the risk from coronary
artery disease. In unstable angina and non-STsegment elevation
myocardial infarction, and in coronary stenting, antilipid drugs,
heparin, and antiplatelet agents are recommended.
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• Angina of effort: For therapy of chronic stable angina, long-acting nitrates,
calcium channel blockers, or β blockers are chosen. The combination therapy
has shown to be more effective than individual drugs used alone.
• Vasospastic angina: Nitrites and calcium channel blockers are effective drugs
for reducing and preventing ischaemic episodes in patients with variant
angina. In approximately 70% of the patients treated with nitrites or calcium
channel blockers, angina attacks are completely abolished.
• Unstable and acute coronary syndromes: In patients with unstable angina
with recurrent ischaemic episodes at rest, recurrent thrombotic occlusions of
the offending coronary artery occur as the result of fi ssuring of
atherosclerotic plagues and platelet aggregation. Anticoagulant and
antiplatelet drugs play an important role in these cases.
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Nitrites and Nitrates
• Mode of action: These types of drugs are rapidly denitrated
enzymatically in the smooth cells to release the reactive free radical
nitric oxide (NO), which activates cytostolic guanyl cyclase and
increases the cyclic guanosine mono phosphate (cGMP) that causes
dephosphorylation of myosin light chain kinase (MLCK) through
cGMP dependent protein kinase.
• The reduction in phosphorylated MLCK interferes with myosin and
fails to cause contraction. Relaxation also occurs due to reduced
Ca2+ entry.
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Calcium channel blockers
• Mode of action: Calcium channel blockers act on the Ca2+ channel
receptors, block the release of calcium, and, therefore, the calcium
interaction with a protein calmodulin to form calcium calmodulin
complex is decreased. This leads to the decreased activation of
myosin light chain phosphorylation, which promotes muscle
contraction by interacting between actin and myosin.
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SAR of Dihydropyridines
• 1, 4-Dihydro pyridine ring is essential for activity. Substitution at N or oxidation or
reduction of the ring reduces or abolishes the activity.
• A phenyl substitution at the 4th position is optimum for the activity. Substitution
at para or unsubstituted phenyl ring reduces the activity.
• The 3rd and 5th position ester group optimizes activity. Placement of electron
withdrawing substitution results in agonistic activity.
• When the ester at C3 and C5 are nonidentical, the C4 become chiral and stereo
selectivity is observed.
• S-enantiomers found to be more effective
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Nitro glycerine
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Isosorbide dinitrite
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Summary
➢ Description of Cardiovascular agents
➢ Anti-angina agents – Coronary artery diseases
➢ Intermediary myocardial metabolism
➢ Ischemic glucose metabolism
➢ Nitrovasodilators – Smooth muscle Contraction/relaxation
➢ Mode of action of nitrovasodilators
➢ Metabolism of nitrovasodilators
➢ Study of individual compounds
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Thank You
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