ANTIANGINAL DRUGS (VASODILATORS) pmc-2,sem 5th

Atherosclerotic disease,myocardial infarction ,stable angina (ischemic chest pain)

1. ANTIANGINAL DRUG Mrs. Sandhya Sujeetkumar Ahire Pharmaceutical Chemistry 8/14/2020 Mrs.SSA( Pharma'chemistry) 1

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3. ANGINA Atherosclerotic disease, also known as coronary artery disease (CAD) or ischemic heart disease (IHD), is the most common cause of mortality worldwide. Atherosclerotic lesions in coronary arteries can obstruct blood flow, leading to an imbalance in myocardial oxygen supply and demand that presents as stable angina (ischaemic chest pain) an acute coronary syndrome - unstable angina. myocardial infarction (MI) (heart attack): caused by the complete occlusion of the coronary artery and associated death of tissue 8/14/2020 Mrs.SSA ( Pharma'chemistry ) 3

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5. Spasms of vascular smooth muscle may also delay cardiac blood flow, reducing perfusion and causing ischemia and anginal pain. Is a characteristic sudden, severe, pressing-like sub sternal chest pain radiating to the neck, jaw, back, and arms. Patients may also present with dyspnea or atypical symptoms such as indigestion, nausea, vomiting, or diaphoresis. 8/14/2020 Mrs.SSA( Pharma'chemistry) 5

6. Is caused by inadequate blood flow through the coronary blood vessels, is a consequence of myocardial O 2 demand exceeding supply. Transient, self-limited episodes (15 seconds to 15 minutes) of myocardial ischemia (stable angina) do not result in cellular death; such as occurs in myocardial infarction (mi). However, acute coronary syndromes and chronic ischemia can lead to deterioration of cardiac function, heart failure, arrhythmias, and sudden death. 8/14/2020 Mrs.SSA( Pharma'chemistry) 6

7. TYPES OF ANGINA 8/14/2020 Mrs.SSA( Pharma'chemistry) 7

8. Stable angina : the most common (90 %) The chest pain caused by a temporary inadequacy of blood flow to the myocardium , The underlying cause is usually occlusion of the coronary arteries by atherosclerosis Usually lasts 1-15 minutes , and is provoked by exercise, stress, extreme cold or heat, heavy meals, alcohol, or smoking. Rx: is promptly relieved by rest or nitroglycerin (a vasodilator). 8/14/2020 Mrs.SSA( Pharma'chemistry) 8

9. Unstable angina : The pathology is similar to that involved in MI: a platelet-fibrin thrombus associated with a raptured atherosclerotic plaque, but without complete occlusion of the blood vessel. chest pains occur with increased frequency, duration, and intensity. precipitated by progressively less effort. Any episode of rest angina longer than 20 minutes, any new-onset angina, any increasing (crescendo) angina, or even sudden development of shortness of breath is suggestive of unstable angina. 8/14/2020 Mrs.SSA( Pharma'chemistry) 9

10. SYMPTOMS OF ANGINA 8/14/2020 Mrs.SSA( Pharma'chemistry) 10

11. MANAGEMENT OF ANGINA Explanation and reassurance Don’t smoke Aim for ideal body weight Regular exercise Avoid severe excretion and vigorous exercise Correction of established risk factor 8/14/2020 Mrs.SSA( Pharma'chemistry) 11

12. CLASSIFICATION 1.NITRATES Short acting - Glyceryl nitrates , amyl nitrate b) Long acting - Isosorbide dinitrate 2.CALCIUM CHANNEL BLOCKER phenyl alkylamine - verampil Benzothiazepine - diltiazem Dihydropyridines - nifedipine, amlodipine 8/14/2020 Mrs.SSA( Pharma'chemistry) 12

13. 4. BETA BLOCKERS - propranolol, metoprolol 5. POTASSIUM CHANNEL BLOCKERS - Nicorandil 6. OTHERS - dipyridamol 8/14/2020 Mrs.SSA( Pharma'chemistry) 13

14. MECHANISM OF ACTION FOR NITRATE Relax vascular smooth muscle by their intracellular conversion to nitrite ions, to nitric oxide, Activates guanylate cyclase (GC) and increases the cgmp. De phosphorylation of the myosin light chain , vascular smooth muscle relaxation 8/14/2020 Mrs.SSA( Pharma'chemistry) 14

15. AMYL NITRATES MOA- Act as vasodilators, decrease blood pressure USE Angina pectoros, cyanide poisoning 8/14/2020 Mrs.SSA( Pharma'chemistry) 15 Pentyl nitrite

16. NITROGLYCERIN MOA Forms free nitric oxide which activates guanylate cyclase resulting in an increase of guanosine3’5’ monophosphate in smooth muscle and other tissues. This leads to dephosphorylation of myosin light chains, which regulate the contractile state in smooth muscle and result in vasodilation USES severe, recurrent prizmental angina 8/14/2020 Mrs.SSA( Pharma'chemistry) 16

17. Iupac name- 1,2,3-Trinitroxypropane 8/14/2020 Mrs.SSA( Pharma'chemistry) 17

18. PENTAERYTHRITOL TETRANITRATE MOA Releases free nitric oxide after the denitration reaction and binds reversibly to the ferrous heme centre of guanylate cyclase causing conformational chain and activating the enzymes which cause increased cellular concentration of cGMP and result vasodilation USES angina pectoris Relaxes s.m 8/14/2020 Mrs.SSA( Pharma'chemistry) 18

19. 8/14/2020 Mrs.SSA( Pharma'chemistry) 19 [3-Nitrooxy-2,2-bis( nitrooxymethyl ) propyl ] nitrate]

20. ISOSORBIDE DINITRITE MOA Activates cytosolic guanylyl cyclase ,increased cGMP, cause dephosphorylation of MLCK raised intracellular cGMP may also reduce ca++ entry contributing to relaxation USES Angina attack, angina pectoris, acute coronary syndromes 8/14/2020 Mrs.SSA( Pharma'chemistry) 20

21. 8/14/2020 Mrs.SSA( Pharma'chemistry) 21 1,4:3,6-dianhydro-2,5-di-O-nitro-D-glucitol

22. DIPYRIDAMOL MOA Inhibit adenosine deaminase interacts with vasodilator adenosine , increase prostacyclin effect and inhibit the platelets aggregation USES Angina pectoris 8/14/2020 Mrs.SSA( Pharma'chemistry) 22

23. 8/14/2020 Mrs.SSA( Pharma'chemistry) 23 2,2',2'',2'''-[( 4,8-Dipiperidin-1-ylpyrimido[5,4-d]pyrimidin-2,6-diyl ) dinitrilo ] tetraethanol

24. BETA BLOCKERS Atenolol , metoprolol , propranolol, bisoprolol are used only for prophylactic therapy of angina ; they are of no value in an acute attack. Effective in preventing exercise-induced angina. 8/14/2020 Mrs.SSA( Pharma'chemistry) 24

25. MECHANISM OF ACTION Suppress the activation of the heart by blocking B 1 receptors I. Decrease the HR, resulting in: Decreased myocardial oxygen demand. Increased oxygen delivery to the heart. II. Decrease myocardial contractility , helping to conserve energy or Decrease demand Reduce the work of the heart by decreasing COP and causing a slight decrease in BP ↓ Hr, ↓Contractility, ↓Systolic wall tension, ↑Perfusion time 8/14/2020 Mrs.SSA( Pharma'chemistry) 25

26. Reasons for Using Nitrates and β-Blockers in Combination in Angina Β-blockers prevent reflex tachycardia and contractility Produced by nitrate-induced hypotension . Nitrates prevent any coronary vasospasm produced by β- blockers. Nitrates prevent increases in left ventricular filling pressure or preload resulting from the negative inotropic effects produced by β-blockers . 8/14/2020 Mrs.SSA( Pharma'chemistry) 26

27. 8/14/2020 Mrs.SSA( Pharma'chemistry ) 27 Thank you for your attention