This document provides information about angina pectoris (angina), including its causes, types, diagnosis, and treatment. It begins by defining angina as a heart condition marked by chest pain due to reduced oxygen to the heart. It then discusses the different types of angina (stable, unstable, variant), symptoms, diagnostic tests, and pharmacological treatments which work to improve the oxygen demand/supply ratio to the heart through vasodilation and other mechanisms. The main drug classes used to treat angina are discussed in detail: nitrates, calcium channel blockers, beta-blockers, and antiplatelets.

1. ANGINA PECTORISBy:- PARTH SHAHM.Pharm(Pharmacology)

2. ANGINA PECTORISA Chronic disease of CVSOccurs with Interminent chest pain spread along the Chest, Shoulders and Arms.

3. Angina pectoris: a heart condition marked by paroxysms of chest pain due to reduced oxygen to the heart

4. Angina pectoris, or angina, as it is commonly referred to, and coronary artery disease or arteriosclerosis are closely related.

5. Angina occurs in people who have some form of blockage in the coronary arteries. In other words, it occurs in people with coronary heart disease.It occurs when the Oxygen Supply to the Myocardium is insufficient for its needs.Factors affecting Oxygen Demand Supply Ratio

6. Various Chemical Factors released from Ischeamic Muscle likeK+H+Adenosine are responsible to stimulate the Nociceptorsi.e Chest Pain when the muscles contract with interrupted supply of blood.Also the same mediators that cause Coronary Vasodilation are responsible for this Pain.

7. Also may occur due to accumulation of the waste products in the heart muscle and stimulate local nerve endings.The usual discomfort is regarded as a pressure, heaviness, tightness, squeezing, burning or choking sensation.The angina – coronary occlusion occurs which leads to the Anginal attack over a period of time.

8. ANGINA-CORONARY OCCLUSIONCORONARY OCCLUSION

9. CORONARY CIRCULATIONMost tissues can increase O2 extraction with demand.Heart extracts near maximal amount of O2 at rest.Therefore can increase O2 demand by increasing the Coronary Blood Flow.Various Coronary Arteries of Heart

10. Types Of Angina PectorisStable AnginaUnstable AnginaVariant Angina (Prinzmetal’s Angina)Anginal Equivalent SyndromeSyndrome- XSilent Ischemia

11. STABLE ANGINAPredictableOccurs on exercise, emotion or eating.Caused by increase demand of the heart and by a fixed narrowing of coronary vessels, almost always by atheroma.Coronary obstruction is ‘fixed’Blood flow fails to increase during increased demand despite the local factors mediated ‘vasodilation’ and so ischeamic pain is felt.

12. So, the diastolic pressure increases and this causes a endocrinal ‘crunch’ and thus causing Ischeamatic pain in this region.Thus, a form of acutely developing and rapidly reversible left ventricular failure results which is relieved by taking rest and reducing the myocardial workload.

13. UNSTABLE ANGINAThis is characterized by Pain that occurs with less excertion , cumulating pain at rest.The pathology is similar to that involved in Myocardial Infraction, namely platelet-fibrin thrombus associated with a ruptured atheromatous plaque, but without complete occulation of the vessels.The risk of infraction is subtanial, and the main aim of therapy is to reduce this.

14. VARIANT ANGINA (PRINZMETAL’S ANGINA)UncommonOccurs at rest generally during sleepCaused by Large Coronary Artery SpasmUsually associated with atheromatous diseaseAbnormally reactive and hypertrophied segments in the Coronary ArteryDrugs aimed at preventing & relieving Coronary Spasm.

15. ANGINAL EQUIVALENT SYNDROMEPatient’s with exertionaldyspnea rather than exertional chest painCaused by exercise induced left ventricular dysfunction

16. ANGINA: SYNDROME XTypical , exertional angina with positive exercise stress testAnatomically normal coronary arteriesReduced capacity of vasodilation in microvasculatureCalcium channel blockers and Beta blockers are effective.

17. ANGINA: SILENT ISCHEMIAVery CommonMore episodes of Silent than Painful angina in the same patient.Difficult to diagnoseGnerally Exercise testing.

18. DIAGNOSISSTRESS (EXERCISE) TEST.ECG (ELECTROCARDIOGRAPHY)CHEST X-RAYCARDIAC ANGIOGRAPHY/ CARDIAC CATHETERIZATIONERGONOVINE TESTBLOOD TEST (BIO-MARKERS)

19. 1. EXERCISE TEST/STRESS TESTUsed to measure heart’s response to exercisePatient asked to walk on a treadmill while the physician takes the ECG So any changes in heart function can be determinedAlternatively the patient recieves an injection of a radioisotope (generally Thallium) which makes the heart visible to a special-linked camera90% accurateBut doesn’t identify the exactly where and how the coronary arteries are blocked.

20. 2. ELECTROCARDIOGRAM (ECG)Measures electrical activity of the heartProvides info about the changes or damages to the heart muscleDoesn’t detect the narrowing of the coronary arteriesDuring an Anginal attack the ECG may show S-T phase depression.T- phase inversion and/orVentricular arrythmiaECG- more abnormal with Unstable Angina where the elevation in S-T segment is found.

21. STABLE ANGINAAt RestAfter Excercise

22. 3. CHEST X-RAYPerformed to rule out any lung disease or heart damage that may be causing the pain.Also may reveal enlargement of heart

23. 4. CARDIAC ANGIOGRAPHY/ CARDIAC CATHETERIZATIONShows the precise size and location of blockages within the Coronary arteriesA cathereter is inserted through the blood vessels from the forearm or groinIt is snaked through arteries till it reaches the heartA fluid is pumpedSo the arteries and the heart are clearly visible

24. 5. ERGONOVINE TESTGenerally done if the person is assumed to suffer from Coronary SpasmDone along with angiographyThe artery-narrowing drug—Ergonovine or Ach is given to cause Coronary SpasmThe persons response to ergonovanine is measured

25. 6. BLOOD TEST/BIOMARKERSBlood test for amount of Lipids within the bloodBecause lipids major cause of anginal attackLipid profile for :- 1. HDL 2. LDL 3. TRIGLYCERIDES Recently the newer biomarkers like the C-reactive proteinandB-type natriuretic protein have been found out and the tests for each of them is doneThese tests are predictive of the moratality of heart disease

26. TREATMENT3 Classes of drugs used according their mode of actionNITRATES- ADRENOCEPTOR ANTAGONISTSCALCIUM CHANNEL ANTAGONISTSANTIPLATELET DRUGS

28. Improving Oxygen Demand:Supply Ratioa. Relaxation of resistance vessels (small arteries and arterioles) ↓TPR -> ↓BP -> ↓Afterload (Nitrates, calcium channel blockers and beta-blockers)b. Relaxation of capacitance vessels (veins and venules) ↓Venous return, ↓heart size, ↓Preload (Nitrates and calcium channel blockers)c. Blockade or attenuation of sympathetic influence on the heart ↓Contactility, ↓HR, ↓O2 demand (Beta-blockers)d. Coronary Dilation, Important mechanism for relieving vasospastic angina, ↑O2 supply (Nitrates)

29. NITRATESProdrugsSources of Nitric OxideEg:- Nitroglycerin, IsosorbideDinitrate Isosorbide-5-MononitrateMechanism Of Action

30. PHARMACO-LOGICAL ACTIONS OF NITRATES

31. Nitrates mainly give Vasoldilation effectThe specificity of their action is in dilating the collateralsUnlike other vasodilators (dipyridamole) which dilate only the arteries but not the collaterals

32. TOXICITY OF NITRATESHeadacheIncreased mortalityRecurrence of Myocardial InfractionDizzinessFlushingRapid heart beatRestlessnessDry mouthSkin rashNausea

33. MARKETED FORMULATIONSGTN Sorbitrate (PIRAMAL)Vasovin (TORRENT)ISMO retard (PIRAMAL)Angicor (NOVARTIS)NitroglycerideIsosorbide-5-monophosphate

34. CALCIUM CHANNEL ANTAGONISTSDisrupt Ca++ through Ca++ channels-veionotrpic effect2 types:-Dihydropyridine (amlodipine, nifedipine, nicardipine)Non-DihydropyridinePhenylalkylamine (verapamil, gallopamil)Benzodiazapenes (diltiazem)Non-selective (bepridil, mibefradil)

35. MECHANISM OF ACTION

36. Pharmacological Actions

37. TOXIC EFFECTS

38. MARKETED PREPARATIONSCalaptin (PIRAMAL)Vasopten (TORRENT)Coriem XL (RANBAXY)Dicard (INTAS)Amtas (INTAS)Cadeut (PFIZER)VerapamilDiltiazemAmplodipine

39. -ADRENOCEPTOR ANTAGONOSTSImportant in prophylaxis of angina and treating unstable anginaDecrease O2 consumption by the heartEffects on coronary vessels-not importantAvoided in variant anginaAs they increase the chances of spasmEg:-AtenololPropranolol

40. PHARMACOLOGICAL ACTIONS

41. MECHANISM OF ACTION

42. MARKETED PREPARATIONSBetacard ( TORRENT)Aten (ZYDUS CADILA)Betacap (SUN PHARMA)Cardilax (INTAS)

43. ANTICOAGULANTS Anticoagulants are often called "blood thinners," although they don't really thin blood. They decrease the blood's ability to clot.Eg Heparin, Dalteparin, Enoxaparin, Warfarin, Aspirin

44. COMPARITIVE TOXIC EFFECTS

45. COMBINATION THERAPYNitrates + -blockers :- in stable anginaCa++ channel blockers + -blockers :-in stable angina when the treatment with nitrates and -blockers has failed.Ca++ channel blockers + Nitrates :- in unstable anginaAll 3 together:- when the combinations of 2 drugs has failed, where:-Nitrates:- decrease PreloadCa++ channel Blockers:- decrease Afterload-blockers:- decrease heart rate and myocardial contractions

46. Recommended Drug therapy for Angina with other medications

49. NEWER DRUGSRANOLAZINE (Ranexa™; CV Therapeutics, Inc.), a drug that has been in development for 20 years. It is a Sodium Channel Blocker.NICORANDIL, a potassium channel activator, and also has a Nitrogen Donating Moeity.IVABRADINE, inhibits the If channel in the sinus node and thereby causes bradycardia without any negative inotropic effects.

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