ANTIANGINAL ( CORONARY ACTIVE ) DRUGS

1. ANTIANGINAL (CORONARY ACTIVE) DRUGS

2. ISCHEMIC HEART DISEASE 2,4 mln. people die from IHD annually

3. ISCHEMIC HEART DISEASE There are 35 risk factors for development of IHD 3 the most important ones are – “big triple” hypercholesterolemia arterial hypertension smoking 95 % of patients with IHD are observed to have atherosclerotic changes in coronary arteries

5. Atherosclerotic changes in coronary arteries

6. ANTIANGINAL (CORONARY ACTIVE) DRUGS І. Nitrates and sidnonimins ІІ. Beta-adrenoblockers ІІІ. Antagonists of calcium ions ІУ. Activators of potassium channels • Inhibitors of ACE • Platelet inhibitors and anticoagulants • Drugs with metabolic influence on myocardium

7. NITRATES nitroglycerin isosorbiddinitrate isosorbid-5-mononitrate

10. NITROGLYCERINE • Tablets (under the tongue) • 1 % alcohol or oil solution(under the tongue) • aerosol Onset - 2-3 min Duration of action - 20-30 min • ampoules1 % solution – intravenously dropply 0,01%solution • prolongedforms of nitroglycerine: trinitrolong, sustak, nitrong, ointment, plaster

11. NITROGLYCERINpharmaceutical forms

12. NITROGLYCERINpill bottles

13. Nitroglycerinetransdermal system in a form of plaster

14. SIDE EFFECTS OF NITROGLYCERINE bursting, pulsating headache decreasing of arterial pressure (tachycardia, dizziness, collapse – postural hypotension) facial flushing, feeling of fever

15. Contraindications for nitroglycerine administration • increasing of intracranial pressure, insult • acute myocardial infarction(in case of presence of hypotonia and collapse)

16. PROLONGED FORMS OF NITROGLYCERINE • Trinitrolong– polymer films (0,001 gor 0,002 gof nitroglycerine)action develops immediately, lasts for 3-5 hours • Sustac- Sustaс-mite (contains 0,0026 g of nitroglycerine) and Sustac-forte (0,0064 g of nitroglycerine) onset – after 10 min, maximal action – after 1 hour, duration of action – 4-5 hours • Nitrong – microcapsule form of nitroglycerine of prolonged action onset – 30-60 min, maximal effect- after 3-4 hours, Duration of action - 6-8 hours

17. Nitroglycerin and Premature Birth • The five-year, randomized check involved 153 women selected at the time they went into pre-term labor (at 24 to 28 weeks). • Employing nitroglycerin patches for pregnant women prolonged their pregnancy and what's new, the babies were born healthy, with less side effects than those induced by other drugs. • In Canada, about 7.5 % of all babies are born prematurely (before 37 weeks) and 1 to 2 % are severe cases, before 34 weeks.

18. Iso MakRetard 20mgIso Mak Retard 40mg IsomakRetard 60mg(isosorbid dinitrate)

19. IsoketIsosorbid dinitrate

20. Mechanism of tolerance to nitrates

21. Other nitrates Nitrosorbid– isosorbiddinitrate onset - 30-50 min, duration of action – 4-6 hours and more With sublingual administration of the drug onset decreases to 3-5 min • buccal form (Dinitrosorbilong) • tablets of prolonged action (Isoket-retard) • ointment • aerosol • drugs for intravenous introduction Isosorbid-5-mononitrate - pharmacologically active metabolite of isosorbiddinitrate duration of action- from 6 till 24 hours

22. SYDNONIMINS Molsydomine –corvaton -sydnopharm • is metabolized by the liver forming a substance – SIN-1awhich contains freeNОgroup (doesn’t need previous interaction withSH-groups) • nitric oxide stimulates guanylatecyclase that activates synthesis ofcGMP • cGMP causes dilation of vessels 2 mg of molsydomine=0,5 mg of nitroglycerin

23. Molsidomine metabolism

25. BETA-ADRENOBLOCKERS Mechanism of action during ischemic attack • blockade of b1-adrenoreceptors of heart:decrease of cardiac output and frequency of heart contractions and as follows cardiac need in oxygen • decreasing of platelets aggregation and prevention of plug formation • increasing durationof diastole – improvement of coronary vessels saturation with blood– improvement of perfusion of ischemic areas of myocardium • Decreasing of calcium ions accumulation – releasing of cardiac muscle tension, improvement of metabolic processes, increasing of ATP synthesis • in case of acute myocardium infarction– increasing of blood supply of ischemic areas of heart, decreasing of size of infarction area, prevention of development of cardiac arrhythmias

26. Beta-adrenoblockers

27. Anaprilinβ1- β 2adrenoblocker

28. Vasocardin100 mgMethoprolol tartrate

29. Nadolol(β1, β 2- adrenoblocker)

30. Nebivolol

31. CALCIUM IONS ANTAGONISTS 1.Derivatives of difenilalkilamin (verapamil) 2. Derivatives of benzothiazepine (dylthiazem) 3. Derivatives of dihydropyridine (nifedipin, amlodipin, nimodipin) Drugs of 1 and 2 groups dominantly influence on heart (depress automatism of sinus node, slow cardiac conduction, decrease heart rate and oxygen demand), show antiarrhythmic, antianginal and hypotensive action Derivatives of dihydropyridine (group of nifedipin) – decrease blood pressure and cause dilation of coronary vessels,cause reflective tachycardia

32. Antagonists of calcium ions – derivatives of dihydropyridine ofІІ generation (amlodipin, isradipin, nicardipin) • don’t cause tachycardia • areindicated for prolonged treatment of patients with stable angina • Are not indicatedin case of unstable angina(long onset)

33. Usage of calcium ions antagonists Illness Drugs -recommended drug --should be used carefully

34. Nifedipin(Са2+ions antagonist of dihydropyridine group)

35. Nifedipin (Са2+ions antagonist of dihydropyridine group)

36. Nifedipin (Са2+ions antagonist of dihydropyridine group)

37. AMLODIPIN

38. ACTIVATORS OF POTASSIUM CANALS NICORANDIL • activates Са2+-depending potassium channels • causesrelaxation of smooth muscles of vessels – coronary, arteriolar and venous vasodilation • improves of blood supply of myocardium, decreasing of pre- and afterloads of heart,decreasing of myocardial need in oxygen, of ischemic damage zone

41. Acetylsalicylic acid 80-100 mg daily • against platelets aggregation,decreases risk of development of acute myocardium infarction and decreases mortality of patients with IHD • Throughout the world it is also used as a drug for basic treatment of IHD (can be used for years) • Main complication – gastric bleeding

42. ACUTE MYOCARDIAL INFARCTION From a 45-year-old man who died of an acute myocardial infarction. Postmortem serum Cholesterol 100 times more than normal.

43. cholesterol lowering drugs • Statins - HMG-CoA reductaseinhibitors • Fibrates

44. Statins - HMG-CoA reductase inhibitors • block the enzyme in the liver that is responsible for making Cholesterol – hydroxy-methylglutaryl-coenzyme reductase • Statins lower Bad Cholesterol Levels, raise Good Cholesterol Levels, and can slow down the formation of plaques in arteries. • lower the chances of a heart attack and death in a group who have an elevated risk of developing Heart Disease or who already have Heart Disease

45. Mechanism of statins action

46. Benefits of Statins • improving on the whole vascular function • reduce the size of plaques in the arteries • stabilize plaques there by reducing the chance of rupture and reduce chance of acute heart attacks • reduce inflammation, believed to be an important component of plaque formation and rupture. • Statin reduces CRP levels

47. Statins

48. Statins

50. Cholesterol-lowering “statin” drugs side effects • fatigue • muscle pain (9 % of patients) • at higher doses and long term administration – myopathy (rhabdomyolysis) acute damage to muscle tissue - can be very serious • reduced proliferation • damage to kidneys • increased risk for cataracts • elevated blood sugar • increased risk for prostate and breast cancer