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. isosorbid-5-mononitrate
NITRATES
nitroglycerin
isosorbid dinitrate
isosorbid-5-mononitrate

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

11. NITROGLYCERIN pharmaceutical forms

12. NITROGLYCERIN pill bottles

13. Nitroglycerine transdermal 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 g or 0,002 g of nitroglycerine) action develops immediately, lasts for 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 – min,
maximal effect - after 3-4 hours,
Duration of action 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 Mak Retard 20mg Iso Mak Retard 40mg Isomak Retard 60mg (isosorbid dinitrate)

19. Isoket Isosorbid dinitrate

20. Mechanism of tolerance to nitrates

21. Other nitrates Nitrosorbid – isosorbid dinitrate
onset 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 isosorbid dinitrate
duration of action - from 6 till 24 hours

22. SYDNONIMINS Molsydomine – corvaton - sydnopharm
is metabolized by the liver forming a substance – SIN-1a which contains free NО group (doesn’t need previous interaction with SH-groups)
nitric oxide stimulates guanylate cyclase that activates synthesis of cGMP
cGMP causes dilation of vessels
2 mg of molsydomine = 0,5 mg of nitroglycerin

23. Molsidomine metabolism

25. Mechanism of action during ischemic attack
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 duration of 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. Anaprilin β1- β 2 adrenoblocker

28. Vasocardin 100 mg Methoprolol 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 of ІІ generation (amlodipin, isradipin, nicardipin)
don’t cause tachycardia
are indicated for prolonged treatment of patients with stable angina
Are not indicated in case of unstable angina (long onset)

33. Usage of calcium ions antagonists
Illness
Drugs
Hypertension
Verapamil
Dylthiazem
Nifedipin
Felodipin
Amlodipin
Stenocardia
Verapamil
Dylthiazem
Nifedipin
Amlodipin
Supraventricular tachy-arrhythmia
Verapamil
Dylthiazem
Possible combination with β-blockers
Dylthiazem
Nifedipin
Felodipin
Amlodipin
-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
causes relaxation 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 reductase inhibitors
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

51. Fibrates entering the market over 40 years

52. Fibrates

55. Fibrates complications
Nausea, diarrhea and abdominal pain
Renal insufficiency
Rhabdomyolysis
Hypersensitivity, rash
formation of gallstones

56. Nicotinic acid or niacin
useful for patients with mixed dyslipidemias
inhibits transport of free fatty acids to the liver from peripheral adipose tissue resulting in decreased triglyceride synthesis
increases in HDL cholesterol and decreases in VLDL and LDL cholesterol
for diabetic dyslipidemia to increase HDL cholesterol