1. CLINICAL PHARMACY IN CARDIOLOGY

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

3. Angina, or angina pectoris, is the medical term used to describe the temporary chest discomfort that occurs when the heart is not getting enough blood
The heart is a muscle (myocardium) and gets its blood supply from the coronary arteries.
Blood carries the oxygen and nutrients the heart muscle needs to keep pumping.
When the heart does not get enough blood, it can no longer function at its full capacity.
When physical exertion, strong emotions, extreme temperatures, or eating increase the demand on the heart, a person with angina feels temporary pain, pressure, fullness, or squeezing in the center of the chest or in the neck, shoulder, jaw, upper arm, or upper back. This is angina, especially if the discomfort is relieved by removing the stressor and/or taking sublingual (under the tongue) nitroglycerin.
The discomfort of angina is temporary, meaning a few seconds or minutes, not lasting hours or all day.

4. An episode of angina is not a heart attack
An episode of angina is not a heart attack. Having angina means the patient have an increased risk of having a heart attack.
A heart attack is when the blood supply to part of the heart is cut off and that part of the muscle dies (infarction).
Angina can be a helpful warning sign if it makes the patient seek timely medical help and avoid a heart attack.
Prolonged or unchecked angina can lead to a heart attack or increase the risk of having a heart rhythm abnormality. Either of those could lead to sudden death.

5. Not all chest pain is angina
Not all chest pain is angina. Pain in the chest can come from a number of causes, which range from not serious to very serious
Chest pain can be caused by:
acid reflux (gastroesophageal reflux disease, GERD),
upper respiratory infection,
asthma, or
sore muscles and ligaments in the chest (chest wall pain)
If chest pain is severe and/or recurrent, the patient should see a healthcare provider.

6. Life-threatning symptoms: chest pain +
sweating,
weakness,
faintness,
numbness or tingling,
nausea
Pain that does not go away after a few minutes
Pain that is of concern in any way

7. Angina is classified as one of the following two types:
Stable angina
People with stable angina usually have angina symptoms on a regular basis. The episodes occur in a pattern and are predictable.
For most people, angina symptoms occur after short bursts of exertion.
Stable angina symptoms usually last less than five minutes.
They are usually relieved by rest or medication, such as nitroglycerin under the tongue.

8. Unstable angina
Angina symptoms are unpredictable and often occur at rest.
This may indicate a worsening of stable angina, but sometimes the first time a person has angina it is already unstable.
The symptoms are worse in unstable angina - the pains are more frequent, more severe, last longer, occur at rest, and are not relieved by nitroglycerin under the tongue.
Unstable angina is not the same as a heart attack, but it warrants an immediate visit to the healthcare provider or a hospital emergency department. The patient may need to be hospitalized to prevent a heart attack.

9. Most cases of coronary heart disease are caused by atherosclerosis (hardening of the arteries).
Atherosclerosis is a condition in which a fatty substance/cholesterol builds up inside the blood vessels. These buildups are called plaques, and they can block blood flow through the vessels partially or completely.
Multiple risk factors:
diabetes,
high blood pressure,
smoking,
high cholesterol, and
genetic predisposition may accelerate this build up.

10. Coronary Artery Spasm
Another cause of unstable angina is coronary artery spasm.
Spasm of the muscles surrounding the coronary arteries causes them to narrow or close off temporarily. This blocks the flow of blood to the heart muscle for a brief time, causing angina symptoms.
This is called variant angina or Prinzmetal angina.
This is not the same as atherosclerosis, although some people have both conditions.
The symptoms often come on at rest (or during sleep) and without apparent cause.
Cocaine use/abuse can cause significant spasm of the coronary arteries and lead to a heart attack.

11. Angina Pectoris Symptoms
Angina itself is a symptom (or set of symptoms), not a disease. Any of the following may signal angina:
An uncomfortable pressure, fullness, squeezing, or pain in the center of the chest
It may also feel like tightness, burning, or a heavy weight.
The pain may spread to the shoulders, neck, or arms.
It may be located in the upper abdomen, back, or jaw.
The pain may be of any intensity from mild to severe.

12. Other symptoms may occur with an angina attack:
Shortness of breath
Lightheadedness
Fainting
Anxiety or nervousness
Sweating or cold, sweaty skin
Nausea
Rapid or irregular heart beat
Pallor (pale skin)
Feeling of impending doom
These symptoms are identical to the signs of an impending heart attack described by the American Heart Association. It is not always easy to tell the difference between angina and a heart attack, except angina only lasts a few minutes and heart attack pain does not go away.

14. Antianginal (coronary active) drugs
a group of drugs which using different mechanisms even out irregularities between myocardium need in oxygen and it’s blood supply by coronary arteries
clinically it is manifested by removal or prevention of angina attacks (improvement of disease current) and increasing of patients’ tolerance to physical load

15. ANTIANGINAL (CORONARY ACTIVE) DRUGS
І. Nitrates and sidnonims which are close to the first ones
ІІ. Beta-blockers
ІІІ. Calcium channel blockers (CCBs):
ІУ. Activators of potassium channels
Hypercholesterolemia drugs
Antiplatelets and anticoagulants
Drugs with metabolic influence on miocardium

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

17. MECHANISM OF ACTION OF NITRATES
Interaction with sulfhydryl (SH-) groups (nitrate receptors) inside cells of vascular smooth muscles
Stimulation of formation of endothelial factor of relaxation of vessels (ЕRF) – nitrogen oxide (NO)
Decreasing of ionized Са2+ contents
Relaxation, dilation of vessels, including coronary vessels

18. MECHANISM OF ACTION OF NITRATES
Decreasing of tone of venules – decreasing of preloading (income of blood into heart during diastole) – decreasing of work of left ventricle and heart output
Decreasing of tone of arterioles – decreasing of afterloading (decreasing of arterial pressure, end diastolic pressure in left ventricle and it’s volume, decreasing of tension of myocardium wall
decreasing of heart need in oxygen
improvement of blood float in ischemic zone of myocardium – redistribution of coronary blood circulation with increasing of perfusion of subendocardial areas
dilation of large coronary vessels if they are in spasm or narrowed with aterosclerotic mass
development of anastomoses between arteries in myocardium (in case of prolonged administration)

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

20. Nitroglycerin is taken only when the patient actually has symptoms or expect to have them. Slow - or long-acting nitroglycerin can be used as a preventative treatment for angina but not until beta blockers are tried first.

21. Nitroglycerine Unique transdermal system in a form of plaster

22. SIDE EFFECTS OF NITROGLYCERINE
bursting, pulsating headache
decreasing of arterial pressure
(heartbeat, dizziness, collapse)
skin redness, feeling of fever

23. Contraindications for nitroglycerine use
Close-angled form of glaucoma
increasing of intracranial pressure, stroke
acute myocardium infarction (in case of presence of hypotension and collapse)

24. PROLONGED FORMS OF NITROGLYCERINE
Trinitrolong – polymer films (0,001 g or 0,002 g of 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)
beginning of action – after 10 min,
maximal action – after 1 hour,
duration of action – 4-5 hours
Nitrong – microcapsule form of nitroglycerine of prolonged action
latent period – min,
maximal effect - after 3-4 hours,
action duration hours

25. Nitrosorbid – isosorbid dinitrate Isosorbid-5-mononitrate
Other nitrates
Nitrosorbid – isosorbid dinitrate
latent period min,
duration of action – 4-6 hours and more
With sublingual administration of the drug latent period grows short to 3-5 min
buccal form (Dinitrolslrbilong)
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

26. Iso Mak Retard 20mg Iso Mak Retard 40mg Isomak Retard 60mg (isosorbid dinitrate)

27. Isoket Isosorbid dinitrate

28. Molsidomine – corvaton - sydnopharm
SYDNONIMINS
Molsidomine – corvaton - sydnopharm
is metabolized in liver forming a substance – SIN-1a which contains free NО group (doesn’t need previous interaction with SH-groups)
nitrogen oxide stimulates guanilatecyclase that activates synthesis of cGMP
cGMP causes dilation of vessels
2 mg of molsidomine= 0,5 mg of nitroglycerine

29. Molsidomine
latent period - 20 min (5-10 min – if administered sublingually), action duration - 6 hours.
can be used for prophylaxis and releasing angina attacks in patients with glaucoma (doesn’t increase intraocular pressure)
indicated for patients who make breaks in using nitrates to decrease tolerance towards them
doesn’t lead to development of tolerance (doesn’t need previous combining with drugs containing SH- groups)
absence of withdrawal syndrome

30. BETA-BLOCKERS Using in Angina
blockade of b1-adrenoreceptors of heart: decreasing of power and frequency of heart contractions and as follows cardiac need in oxygen
decreasing of thrombocyte aggregation and prevention of clotts formation
increasing of diastole duration – 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 seat, prevention of development of cardiac arrhythmias

31. Anaprilin β1- β 2 adrenoblocker

32. Vasocardin 100 mg Methoprolol tartrate

33. Nebivolol beta-blocker that also causes vasodilation by stimulating the release of nitric oxide

34. Beta blockers are taken every day, regardless of whether the patient is having symptoms, because they are proven to prevent heart attacks and sudden death.

35. Calcium channel blockers
1. Derivatives of difenilalkilamin (verapamil)
2. Derivatives of benzothiazepine (dylthiazem)
3. Derivatives of dyhydropyridine (nifedipin, amlodipin, nimodipin)
Drugs of 1 and 2 groups dominantly influence on heart (depress automatism of sinus node, conductivity through conductive heart system), show antiarrhythmic, antianginal and hypotensive action.
Derivatives of dyhydropyridine (group of nifedipin) – decrease blood pressure and cause dilation of coronary vessels, cause reflective tachycardia

36. Calcium channel blockers classification

37. Nifedipin - corinfar - fenigidin - adalate
Doesn’t depress conductivity in myocardium,
has a weak antiarrhythmic action
Maximal concentration of the drug in blood occurs after min after administration orally and after 2-3 min – if administered sublingually
Effect lasts for 4-6 hours

38. Antagonists of calcium ions – derivatives of dyhydropyridine of ІІ generation (amlodipin, isradipin, nicardipin)
almost don’t cause tachycardia
are indicated for prolonged treatment of patients with stable angina
aren’t indicated in case of non stable angina (long lasting latent period)

39. Indications

40. Nifedipin (Са2+ ions antagonist of dyhydropyrydine series)

41. Nifedipin (

42. Calcium channel blockers are used primarily when beta blockers cannot be used and/or the patient is still having angina with beta blockers. Calcium channel blockers also lower blood pressure and certain ones slow heart rate. Calcium channel blockers have to be taken every day.

43. Common side effects of calcium channel blockers include:
headache,
constipation,
rash,
nausea,
flushing,
edema (fluid accumulation in tissues),
drowsiness,
low blood pressure, and
dizziness.
Sexual dysfunction, overgrowth of gums, and liver dysfunction also have been associated with calcium channel blockers. Verapamil (Covera-HS, Verelan PM, Calan) and diltiazem (Cardizem LA, Tiazac) worsen heart failure because they reduce the ability of the heart to contract and pump blood.

44. POTASSIUM-CHANNEL ACTIVATORS
NICORANDIL Ikorel
activates Са2+-depending potassium channels
causes relaxation of smooth muscles of vessels –
coronary, arteriolar and venous vasodilation
improvement of blood supply of myocardium, decreasing of pre- and afterloads of heart, decreasing of myocardial need in oxygen, separation of ischemic damage zone

45. Antiplatelet agents Commonly prescribed include: Aspirin Ticlopidine
Clopidogrel
Dipyridamole

46. Acetylsalicylic acid
mg per day – as antiplatelet drug, decreases risk of development of acute myocardial infarction and decreases mortality of patients with IHD
Helps prevent clotting in patients who have had a heart attack, unstable angina, ischemic strokes, TIA (transient ischemic attacks, or "little strokes") and other forms of cardiovascular disease.
Usually prescribed preventively when plaque buildup is evident but there is not yet a large obstruction in the artery.

47. Common types of cholesterol-lowering drugs include:
statins
resins
nicotinic acid (niacin)
gemfibrozil
clofibrate
Various medications can lower blood cholesterol levels. They may be prescribed individually or in combination with other drugs. They work in the body in different ways. Some affect the liver, some work in the intestines and some interrupt the formation of cholesterol from circulating in the blood.  
Reason for Medication
Used to lower LDL ("bad") cholesterol, raise HDL ("good") cholesterol and lower triglyceride levels

48. Choose good nutrition Reduce blood cholesterol Lower high blood pressure Be physically active every day Aim for a healthy weight Manage diabetes Reduce stress Limit alcohol Stop smoking

49. ACUTE MYOCARDIAL INFARCTION
one of the main reasons of disablement and mortality of people of employed age in many world countries, including Ukraine
men suffer from MI almost 5 times more often than women
Mortality of patients with MI during first two hours starting from the beginning of the process makes around 50 % of all mortal cases connected with MI
the most often death causes – acute cardiac-vascular insufficiency (angina pectoris, lung edema, cardiogenic shock), heart rupture, heavy cardiac arrhythmia
other complications of MI – thrombosis and emboli, acute and chronic heart aneurisms, Dresler’s syndrome, chronic cardiac insufficiency

50. TREATMENT OF MYOCARDIAL INFARCTION
three stages
Immediate treatment – decreasing pain and treatment of heart beats arrest
Early treatment – separation of zone of infarction seat and prevention of early life threatening complications (cardiac arrhythmias, acute cardiac insufficiency)
Further treatment – prevention and therapy of late complications of MI, prophylaxis of recurrent MI and death of the patients

51. TREATMENT OF ACUTE MYOCARDIAL INFARCTION
Releasing of pain and
cardiogenic shock prophylaxis
nitroglycerin (1 tablet under the tongue every 7-10 min.)
Neuroleptanalgesia (fentanil with droperidol), morphine, omnopon, promedol (in combination with atropine, dimedrol, aminasine)
nitrous oxide in combination with neuroleptics
in case of remaining pain – non narcotic analgesics in combination with antihistamine and neuroleptic drugs
to increase arterial pressure during cardiogenic shock – intravenously dropply dopamine (drugs of choice), noradrenalin, mesaton
sometimes glucocorticosteroids are used

52. TREATMENT OF ACUTE MIOCARDIAL INFARCTION (cont’d)
Size limitation
of infarction seat
Intravenous dropply introduction of
0,01 % nitroglycerin solution
Administration of b-blockers

53. TREATMENT OF ACUTE MYOCARDIAL INFARCTION (cont’d)
Treatment and prophylaxis of heart arrhythmias
Treatment of ventricular arrhythmias – i.v. slowly 0,2 % solution of xycain, novocainamid intramuscularly
Prophylaxis of ventricular extrasystole and tachycardia – magnesium sulfate (intravenous dropping introduction of 4-5 % solution),
-adrenoblockers
Arrhythmias of atrial origin – heart glycosides, antagonists of calcium channels
Bradycardia - isadrin, atropine sulfate, alupent (i.v.)

54. TREATMENT OF ACUTE MYOCARDIAL INFARCTION (cont’d)
CORRECTION OF BLOOD CLOTTING
thrombolytic drugs
streptokinase (1,5 mln OD), urokinase (2 mln OD), aktilise – recombinant tissue activator of plasminogen (100 mg) intravenous
after performing of thrombolytic therapy – intravenous introduction of heparin, at first OD, after 1000 OD per hour during hours
anticoagulants of indirect action
acetylsalicylic acid
( mg per day)

55. Treatment of heart insufficiency
i.v. furosemid ( mg); i.v. dropply nitroglycerine (12-20 hours), morphine
i.v. dropply dopamin and dobutamin
heart glycosides – in tachysystolic form of scintillating arrhythmia or fluttering of atria with moderate left-ventricular insufficiency
General measures
oxygen inhalation
correction of acid-base balance

58. ANTIARRHYTHMIC DRUGS CLASS. Mechanism of Action. Drug name. IA
ANTIARRHYTHMIC DRUGS CLASS Mechanism of Action Drug name IA Na+Channel blocker Disopyramide, procainamide, quinidine IB Na+Channel blocker Lidocaine, mexiletine, tocainide IC Na+Channel blocker Flecainide, propafenone II  Adrenoreceptor blocker Esmolol, metoprolol, pindolol, propranolol III K+Channel blocker Amiodarone, bretylium, sotalol IV Ca++ Channel blocker Diltiazem, verapamil Other antiarrhythmic drugs Adenosine, digoxin