Clinical Pharmacology of Clinical Pharmacology of Antianginal DrugsAntianginal Drugs

ISCHEMIC HEART DISEASEISCHEMIC HEART DISEASE

There are 35 risk factors for development of IHD–

The most important risk factors for coronary artery disease

• Smoking• Hypertension• Hyperlipidaemia• Diabetes mellitus

95 % of patients with IHD are observed to have aterosclerotic changes in coronary arteries

Angina pectoris

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

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.

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.

ANTIANGINAL (CORONARY ACTIVE) DRUGS

І. Nitrates and sidnonims

ІІ. Beta-adrenoblockers

ІІІ. Calcium channel blockers

ІУ. Activators of potassium channels

NITRATES

NITRATES Glyceryl trinitrate

isosorbid dinitrate isosorbid-5-mononitrate

INDICATIONS Treatment and prevention of angina. Treatment of acute left ventricular failure.

Nitrates mechanism of action

NITRATES

NitroglycerineUnique transdermal system in a form of plaster

Contraindications for nitroglycerine use

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

SYDNONIMINSSYDNONIMINS

MolsidomineMolsidomine – – corvatoncorvaton - - sydnopharmsydnopharm

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

Beta-adrenoceptor antagonists

NebivololNebivololbeta-blocker that also causes vasodilation by stimulating the beta-blocker that also causes vasodilation by stimulating the

release of nitric oxiderelease of nitric oxide

Calcium channel blockers classification

Calcium channel blockers1. Phenyalkylamines(verapamil)

2. Benzthiazepines(dilthiazem)

3. Derivatives of Dihydropyridine (nifedipine, amlodipine, nimodipine)

Indications

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.

Hypertension

Verapamil Dylthiazem Nifedipin Felodipin Amlodipin

Stenocardia Dylthiazem

Nifedipin Amlodipin Verapamil

Supraventricular tachy-arrhythmia

Verapamil Dylthiazem

Possible combination with β-blockers

Dylthiazem Nifedipin Amlodipin

-recommended drug --should be used carefully

Usage of calcium channel antagonistsUsage of calcium channel antagonists

Disease Drugs

Felodipin

Nifedipin (Са2+ ions antagonist of dyhydropyrydine series)

NicorandilPotassium channel activator

Adjunctive Antianginal Drugs Acetylsalicylic acid

Adjunctive Antianginal Drugs Antihypertensives .

AmiodaroneAntiarrhythmic drug acting on atrial and ventricular tissues

Amiodarone

Treatment by mouth 200 mg 3 times daily for 1 week reduced to 200 mg twice daily

for a further week. Maintenance dose, usually 200 mg daily or the minimum

required to control the arrhythmia. Treatment by intravenous infusion

Via a central line, 5 mg/kg over 20-120 minutes with ECG monitoring; maximum 1.2 g in 24 hours.

Emergency treatment during cardiopulmonary resuscitation VF or pulseless VT, 300 mg by intravenous injection over at least

3 minutes (pre-filled syringe).

Common types of cholesterol-lowering drugs include:

• statins • resins • nicotinic acid (niacin) • gemfibrozil • clofibrate

•  Reason for Medication• Used to lower LDL ("bad") cholesterol, raise

HDL ("good") cholesterol and lower triglyceride levels

Cholesterol-lowering drugs

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