Clinical Pharmacology of Clinical Pharmacology of Antianginal DrugsAntianginal Drugs

Clinical Pharmacology of Clinical Pharmacology of Antiarrhythmic DrugsAntiarrhythmic 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 is a clinical syndrome characterized by episodes of chest pain. It occurs when there is a deficit in myocardial oxygen supply (myocardial ischemia) in relation to myocardial oxygen demand. It is most often caused by atherosclerotic plaque in the coronary arteries but may also be caused by coronary vasospasm. The development and progression of atherosclerotic plaque is called coronary artery disease.

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.

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

Glyceryl trinitrate

isosorbid dinitrate isosorbid-5-mononitrate

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

failure.

NITRATES1. Nitrates are first-line treatments for the symptoms of

angina but do not affect the course of the underlying disease.

2. They cause vasodilatation; this can be hazardous in some patients:

Patients who are hypovolaemic (severe hypotension).

Patients with cardiac disease such as hypertrophic cardiomyopathy or mitral stenosis.

Patients with bleeding (e.g. following head trauma or cerebral haemorrhage).

No dosage adjustment is usually required in renal or hepatic insufficiency.

Avoid these drugs during pregnancy; the effects on blood pressure can affect placental blood flow.

NitroglycerineUnique transdermal system in a form of plaster

Contraindications for nitroglycerine use

Close-angled form of glaucoma

Increasing of intracranial pressure, insult

Acute myocardium infarction (in case of presence of hypotension and

collapse)

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

Coronary artery disease. Prophylaxis against angina. Adjunct to the treatment of, and following myocardial

infarction.There are many beta-blockers and the choice can

seem daunting. The main choice is between those that are relatively selective for beta1 adrenoceptors (sometimes called cardioselective) and those that are not.

Do not stop treatment with a beta-blocker suddenly. Rebound symptoms can be severe, including precipitation of an acute coronary syndrome.

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

Treatment of arrhythmias

Beta-blockers can be useful in the treatment of (tachy)arrhythmias in the peri-infarction period.

A short-acting beta-blocker such as esmolol can be used for the treatment of acute SVT.Longer-acting drugs have a role in

prophylaxis against SVT.

Treatment of arrhythmias Beta-blockers will reduce the heart rate in patients

with AF. Always consider whether cardioversion would be

more appropriate. This can be electrical or chemical(options include flecainide, verapamil, amiodarone).

Sotalol also has class III antiarrhythmic actions, it is only used for treating arrhythmias.

It is more effective than lidocaine for the treatment of sustained ventricular tachycardia.

It will prolong the QT interval, and so carries a risk of inducing the arrhythmia torsade de pointes

Calcium channel blockers classification

Calcium channel blockers1. Phenyalkylamines(verapamil)

2. Benzthiazepines(dilthiazem)

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

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 dihydropyridine (nifedipine group) – decrease blood pressure and cause dilation of coronary vessels, cause reflective tachycardia

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

Nicorandil is not a treatment for acute angina or acute coronary syndromes.

Avoid nicorandil in patients with acute myocardial infarction or acute heart failure.

Avoid nicorandil in patients with hypotension; it can lower the blood pressure.

No dosage adjustment is usually required in renal or hepatic insufficiency.

There is no information as to the safety of nicorandil during pregnancy; avoid it unless absolutely essential.

Adjunctive Antianginal Drugs Acetylsalicylic acid

80-100 mg per day – as antiplatelet drug, decreases risk of development of acute myocardium infarction and decreases mortality of patients with IHD

Primary and secondary prevention of complications of atherosclerotic disease.

Angina. Myocardial infarction. Stroke. Peripheral vascular disease.

Adjunctive Antianginal Drugs

Antihypertensives. These drugs needed for clients with hypertension. Because beta-blockers and calcium channel blockers are used to manage hypertension as well as angina, one of these drugs may be effective for both disorders.

AmiodaroneAntiarrhythmic drug acting on atrial and ventricular tissues Amiodarone has a complex mechanism of action

that is incompletely understood, but is probably mediated through effects on cardiac potassium channels.

Amiodarone prolongs the action potential and refractory period homogeneously throughout the heart.

The principal ECG change is a prolongation of the QT interval.

Amiodarone is a class III antiarrhythmic drug in the Vaughanв-Williams classification.

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

• 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

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