clinical pharmacology of antianginal drugs clinical pharmacology of antiarrhythmic drugs
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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