Anti-anginal agents

PROF DR SHAH MURAD HOD, Pharmacology LM&DC, Lahore shahhmurad65@yahoo.com

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Angina
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CARDIAC ISCHEMIA
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MYOCARDIAL INFARACTION
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HEART BLOCK
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HEART FAILURE
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HEART ATTACK
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General tight, band like, crushing pain felt across the front of the chest.
It is generally brought on by exertion and relieved within 5 minutes of rest.

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Angina pain occurs when the heart muscle is starved for oxygen generally caused by narrowing of the coronary arteries.

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The pain has also been known to start as chest pain and radiate towards the jaw or down into the left or both arms.

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If the chest pain lasts longer than 20 minutes it is most likely due to myocardial infarction.

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In order to understand angina, it is often helpful to understand the heart and the coronary arteries.

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Like any muscle, the heart needs a constant supply of oxygen and nutrients, which are carried to it by the blood in the coronary arteries.
Similar to other muscles, the harder the heart is working, the more oxygen and nutrients it needs.
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However, the coronary arteries can become narrowed or clogged, which can decrease the amount of blood that goes to the heart muscle.
When the coronary arteries cannot supply enough oxygen-rich blood to the heart, angina symptoms can occur.
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Types of Angina
Decubitus Angina Chest pain when laying flat, generally appears with myocardial ischaemia

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Nocturnal Angina Chest pains which awaken the individual while sleeping

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Acute Coronary Insufficiency Angina Severe chest pain suggesting myocardial infarction but without any investigatory confirmation of infarction.

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Unstable Angina Chest pain that has become significantly worse within the previous 4 weeks (approximately). It may have started as stable angina but progressed to this unstable state.

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Crescendo Angina Chest pain which slowly increases in frequency and severity over a very short period of time.
It is usually a pre-infarctive condition.

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Aortic Dissection
Severe and tearing pain located in the chest or in the abdomen depending on where in the aorta the tearing is situated.
Dissections occurs when there is a tear in the innermost layer of the arterial wall.

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Myocardial Infarction
Sudden Chest pain which is severe in nature and often described as a heavy and tight pain People have described the pain as if an elephant was standing on my chest. profuse sweating. shortness of breath light headed ness collapse. inadequate oxygenation of the heart muscle causes heart cell death or necrosis.
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Pericarditis
Sudden sharp chest pain mimicking the same symptoms of a myocardial infarction or angina. The chest pain my be affected by breathing and may persist for several days and may recur. Generally, pericarditis is presumed to have a viral cause and therefore show flu like symptoms prior to the attack.
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Pleuritic Chest Pain

A sharp, stabbing, well-localized chest pain which is aggravated on deep inspiration. The pain is caused by an irritation of the outer pleura which becomes inflamed
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Superficial Chest pain

This type of chest pain has many causes and many types of pain. It can be sharp and localized (along a nerve ganglia) or dull and continuous as in intrapulmonary malignancies.

There are many types of pains and many diseases which may cause this type of pain.
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Tracheal Pain
Generally tracheal chest pain is felt behind the sternum. And pain may feel similar to cardiac pain.
Tracheal pain is distinguished from cardiac pain in that it is not aggravated by exercise.
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Coronary disease (or coronary heart disease) refers to the failure of coronary circulation to supply adequate circulation to cardiac muscle and surrounding tissue.

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It is sometimes equated with atherosclerotic coronary artery disease, but coronary disease can be due to other causes, such as coronary vasospasm. It is possible for the stenosis to be caused by the spasm

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Common Types of Angina

Stable
Unstable Variant angina (also known as Prinzmetal's angina).

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Stable angina
is the most common angina type. It can also be referred to as exertional angina. With exertion, like walking up a hill or climbing stairs, the heart works harder and needs more oxygen. If it can't get enough oxygen, a person develops symptoms of angina. With rest, the angina attack symptoms generally improve. 48

Unstable angina
is the second most common angina type. This is a dangerous condition that requires emergency treatment. It occurs more often in older adults and is a sign that a heart attack could occur soon. In fact, 10 to 20 percent of people with unstable angina symptoms will likely have a heart attack.
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VaRiAnT ANGINA
Variant angina is a rare angina type caused by a spasm in a coronary artery. This spasm causes the walls of the artery to tighten. This narrows the artery, causing the blood flow to the heart to slow or stop.

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Symptoms of Angina
Rest and medicine can often relieve symptoms of angina.

The most common signs and symptoms include chest pain, shortness of breath, and an indigestion-type sensation.

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An episode of angina is not a heart attack, but the symptoms of the two conditions can be similar. If the pain or discomfort continues to worsen or lasts longer than 20 minutes, seek immediate medical attention.

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Generalized anginal symptoms

Indigestion or heartburn-type sensation Nausea Fatigue Shortness of breath Sweating Lightheadedness Weakness.
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What Is Angina? Angina Types Angina Risk Factors Causes of Angina Symptoms of Angina Angina Symptoms in Women Angina Diagnosis Treatment for Angina Living With Angina Angina Prevention Heartburn Vs. Angina
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Angina Symptoms Versus a Heart Attack

An episode of angina is not a heart attack, but it does mean that patient have a greater chance of having a heart attack.

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Angina pain is an indication that some of the heart muscle is temporarily not getting enough blood

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A heart attack, occurs when the blood flow to a part of the heart is suddenly and permanently cut off, usually by a blood clot. This can lead to serious heart damage.

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Certain symptoms indicate that patient is experiencing heart attack:

Pain or discomfort that is very bad, gets worse, and lasts longer than 20 minutes Pain or discomfort along with weakness, feeling sick to his stomach, sweating, or fainting Pain or discomfort that does not go away when he takes angina medicine Pain or discomfort that is worse than patient have ever had before.

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Risk Factors for Angina

Coronary artery disease, also known as coronary heart disease aortic stenosis or hypertrophic cardiomyopathy Previous heart attack Age (stable angina occurs more often in older adults).
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Because heart disease is a risk factor for stable angina, factors that increase a person's chances of developing heart disease are also considered risk factors for angina.

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Heart disease risk factors include:

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Age Family history of early heart disease High cholesterol levels, also known as hypercholesterolemia High blood pressure Cigarette smoking Diabetes Lack of physical activity Being overweight or obese
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Treatment
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Treatment options for heart attack, and acute coronary syndrome, include:

Oxygen therapy Relieving pain and discomfort using nitroglycerin or morphine Controlling any arrhythmias Blocking further clotting, using aspirin, as well as possibly anticoagulant drugs such as heparin Opening up the artery that is blocked as soon as possible, by using medicines that open up the clot or by performing angioplasty Giving the patient beta blockers, calcium channel blockers, or angiotensin converting enzyme inhibitor drugs to help the heart muscle and arteries work better
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Oxygen. Oxygen is almost

always administered right away, usually through a tube that enters through the nose.

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Aspirin. The patient is given aspirin if

one was not taken at home.

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Medications for Relieving Symptoms

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Nitroglycerin
Most patients will receive nitroglycerin during and after a heart attack, usually under the tongue.

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Nitroglycerin decreases blood pressure and opens the blood vessels around the heart, increasing blood flow.

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Nitroglycerin may be given intravenously in certain cases (recurrent angina, heart failure, or high blood pressure).

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Heroin
Heroin not only relieves pain and reduces anxiety but also opens blood vessels, aiding the circulation of blood and oxygen to the heart. Morphine (Heroin) can decrease blood pressure and slow down the heart.

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Opening the Arteries: Emergency Angioplasty & Thrombolytic Drugs

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With a heart attack, clots form in the coronary arteries that supply oxygen to the heart muscle.
Opening a clotted artery as quickly as possible is the best approach to improving survival and limiting the amount of heart muscle that is permanently damaged.
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The standard medical and surgical solutions for opening arteries are:

(1) Angioplasty, also called

percutaneous coronary intervention (PCI), is the preferred emergency procedure for opening the arteries.

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Angioplasty should be performed promptly, preferably within 90 minutes of arriving at the hospital and no later than 12 hours after a fullthickness (STEMI) heart attack.

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Thrombolytics
Thrombolytics, known as blood-clot-busting drugs,
are the standard medications used to open the arteries.

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A thrombolytic drug needs to be given within 3 hours after the onset of symptoms.

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Factors considered in choosing a strategy include:

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How likely it is the patient is having a heart attack Patient's age (preferably less than age 75 years) Presence of risk factors for bleeding or history of recent bleeding Elapsed time since symptoms began (preferably fewer than 12 hours) Whether a patient needs to be transported in order to have angioplasty Blood pressure level History of stroke or cancer Which and how many coronary arteries are blocked
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Treatment for Patients in Shock or with Heart Failure

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Severely ill patients, particularly those with heart failure or who are in cardiogenic shock (a dangerous condition that includes a drop in blood pressure and other abnormalities), will be monitored closely and stabilized.
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Oxygen is administered, and fluids are given or replaced when it is appropriate to either increase or reduce blood pressure.

Such patients may be given dopamine, dobutamine, or both.

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Heart failure
Intravenous furosemide may be administered.

Patients may also be given nitrates, and ACE inhibitors, unless they have a severe drop in blood pressure or other conditions that preclude them.

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Clot-busting drugs or angioplasty may be appropriate and lifesaving in many of these patients

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Cardiogenic Shock
A procedure called intra-aortic balloon counterpulsation (IABP) can help patients with cardiogenic shock when used in combination with thrombolytic therapy. IABP involves inserting a catheter containing a balloon, which is inflated and deflated within the artery to boost blood pressure.
Left ventricular assist devices and early angioplasty might also be considered.
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Diagnosis of MI
Echocardiography Exercise stress test Nuclear stress test In-Depth Diagnosis

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Managing Arrhythmias after MI

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An arrhythmia is a deviation from the heart's normal beating pattern caused when the heart muscle is deprived of oxygen and is a dangerous side effect of a heart attack.

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A very fast or slow rhythmic heart rate often occurs in patients who have had a heart attack, and is not usually a dangerous sign.

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Premature beats or very fast arrhythmias called tachycardia, however, may be predictors of ventricular fibrillation. This is a lethal rhythm abnormality, in which the ventricles of the heart beat so rapidly that they do not actually contract but quiver ineffectually. The pumping action necessary to keep blood circulating is lost.

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Preventing Ventricular Fibrillation

People who develop ventricular fibrillation do not always experience warning arrhythmias, and to date, there are no effective drugs for preventing arrhythmias during a heart attack.

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Potassium and magnesium levels should be monitored and maintained.

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Intravenous beta blockers followed by oral administration of the drugs may help prevent arrhythmias in certain patients

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Treating Ventricular Fibrillation.

Defibrillators >>>>>>>> Patients who develop ventricular arrhythmias are given electrical shocks with defibrillators to restore normal rhythms.

Implantable cardioverterdefibrillators (ICDs) may prevent further arrhythmias in heart attack survivors of these events who are at risk for further arrhythmias.

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Antiarrhythmic Drugs
Antiarrhythmic drugs include lidocaine, procainamide, or amiodarone.

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Amiodarone or another antiarrhythmic drug may be used afterward to prevent future events

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People with an arrhythmia called atrial fibrillation have a higher risk for stroke after a heart attack and should be treated with anticoagulants such as warfarin (Coumadin).

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Other rhythm disturbances called bradyarrhythmias (very slow rhythm disturbances) frequently develop in association with a heart attack and may be treated with atropine or pacemakers.

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Aspirin and Other Anti-Clotting Drugs

Anti-clotting drugs that inhibit or break up blood clots are used at every stage of heart disease.

They are generally classified as either antiplatelets or anticoagulants.

Appropriate anticlotting medications are started immediately in all patients.
Such drugs are sometimes used along with thrombolytics, and also as on-going maintenance to prevent a heart attack.

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All anti-clotting therapies carry the risk of bleeding, which can lead to dangerous situations, including stroke.

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Anti-Platelet Drugs
These drugs inhibit blood platelets from sticking together, and therefore help to prevent clots.
Platelets are very small disc-shaped blood cells that are important for bloodclotting.
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Aspirin
Aspirin is an antiplatelet drug. An aspirin should be taken immediately after a heart attack begins. It can be either swallowed or chewed, but chewing provides more rapid benefit. If the patient has not taken an aspirin at home, it will be given at the hospital. It is then continued daily.
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Aspirin: miraculous drug in medical sciences

Using aspirin for heart attack patients has been shown to reduce mortality. It is the most common anticlotting drug, and most people with heart disease are advised to take it daily in low dose on an ongoing basis.

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Clopidogrel (Plavix), a thienopyridine, is another type of anti-platelet drug. Clopidogrel is started either immediately or right after percutaneous intervention is performed for patients with heart attacks.

It is also begun after thrombolytic therapy.

Patients admitted for unstable angina should receive clopidogrel if they are unable to take aspirin.

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Clopidogrel should also be given to patients with unstable angina for whom an invasive procedure is planned. Even for conservatively treated patients, Clopidogrel should be started and continued for up to 1 year. Some patients may need to take clopidogrel on an ongoing basis.
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Glycoprotein IIb/IIIa Inhibitors

These powerful blood-thinning drugs include abciximab , eptifibatide , tirofiban, and lamifiban. They are administered intravenously in the hospital

They are proving to be helpful for ACS patients with NSTEMI (non ST-segment elevation myocardial infarction), particularly when invasive procedure is planned or patients are still unstable after receiving aspirin and clopidogrel.
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Anticoagulant Drugs
Anticoagulants thin blood.

Heparin is usually begun during or at the end of treatment with thrombolytic drugs and continued for at least 2 days if not the whole time in the hospital.
Fondaparinux (Arixtra) is a newer blood thinner that may be used

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Warfarin
Direct thrombin inhibitors, such as argatroban (Novastan), danaparoid (Orgaran), lepirudin (Refludan), and bivalirudin (Angiomax).
A clear benefit for these drugs over heparin has not been shown but.. Still is being used !!!!!! They also carry an increased risk for bleeding.
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Beta blockers

Beta blockers reduce the oxygen demand of the heart by slowing the heart rate and lowering pressure in the arteries. They are effective for reducing deaths from heart disease. Beta blockers are often given to patients early in their hospitalization, sometimes intravenously.
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Beta blockers
Patients with heart failure or who are at risk of going into cardiogenic shock should not receive intravenous Beta blockers.
Long-term oral beta blocker therapy for patients with symptomatic coronary artery disease, particularly after heart attacks, is recommended in most patients.
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Beta blockers
Administration During a Heart Attack
The beta blocker metoprolol may be given through an IV within the first few hours of a heart attack to reduce the destruction of heart tissue.

Prevention After a Heart Attack

Beta blockers taken by mouth are also used on a long-term basis (as maintenance therapy) after a first heart attack to help prevent future heart attacks.
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Side Effects
Beta blocker side effects include fatigue, lethargy, vivid dreams and nightmares, depression, memory loss, and dizziness. They can lower HDL (good) cholesterol. Beta blockers are categorized as non-selective or selective >>>>>>>> Non-selective beta blockers, such as carvedilol and propranolol, can narrow bronchial airways >>>>>>> Patients with asthma, emphysema, or chronic bronchitis, should not take these beta blockers.

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Patients should not abruptly stop taking these drugs. The sudden withdrawal of Beta blockers can rapidly increase heart rate and blood pressure. The doctor may want the patient to slowly decrease the dose before stopping completely.

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Statins and Other Cholesterol and Lipid-Lowering Drugs

After being admitted to the hospital for acute coronary syndrome or a heart attack, patients should not be discharged without statins or other cholesterol medicine unless their LDL ("bad") cholesterol is below 100 mg/dL.
Some doctors recommend that LDL should be below 70 mg/dL.

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Angiotensin Converting Enzyme Inhibitors

Angiotensin converting enzyme (ACE) inhibitors are important drugs for treating patients who have had a heart attack, particularly for patients at risk for heart failure. ACE inhibitors should be given on the first day to all patients with a heart attack, unless there are medical reasons for not taking them. Patients admitted for unstable angina or acute coronary syndrome should receive ACE inhibitors if they have symptoms of heart failure or evidence of reduced left ventricular fraction echocardiogram.

These drugs are also commonly used to treat high blood pressure (hypertension) and are recommended as first-line treatment for people with diabetes and kidney damage.

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ACE Inhibitors
ACE inhibitors include captopril (Capoten), ramipril (Altace), enalapril (Vasotec), quinapril (Accupril), benazepril (Lotensin), perindopril (Aceon), and lisinopril (Prinivil, Zestril). Side Effects: Side effects of ACE inhibitors are uncommon but may include an irritating cough, excessive drops in blood pressure, and allergic reactions.

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Calcium Channel Blockers

Calcium channel blockers may provide relief in patients with unstable angina whose symptoms do not respond to nitrates and beta blockers, or for patients who are unable to take beta blockers.

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calcium channel blockers

either Class I agents (e.g., verapamil) Class II agents (e.g., amlodipine, nifedipine), or the Class III agent diltiazem.

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Nitrates cause vasodilation of the venous capacitance vessels by simulating the endothelium-derived relaxing factor (EDRF).
Used to relieve both exertional and vasospastic angina by allowing venous pooling, reducing the pressure in the ventricles and so reducing wall tension and oxygen requirements in the heart.
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Short-acting nitrates are used to abort angina attacks that have occurred, while longer-acting nitrates are used in the prophylactic management of the condition.

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Beta blockers are used in the prophylaxis of exertional angina by reducing the work the heart is allowed to perform below the level that would provoke an angina attack.
They cannot be used in vasospastic angina and can precipitate heart failure.

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Calcium channel blockers

Calcium ion (Ca++) antagonists (Calcium channel blockers) are used in the treatment of both exertional and vasospastic angina. In vitro, they dilate the coronary and peripheral arteries and have negative inotropic and chronotropic effects - decreasing afterload, improving myocardial efficiency, reducing heart rate and improving coronary blood flow.

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The vasodilation and hypotension trigger the baroreceptor reflex. Therefore the net effect is the interplay of direct and reflex actions. Class I agents have the most potent negative inotropic effect and may cause heart failure Class II agents do not depress conduction or contractility Class III agent has negligible inotropic effect and causes almost no reflex tachycardia.
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Exams and Tests

A doctor or nurse will perform a physical exam and listen to your chest using a stethoscope. The doctor may hear abnormal sounds in your lungs (called crackles), a heart murmur, or other abnormal sounds. You may have a rapid pulse. Your blood pressure may be normal, high, or low. A troponin blood test can show if you have heart tissue damage. This test can confirm that you are having a heart attack. Coronary angiography is often done right away or when you are more stable. You may also have tests such as anelectrocardiogram (ECG). This test uses a special dye and x-rays to see how blood flows through your heart. It can help your doctor decide which treatments you need next.

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Other tests while patient is admitted in the hospital

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New Slant on Thrombolytics

Thrombolytic, also called clot-busting or fibrinolytic, drugs are recommended as alternatives to angioplasty.

These drugs dissolve the clot, or thrombus, responsible for causing artery blockage and heart-muscle tissue death. Generally speaking, thrombolysis is considered a good option for patients with full-thickness (STEMI) heart attacks when symptoms have been present for fewer than 3 hours. Ideally, these drugs should be given within 30 minutes of arriving at the hospital if angioplasty is not a viable option. Other situations where it may be used include when: Prolonged transport will be required Too long of a time will pass before a catheterization lab is available PCI procedure is not successful or anatomically too difficult

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Thrombolytics should be avoided or used with great caution in the following patients after heart attack: Patients older than 75 years When symptoms have continued beyond 12 hours Pregnant women People who have experienced recent trauma (especially head injury) or invasive surgery People with active peptic ulcers Patients who have been given prolonged CPR Current users of anticoagulants Patients who have experienced any recent major bleeding

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Patients with low ST segments Patients with a history of stroke Patients with uncontrolled high blood pressure, especially when systolic is higher than 180 mm Hg

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Specific Thrombolytics. The standard thrombolytic

drugs are recombinant tissue plasminogen activators or rt-PAs. They include alteplase (Activase) and reteplase (Retavase) as well as a newer drug tenecteplase (TNKase).

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Thrombolytic Administration. The sooner that thrombolytic drugs are

given after a heart attack, the better. The benefits of thrombolytics are highest within the first 3 hours. They can still help if given within 12 hours of a heart attack. Complications. Hemorrhagic stroke, usually occurring during the first day, is the most serious complication of thrombolytic therapy, but fortunately it is rare.

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