Angina Pectoris

Angina pectoris is the medical term for chest pain or discomfort due to coronary heart disease. It occurs when the heart muscle doesn't get as much blood as it needs. This usually happens because one or more of the heart's arteries is narrowed or blocked, also called ischemia.

1. Gopal Khodve 1 st Year(M.S.Pharmacology & Toxicology) Anti-Anginal Drugs

2. Angina Angina is a type of chest pain that results from reduced blood flow to the heart. The pain is often triggered by physical activity or emotional stress.It   occurs  when an area of the heart muscle receives less blood oxygen than usual. Angina is not a disease but a symptom. It usually happens due to ischemia, when one or more of the coronary arteries becomes narrow or blocked. It is often a symptom of  coronary heart disease (CHD) . Alone, angina is not life threatening, but it can resemble the symptoms of a heart attack, and it is a sign of heart disease. Myocardial cells

3. Types of Angina Variant Angina Variant (Prinzmetal's) angina results from coronary vasospasm, which temporarily reduces coronary blood flow. Thereby decreasing the oxygen supply/demand ratio . Stable Angina predictable & consistent pain that occurs on exertion and relieved by rest. Stable angina  occurs when the heart is working harder than usual for instance, during exercise. It usually lasts around  5 minutes. It has a regular pattern, and a person may experience it for months or years. Unstable angina   Unstable angina  is a condition in which your heart doesn't get enough blood flow and oxygen. It may lead to a heart attack.  Due to spasm and partial obstruction of coronaries All three forms are associated with a reduction in the oxygen supply/demand ratio

4. Etiology and pathogenesis Symptoms are results of myocardial ischemia due to insufficient blood flow through atherosclerotically changed coronary vessels

5. Clinical symptoms Patient history is a˝golden standard˝ Retrosternal pain Dyspnea Nausea Arrhythmia Restlessness Pain eased after taking nitrates

6. Physical examination Hypertension Obesity Hyperglycemia Hyperlipidemia Auscultation

7. Diagnosis of angina Electrocardiogram (ECG) Stress test Echocardiogram Chest X-ray Coronary angiography Cardiac computerized tomography (CT) scan Cardiac MRI C-reactive protein ( CRP) is a marker for inflammation of vascular endothelium which caused by CAD.

8. Treatment of Angina Pectoris Drugs used in angina exploit two main strategies: Drugs that reduce myocardial oxygen demand are commonly used to prevent and treat episodes of ischemic pain associated with fixed stenotic lesions (i.e.,  chronic stable angina ).  Some of these drugs reduce oxygen demand by decreasing heart rate (decreased chronotropy) and contractility (decreased  inotropy ), while other drugs reduce  afterload  and or  preload on the heart. Afterload and preload reducing drugs act by dilating peripheral arteries and veins. Increase of oxygen delivery to the myocardium Reduction of oxygen demand

9. Anti Anginal Drugs By both ways the anti-anginal drugs work

10. Antianginal drugs Classification Nitrates – Nitroglycerine (prototype) Isosorbide dinitrate, Isosorbide mononitrate Erythrityl tetranitrate β- blockers – Propranolol M e t o p r o l o l Atenolol

11. Calcium channel blockers – V er a p ami l Diltiazem Nifedipine, Nimodipine, Amlodipine , Felodipine Potas s i u m c h a nne l o p e n e r – N i c o r a n d i l Others – Aspirin Dipyridamole T r i m e ta z idi ne

12. N i t r ates & Nitrates Nitroglycerin , which has been used since the 19th century, is commonly used in the treatment of angina because it is very fast acting (within 2 to 5 minutes) when administered sublingually. Its effects usually wear off within 30 minutes. Therefore, nitroglycerin is particularly useful for preventing or terminating an acute anginal attack. Longer-acting preparations of nitroglycerin (e.g., transdermal patches) have a longer onset of action (30 to 60 minutes), but are effective for 12 to 24 hours. Intravenous nitroglycerin is used in the hospital setting for unstable angina and acute heart failure.

13. N i t r ates MOA- Nitrates Release nitric oxide GTP c GMP guanylyl cyclase Myosin light chain-PO4 Myosin light chain Contraction A c t in Denitrated in the smooth muscle cell Relaxation Venodilatation, arteriolar dilatation & dilatation of coronary vessels ( + )

14. Side Effects Headache Dizziness Lightheadedness Nausea Flushing Burning and tingling under the tongue Low blood pressure Nitrates can slow down metabolism of  cabergoline   and ergonovine, resulting in an increase in systolic  blood pressure   and an increased likelihood of angina symptoms. Sildenafil ,   tadalafil and   vardenafil   increase the blood pressure lowering effects of nitrates and may cause excessive blood pressure reduction. Men taking nitrates should not take  sildenafil , tadalafil, or vardenafil. D rugs interact with nitrates

15. Special Condition To abort or terminate anginal attack: Nitroglycerin(sublingually) Isosorbide dinitrate(sublingually) For chronic prophylaxsis : Nitrates, β-blockers, CCBs, potassium channel openers & others drugs

16. β Blockers β-adrenoceptors Blockers Activation of β1 adrenoreceptor on the heart Cardiac Output Decrease blood Pressure Β -Blockers b locks the action of substances, such as adrenaline, on nerve cells and causes blood vessels to relax and dilate (widen). This allows blood to flow more easily and lowers blood pressure and the heart rate. Beta-blockers are used to treat high blood pressure, chest pain (angina).

17. Side effects of B Blockers Fatigue and dizziness - Beta-blockers slow down your heart rate. This can trigger symptoms associated with  low blood pressure (hypotension). Poor circulation - Heart beats more slowly when you take beta-blockers. This makes it more difficult for blood to reach your extremities. might experience coldness or tingling in your hands and feet. Gastrointestinal symptoms -  These include upset stomach, nausea, and diarrhea or constipation. Taking beta-blockers with food may help relieve stomach symptoms. Sexual dysfunction- Some people report erectile dysfunction when taking beta-blockers. This is a common side effect with medications that lower blood pressure. Weight gain - This is a side effect of some older, nonselective beta-blockers. Doctors aren’t sure why it happens, but it may be related to how beta-blockers affect your metabolism. Beta blockers are the only anti-anginal drugs that decrease mortality in patients with CAD (Post-MI) & contra-indicated in variant angina

18. calcium-channel blockers Currently approved calcium-channel blockers (CCBs) bind to L-type calcium channels located on the vascular smooth muscle, cardiac myocytes, and cardiac nodal tissue (sinoatrial and atrioventricular nodes). These channels are responsible for regulating the influx of calcium into muscle cells, which in turn stimulates smooth muscle contraction and cardiac myocyte contraction. In cardiac nodal tissue, L-type calcium channels play an important role in pacemaker currents and in phase 0 of the action potentials. Therefore, by blocking calcium entry into the cell, CCBs cause vascular smooth muscle relaxation (vasodilation), decreased myocardial force generation (negative inotropy ), decreased heart rate (negative chronotropy ), and decreased conduction velocity within the heart (negative dromotropy ), particularly at the atrioventricular node.

19. Calcium channel blockers CCB’s binds to α 1 subunit of L- type Ca 2+ channels & block their activity decrease in transmembrane calcium current smooth muscle relaxation, decreased contractility in cardiac muscle, decrease in pacemaker activity & conduction velocity Calcium channel blockers lower your blood pressure by preventing calcium from entering the cells of your heart and arteries. Calcium causes the heart and arteries to contract more strongly. By blocking calcium, calcium channel blockers allow blood vessels to relax and open

20. Side effects of CCB Constipation Dizziness Fast heartbeat (palpitations) Fatigue Flushing Headache Nausea Rash Swelling in the feet and lower legs Avoid grapefruit products while taking certain calcium channel blockers. Grapefruit juice interacts with the drug and can affect heart rate and blood pressure

21. POTASSIUM CHANNEL OPENERS Nicorandil Nicorandil is the agent that causes coronary dilation by activating myocardial ATP sensitive K+ channels. In addition it possesses Nitric Oxide releasing property ; to which tolerance does not develop

22. PARTIAL FATTY ACID OXIDATION INHIBITORS Trimetazidine is a drug which act in angina by this new strategy. Heart normally utilizes fatty acids as fuel (not very efficient fuel). Heart starts utilizing glucose (very efficient fuel) as a fuel, if oxidation of fatty acids is inhibited by these drugs F urther by inhibiting the lipid peroxidation, these drugs reduce the generation of free radicals and protect the myocardium from harmful effects of ischemia. Thus, it can provide beneficial effects in angina nonhemodynamic mechanisms

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