ANGINA.pptx

Pharmacology

1. ANGINA

2. ANGINA: Angina pectoris = Ischemic Heart Disease. Angina pectoris is a syndrome characterized by uncomfortable sensation in the chest or neighbouring anatomic structure resulting from an imbalance between oxygen supply and demand, and is most commonly caused by the inability of atherosclerotic coronary arteries to perfuse the heart under conditions of increased myocardial oxygen consumption.

3. Classification of Angina Pectoris: Stable or typical angina: the most common form of angina. consequence of coronary atherosclerosis. presents in physical activity, emotional stress etc. predictable, reproducible (exertion). worse in cold conditions and after meals Unstable angina (crescendo/pre-infarction angina) - intermediate state between stable angina and MI -a presentation of “acute coronary syndromes” (ACS) -may appear unexpectedly, at rest -often not associated with physical activity -usually a consequence of severe coronary atherosclerosis possibly complicated by a rupture and thrombus formation Prinzmetal angina (variant/ vasospastic angina): an uncommon form of angina Consequence of coronary artery spasm, occurs at rest, patients may be younger, with lower risk, typical ECG profile

4. E T I O L O G Y Sedentary Lifestyle Genetic factor Arteriosclerosis Gender(Male) Hypertension Obesity Some other factors are associated with angina – 1. Positive family history 2. Smoking 3. Alcohol 4. Age 5. Drug abuse 6. Stress 7. Myocardium hypoxia.

5. Pathophysiology: Patent Lumen Normal Endothelial function Platelets aggregation inhibited No overt plaques Intense Vasospasm Plaque ruptured Platelet aggregation Thrombus formation Unopposed vasoconstriction Lumen narrowed by plaque Inappropriate vasoconstriction

6. During ischemia, ATP is degraded to adenosine, which, after diffusion to the extracellular space, causes anginal pain. Myocardial ischemia develops when coronary blood flow becomes inadequate to meet myocardial oxygen demand This causes myocardial cells to switch from aerobic to anaerobic metabolism, with a progressive impairment of metabolic, mechanical, and electrical functions. Studies have shown that adenosine may be the main chemical mediator of anginal pain.

7. ANGINA SYMPTOMS Nausea Epigastric pain Pain in Neck and Jaw Diaphoresis Pressure on Heart Fatigue Breathlessness Pain in Shoulder and Arms Tightness Pain Burning sensation Dizziness

8. DIAGNOSIS OF ANGINA: Electrocardiogram (ECG or EKG).  Each beat of your heart is triggered by an electrical impulse generated from special cells in your heart. An electrocardiogram records these electrical signals as they travel through your heart. Stress test.  Sometimes angina is easier to diagnose when your heart is working harder. During a stress test, you exercise by walking on a treadmill or pedaling a stationary bicycle. Your blood pressure and  ECG  readings are monitored as you exercise. Other tests also may be done at the same time as a stress test. If you're unable to exercise, you may be given drugs that cause your heart to work harder to simulate exercising followed by an imaging test. Echocardiogram.  An echocardiogram uses sound waves to produce images of the heart. Your doctor can use these images to identify angina-related problems, including heart muscle damage due to poor blood flow. Nuclear stress test.  A nuclear stress test helps measure blood flow to your heart muscle at rest and during stress.

9. Chest X-ray.  This test takes images of your heart and lungs. This is to look for other conditions that might explain your symptoms and to see if you have an enlarged heart. Blood tests.  Certain heart enzymes slowly leak out into your blood if your heart has been damaged by a heart attack. Samples of your blood can be tested for the presence of these enzymes Coronary angiography.  Coronary angiography uses X-ray imaging to examine the inside of your heart's blood vessels. It's part of a general group of procedures known as cardiac catheterization. Cardiac computerized tomography (CT) scan.  In a cardiac  CT  scan, you lie on a table inside a doughnut-shaped machine. An X-ray tube inside the machine rotates around your body and collects images of your heart and chest, which can show if any of your heart's arteries are narrowed or if your heart is enlarged. Cardiac MRI.  In a cardiac  MRI , you lie on a table inside a long, tubelike machine that produces detailed images of your heart's structure and its blood vessels.

10. Ca 2 + CHANNEL BLOCKERS

11. MOA: Entry of Ca2+ through L-type calcium channels lead to activation of myosin light chain kinase, which then leads to phosphorylation of light chain myosin, finally resulting actin-myosin cross bridging – and contraction of vascular smooth muscle – resulting in vasoconstriction. • CCB blocks calcium channels – resulting – vasodilation – predominantly arteriolar smooth muscle. Effects on vascular smooth muscle • Vasodilation of systemic arterial smooth muscle → systemic blood pressure • Vasodilation of coronary arterial smooth muscle → blood supply to cardiac muscles. Cardiac muscle • SA node → rate of nodal discharge • AV node → AV conduction • heart rate • myocardial contractility • conduction Pharmacokinetics: Nifedipine is extensively converted to inactive metabolites and approximately 80% of nifedipine and metabolites are eliminated via the kidneys The half-life of nifedipine in plasma is approximately 2 hours Since hepatic biotransformation is the predominant route for the disposition of nifedipine , the pharmacokinetics may be altered in patients with chronic liver disease Side Effects: Dizziness Flushing Headache Transient hypotension Peripheral edema Major drug interactions: Cimetidine (80% increase in nifedipine plasma levels)

12. Pharmacokinetics: Oral administration. Plasma elimination half-life is approximately 3.0 to 4.5 hours. Side Effects: Hypotension, AV conduction block, Bradycardia , Constipation Major drug interactions: Diltiazem can produce additive effects with other antihypertensive drugs & with cardiac effects of beta blockers Contraindications: Hypotension, AV block (2nd- or 3rd-degree) or sick sinus syndrome, except in the presence of a functioning ventricular pacemaker, Acute MI, Pulmonary congestion, Lactation Indications: 1. Vasospastic & Classic Angina (prophylactic treatment) 2. Hypertension 3. Control of ventricular rate in atrial fibrillation of flutter Diltiazem

13. Thrombin ADP Thromboxane A2 Glycoprotein IIb / IIIa Activation Platelet Aggregation Thrombus Formation P2Y12 Receptor Antagonist Clopidogrel . Glycoprotein IIb / IIIa Inhibitor - Abciximab . Aspirin ANTIPLATELET DRUGS

14. Aspirin: AE- Irritation in stomach and intestine, Feel like thrown up, Heartburn, Ringing of ears, Haemorrhage in skull, Decrease blood platelet, Anaemia, Decrease WBC. CI- GI bleeding, Coagulation disorder, G6PD deficiency, Thrombocytopenia, Hypersensitivity reaction, Renal dysfunction, Asthma, Reye’s syndrome. DI- Alcohol, Anti Coagulant, Anti diabetic produce hypoglycaemia, Ibuprofen USE- Treatment of exertional and unstable angina, Ischemic stroke, Preventing and treating Heart attack, as an analgesic. Clopidogrel : AE- Easy bleeding, Abdominal pain, Diarrhoea, Fainting, Fever, Headache, Serious bleeding in gut, eye, stomach or brain may occour. CI- Allergic disease, Peptic ulcer, Bleeding from eye or brain, Recent surgery, Serious trauma, Liver disease, Haemophilia, Pregnancy . DI- Anti depressant, PPI’s, Ibuprofen, Naproxen or aspirin. USE- Unstable angina, Preventing and treating Heart attack, Peripheral Vascular disease. Abciximab : AE- Nausea, Vomiting, Minor bleeding, Irritation at the injection site, Serious bleeding is the main serious side effect. CI- Bleeding within last 6 weeks, Stroke in the last 2 years, Brain tumour or blood vessel problems in the brain, Thrombocytopenia, Pregnancy, Liver disease, Inflammatory bowel disease. DI- Dextran, Anti coagulant, NSAIDs(Ibuprofen, naproxen), Anti platelet drugs( dipyridamole , ticlopidine ). USE- It’s a type of blood thinner, Used in balloon angioplasty, coronary stent placement, preccutaneous coronary intervention,

15. Glycolysis and Beta oxidation of Fatty acid Acetyl - CoA HMG - CoA HMG – CoA Reductase Inhibitor – Atrovastatin. Mevalonate Cholesterol VLDL and Bile acid LIPID LOWERING DRUGS: HMG COA REDUCTASE INHIBITORS Statins: AE- Headache, Nausea, Vomiting, Constipation, Diarrhoea, Rash, Muscle pain, Liver failure and rhabdomyolysis , Memory loss, Amnesia. CI- Liver disease, Pregnancy, DI- Protease inhibitor(Ritonavir), Antibiotics(Erythromycin, Clarithromycin), Calcium channel blockers, Grape juice. USE- Treating Atherosclerosis that causes chest pain, Strokes, Heart attacks. MOA:

16. I F (SODIUM LEAK CHANNEL) BLOCKER- Ivabradine

17. MOA: It selectively inhibits the funny current ( I f ) in sinoatrial nodal tissue, resulting in a decrease in the rate of diastolic depolarization and, consequently, the heart rate, a mechanism that is distinct from those of other negative chronotropic agents. Thus, it has been evaluated and is used in select patients with systolic heart failure and chronic stable angina without clinically significant adverse effects AE- Blurred vision, Slow down the Heart rate, Palpitation, Change Heart rhythm, Vertigo, Shortness of Breath, Muscle cramp, Increased blood Uric acid and Creatinine level. CI- Caution in patients with symptoms of tiredness or shortness of breath, chronic retinal (eye) disease, chronic heart failure, moderate liver disease, severe renal disease, mild to moderate low blood pressure. Pregnancy and Brest feeding women. DI- Ketoconazole, Itraconazole , Clarithromycin, Telithromycin , Erythromycin, Nelfinavir , Ritonavir, Nefazodone . USE- Mild to severe chronic heart failure. Stable angina, Chronic Heart failure.

18. Ischemia Increased Late I Na Na + Overload Ca ++ Overload Diastolic Relaxation Failure (Increased diastolic tension) Extra vascular Compression Renolazine inhibits the late inward Na + current. LATE SODIUM CHANNEL BLOCKER Renolazine : AE- Dizziness, Nausea, Constipation, Headache, Swelling in hands, ankles, or feet, Slow, fast, or irregular heartbeats, Tremors, Blood in the urine and Shortness of breath. DI- Clarithromycin, Ritonavir, Fluconazole, Cyclosporine, Rifampin , Phenytoin, Carbamazepine, Simvastatin. CI- Hepatic impairment, Pregnancy- C, USE- Treatment of Chronic angina and also potentially used in other cardiovascular conditions.

19. Beta Blockers

20. Sites of action of beta blockers in the treatment of angina. Beta blockers exert the majority of their effects on heart tissue by antagonizing beta-1 receptors (the subtype most heavily expressed in heart tissue). Beta blockers will block the effects of circulating and neuronal catecholamines , which have the greatest effect on heart rate and ventricular contractility. Reductions in both heart rate and contractility will reduce the work of the heart, resulting in a decrease in myocardial oxygen demand, which is “ anti-ischemic ”. In addition, beta blockers also produce a reduction in total peripheral resistance, with an associated decrease in blood pressure & afterload. These effects also contribute to decreased work of the heart & myocardial oxygen demand.

21. Indications: Angina of effort (classic angina) but NOT vasospastic angina Contraindications: Asthma & other bronchospastic conditions Severe bradycardia AV block Severe unstable LV failure Beta Bockers are Contraindicated in Vasospastic Angina . Side Effects: increase in end-diastolic volume & increased ejection time , which ends up increasing oxygen requirements, which partially offsets the beneficial effects to reduce oxygen demands. This can be balanced by the concomitant use of nitrates Others - fatigue, impaired exercise tolerance, insomnia, unpleasant dreams, erectile dysfunction.

22. Side Effects  are flushing, palpitation, weakness,   headache, dizziness, nausea and vomiting. Large painful aphthous ulcers in the mouth, which heal on stopping nicorandil have been reported.

23. Mechanism of Action of DP. DP increases local concentrations of adenosine, which stimulates adenylyl cyclase in platelets leading to increased intracellular cAMP levels. In addition, by inhibiting PDE, DP prevents the breakdown of cAMP . Increased intracellular levels of cAMP keep platelets from being activated. Furthermore, by inhibiting PDE in the vascular wall, DP increases PGI2 production and vascular smooth muscle cGMP levels, leading to vasodilation Related to Antianginal Drugs

24. Summary of Maintenance Therapy for Angina Acute Emergency Treatment of Angina Oxygen Nitroglycerin Aspirin Morphine- reduces central anxiety and relieves pain Chronic Stable Angina of Effort Long-acting Nitrates Calcium Channel Blockers Beta Blockers Vasospastic (Variant) Angina Nitrates Calcium Channel Blockers Unstable Angina Management Antiplatelet agents, Nitroglycerin , Beta-blocker, ACE-inhibitor, Statin or other lipid-lowering agent if applicable, In high-risk patients: catheter-based myocardial revascularization.

25. https://quizlet.com/217572390/pharmacologic-management-of-angina-pectoris-flash-cards/ https://www.slideshare.net/ckoppala/pathophysiology-of-angina-and-atheroslerosis?from_action=save https://pt.slideshare.net/aishuanju/angina-pectoris-45012725/5 https://www.mayoclinic.org/diseases-conditions/angina/diagnosis-treatment/drc-20369378 Jacob S.  Koruth ,  Anuradha   Lala , Sean  Pinney ,  Vivek Y. Reddy,  Srinivas R.  Dukkipati . The Clinical Use of Ivabradine . J Am Coll Cardiol .  2017 Oct, 70 (14) 1777-1784. https://www.researchgate.net/publication/40692425_New_Investigational_Drugs_for_the_Management_of_Acute_Heart_Failure_Syndromes/figures?lo=1 http://www.pharmacy180.com/article/antianginal-drugs-1187/ https://www.slideshare.net/hhnoel/calcium-channel-blockers-62954171 rxlist.com [http://www.rxlist.com/procardia-drug.htm] http://tmedweb.tulane.edu/pharmwiki/lib/exe/detail.php/bb_moa.png?id=treatment_of_angina https://prevent-hypertency.blogspot.com/2016/08/hypertension-beta-blockers.html https://prevent-hypertency.blogspot.com/2016/08/hypertension-beta-blockers.html

26. Katzung BG (2012) [http://libproxy.tulane.edu:2048/login?url=http://www.accessmedicine.com/content.aspx?aID=55821947]: Vasodilators & the treatment of angina pectoris (Chapter 12). In: Basic and Clinical Pharmacology. 12e. Katzung BG, Masters SB, Trevor AJ (Editors). McGraw-Hill / Lange https://slideplayer.com/slide/8035551/ https://www.semanticscholar.org/paper/Translational-therapeutics-of-dipyridamole.-Kim-Liao/c62473f1aed16112d0420e1a76a4e62ffafb8c74/figure/0 http://tmedweb.tulane.edu/pharmwiki/doku.php/all_cv_drugs