Myocardial Infarction. Pharmacotherapeutics pptx

Myocardial Infarction: Definition, Introduction, Etiology, Epidemiology, Clinical Presentation, Diagnosis and Prognosis, Management—pharmacological and non-pharmacological, and Counseling.

1. Myocardial infarction (MI) Mr. Ravinandan A P Asst. Prof. Department of Pharmacy Practice Sree Siddaganga College of Pharmacy Tumkur, Karnataka

2. Introduction Myocardial infarction (MI) ( ie , heart attack) is the irreversible death (necrosis) of heart muscle secondary to prolonged lack of oxygen supply (ischemia). MI usually results from an imbalance in oxygen supply and demand, which is most often caused by plaque rupture with thrombus formation in an epicardial coronary artery, resulting in an acute reduction of blood supply to a portion of the myocardium.

3. MI, commonly known as a heart attack D efined pathologically as the irreversible death of myocardial cells caused by ischemia. Clinically, MI is a syndrome that can be recognized by a set of symptoms, chest pain being the hallmark of these symptoms in most cases, supported by biochemical laboratory changes, electrocardiographic (ECG) changes, or findings on imaging modalities able to detect myocardial injury and necrosis

4. Aetiology Atherosclerosis is the disease primarily responsible for most acute coronary syndrome (ACS) cases. Approximately 90% of myocardial infarctions (MIs) result from an acute thrombus that obstructs an atherosclerotic coronary artery. Nonmodifiable risk factors for atherosclerosis include the following: Age Sex Family history of premature coronary heart disease Male-pattern baldness Mainly divided in to 2 reasons: Atherosclerotic causes- 75% Non-Atherosclerotic causes- Like Coronary Vasospasm, arteritis, thrombotic disorders, trauma, coronary stenosis

5. Modifiable risk factors for atherosclerosis include the following   Smoking or other tobacco use Hypercholesterolemia and hypertriglyceridemia, including inherited lipoprotein disorders Dyslipidaemia Diabetes mellitus Hypertension Obesity (abdominal obesity) Psychosocial stress Sedentary lifestyle and/or lack of exercise Reduced consumption of fruits and vegetables Poor oral hygiene Elevated homocysteine levels Presence of peripheral vascular disease

6. Epidemiology The death rate related to acute MI is approximately three times higher in men than in women . It is more frequent in black patients compared to white patients, an excess that disappears by age 75 years. The incidence of CAD and related mortality is expected to rise dramatically in other developing countries including India, Latin America, the Middle East and Sub-Saharan Africa, with an estimated 80% increase, from approximately 9 million in 1990 to a projected 20 million by 2020.

7. It is believed that these international trends in the incidence of CAD and subsequent acute MI are largely related to consequences of social and economic changes in these countries, resulting in better healthcare access and increases in life expectancy, in addition to adoption of westernized diets, reduction in physical activity, and higher rates of smoking. 20 % of patients shows no pain, hence it is called as Silent MI especially occurs with diabetes and elderly.

8. Symptoms Severe chest pain ( similar to exertional angina) Sweating Dyspnea Chest pain radiates to jaw, shoulders, arms, and back Epigastric discomfort with or without nausea and vomiting Frothy sputum Hemoptysis Weakness Dizziness Anxiety Indigestion Arrythmia

9. Diagnosis of MI Laboratory tests used in the diagnosis of MI include the following: Cardiac biomarkers/enzymes: The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines recommend that cardiac biomarkers should be measured at presentation in patients with suspected MI, and that the only biomarker that is recommended to be used for the diagnosis of acute MI at this time is cardiac troponin due to its superior sensitivity and accuracy. Troponin levels: Troponin is a contractile protein that normally is not found in serum; it is released only when myocardial necrosis occurs Complete blood cell count Comprehensive metabolic panel Lipid profile

10. Electrocardiography The ECG is the most important tool in the initial evaluation and triage of patients in whom an acute coronary syndrome (ACS), such as MI, is suspected. It is confirmatory of the diagnosis in approximately 80% of cases. Cardiac imaging For individuals with highly probable or confirmed acute MI, coronary angiography can be used to definitively diagnose or rule out coronary artery disease.

11. Prognosis Acute myocardial infarction (MI) is associated with a 30% mortality rate; about 50% of the deaths occur prior to arrival at the hospital. An additional 5-10% of survivors die within the first year after their myocardial infarction. Approximately half of all patients with an MI are re-hospitalized within 1 year of their index event. Overall, prognosis is highly variable and depends largely on the extent of the infarct, the residual left ventricular function, and whether the patient underwent revascularization.

12. Treatment goal and Management The aims in managing MI are, in sequence, to: Act promptly to save life and reduce complications. Treat acute symptoms. Restore flow through the affected artery (revascularization). Minimize subsequent infarct size. Treat complications. Rehabilitate. Ensure secondary prevention of subsequent attack.

13. Immediate management The emergency management of MI is primarily symptomatic and supportive. The IV route is preferred because reduced peripheral perfusion delays uptake from IM sites, and frequent injections are more conveniently given via an in situ IV line. Early revascularization by thrombolysis or PTCA is mandatory but is not always immediately available. Opioids are invaluable as analgesics, tranquilizers, and vasodilators . Paradoxically, their respiratory depressant action is also useful: it reduces the ineffectual fast respiration associated with panic. In the UK, diamorphine (heroin) is routinely used, but morphine or pethidine (meperidine) is also suitable; an anti-emetic (e.g., cyclizine or metoclopramide ) may be required.

14. A 300-mg aspirin tablet (for its antiplatelet effect, not analgesia) is chewed to promote more rapid absorption. A GTN tablet is taken sublingually or buccally. High-concentration oxygen (40% or more by mask, unless the patient is known to have chronic airways disease) is often needed.

15. Routine acute management of MI symptoms

16. Myocardial salvage: reducing infarct size It was previously thought that after an MI, little could be done to prevent myocardial damage, which was assumed already to have occurred irreversibly. However, several interventions have been developed. They are best initiated within 3 hours of the onset of symptoms. However, evidence is emerging that the thrombotic process in some infarctions evolves continuously over the first 24 hours, so later interventions may still be beneficial. Audit criteria for this phase include ‘pain to vein’ time – the time between the onset of symptoms and the start of treatment ‘door to needle’ time – the speed with which patients admitted to an A&E department are started on treatment, ideally 30 min.

17. Antithrombotics Aspirin is given as soon as possible and continued, with the aim of preventing extension of the existing thrombus or re-thrombosis. It does not reduce the size of the culprit thrombus. There is some evidence that clopidogrel enhances this action, but glycoprotein IIb/IIIa inhibitors probably do not. There is no evidence to support the routine use of heparin except in association with angioplasty or thrombolysis.

18. Non-vitamin K oral anticoagulants (NOACs) are also known as direct oral anticoagulants (DOACs) or target-specific oral anticoagulants (TSOACs).  They are used to prevent strokes and systemic embolism.

19. Reperfusion: thrombolysis The key to improving outcomes in MI is to restore blood flow to the ischemic area by opening up the occluded coronary artery as soon as possible. In some areas, it is possible to organize balloon angioplasty or even bypass surgery sufficiently rapidly as a primary intervention, and this is becoming more common. However, pharmacological thrombolysis (fibrinolysis) is the usual treatment. Angioplasty is also used where thrombolysis has failed.

20. Indication and use Pharmacological thrombolysis is now considered for all patients with symptoms strongly suggestive of MI and confirmed by ECG. Thrombolysis recanalizes up to 50% of patients and reduces mortality rate by 25%. Patients with anterior infarcts benefit the most; the benefit is most excellent for those patients treated as soon as possible. Ideally, this should be within 2 h of onset of symptoms (i.e., usually before reaching the hospital), but 4–6 h is probably more realistic, and 12 h is the maximum for significant benefit.

21. There are only small gains after longer delays. Heparin is used routinely as an adjunct to alteplase therapy, because alteplase has a short half-life. It is also indicated in patients with a tendency to thrombosis, to reduce venous thrombosis and pulmonary embolism. However, there is an increased chance of bleeding and heparin is not recommended routinely.

22. Side-effects, contra-indications and precautions. Early fears that thrombolysis would cause massive haemorrhage proved unfounded, but bleeding is still the major risk. This may be at the site of injection, so that further venipuncture should be delayed and cautious. More serious is internal bleeding, especially intracerebrally (e.g. hemorrhagic stroke). Major contraindications include recent surgery (including dental extraction), recent head injury, a history of cerebrovascular disease or if there is a risk of bleeding from a peptic ulcer.

23. Contra-indications and cautions with thrombolytic therapy Active problems Anticoagulation therapy Peptic ulceration Oesophageal varices Severe liver disease (varices) Diabetic retinopathy Severe systolic hypertension Pregnancy Severe menorrhagia Recent history of: General surgery Stroke Subarachnoid haemorrhage Major head injury

24. Streptokinase (SK) is a foreign protein and therefore antigenic; it acts directly on plasminogen anywhere in the circulation. Infuse a total dose of 1,500,000 within 60 min. Alteplase (rt-PA) is a genetically engineered human tissue plasminogen activator that has a greater affinity than SK for fibrin. Reteplase and tenecteplase are similar but modified to be more clot-specific by being selective for plasminogen in the presence of fibrin. They also have a longer half-life.

25. SK is currently the cheapest agent. Because it is antigenic, antibodies form within 4 days. This may cause allergic reactions, but fortunately anaphylaxis is uncommon. The outstanding problem is the lack of effect if treatment is repeated after 4 days, because the antibodies bind the drugs and prevent them from acting. Another thrombolytic must be used if a patient has a second infarct after SK treatment. Alteplase and reteplase , although more expensive, permit lower doses and hence reduce systemic bleeding by targeting the coronary clot.

26. Primary angioplasty There is increasing evidence that prompt angioplasty, if it can be arranged, produces better long-term outcomes than thrombolysis.

27. Cardiac workload reduction Surrounding an evolving infarct there are relatively hypoxic, but not completely anoxic, areas. Reducing the oxygen deficit of these might be expected to aid their recovery, reduce the size of the subsequent infarct, and thus improve prognosis. In addition this contributes to the management of any heart failure. The strategies used are similar to those in angina: Reduction of heart rate and contractility using beta-blockers. Reduction of afterload using arterial dilators, e.g. ACEIs. Reduction of preload using venodilators, e.g. nitrates, ACEIs.

28. Early IV beta-blockers have been shown to reduce infarct size, arrhythmias and cardiac rupture. Because the usual cardiac contraindications to beta-blockers are all common after MI (especially serious heart failure, bradycardia, heart block and hypotension) many patients who might benefit would normally be excluded. However, cautious use of certain beta-blockers (e.g. carvedilol) in heart failure is now known to be beneficial.

29. Oral ACEIs started within 24 h of infarction have also been shown to improve outcome, especially when there is overt failure, impaired ventricular function or hypertension. They appear to counter the ventricular enlargement (remodeling) that occurs after infarction and worsens ventricular function and prognosis. They are particularly useful when beta-blockers are contra-indicated but may be used together with them. ACEIs are routinely used for at least 6 weeks if not contra-indicated, e.g. by hypotension, and are continued if heart failure persists. As usual, ARAs may be substituted where ACEIs are not tolerated. Neither beta-blockers nor ACEIs should be started before the patient has been stabilized hemodynamically.

30. Rehabilitation Patients without complications are mobilized within 2–3 days and discharged soon after. This reduces the chance of venous thrombosis and is good for morale. Rehabilitation and general health education after Myocardial Infarction Gradual re-establishment of regular activity, including work and sex  Counselling and reassurance Little interference with normal activity expected  Improve general fitness Stop smoking Moderate routine aerobic exercise Attain ideal body weight Join the ‘post-MI’ self-help group  Stress reduction? simple psychotherapy, relaxation therapy, group therapy

31. Secondary prevention (Hint: LABAA) Antiplatelet therapy Anticoagulants Beta-blockers ACE inhibitors Lipid-regulating agents

32. Overview of the management of myocardial infarction. Precise treatment will depend on the severity of Infarction and occurrence of complications. ACEI, angiotensin-converting enzyme inhibitor; GTN, glyceryl trinitrate; IV, intravenous; s/l, sublingual.

33. Monitoring Parameters For Myocardial Infarction Patients with acute myocardial infarction (AMI) should be continuously monitored for the first 24 hours after being hospitalized. Monitoring parameters include: Electrocardiography Serial ECGs Measurements of serum cardiac markers of myocyte necrosis  Creatine-Kinase-MB isoform Cardiac Troponin CRP

34. Myocardial Infarction

35. Thank you