1. PHARMACOTHERAPY - I PHCY 310
University of Nizwa
College of Pharmacy and Nursing
School of Pharmacy
PHARMACOTHERAPY - I
PHCY 310
Lecture – 4 Cardiovascular Disorders “Acute Myocardial Infarction” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

2. Course Outcome
Upon completion of this lecture the students will be able to
Explain the cause and diagnosis of acute myocardial infarction,
Describe non-pharmacological and pharmacological treatment for acute myocardial infarction,
Recommend the treatment for patients with ST elevation myocardial infarction (STEMI).

3. Acute myocardial infarction (AMI), referred to as ST segment elevation myocardial infarction (STEMI), is a manifestation of ischemic heart disease characterized by cellular death or necrosis occurring in the setting of severe or prolonged ischemia.
Myocardial infarction (MI) is defined as death of myocardial tissue.
STEMI is thought to be the result of complete occlusion in the coronary artery.
At-risk patients (e.g., genetic predisposition, smoking, poor dietary habits, or physical inactivity) include diabetics, elderly patients, and other individuals with metabolic syndrome.

4. Noncompliance with secondary preventive measures leads to post-MI patients at risk for recurrent events and death.
Twenty to thirty percent of these patients die before reaching a hospital.
Prompt recognition and treatment of AMI reduces the mortality.

5. Pathophysiology
Ischemia episodes that lasts more than 30 minutes usually cause MI.
Most common cause of AMI is artherosclerosis of coronary artery which narrows the coronary lumen and reduces myocardial blood supply.
Majority of MIs result from occlusion of a coronary artery secondary to thrombus formation overlying a lipid-rich atheromatous plaque that ruptured.
Damage to the plaque results in blood being exposed to collagen and fatty acids; this in turn activates platelets, the first step in thrombosis and formation of a fibrin clot.

6. A change in the glycoprotein (GP) IIb/IIIa surface receptors of platelets occurs that cross-links platelets to each other through fibrinogen bridges (the final common pathway of platelet aggregation).
Some patients develop permanent electrocardiographic (ECG) abnormalities (Q waves) following an AMI.
Q-wave MI is now called STEMI and non–Q-wave MI is now called non-ST segment elevation MI (NSTEMI).
Endothelial dysfunction leads to the formation of fatty streaks in the coronary arteries and eventually to atherosclerotic plaques.
Factors responsible for development of atherosclerosis include hypertension, age, male gender, tobacco use, diabetes mellitus, obesity, and dyslipidemia.

7. Clinical Presentations
Patients may complain of prolonged substernal chest pain or pressure; radiates to neck, throat, jaw, shoulders and arms, shortness of breath, diaphoresis, nausea, and vomiting.
The pain might be described as stabbing or knife-like, and it may occur in the arms, shoulder, neck, jaw, or back.
Significant tachycardia (heart rate >120 beats/min) suggests a large area of damage.
On cardiac auscultation, a fourth heart sound (S4) may be heard.

10. Diagnosis
A 12-lead ECG should be obtained within 10 minutes of patient presentation.
Key findings indicating myocardial ischemia or MI are ST-segment elevation, ST-segment depression, and T-wave inversion. Ischemia (T-wave inversion), injury (ST-segment elevation), and infarction (pathologic Q waves)
Biochemical markers of myocardial cell death are important for confirming the diagnosis of MI.
An evolving MI is defined as a typical rise and gradual fall in troponin I or T or a more rapid rise and fall of CK-MB (Myocardial Necrosis). CK is increased after skeletal muscle trauma related to surgery, exercise, or intramuscular injections, the MB fraction of CK is released only from heart muscle.
Both troponin-I (cardiac specific) and CK-MB are detectable within 6 hours of MI.
Troponins remain elevated for up to 10 days, whereas CKMB returns to normal within 48 hours.

11. LDH2 is the major LDH isoenzyme in blood; thus, the normal serum pattern shows more LDH2 than LDH1. Within 48 hours after AMI, this serum pattern reverses in 80% of patients, who now show higher LDH1 concentrations than LDH2 concentrations.

12. NONPHARMACOLOGIC THERAPY
For patients with STEMI, either fibrinolysis or primary Percutaneous Coronary Intervention (with either balloon angioplasty or stent placement) is the treatment of choice for re-establishing coronary artery blood flow. In patients with NSTEMI, coronary artery bypass grafting revascularization is an early treatment for high-risk patients.

14. EARLY PHARMACOTHERAPY FOR STEMI
According to the American College of Cardiology/American Heart Association (ACC/AHA) practice guidelines, early pharmacologic therapy should include:
(1) Intranasal oxygen (if oxygen saturation is less than 90%)
(2) Sublingual (SL) nitroglycerin (NTG)
(3) Aspirin
(4) β-blocker
(5) Unfractionated heparin (UFH) or enoxaparin
(6) Fibrinolysis in eligible candidates
Morphine is administered to patients as an analgesic and venodilator (a potent vasodilator) that lowers preload.(A dose of 2 to 4mg IV over 1 to 2 min repeated at 5 to 15min until pain relieve or side effects occur)

15. Anxiolytic medications (e. g
Anxiolytic medications (e.g., benzodiazepines) in STEMI patients to alleviate short-term anxiety or altered behavior related to hospitalization for STEMI, and to routinely assess the patient’s anxiety level.
Nitrates
Immediately upon presentation, one SL -NTG tablet should be administered every 5 minutes for up to three doses to relieve chest pain and myocardial ischemia.
Intravenous NTG should be initiated in all patients with an ACS who do not have a contraindication and who have persistent ischemic symptoms, heart failure, or uncontrolled high BP.
The usual dose is 5 to 10 mcg/min by continuous infusion, titrated up to 200 mcg/min until relief of symptoms or limiting side effects (e.g., headache or hypotension).

16. Treatment should be continued for approximately 24 hours after ischemia is relieved.
NTG causes venodilation, which lowers preload and myocardial oxygen demand.
Nitrates should not be administered to patients with systolic blood pressure <90 mm Hg or 30 mm Hg or more below baseline, severe bradycardia (50 bpm), tachycardia (100 bpm), or RV infarction.
Fibrinolytic/Thrombolytic Therapy
It should be considered in patients with those findings and persistent symptoms of ischemia who present within 12 to 24 hours of symptom onset.
Practice guidelines indicate that a more fibrin-specific agent (alteplase, reteplase, tenecteplase) is preferred over the non–fibrin-specific agent streptokinase.

17. A daily maintenance dose of 75 to 162 mg is recommended.
Streptokinase: 1.5 million units in 50 mL of normal saline or 5% dextrose in water IV over 60 minutes.
Alteplase: 15-mg IV bolus followed by 0.75-mg/kg infusion (maximum 50 mg) over 30 minutes, followed by 0.5-mg/kg infusion (maximum 35 mg) over 60 minutes (maximum dose 100 mg).
Intracerebral Haemorrhage (ICH) and major bleeding are the most serious side effects.
Aspirin
Aspirin should be administered to all patients without contraindications within the first 24 hours of hospital admission.
In patients experiencing an ACS, non–enteric-coated aspirin, 162 to 325 mg, should be chewed and swallowed as soon as possible after the onset of symptoms or immediately after presentation to the emergency department.
A daily maintenance dose of 75 to 162 mg is recommended.

18. Low-dose aspirin is associated with a reduced risk of major bleeding, particularly GI bleeding.
Other GI disturbances (e.g., dyspepsia, nausea) are infrequent with low-dose aspirin.
Ibuprofen should not be administered concurrently with aspirin because it may block aspirin’s antiplatelet effects.
Clopidogrel (75 mg OD) or Ticlopidine (250 mg bid) may be given for patients with aspirin allergy
Aspirin is contraindicated in those with a hypersensitivity to salicylate.
Aspirin suppositories (300 mg) can be used safely, and this is the recommended route of administration for patients with severe nausea and vomiting or known upper gastrointestinal disorders.

19. β-Adrenergic Blockers.
If there are no contraindications, a β-blocker should be administered early (within the first 24 hours) and continued indefinitely.
β-blockers reduce the risk for recurrent ischemia, infarct size, risk of re-infarction, and occurrence of ventricular arrhythmias.
Calcium channel blockers are reserved for patients who have contraindications to β-blockers.
They are used for relief of ischemic symptoms only.

20. ACE Inhibitors and Angiotensin Receptor Blockers
ACE inhibitors should be initiated in all patients after MI to reduce mortality, decrease reinfarction, and prevent the development of heart failure.
The dose should be low initially and titrated to higher dose if tolerated.
Glycoprotein IIb/IIIa Receptor Inhibitors
Abciximab is a first-line GP IIb/IIIa inhibitor for patients undergoing primary PCI who have not received fibrinolytics.
Electrolytes
Magnesium should be reserved for use in patients with documented hypomagnesemia or hypokalemia (maintain 4 and 6 mEq per L).

21. Anticoagulants
To prevent coronary artery reocclusion after thrombolytic therapy Unfractionated Heparin (UHF) is used.
The risk of reocclusion is high immediately after thrombolysis because blood flowing through the newly opened coronary artery is exposed to thrombin bound to fibrin on the residual thrombus.
UFH is a first-line anticoagulant for STE-ACS, both for medical therapy and PCI.
It should be initiated in the emergency department and continued for at least 48 hours.

22. The dosing of UFH is as follows: bolus of 60 U per kg (maximum 4,000 U) followed by an infusion of 12 U/kg/hr (maximum 1,000 U) initially adjusted to maintain the activated partial thromboplastin time (aPTT) at 1.5 to 2.0 times control (approximately 50 to 70 seconds).
Standard practice was to administer IV heparin for 3 to 5 days, although patients are now often discharged after only 3 days.
Side effects of UFH include hemorrhage (intracranial or gastrointestinal) and thrombocytopenia.
Heparin is contraindicated in patients who have a history of hemorrhage, uncontrolled hypertension, vasculitis, blood dyscrasies, active bleeding, or a bleeding ulcer or who have recently had major surgery.

23. Low-Molecular-Weight Heparins, its advantages.
Questions to Answer
Low-Molecular-Weight Heparins, its advantages.
Glucose control during STEMI
Contraindications of thrombolytic therapy
Precautions for Streptokinase
Reference:
Richard A. Helms, David J. Quan, Eric T. Herfindal, Dick R.Gourley. Textbook of Therapeutics. Drug and Disease Management. 8th Edition. Lippincott Williams and Wilkins.