1. Pharmacodynamics IV Spring 2011 Acute Myocardial Infarction Kyoungmin Lee Angela Paul Cory Phillips Jaime Tausend Sonia Tadjalli
2. Introduction Occlusion of a coronary artery Death of cardiac myocyte Wide range of clinical sequelae Result in cardiogenic shock and death About 1.5 million people experience MI
3. Risk Factors Age Gender (male) Dyslipidemia Diabetes Hypertension Obesity Lack of physical activity Alcohol overconsumption Tobacco use Family history of atherosclerotic disease
15. Diagnosis Patient History Perform an electrocardiogram (EKG) STEMI vs NSTEMI Cardiac Enzymes Series of blood draws Myoglobin Creatine phosphokinase (CK-MB) Troponin
16. Treatment Overview MONA- B Morphine Oxygen Nitroglycerin Aspirin / Clopidogrel Beta-Blockers Other Early Hospital Therapies for MI ACE Inhibitors/ ARBs Calcium Channel Blockers Mechanical Reperfusion Fibrinolytics
33. Clopidogrel Alternative to aspirin is contraindication exists 75mg on presentation and indefinitely is aspirin is contraindicated Dual therapy after stent: 12-15 months Common adverse reactions: Rash, pruritis, bleeding and epistaxis Contraindications: Pathological bleeding, liver disease and caution with PPIs
34. Beta-Blockers All STEMI patients should receive Evaluate at admission and 24hrs for contraindications Decreases HR, BP and contractility Common adverse reactions: Bradycardia, dizziness, hypotension, edema, glycemic changes, lowered HDL, elevated triglycerides and fatigue Contraindications: HF, low Co, risk of cardiogenic shock, bradycardia,
35. Angiotensin-Converting Enzyme (ACE) Inhibitors Indicated within 24hrs if patient has: Heart failure LVEF < 40% Type 2 diabetes Chronic kidney disease CI to IV therapy CAD Reductions in death, heart failure, and stroke Common adverse reactions: Hyperkalemia Increased SCr Andioedema Cough If pt intolerant to ACEi, switch to ARB
36. Non- Dihydropyridine Calcium Channel Blockers (CCBs) Recommended in pts with: Frequent ischemia and CI to BBs Recurrent ischemia after BB and nitrates are used Two drugs: Verapamil Diltiazem MOA: Selectively block calcium channels and prevent influx of calcium ions into cells Prevents constriction of arterial smooth muscles and lowers blood pressure
37. Non-CCB Use is primarily for symptom relief and has no real benefit or detriment to mortality Adverse effects: Peripheral edema Gastroesophageal reflux Constipation ED Gynecomastia
39. DES Coated with antiproliferative agents Paclitaxel Sirolimus Beneficial in preventing restonosis after PCI: Prevent elastic recoil Negative remodeling Neointimal proliferation Restenosis rates from DESs are 5-10% in comparison to 15-20% that is achieved with BMSs
40. Antiplatelet Therapy with DES Prior to PCI Loading dose of clopidogrel (Plavix) of up to 900 mg Post PCI Aspirin 325 mg for 3-6 months along with clopidogrel 75 mg daily for at least 12 months Following this time period, maintenance therapy with aspirin 81 mg continued indefinitely 2009 Prasugrel (Effient) also approved for PCI with a 60 mg loading dose followed by 10 mg daily dose Prasugrel is more potent, more consistent at platelet inhibition, and has faster onset of action than clopidogrel Although prasugrel has proven to be superior to clopidogrel, it has increased chance of bleeding
41. Pharmacologic Reperfusion: Fibrinolytics Only indicated for STEMI within 12hrs of symptoms onset and for patients <75 y.o. MOA: Converts plasminogen to plasmin, resulting in thrombus breakdown Opens arteries in 60-90% of patients decreases mortality by 20% Greatest benefit when administered early Preferred method of reperfusion if: (“door-to-balloon” – “door-to-needle”) > 1 hr
42. Fibrinolytics In order of specificity: Greater specificity = less chance of bleeding Tenecteplase (TNK) Alteplase (t-PA) Reteplase (r-PA) Streptokinase (SK) Anistreplase (APSAC) Absolute Contraindications: Active internal bleeding Previous hemorrhagic stroke at any time Any other stroke within the previous year
43. Supportive Treatment Supportive care Bed rest Correction of precipitating factors Hypoxia Give oxygen Anemia Give blood Hypertension Patient education
45. Non-Pharmacological Therapies Balloon angioplasty Catheter with balloon is placed into artery Balloon is inflated Balloon crushes plaque Balloon is deflated and removed Nothing stays inside the patient Bare metal stents (BMS) Involves a balloon catheter with a mesh stent Mesh stent stays in the patient after balloon deflation Prevents elastic recoil and negative remodeling
46. Conclusion Most MIs are caused by a disruption in the vascular endothelium associated with a fibrous atherosclerotic plaque Leads to thrombus formation and occlusion of coronary artery About 1.5 million people experience a MI in the United States each year There are many modifiable risk factors associated with MIs Can be treated pharmacologically and non-pharmacologically Main goals of therapy Reperfusion of the occluded artery Salvaging as much myocardial tissue as possible
48. References Boyle JA, Jaffe SA. Acute myocardial infarction. Current Diagnosis & Treatment Cardiology. 2010;3. http://online.statref.com/document.aspx?fxid=19&docid=33. Berger BP, Orford LJ. Acute myocardial infarction. ACP Medicine. 2010. http://online.statref.com/document.aspx?fxid=48&docid=208. Acute Myocardial Infarction. Cleveland Clinic Center for Continuing Education website. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/acute-myocardial-infarction/. Accessed April 8, 2011. Booziotis, K. IHD & ACS. Pathophysiology/Therapeutics II. Belmont University, McWhorter Hall. March 31, 2011. Heart Attack (Myocardial Infarction). MedicineNet. Available at: http://www.medicinenet.com/heart_attack/article.htm#tocb. Accessed: April 7, 2011. ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction- Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. American Heart Association. 2004. Accessed April 10, 2011. Nitroglycerin. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Morphine. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011.
49. References continued… Aspirin. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Clopidogrel. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Williams, M. Lecture on Chronic Heart Failure. Pathophysiology & Therapeutics II. Belmont School of Pharmacy. March 28, 2011. Thompson-Odom, M. Lecture on Hypertension. Pharmacodynamics IV. Belmont School of Pharmacy. February 2, 2011. Atenolol. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Captopril. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Irbesartan. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Thompson-Odom, M. Lecture on Vasopressin/Renin-Angiotensin-Aldosterone System. Pharmacodynamics IV. Belmont School of Pharmacy. January 21, 2011. Thompson-Odom, M. Lecture on Myocardial Ischemia 2. Pharmacodynamics IV. Belmont School of Pharmacy. January 28, 2011. Verapamil. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011. Alteplase. Lexi-Comp ONLINE [database online]. Hudson, OH: Lexi-Comp, Inc.; 2010. Available at: http://www.lexi.com. Accessed April 13, 2011.
Angela beginsNot an all-inclusive listing, presentation of an acute MI is patient specificWomen are likely to present with back painSilent heart attacks- are still serious and patients still should seek treatmentDyspnea (SOB)Diaphoresis (excessive sweating)
Use this as a guide when a patient is suspected of having an acute MI
Patient History- specifically anything to do with chest painSTEMI-above baseline- ST elevationNSTEMI- below baseline- often inverted T waveLook for cardiac enzymes- do a series of 3 draws at time 0, 12, and 24 hoursMyoglobin- first to be elevated- ~1 hourTroponin- most common lab value to see, longest lasting enzyme as last as 7-14 weeks laterAlso presents a challenge when assessing new myocardial damage within that time frame- levels are still elevated
Transition slide to treatment- Angela Jaime
Jaime start
Only if they didn’t take it at homeDaily dose dependant on oterh factors… stent placement… etc
Early contraindications may resolve w/I 24 hrs
Sonia Start-Took out- RASS reduces blood pressureMOA: Suppresses rennin-angotensinaldosterone system Block conversion of angiotensin I to angiotensin II by the angiotensin-converting enzyme (ACE).ContraindicationsHypersensitivity or angioedema related to previous ACE inhibitor treatmentPregnancy
Calcium channel blockers (CCBs) are used mainly for symptom relief and have little effect on mortality. 4
CCBs should not be used in combination with tolvaptan, topotecan, dofetilide, and disopyramide. Therapy changes should be considered when using CCBs in combination with amifostine, amiodarona, antifungal agents, atorvastatin, benzodiazepines, buspirone, carbamazepine, cardiac glycosides, cimetidine, colchicines, conivaptan, cyclosporine, CYP3A4 inhibitors, dabigatran, dronedarone, everolimus, halofantrine, lovastatin, macrolides, nafcillin, protease inhibitors, ranolazine, rifamycin, rituximab, and simvastatin.
Percutaneous coronary intervention (PCI)neointimal proliferation specific for DES … others are have BMS too
Prasugrel (Effient) also approved for PCI with a 60 mg loading dose followed by 10 mg daily dosePrasugrel is more potent, more consistent at platelet inhibition, and has faster onset of action than clopidogrelAlthough prasugrel has proven to be superior to clopidogrel, it has increased chance of bleeding
Preferred method if:Early presentation 3 hours or less from sx onset & delay to PCIPCI not an option Catheterization lab occupied/not available Vascular access difficulties Loss of access to a skilled PCI lab
care should be taken in patients with severe uncontrolled hypertension, history of stroke, concurrent anticoagulant therapy, known bleeding disorders, recent trauma, traumatic or prolonged cardiopulmonary resuscitation, recent surgery, non-compressible vascular punctures, recent internal bleeding, pregnancy, active peptic ulcers, or prior exposure to streptokinase when it is considered for use. 4
