18. Pharmacology of Agents Used in the Treatment of MI Flashcards
What are 8 Drugs that can be used in the Treatment of Myocardial Infarction?
Examples of each?
Drug Treatment of Myocardial Infarction
- Plasminogen activators - e.g. alteplase
- Anticoagulants - e.g. heparin
- Antiplatelet medications - e.g. aspirin, clopidogrel
- Organic nitrates - e.g. glyceryl trinitrate
- Strong analgesics - e.g. morphine
- Beta blockers - e.g. metoprolol
- ACE inhibitors - e.g. ramipril (or an angiotensin II receptor antagonist)
- Statins - e.g. atorvastatin
What is an Acute Coronary Syndrome?
What are 3 types of ACS?
Acute Coronary Syndrome
- An acute coronary syndrome (ACS) occurs when there is a significant decrease in coronary blood flow leading to acute myocardial ischaemia
- 3 Types:
- Unstable Angina → anginal pain which occurs with less and less exertion, and ultimately at rest
- STEMI → sudden and complete block of a coronary artery causing full thickness damage of the ventricular wall (transmural)
- NSTEMI → severely narrowed, but not completely blocked coronary artery (similar to unstable angina)
Plasminogen Activators
- 3 Examples?
- Mechanism of Action?
- Indications?
- Adverse Effects?
Plasminogen Activators
-
Examples
- Alteplase
- Reteplase
- Tenecteplase
-
Mechanism of Action
- They convert plasminogen to plasmin
- Plasmin breaks down fibrin (fibrinolytic effect) which results in degradation of the thrombus
-
Indications
- Used in the acute treatment of occlusive coronary artery disease and myocardial infarction (STEMI)
- Initiated within 6 to 12 hours of onset of symptoms
-
Adverse Effects
- May produce bleeding and haemorrhage, which can be life threatening (e.g. intracranial, gastrointestinal)
What is Alteplase and how does it work?
Plasminogen Activators - Alteplase
- Alteplase = a serine protease tissue plasminogen activator in the presence of fibrin
- Alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin
- This initiates local fibrinolysis (thrombolysis)
What are 2 examples of Anticoagulants?
Anticoagulants - Examples
- Heparin
- Warfarin
What is Heparin and how does it work?
What does it combine with?
Which 2 clotting factors does it inhibit?
Anticoagulants - Heparin
- Antithrombin III is a glycoprotein which mainly inhibits the activity of thrombin (IIa) and activated factor X (Xa)
- Heparin exerts an anticoagulant effect by combining with antithrombin III and enhancing the rate at which antithrombin III inhibits thrombin (IIa) and activated factor X (Xa)
What is Warfarin and how does it work?
What does it inhibit the synthesis of? (which 4 clotting factors)
Anticoagulants - Warfarin
- Is a coumarin anticoagulant which inhibits the synthesis of vitamin K dependent clotting factors
- Vitamin K dependent clotting factors are factors II, VII, IX and X
- Inhibits the vitamin K epoxide reductase (VKORC1) enzyme complex, which inhibits the reduction of vitamin K epoxide to its active hydroquinone form
- The hydroquinone form is necessary for the carboxylation and activity of factors II, VII, IX and X
- Does not directly inhibit factors II, VII, IX and X
Why is the onset of warfarin’s anticoagulant activity is delayed?
Anticoagulants - Warfarin
- Does not inhibit the activity of factors II, VII, IX and X formed and carboxylated prior to warfarin administration
- Onset of anticoagulant activity is delayed
What is the ffect of warfarin is monitored by measuring?
What is the normal range?
Warfarin - International Normalised Ratio (INR)
- The effect of warfarin is monitored by measuring the International Normalised Ratio (INR)
- The INR target range for most conditions is 2-3
What are some of the newer anticoagulants and which clotting factor/molecule do they inhibit?
Newer Anticoagulants
- Apixaban → Factor Xa
- Rivaroxaban → Factor Xa
- Dabigatran → Thrombin
What are Antiplatelet Medications and how do they work?
Antiplatelet Medications
- Atherosclerotic plaque on the inside of blood vessel walls can precipitate the aggregation of platelets (plug formation) and thrombus formation
- Antiplatelet drugs reduce thrombus formation by inhibiting platelet aggregation
- Used to prevent atherothrombotic events such as myocardial infarction
- Give all patients presenting with a STEMI dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (clopidogrel, prasugrel, ticagrelor).
- Examples: Lose Dose Aspirin, NSAIDs, Dipyridamole
What are Organic Nitrates and how do they work?
Organic Nitrates
- Organic nitrates e.g. glyceryl trinitrate are metabolised to nitric oxide (NO), in a reaction possibly involving sulfhydryl (SH) groups
- Increase cyclic guanosine monophosphate levels (cGMP) and activate protein kinase G
- Produce vascular smooth muscle relaxation
- Relaxation of vascular smooth muscle produces vasodilation
- Relax and dilate both arteries and veins
What are 3 reasons why Organic Nitrates are effective in the treatment of coronary syndromes?
Organic Nitrates - Are effective in the treatment of coronary syndromes because they:
- Cause venous dilation which reduces venous return and preload, and reduces cardiac work and oxygen demand
- Cause artery/arteriolar dilation which reduces peripheral resistance and afterload, and reduces cardiac work and oxygen demand
- Dilate coronary vessels and increase coronary blood flow, particularly to ischaemic areas, which increases myocardial oxygen supply
What are Beta Adrenoceptor Antagonists (Beta Blockers) and how do they work?
2 Types?
Beta Adrenoceptor Antagonists (Beta Blockers)
- Beta adrenergic receptor antagonists competitively antagonise the actions of adrenaline and noradrenaline at beta adrenergic receptors
- 2 types:
- Non-selective
- Selective
What are Non-selective beta blockers?
1 Example?
Non-Selective Beta Blockers
Some are nonselective beta blockers which competitively antagonise the actions of adrenaline and noradrenaline at all adrenergic beta receptors - β1, β2 and β3 receptors
Example = propranolol
