Elm 13 ACS

Question 1

Question: What is the fundamental difference between stable angina and acute coronary syndrome (ACS)?

Answer 1

Answer: In ACS, blood vessels are not just partially blocked by atherosclerotic plaque; there is also involvement of a blood clot.

Question 2

Question: How is ACS classified, and what are the diagnostic tools used?

Answer 2

Answer: ACS is classified into three main categories: unstable angina (least serious), NSTEMI, and STEMI (most serious). Diagnostic tools include ECG, which shows elevation of the ST interval in STEMI and ST depression/no change in NSTEMI/unstable angina. Blood tests are also used to detect specific markers and proteins indicative of cardiac tissue damage.

Question 3

Question: What are some treatment options for ACS?

Answer 3

Answer: Treatment for ACS involves addressing pain, reducing cardiac workload, preventing further thrombosis, and initiating reperfusion therapy. Pain management may involve opioids and GTN. Cardiac workload can be reduced using beta-blockers. Further thrombosis can be prevented with medications such as aspirin, ticagrelor/clopidogrel, heparins, and atorvastatin. Reperfusion therapy options include PCI, CABG, and thrombolysis.

Question 4

Question: What is the difference between thrombosis and embolism?

Answer 4

Answer: Thrombosis is the pathological formation of blood clots within blood vessels, which can lead to conditions such as deep vein thrombosis (DVT), stroke, heart attack, and limb infarction. On the other hand, embolism occurs when a fragment or whole thrombus detaches from the vessel wall and travels through the bloodstream, potentially blocking small vessels in organs such as the lungs, heart, brain, or limbs.

Question 5

Question: What are the key roles of coagulation and platelet aggregation in thrombosis?

Answer 5

Answer: Coagulation plays a major role in venous thrombosis, while platelet aggregation is more important in arterial thrombosis. However, both processes can be involved in either type of thrombosis, and the relative contributions may influence treatment strategies.

Question 6

Aim of drug intervention in thrombosis:

Answer 6

Inhibit thrombus formation without preventing normal hemostasis. Targets include modification of coagulation for venous thrombosis and platelet aggregation for arterial thrombosis.

Question 7

Targets for modifying thrombosis:

Answer 7

Modify coagulation for venous thrombosis.
Modify platelet aggregation for arterial thrombosis.
Modify clot and thrombus breakdown after prophylaxis fails.

Question 8

Therapeutic uses of drug intervention:

Answer 8

Prevention of heart attacks and strokes.
Reduction of damage after heart attacks and strokes.
Management of patients with atrial fibrillation.
Post-heart valve replacement surgery.

Question 9

Heparins:

Answer 9

Anticoagulants that modify coagulation. Act on factors in the coagulation cascade, primarily inhibiting thrombin, factors Xa, and IXa.

Question 10

Mechanism of action of heparins:

Answer 10

Enhance the activity of antithrombin III (AT3), leading to inhibition of thrombin, as well as factors Xa and IXa.

Question 11

Other actions of heparins:

Answer 11

Reduce platelet aggregation.
Influence lipid metabolism beneficially by activating lipoprotein lipase and removing lipids from plasma.

Question 12

Clinical uses of heparins:

Answer 12

Venous thrombosis/embolism.
Post-heart attack/stroke.
Reduction of deep vein thrombosis (DVT) risk after orthopedic surgery.
Low molecular weight heparins preferred for self-administration via subcutaneous injection (not for patients with renal impairment).

Question 13

What is Fondaparinux?

Answer 13

Fondaparinux is a synthetic version of low molecular weight heparin (LMW) with a similar action and possibly a better side effect profile.

Question 14

What are some problems associated with Heparin?

Answer 14

Poor absorption from oral administration.
Risk of allergic reactions.
Dosing needs to be individualized.
Monitoring may be required.
Risk of hemorrhage, which may require cessation or administration of complex heparin with protamine in severe cases.

Question 15

How was Warfarin originally discovered?

Answer 15

Warfarin was discovered after cows died from bleeding post-surgery due to ingestion of dicoumarol, a compound found in Sweet Clover disease.

Question 16

What are the therapeutic uses of Warfarin?

Answer 16

Warfarin is used in venous thromboembolism, prevention of stroke in patients with atrial fibrillation, and heart valve replacement.

Question 17

What is the mechanism of action of Warfarin?

Answer 17

Warfarin antagonizes Vitamin K’s role in the formation of clotting factors II, VII, IX, and X by preventing gamma-carboxylation of precursors.

Question 18

What are some problems associated with Warfarin?

Answer 18

Slow onset of action.
Activity influenced by Vitamin K intake, absorption, and gut flora.
Existence as R and S isomers with differing activity and metabolic pathways.
Risk of hemorrhage.
Teratogenicity, so it should be avoided in early pregnancy.
Prone to drug interactions.

Question 19

Question 1: What are direct-acting oral anticoagulants (DOACs)?

Answer 19

Answer 1: DOACs are newer drugs that include dabigatran, a direct inhibitor of thrombin, and rivaroxaban, which inhibits factor 10a.

Question 20

Question 2: How do DOACs differ from warfarin in terms of usage and monitoring?

Answer 20

Answer 2: DOACs are easier to use as they do not require frequent monitoring like warfarin. They also seem to have better outcomes in preventing strokes and embolisms over time.

Question 21

Question 3: What are some common uses of direct-acting oral anticoagulants?

Answer 21

Answer 3: DOACs are commonly used to prevent strokes in patients with atrial fibrillation and to treat deep vein thrombosis (DVT).

Question 22

Question 4: Describe the controversy surrounding dabigatran.

Answer 22

Answer 4: Boehringer Ingelheim, the manufacturer of dabigatran, faced controversy for withholding information about the need for monitoring its effects. While better outcomes were observed without monitoring, it was suggested that outcomes could potentially be even better with monitoring.

Question 23

Question 5: How does hirudin, released by medical leeches, affect blood clotting?

Answer 23

Answer 5: Hirudin attaches to thrombin on both its active site and an exosite, blocking its ability to convert fibrinogen to fibrin, thus preventing blood clot formation.

Question 24

Question 6: Why is it not feasible to extract hirudin in medically useful amounts from leeches?

Answer 24

Answer 6: Extracting hirudin from leeches in medically useful amounts requires a large number of leeches, which is not practical.

Question 25

Question 7: What are some characteristics of platelets?

Answer 25

Answer 7: Platelets are flat, disc-shaped fragments of cytoplasm derived from megakaryocytes. They contain glycoprotein receptors on their membranes and play a crucial role in hemostasis.

Question 26

Question 8: How do platelets respond to damage in blood vessels?

Answer 26

Answer 8: Platelets recognize damaged blood vessels, adhere to the damage, become activated, and aggregate to form a plug that stops blood leakage.

Question 27

Question 9: What triggers the activation of platelets?

Answer 27

Answer 9: Platelets become activated upon interacting with collagen, which leads to a conformational change in their receptors, causing them to change from a flat disc shape to a spiky structure.

Question 28

Question 10: What molecules are released during platelet activation, and what is their role?

Answer 28

Answer 10: Platelet activation leads to the release of molecules such as thromboxane A2 (TXA2) and ADP, which activate neighboring platelets. Additionally, receptors 2b and 3a transition from inactive to active conformation, enabling platelets to aggregate.

Question 29

Question 1: How is thromboxane A2 (TXA2) synthesized, and what is its role in platelet aggregation?

Answer 29

Answer 1: TXA2 is synthesized from arachidonic acid by cyclo-oxygenase (COX) in platelets. It is released by platelets to increase the expression of receptors 2b and 3a, facilitating platelet aggregation by binding fibrinogen and forming clumps of activated platelets.

Question 30

Question 2: What is the significance of the positive feedback loop in platelet activation, and what regulates it?

Answer 30

Answer 2: The positive feedback loop in platelet activation can lead to uncontrolled clotting if left unchecked. Prostacyclin serves as a regulatory mechanism by inhibiting platelet activation and aggregation, preventing the spread of clotting beyond the immediate area of damage.

Question 31

Question 3: How does ADP contribute to platelet activation, and what receptor does it bind to?

Answer 31

Answer 3: ADP binds to PY2 receptors on platelets, leading to decreased levels of cAMP and increased platelet activation.

Question 32

Question 4: Describe the role of cyclo-oxygenase (COX) in platelet function and inflammation.

Answer 32

Answer 4: COX has several isoforms, with COX-1 being responsible for the synthesis of TXA2 and prostacyclin. COX-2 is expressed in inflamed tissues and is targeted by anti-inflammatory drugs. COX-3, however, has a frameshift mutation and does not produce an active enzyme.

Question 33

Question 5: How do nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects on COX enzymes, and what are the implications of COX inhibition?

Answer 33

Answer 5: NSAIDs exert their effects by inhibiting COX enzymes, primarily COX-1 and COX-2. While COX-2 selective NSAIDs were initially developed to avoid gastrointestinal tract problems associated with COX-1 inhibition, they later showed a higher rate of serious cardiovascular problems. Most COX-2 inhibitors have been withdrawn due to these risks, though the exact mechanisms behind the increased risk remain unclear.

Question 34

Question 1: How does aspirin exert its antiplatelet effects, and why is low-dose administration preferred?

Answer 34

Answer 1: Aspirin irreversibly blocks the platelet cyclo-oxygenase (COX) enzyme, reducing the synthesis of thromboxane A2 (TXA2). Low-dose administration is preferred to avoid reducing the enzyme in endothelial cells, which are a source of prostacyclin. Aspirin alters the balance between platelet TXA2 and endothelial prostacyclin, contributing to its antiplatelet effects.

Question 35

Question 2: What are some unwanted effects associated with aspirin usage?

Answer 35

Answer 2: Unwanted effects of aspirin include extended bleeding time, indigestion, allergies, provocation of asthma attacks, and Reye’s syndrome, particularly in individuals under 16 years old, which can lead to liver and brain damage when aspirin is used during viral illnesses.

Question 36

Question 3: How do clopidogrel and ticagrelor exert their antiplatelet effects, and what distinguishes them in terms of mechanism of action?

Answer 36

Answer 3: Clopidogrel inhibits the expression of receptors 2b and 3a on platelets by irreversibly blocking ADP receptors. Ticagrelor, on the other hand, allosterically inhibits ADP receptors.

Question 37

Question 4: What were the key findings of the PLATO trial comparing clopidogrel and ticagrelor?

Answer 37

Answer 4: The PLATO trial found that ticagrelor showed a 16% lower mortality rate compared to clopidogrel. Additionally, ticagrelor was found to be superior even when considering genetic variations that affect clopidogrel’s effectiveness.

Question 38

Question 5: What are some unwanted effects associated with clopidogrel and ticagrelor usage?

Answer 38

Answer 5: Unwanted effects of clopidogrel and ticagrelor include extended bleeding time, gastrointestinal tract issues, headaches, dizziness, and specific to ticagrelor, gout and breathlessness.

Question 39

Question 6: How does dipyridamole exert its antiplatelet effects, and what are its unwanted effects?

Answer 39

Answer 6: Dipyridamole raises cyclic adenosine monophosphate (cAMP) levels in platelets by inhibiting phosphodiesterase type 3 (PDE3), preventing the breakdown of cAMP. Unwanted effects of dipyridamole include gastrointestinal tract issues, headaches, dizziness, muscle pain, flushing, and it can precipitate or worsen angina.

Question 40

Question 7: What is the mechanism behind dipyridamole worsening angina?

Answer 40

Answer 7: Dipyridamole can worsen angina through a phenomenon known as coronary steal. With dipyridamole, healthy blood vessels dilate, but collateral vessels do not, leading to decreased blood flow in stenosed vessels.

Question 41

Question 1: What is the significance of reperfusion time in the treatment of conditions like heart attack and stroke?

Answer 41

Answer 1: Reperfusion time is crucial in these conditions as delayed treatment can result in irreversible damage to muscle tissue. Hence, it’s imperative to administer treatment as quickly as possible to restore blood flow and prevent further damage.

Question 42

Question 2: What are PCI and CABG, and when are they typically used in the context of heart attacks?

Answer 42

Answer 2: PCI (percutaneous coronary intervention) and CABG (coronary artery bypass grafting) are surgical procedures used to treat heart attacks. PCI involves the insertion of a stent to open a blocked coronary artery, while CABG involves bypassing blocked arteries using blood vessels from other parts of the body. PCI is less invasive but may not be suitable for all cases, while CABG is more invasive and is typically used when PCI is not feasible or has poorer outcomes.

Question 43

Question 3: How do thrombolytic drugs work, and what are some examples of these drugs?

Answer 43

Answer 3: Thrombolytic drugs work by promoting the breakdown of blood clots. They function by converting plasminogen into plasmin, which can then attack fibrin, the main component of blood clots. Examples of thrombolytic drugs include reteplase, alteplase, and streptokinase.

Question 44

Question 4: What is the time window for administering thrombolytic treatment, and why is early administration important?

Answer 44

Answer 4: Thrombolytic treatment should ideally be administered within a 4.5-hour window from the onset of symptoms. Early administration is crucial because as clots mature, they become resistant to thrombolytic drugs, making them less effective over time.

Question 45

Question 5: Compare the advantages and disadvantages of PCI and thrombolysis in terms of speed, risk, and equipment requirements.

Answer 45

Answer 5: PCI is rapid, relatively safe, and requires specialized centers, which are now more common. Thrombolysis is very rapid, but relatively riskier and requires less equipment. However, thrombolysis can be administered more widely since it does not require the same specialized facilities as PCI.