MCQ Quiz: Pharmacology of Fibrinolytic Agents

Fibrinolytic agents, also known as thrombolytics, play a critical role in emergency medicine by dissolving existing intravascular thrombi, thereby restoring blood flow in conditions like ST-segment elevation myocardial infarction (STEMI), acute ischemic stroke, and massive pulmonary embolism. A comprehensive understanding of the pharmacology of these potent drugs—including their mechanisms of action, classifications, pharmacokinetic profiles, indications, and significant risks, particularly bleeding—is essential for PharmD students to ensure their appropriate and safe use in critical care settings. This MCQ quiz will test your knowledge on the pharmacological principles governing fibrinolytic therapy.

1. Fibrinolytic agents primarily exert their therapeutic effect by promoting the conversion of:

• A. Prothrombin to thrombin
• B. Fibrinogen to fibrin
• C. Plasminogen to plasmin
• D. Factor X to Factor Xa

Answer: C. Plasminogen to plasmin

2. The active enzyme responsible for degrading the fibrin matrix of a thrombus is:

• A. Thrombin
• B. Plasmin
• C. Urokinase
• D. Streptokinase

Answer: B. Plasmin

3. Streptokinase, a first-generation fibrinolytic agent, works by:

• A. Directly cleaving fibrin.
• B. Forming a complex with plasminogen, which then activates other plasminogen molecules to plasmin.
• C. Selectively binding to fibrin-bound plasminogen.
• D. Inhibiting Plasminogen Activator Inhibitor-1 (PAI-1).

Answer: B. Forming a complex with plasminogen, which then activates other plasminogen molecules to plasmin.

4. Alteplase (recombinant tissue plasminogen activator, t-PA) is considered a more fibrin-specific agent compared to streptokinase because it:

• A. Only activates plasminogen in the absence of fibrin.
• B. Preferentially activates plasminogen bound to fibrin within the thrombus.
• C. Has a much longer plasma half-life.
• D. Is not antigenic.

Answer: B. Preferentially activates plasminogen bound to fibrin within the thrombus.

5. Which of the following is a key characteristic of second-generation fibrinolytic agents like tenecteplase and reteplase compared to alteplase?

• A. Oral route of administration
• B. Generally longer plasma half-lives allowing for bolus administration and/or greater fibrin specificity
• C. Complete absence of bleeding risk
• D. Mechanism independent of plasminogen activation

Answer: B. Generally longer plasma half-lives allowing for bolus administration and/or greater fibrin specificity

6. The primary therapeutic indication for the administration of fibrinolytic therapy in ST-segment elevation myocardial infarction (STEMI) is when:

• A. The patient has unstable angina.
• B. Primary percutaneous coronary intervention (PCI) is readily available within 30 minutes.
• C. Primary PCI cannot be performed in a timely manner (e.g., within 120 minutes of first medical contact).
• D. The patient is already on dual antiplatelet therapy and anticoagulation.

Answer: C. Primary PCI cannot be performed in a timely manner (e.g., within 120 minutes of first medical contact).

7. In acute ischemic stroke, fibrinolytic therapy (e.g., alteplase) is most effective and indicated if administered within a specific time window from symptom onset, typically:

• A. 12 to 24 hours
• B. 6 to 12 hours
• C. 3 to 4.5 hours (for many eligible patients)
• D. Only within the first 60 minutes

Answer: C. 3 to 4.5 hours (for many eligible patients)

8. What is the most common and serious adverse effect associated with fibrinolytic therapy?

• A. Allergic reactions
• B. Bleeding, including intracranial hemorrhage
• C. Hypotension
• D. Reperfusion arrhythmias

Answer: B. Bleeding, including intracranial hemorrhage

9. Which of the following is an ABSOLUTE contraindication to fibrinolytic therapy?

• A. Age greater than 65 years
• B. Systolic blood pressure > 180 mmHg (relative, but can be absolute if very high or uncontrolled)
• C. History of ischemic stroke 6 months ago
• D. Active internal bleeding or history of recent intracranial hemorrhage

Answer: D. Active internal bleeding or history of recent intracranial hemorrhage

10. Reteplase (r-PA) is a genetically engineered variant of t-PA that:

• A. Lacks fibrin-binding domains, leading to less fibrin specificity but potentially better clot penetration.
• B. Requires a complex with streptokinase for activity.
• C. Is administered orally.
• D. Has a very long half-life of several hours.

Answer: A. Lacks fibrin-binding domains, leading to less fibrin specificity but potentially better clot penetration. (It’s a mutant of t-PA lacking certain domains, designed for easier administration)

11. Tenecteplase (TNK-tPA) offers an advantage over alteplase in STEMI management due to its:

• A. Lower cost
• B. Ability to be administered as a single intravenous bolus and greater fibrin specificity/resistance to PAI-1
• C. Oral formulation
• D. Complete lack of antigenicity

Answer: B. Ability to be administered as a single intravenous bolus and greater fibrin specificity/resistance to PAI-1

12. Urokinase, another fibrinolytic agent, directly converts plasminogen to plasmin. It is naturally produced by:

• A. Vascular endothelial cells
• B. Streptococci bacteria
• C. Renal tubular cells
• D. Platelets

Answer: C. Renal tubular cells

13. The “systemic lytic state” induced by less fibrin-specific fibrinolytics (like streptokinase) refers to:

• A. Targeted dissolution of the occluding thrombus only.
• B. Widespread activation of plasminogen throughout the circulation, leading to degradation of fibrinogen and other clotting factors, increasing bleeding risk.
• C. A state of increased platelet aggregation.
• D. Enhanced synthesis of clotting factors by the liver.

Answer: B. Widespread activation of plasminogen throughout the circulation, leading to degradation of fibrinogen and other clotting factors, increasing bleeding risk.

14. Allergic reactions, including anaphylaxis, are a concern particularly with which fibrinolytic agent due to its bacterial origin?

• A. Alteplase
• B. Reteplase
• C. Streptokinase
• D. Tenecteplase

Answer: C. Streptokinase

15. The plasma half-life of most fibrinolytic agents, such as alteplase, is generally:

• A. Very long (days)
• B. Moderately long (12-24 hours)
• C. Relatively short (minutes)
• D. Extremely variable and unpredictable

Answer: C. Relatively short (minutes)

16. Adjunctive therapy with anticoagulants (e.g., heparin) and antiplatelet agents is commonly administered with fibrinolytics in STEMI to:

• A. Prevent allergic reactions to the fibrinolytic.
• B. Reduce the risk of reocclusion and further thrombus formation.
• C. Directly enhance the fibrinolytic activity of plasmin.
• D. Reverse bleeding complications.

Answer: B. Reduce the risk of reocclusion and further thrombus formation.

17. Plasminogen Activator Inhibitor-1 (PAI-1) is an endogenous substance that:

• A. Activates plasminogen to plasmin.
• B. Inhibits the activity of tissue plasminogen activator (t-PA) and urokinase.
• C. Degrades fibrinogen.
• D. Promotes platelet aggregation.

Answer: B. Inhibits the activity of tissue plasminogen activator (t-PA) and urokinase.

18. Monitoring parameters after administration of fibrinolytic therapy for STEMI include all of the following EXCEPT:

• A. Resolution of ST-segment elevation on ECG
• B. Relief of chest pain
• C. Assessment for signs of bleeding
• D. Routine measurement of INR to guide fibrinolytic dosing

Answer: D. Routine measurement of INR to guide fibrinolytic dosing (INR is for warfarin; coagulation parameters are checked but not typically for guiding fibrinolytic dose itself).

19. “Reperfusion arrhythmias” can occur following successful fibrinolysis and restoration of blood flow to ischemic myocardium. These are generally:

• A. A sign of failed fibrinolysis.
• B. Often transient and may indicate successful reperfusion, but require monitoring.
• C. Always life-threatening and require immediate cardioversion.
• D. Prevented by increasing the dose of the fibrinolytic agent.

Answer: B. Often transient and may indicate successful reperfusion, but require monitoring.

20. What is a key pharmacological difference between alteplase and streptokinase regarding their interaction with plasminogen?

• A. Alteplase directly cleaves fibrin; streptokinase activates plasminogen.
• B. Streptokinase is a direct enzyme; alteplase requires a cofactor.
• C. Alteplase has a higher affinity for fibrin-bound plasminogen; streptokinase forms a complex with plasminogen that becomes an activator.
• D. Alteplase is antigenic; streptokinase is not.

Answer: C. Alteplase has a higher affinity for fibrin-bound plasminogen; streptokinase forms a complex with plasminogen that becomes an activator.

21. The route of administration for all currently available fibrinolytic agents for systemic use (e.g., STEMI, PE, stroke) is:

• A. Oral
• B. Subcutaneous
• C. Intramuscular
• D. Intravenous

Answer: D. Intravenous

22. Which fibrinolytic agent is a non-enzymatic protein derived from beta-hemolytic streptococci?

• A. Alteplase
• B. Urokinase
• C. Streptokinase
• D. Tenecteplase

Answer: C. Streptokinase

23. The term “clot busters” is a common layman’s term for which class of drugs?

• A. Anticoagulants
• B. Antiplatelet agents
• C. Fibrinolytic agents
• D. Statins

Answer: C. Fibrinolytic agents

24. In the management of acute massive pulmonary embolism causing hemodynamic instability, fibrinolytic therapy aims to:

• A. Prevent DVT formation in the legs.
• B. Rapidly dissolve the obstructing pulmonary embolus and improve right ventricular function.
• C. Primarily reduce inflammation in the lungs.
• D. Lower pulmonary artery pressure by vasodilation only.

Answer: B. Rapidly dissolve the obstructing pulmonary embolus and improve right ventricular function.

25. If a patient develops a severe allergic reaction to streptokinase, future use of streptokinase is:

• A. Permissible if premedicated with antihistamines.
• B. Generally contraindicated due to pre-formed antibodies.
• C. Safe after a 6-month waiting period.
• D. Only allowed if no other fibrinolytic is available.

Answer: B. Generally contraindicated due to pre-formed antibodies.

26. What is the mechanism by which plasmin degrades fibrin?

• A. It inhibits fibrin polymerization.
• B. It cleaves fibrinogen into fibrin monomers.
• C. It proteolytically cleaves fibrin polymers into soluble degradation products.
• D. It cross-links fibrin to make it more stable.

Answer: C. It proteolytically cleaves fibrin polymers into soluble degradation products.

27. The fibrin specificity of a fibrinolytic agent refers to its ability to:

• A. Dissolve only arterial thrombi.
• B. Preferentially activate plasminogen that is bound to fibrin in a thrombus, rather than circulating plasminogen.
• C. Only be effective against fresh clots.
• D. Bind specifically to platelets.

Answer: B. Preferentially activate plasminogen that is bound to fibrin in a thrombus, rather than circulating plasminogen.

28. Why is rapid administration crucial for fibrinolytic therapy in conditions like STEMI or acute ischemic stroke?

• A. To minimize the cost of the drug.
• B. “Time is tissue”; earlier reperfusion limits the extent of ischemic damage and improves outcomes.
• C. To prevent allergic reactions.
• D. To ensure the drug is fully metabolized before reaching the target.

Answer: B. “Time is tissue”; earlier reperfusion limits the extent of ischemic damage and improves outcomes.

29. Anistreplase (APSAC) was a first-generation fibrinolytic that was an acylated complex of streptokinase and plasminogen. The acylation was intended to:

• A. Increase its antigenicity.
• B. Protect the active site until it reached the clot, prolonging its half-life and allowing bolus administration.
• C. Make it orally bioavailable.
• D. Reduce its fibrinolytic activity.

Answer: B. Protect the active site until it reached the clot, prolonging its half-life and allowing bolus administration.

30. Which of the following situations would make a patient a poorer candidate for fibrinolytic therapy due to increased bleeding risk?

• A. Well-controlled hypertension
• B. Recent major surgery or significant trauma (within 2-3 weeks)
• C. History of stable angina
• D. Age 50 years

Answer: B. Recent major surgery or significant trauma (within 2-3 weeks)

31. Tenecteplase has modifications to its structure compared to alteplase that result in:

• A. Decreased fibrin specificity
• B. Increased resistance to inactivation by PAI-1 and a longer half-life
• C. A need for continuous infusion
• D. Activation by antithrombin III

Answer: B. Increased resistance to inactivation by PAI-1 and a longer half-life

32. While fibrinolytics dissolve existing clots, they do not prevent new clot formation. Therefore, they are often followed by or given with:

• A. Vitamin K
• B. Anticoagulant and/or antiplatelet therapy
• C. Procoagulant factors
• D. Plasma expanders only

Answer: B. Anticoagulant and/or antiplatelet therapy

33. The primary clearance mechanism for recombinant t-PA (alteplase) from the circulation is:

• A. Renal excretion as unchanged drug
• B. Hepatic metabolism
• C. Degradation by circulating plasmin
• D. Binding to red blood cells

Answer: B. Hepatic metabolism

34. The development of antibodies against streptokinase can lead to:

• A. Enhanced fibrinolytic effect on subsequent administration.
• B. Neutralization of the drug and reduced efficacy, or allergic reactions on re-exposure.
• C. A longer plasma half-life.
• D. Increased fibrin specificity.

Answer: B. Neutralization of the drug and reduced efficacy, or allergic reactions on re-exposure.

35. Which of the following is NOT a direct action of plasmin?

• A. Degradation of fibrin
• B. Degradation of fibrinogen
• C. Degradation of other clotting factors (e.g., Factor V, VIII)
• D. Activation of prothrombin to thrombin

Answer: D. Activation of prothrombin to thrombin

36. The success of fibrinolytic therapy in STEMI can be clinically assessed by observing:

• A. A rapid increase in cardiac enzyme levels (washout phenomenon) and resolution of chest pain/ST elevation.
• B. A gradual decrease in blood pressure over 24 hours.
• C. An increase in platelet count.
• D. The development of a bleeding complication.

Answer: A. A rapid increase in cardiac enzyme levels (washout phenomenon) and resolution of chest pain/ST elevation.

37. Compared to intravenous UFH, fibrinolytic agents have a fundamentally different role in ACS because fibrinolytics:

• A. Prevent platelet aggregation.
• B. Inhibit the coagulation cascade.
• C. Actively dissolve an already formed thrombus.
• D. Are administered orally.

Answer: C. Actively dissolve an already formed thrombus.

38. If intracranial hemorrhage is suspected after fibrinolytic administration, the immediate first step is to:

• A. Administer another bolus of the fibrinolytic.
• B. Stop the fibrinolytic infusion and any concomitant anticoagulants/antiplatelets.
• C. Administer aspirin.
• D. Perform elective PCI.

Answer: B. Stop the fibrinolytic infusion and any concomitant anticoagulants/antiplatelets.

39. What is the main pharmacological reason why fibrinolytics are not typically used for unstable angina or NSTEMI without ST elevation (unless specific circumstances apply, like posterior MI with ST depression)?

• A. The thrombus in these conditions is usually not fibrin-rich or fully occlusive, and the risk of harm from bleeding outweighs the benefit.
• B. These conditions are always managed with surgery.
• C. Fibrinolytics are too expensive for these conditions.
• D. Patients with NSTE-ACS always have contraindications to fibrinolytics.

Answer: A. The thrombus in these conditions is usually not fibrin-rich or fully occlusive, and the risk of harm from bleeding outweighs the benefit.

40. The discovery of t-PA (tissue plasminogen activator) as an endogenous fibrinolytic was a key step towards developing:

• A. More antigenic fibrinolytic agents.
• B. Fibrinolytic agents with greater fibrin specificity.
• C. Oral fibrinolytic drugs.
• D. Fibrinolytic inhibitors.

Answer: B. Fibrinolytic agents with greater fibrin specificity.

41. Which statement best describes the current place of streptokinase in the management of STEMI in developed countries with access to newer agents or PCI?

• A. It is the first-line fibrinolytic agent due to its low cost.
• B. Its use has largely been superseded by more fibrin-specific agents with better safety/efficacy profiles or by primary PCI.
• C. It is preferred for patients with a high risk of intracranial hemorrhage.
• D. It is only administered via intra-arterial route.

Answer: B. Its use has largely been superseded by more fibrin-specific agents with better safety/efficacy profiles or by primary PCI.

42. The “time window” for administering fibrinolytics in acute ischemic stroke is critical because beyond this window:

• A. The drug becomes ineffective at dissolving the clot.
• B. The risk of intracranial hemorrhage significantly increases and outweighs potential benefits.
• C. Allergic reactions are more likely.
• D. The clot spontaneously dissolves.

Answer: B. The risk of intracranial hemorrhage significantly increases and outweighs potential benefits.

43. Pharmacologically, the ideal fibrinolytic agent would possess:

• A. High antigenicity and a long half-life.
• B. High fibrin specificity, low antigenicity, convenient administration, and a favorable risk-benefit profile.
• C. The ability to cause a profound systemic lytic state.
• D. Oral bioavailability and slow onset of action.

Answer: B. High fibrin specificity, low antigenicity, convenient administration, and a favorable risk-benefit profile.

44. A patient who has received streptokinase within the last 6-12 months should generally not receive it again due to:

• A. The risk of profound hypotension.
• B. The presence of neutralizing antibodies reducing efficacy and increasing allergy risk.
• C. The development of resistance by the fibrin clot.
• D. The drug’s accumulation in tissues.

Answer: B. The presence of neutralizing antibodies reducing efficacy and increasing allergy risk.

45. Aminocaproic acid and tranexamic acid are pharmacological agents that act as:

• A. Fibrinolytic activators
• B. Antidotes to fibrinolytic therapy (antifibrinolytic agents) by inhibiting plasmin and plasminogen activation
• C. Direct thrombin inhibitors
• D. Vitamin K antagonists

Answer: B. Antidotes to fibrinolytic therapy (antifibrinolytic agents) by inhibiting plasmin and plasminogen activation

46. The administration of fibrinolytic agents is guided by strict protocols and patient selection criteria primarily to:

• A. Maximize the drug manufacturer’s profit.
• B. Minimize the risk of life-threatening bleeding complications while maximizing the potential for benefit.
• C. Ensure only young patients receive the therapy.
• D. Simplify the treatment process for clinicians.

Answer: B. Minimize the risk of life-threatening bleeding complications while maximizing the potential for benefit.

47. How does the fibrinolytic system differentiate between pathological thrombi and physiological hemostatic plugs that prevent bleeding from injury?

• A. It doesn’t; it lyses all fibrin indiscriminately, leading to bleeding risk.
• B. Physiological hemostatic plugs are more resistant to lysis due to higher concentrations of PAI-1 and cross-linked fibrin. Fibrin-specific agents preferentially target thrombi.
• C. Fibrinolytics are only administered to sites of pathological thrombi.
• D. Pathological thrombi are composed of different types of fibrin.

Answer: B. Physiological hemostatic plugs are more resistant to lysis due to higher concentrations of PAI-1 and cross-linked fibrin. Fibrin-specific agents preferentially target thrombi. (Though some systemic effect still occurs).

48. One of the earliest signs of successful reperfusion after fibrinolytic therapy for STEMI can be:

• A. Worsening chest pain
• B. Sudden resolution of ST-segment elevation on ECG
• C. A rapid drop in blood pressure to shock levels
• D. An increase in cardiac troponin levels without any change in symptoms or ECG

Answer: B. Sudden resolution of ST-segment elevation on ECG

49. The choice between different fibrinolytic agents (e.g., alteplase vs. tenecteplase) in clinical practice may be influenced by:

• A. Patient’s hair color
• B. Ease of administration (bolus vs. infusion), cost, and specific clinical trial data for the indication
• C. The brand name only
• D. The time of day the event occurred

Answer: B. Ease of administration (bolus vs. infusion), cost, and specific clinical trial data for the indication

50. Which factor is NOT typically considered a major component in the decision-making process for administering fibrinolytic therapy in STEMI?

• A. Time since symptom onset
• B. ECG findings
• C. Presence of contraindications
• D. Patient’s baseline cholesterol level

Answer: D. Patient’s baseline cholesterol level (While a risk factor for IHD, it’s not an acute decision point for thrombolysis in STEMI).