Tag: Fibrinolytic Drugs

Fibrinolytic Drugs

FIBRINOLYTIC DRUGS

Q. 1 The     following     statements     regarding streptokinase are true, except:
 A It is a protein produced by streptococci.
 B Its  complex  with  plasminogen  is  inhibited  by aIpha2-anti plasmin.
 C It may rarely produce anaphylaxis
 D It is initially given as a loading dose.
Q. 1 The     following     statements     regarding streptokinase are true, except:
 A It is a protein produced by streptococci.
 B Its  complex  with  plasminogen  is  inhibited  by aIpha2-anti plasmin.
 C It may rarely produce anaphylaxis
 D It is initially given as a loading dose.
Ans. B

Explanation:

Streptokinase is a 47-kDa protein produced by beta-hemolytic streptococci. It forms a stable complex with plasminogen,

which is not inhibited by antiplasmih. A large loading dose is given intravenously to overcome antibodies that may be

formed from prior streptococcal infections. Being a foreign protein it may rarely cause anaphylaxis.


Q. 2 The following statements regarding tissue plasminogen activator are  true, except: 
 A It is produced by recombinant DNA technology. 
 B Induction of systemic lytic state is limited with its use.
 C It is ineffective in lysing thrombi of myocardial infarction.
 D It is a poor plasminogen activator in the absence of fibrin.
Q. 2 The following statements regarding tissue plasminogen activator are  true, except: 
 A It is produced by recombinant DNA technology. 
 B Induction of systemic lytic state is limited with its use.
 C It is ineffective in lysing thrombi of myocardial infarction.
 D It is a poor plasminogen activator in the absence of fibrin.
Ans. C

Explanation:

Tissue plasminogen activator (alteplase) is produced by recombinant DNA technology. It is a poor plasminogen

activator in the absence of fibrin. Its specificity for fibrin limits systemic formation of plasminand induction of systemic

lytic state. It is given as intravenous bolus for coronary thrombolysis during treatment of myocardial infarction.


Q. 3

A 60-year-old male with angina comes to the emergency with severe chest pain unresponsive to sublingual nitroglycerin. An ECG shows ST segment elevation in the anterolateral leads, and thrombolytic therapy is initiated. If streptokinase is given to this patient, it may produce thrombolysis after binding to which of the following proteins?

 A

Antithrombin III

 B

Fibrin

 C

Plasminogen

 D

Protein C

Q. 3

A 60-year-old male with angina comes to the emergency with severe chest pain unresponsive to sublingual nitroglycerin. An ECG shows ST segment elevation in the anterolateral leads, and thrombolytic therapy is initiated. If streptokinase is given to this patient, it may produce thrombolysis after binding to which of the following proteins?

 A

Antithrombin III

 B

Fibrin

 C

Plasminogen

 D

Protein C

Ans. C

Explanation:

The fibrinolytic activity of streptokinase is due to its ability to bind and cleave plasminogen, producing plasmin.

Plasmin directly cleaves fibrin, both between and within the fibrin polymers, thus breaking up thrombi and potentially restoring blood flow to ischemic cardiac muscle.

This same mechanism of fibrinolysis is shared by urokinase and tissue-plasminogen activator (tPA).

Antithrombin III is a coagulation inhibitor that binds to and inactivates thrombin. Antithrombin III is anticoagulant, not fibrinolytic.
 
Fibrin is not directly acted upon by streptokinase. It is indirectly cleaved through the action of plasmin.
 
Protein C is a glycoprotein that modulates coagulation by inhibiting the procoagulant activities of factors V/Va and VIII/VIIIa. Protein C has no inherent fibrinolytic activity.

Quiz In Between


Q. 4

Scenario: Mr Kapoor has high level of Lp (a) and he has been warned of the high risk to his health.
 
Assertion: Lipoprotein (a) is very strongly associated with Myocardial infarction.
 
Reason: It interferes with plasminogen activation and impairs fibrinolysis.
 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Q. 4

Scenario: Mr Kapoor has high level of Lp (a) and he has been warned of the high risk to his health.
 
Assertion: Lipoprotein (a) is very strongly associated with Myocardial infarction.
 
Reason: It interferes with plasminogen activation and impairs fibrinolysis.
 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Ans. A

Explanation:

Lipoprotein (a) is very strongly associated with Myocardial infarction and is sometimes called the little ‘rascal’. It is associated with LDL.Lp (a) has significant homology with plasminogen. So it interferes with plasminogen activator and impairs fibrinolysis. This leads to unopposed intravascular thrombosis and possible myocardial infarction.

Ref: Textbook of Biochemistry By DM Vasudevan, 5th Edition, Page 156

Q. 5

Plasminogen domain structurally resembles which of the following?

 A

Fibrinogen

 B

LDL receptor

 C

Apolipoprotein (a)

 D

Prothrombin

Q. 5

Plasminogen domain structurally resembles which of the following?

 A

Fibrinogen

 B

LDL receptor

 C

Apolipoprotein (a)

 D

Prothrombin

Ans. C

Explanation:

Apo(a) of Lp(a) is structurally related to plasminogen and appears to be atherogenic by interfering with fibrinolysis of thrombi on the surfaces of plaques. 

Imprortant – Apo(a) shares a remarkable degree of homology with plasminogen in

3 main respects:
a) multiple tandem repeats of domains similar to kringle four
b) a single region resembling kringle five
c) pseudoprotease segment. 

Plasminogen and apo(a) are genetically linked on chromosome 6 and may have arisen from a common ancestral gene.

Ref: Hajjar K.A., Marcus A.J., Muller W.A. (2010). Chapter 117. Vascular Function in Hemostasis. In J.T. Prchal, K. Kaushansky, M.A. Lichtman, T.J. Kipps, U. Seligsohn (Eds), Williams Hematology, 8e.


Q. 6

All are fibrinolytic, except –

 A

Streptokinase

 B

Urokinase

 C

Alteplase

 D

Epsilon amino caproic acid

Q. 6

All are fibrinolytic, except –

 A

Streptokinase

 B

Urokinase

 C

Alteplase

 D

Epsilon amino caproic acid

Ans. D

Explanation:

Ans. is ‘d’ i.e., Epsilon amino caproic acid

Quiz In Between


Q. 7

Which one of the following preferentially activates plasminogen bound to fibrin and avoids the systemic lytic state –

 A

Streptokinase

 B

Aminocaproic acid

 C

Tranexamic acid

 D

Alteplase

Q. 7

Which one of the following preferentially activates plasminogen bound to fibrin and avoids the systemic lytic state –

 A

Streptokinase

 B

Aminocaproic acid

 C

Tranexamic acid

 D

Alteplase

Ans. D

Explanation:

Ans. is ‘d’ i.e., Alteplase

o Alteplase, Reteplase and tenecteplase are recombinant t-PA. These are nonantigenic. They activate fibrin bound plasminogen only.

o Streptokinase activates both free as well as fibrin bound plasminogen.


Q. 8

Which prevents plasminogen activators‑

 A

Streptokinase

 B

Aminocaproic acid

 C

Reteplase

 D

Clopidogrel

Q. 8

Which prevents plasminogen activators‑

 A

Streptokinase

 B

Aminocaproic acid

 C

Reteplase

 D

Clopidogrel

Ans. B

Explanation:

Ans. is ‘b’ i.e., Aminocaproic acid

o Epsilon amino caproic acid (EACA) competitively inhibits plasminogen activation.


Q. 9

In pulmonary embolism, fibrinolytic therapy is responsible for –

 A

Risk of haemorrhage

 B

Prognosis good

 C

Massive emboli

 D

All of the above

Q. 9

In pulmonary embolism, fibrinolytic therapy is responsible for –

 A

Risk of haemorrhage

 B

Prognosis good

 C

Massive emboli

 D

All of the above

Ans. A

Explanation:

Answer is ‘a’ i.e. Risk of Hemorrhage 

Hemorrhage is the main complication of fibrinolytic therapy, so it is contraindicated in all situations where the risk of bleeding is increased – recent trauma, surgery, biopsies, stroke, peptic ulcer, aneurysms, bleeding disorders, diabetes, acute pancreatitis etc.)

Quiz In Between


Q. 10

All of the following drugs are used in the management of acute myocardial infarction, except:

 A

Tissue Plasminogen activator

 B

Intravenous beta blockers

 C

Acetylsalicylic acid

 D

Calcium channel blockers

Q. 10

All of the following drugs are used in the management of acute myocardial infarction, except:

 A

Tissue Plasminogen activator

 B

Intravenous beta blockers

 C

Acetylsalicylic acid

 D

Calcium channel blockers

Ans. D

Explanation:

Answer is D (Calcium channel blockers)

Results of multiple trials of different calcium antagonists have failed to establish a role for these agents in the treatment of most patients with MI, in contrast to the more consistent data that exist for other drugs eg. beta blockers, aspirin and fibrinolytic agents. The routine use of calcium channel blockers can not be recommended’


Q. 11

In MI following are used Except:

 A

Fibrinolytics

 B

Plasminogen activator inhibitor

 C

Anti thrombin

 D

Platelet inhibitor

Q. 11

In MI following are used Except:

 A

Fibrinolytics

 B

Plasminogen activator inhibitor

 C

Anti thrombin

 D

Platelet inhibitor

Ans. B

Explanation:

Answer is B (Plasminogen activator inhibitor)

Plaminogen Activators are used in Ml and not inhibitors of Plasminogen activators.

The management of MI requires fibrinolysis, which is achieved by Plasminogen activators and not by Plasminogen inhibitor.


Q. 12

Streptokinase and Urokinase are contraindicated in:

 A

Intracranial malignancy

 B

Pulmonary Embolism

 C

AV fistula

 D

Thrombophlebitis

Q. 12

Streptokinase and Urokinase are contraindicated in:

 A

Intracranial malignancy

 B

Pulmonary Embolism

 C

AV fistula

 D

Thrombophlebitis

Ans. A

Explanation:

Answer is A (Intracranial malignancy)

Malignant Intracranial Neoplasm is an absolute contraindication for Thrombolysis (Streptokinase / Urokinase).

Contraindications and Cautions for Fibrinolytic Use in STEMI:

Absolute Contraindications

 

Relative Contraindications

•  Any prior intracranial hemorrhage

 

•  History of chronic severe poorly controlled hypertension

•  Known structural cerebral vascular lesion

 

•  Severe uncontrolled hypertension on presentation

(e.g., arteriovenous malformation)

 

(SBP > 180 Hg or DBP > 110 Hg)

•   Known malignant intracranial neoplasm

 

•  History of prior ischemic stroke > 3 months, dementia, or known

(primary or metastatic)

 

intracranial pathology not covered in contraindications

•  Ischemic stroke within 3 months

 

•  Traumatic or prolonged (>10 min) CPR or major surgery (<3 wk)

(Except acute inschemic stroke within 3 hr.)

 

•  Recent (within 2-4 week) internal bleeding

•  Suspected aortic dissection

 

•  Non compressible vascular punctures

•  Active bleeding diathesis (excluding menses)

 

•  For streptokinase/anistreplase: prior exposure (>5 days ago) or

•  Significant closed head or facial trauma within

3 mo.

prior allergic reaction to these agents

 

 

•  Pregnancy

 

 

•  Active peptic, ulcer

 

 

•  Current use of anticoagulants

 

 

(the higher the INR, the higher the risk of bleeding)

Quiz In Between


Q. 13

All of the following are complications of streptokinase, Except:

 A

Joint pain

 B

Inctracranial bleed

 C

Fever

 D

Anaphylaxis

Q. 13

All of the following are complications of streptokinase, Except:

 A

Joint pain

 B

Inctracranial bleed

 C

Fever

 D

Anaphylaxis

Ans. A

Explanation:

Answer is A (Joint Pain)

Joint pain is not a recognized complication of streptokinase usage.

Complication of streptokinase

  • Hypersensitivity reaction and Anaphylaxis (specially when used second time)
  • Haemorrhage (Intracranial bleed: Risk of stroke)
  • Fever
  • Hypotensin
  • Arrhythmia

Q. 14

The treatment of choice in a patient with Massive Pulmonary Embolism in Shock is:

 A

Thrombolytic Therapy

 B

Low Molecular Weight Heparin

 C

Aggressive fluid resuscitation

 D

Diuretic Therapy

Q. 14

The treatment of choice in a patient with Massive Pulmonary Embolism in Shock is:

 A

Thrombolytic Therapy

 B

Low Molecular Weight Heparin

 C

Aggressive fluid resuscitation

 D

Diuretic Therapy

Ans. A

Explanation:

Answer is A (Thrombolytic Therapy):

Normotension with Right ventricular hypokinesia suggests a diagnosis of submassive pulmonary embolism and stratifies the patient into an intermediate risk category. Treatment for intermediate risk patients with submassive PE is controversial. Guidelines recommend individual risk assessment for the thrombotic burden versus risk of bleeding. According to Harrisons textbook young patients without any comorbidities that fall into the intermediate risk category are excellent candidates for thrombolysis. The patient in question is a young 20 years old patient and the question makes no mention of any comorbidities, hence thrombolysis is the single best answer of choice.


Q. 15

A young patient presents to the Emergency with Acute pulmonary embolism. Patient’s blood pressure is normal but echocardiography reveals Right ventricular hypokinesia and compromised cardiac output.

The treatment of choice in this patient is:

 A

Thrombolytic therapy

 B

Anticoagulation with low molecular weight heparin

 C

Anticoagulation with warfarin

 D

Inferior vena cora filters

Q. 15

A young patient presents to the Emergency with Acute pulmonary embolism. Patient’s blood pressure is normal but echocardiography reveals Right ventricular hypokinesia and compromised cardiac output.

The treatment of choice in this patient is:

 A

Thrombolytic therapy

 B

Anticoagulation with low molecular weight heparin

 C

Anticoagulation with warfarin

 D

Inferior vena cora filters

Ans. A

Explanation:

Answer is A (Thrombolytic Therapy):

Guidelines on the diagnosis and management of acute pulmonary embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC); (Link: http://eurheartj.oxfordjournals.org/content/29/18/2276full#sec-40)

Thrombolytic therapy is the treatment of choice in patients with High-risk Pulmonary Embolism presenting with cardiogenic shock and/or persistent arterial hypotension. Intravenous unfractionated heparin should be the preferred mode qf initial anticoagulation in these patients, as LMWH and fondaparinux have not been tested in the setting of hypotension and shock. Aggressive fluid challenge is not recommended. Experimental studies indicate that aggressive volume expansion may worsen RV. function by causing mechanical overstretch and/or by reflex mechanisms that depress contractility.

Non-High Risk Pulmonary Embolism

High Risk Pulmonary Embolism (Clinically Massive) Shock Or Hypotension

  • Anticoagulation should be initiated without delay (Intravenous unfractionated heparin should be the preferred mode of initial anticoagulation in these patients)
  • Thrombolysis is the treatment of choice in patients with high-risk PE unless there are absolute contraindications to its use.
  • Surgical embolectomy is the preferred therapy in patients with absolute contraindications to thrombolysis and in those in whom thrombolysis has failed to improve haemodynamic status. (If this is not immediately available, catheter embolectomy or thrombus  fragmentation may be considered, though the safety and efficacy of such interventions has not been adequately documented)

Note (For High Risk Pulmonary Embolism)

  • Systemic hypotension should be corrected to prevent progression of RV failure and death due to PE.
  • Vasopressive drugs are recommended.for hypotensive patients with PE.
  • Aggressive fluid challenge is not recommended

Intermediate Risk (Sub-massive) Normotension but Right Ventricular Hypokinesis

  • Anticoagulation should be initiated without delay (Use of LMWH or fondaparinux is the recommended form of initial treatment for most patients)
  • Thrombolysis: Routine use of thrombolysis in non–high­risk PE patients is not recommended, but it may be considered in selected patients with intermediate-risk PE

Note:

  • Controversy still surrounds the appropriate treatment of this patient group.
  • Therapy needs to be individualized

Quiz In Between


Q. 16

The only thrombolytic agent approved for the treatment of acute ischemic stroke is :

 A

Tissue Plasminogen activator

 B

Streptokinase

 C

Urokinase

 D

Pro-urokinase

Q. 16

The only thrombolytic agent approved for the treatment of acute ischemic stroke is :

 A

Tissue Plasminogen activator

 B

Streptokinase

 C

Urokinase

 D

Pro-urokinase

Ans. A

Explanation:

Answer is A (Tissue plasminogen activator):

Recombinant Tissue plasminogen Activator (RtPA) is the only thrombolytic agent that is approved for the treatment of acute ischaemic stroke

The use of all other thrombolytics except Recombinant Tissue plasminogen activator has been stopped because of associated high rates of intracranial hemorrhage.

`The National Institute of Neurological disorders and recombinant tPA stroke study showed a clear benefit of intravenous rtPA in selected patients with Acute stroke’ — Harrisons 16th/ 2374

The use of thrombolysis has always been an issue of controversy in the management of ischaemic strokes. The theoretical advantage of these agents in clearing arterial occlusions has to be weighed against the risk of intracranial haemorrhage.

`Despite an increased incidence of symptomatic intracerebral bleed, treatment with intravenous rtPA within 3 hours of onset of ischaemic stroke improved clinical outcome’ – Harrison 171h/ 2515.

 

 

 

Q. 17

The only thrombolytic agent approved for the treatment of acute ischemic stroke is:

 A

Tissue Plasminogen activator

 B

Streptokinase

 C

Urokinase

 D

Pro-urokinase

Q. 17

The only thrombolytic agent approved for the treatment of acute ischemic stroke is:

 A

Tissue Plasminogen activator

 B

Streptokinase

 C

Urokinase

 D

Pro-urokinase

Ans. A

Explanation:

Answer is A (Tissue plasmiogen Activator):

Recombinant Tissue plasminogen Activator (RtPA) is the only thrombolytic agent that is approved for the treatment of acute ischaemic stroke

The use of all other thrombolytics except Recombinant Tissue plasminogen activator has been stopped because of associated high rates of intracranial hemorrhage.


Q. 18

Amongst the following, thrombolytics are LEAST in:

 A

Acute myocardial infarction

 B

Peripheral arterial occlusion

 C

Hemorrhagic stroke

 D

Deep venous thrombosis

Q. 18

Amongst the following, thrombolytics are LEAST in:

 A

Acute myocardial infarction

 B

Peripheral arterial occlusion

 C

Hemorrhagic stroke

 D

Deep venous thrombosis

Ans. C

Explanation:

Ans. C i.e. Hemorrhagic stroke

Thrombolytic agents

  • They are used for the treatment of myocardial infarction (heart attack), thromboembolic strokes, deep vein thrombosis and pulmonary embolism to clear a blocked artery and avoid permanent damage to the perfused tissue (e.g. myocardium, brain, leg) and death.
  • They may also be used to clear blocked catheters that are used in long-term medical therapy.
  • Thrombolytic therapy in hemorrhagic strokes is contraindicated, as its use in that situation would prolong bleeding into the intracranial space and cause further damage.

Quiz In Between


Q. 19

Which of the following drug inhibits plasminogen activation : 

March 2009

 A

Aspirin

 B

Tranexaemic acid

 C

Alteplase

 D

Streptokinase

Q. 19

Which of the following drug inhibits plasminogen activation : 

March 2009

 A

Aspirin

 B

Tranexaemic acid

 C

Alteplase

 D

Streptokinase

Ans. B

Explanation:

Ans.B: Tranexaemic Acid

Tranexaemic acid is an antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin, a molecule responsible for the degradation of fibrin.

It has roughly 7 times the antifibrinolytic activity of an older analogue, Epsilon-amino-caproic acid (EACA).

Main side-effects are nausea and diarrhea.headache, giddiness and thrombophlebitis of injected vein are other adverse effects.


Q. 20

Treatment of choice in a patient of pulmonary embolism with right ventricular hypokinesia and compromised cardiac output but normal blood pressure is:    

March 2013

 A

Thrombolytic agent

 B

Low molecular weight heparin

 C

Warfarin

 D

IVC filters

Q. 20

Treatment of choice in a patient of pulmonary embolism with right ventricular hypokinesia and compromised cardiac output but normal blood pressure is:    

March 2013

 A

Thrombolytic agent

 B

Low molecular weight heparin

 C

Warfarin

 D

IVC filters

Ans. A

Explanation:

Ans. A i.e. Thrombolytic agents

Thrombolytic/ fibrinolytic agents are given when rapid lysis of clot is important.

Because thrombolytic agents increase the risk of hemorrhage, they are reserved for use when occlusion has produced right sided heart failure and hemorrhagic instability

Remember: Unless contraindicated, the drug of choice for documented or suspected pulmonary embolism is heparin


Q. 21

Fibrin is degraded by ‑

 A

Thrombin

 B

Fibrin

 C

Plasmin

 D

None

Q. 21

Fibrin is degraded by ‑

 A

Thrombin

 B

Fibrin

 C

Plasmin

 D

None

Ans. C

Explanation:

 

  • Coagulation must be balanced with fibrinolysis to limit the hemostatic plug to the site of injury.
  • Injured vascular endothelium secret plasminogen activator that converts inactive plasminogen to active plasmin.
  • Plasmin breaks down fibrin resulting in production of fibrin degradation products.
  • Fibrinolytic system is regulated by plasminogen activator inhibitors (PAIs) that are secreted by endothelium.

Quiz In Between


Q. 22

Streptokinase causes increase in ‑

 A

Plasmin

 B

Thrombin

 C

Kallikrein

 D

Angiotensin II

Q. 22

Streptokinase causes increase in ‑

 A

Plasmin

 B

Thrombin

 C

Kallikrein

 D

Angiotensin II

Ans. A

Explanation:

Ans. is ‘a’ i.e., Plasmin

Streptokinase

  • Fibrinolytic drug
  • Obtained from group C streptococci
  • Streptokinase is inactive as such. It combines with’ circulating plasminogen molecules to form an activator complex, which then causes limited proteolysis of other plasminogen molecules to generate active enzyme plasmin.

Q. 23

Dose of rTPA in ischaemic stroke is

 A

60 mg

 B

90 mg

 C

100 mg

 D

120 mg

Q. 23

Dose of rTPA in ischaemic stroke is

 A

60 mg

 B

90 mg

 C

100 mg

 D

120 mg

Ans. B

Explanation:

Ans. is ‘b’ i.e., 90 mg

  • Recommended dose for thrombolysis with IV TPA is 0.9 mg/kg with the maximum dose being 90 mg. 10% should be given as a bolus over one minute, followed by remaining 90% as a continuous infusion over 60 minutes.

Q. 24

The treatment of a patient with myocardial infarction is thrombolytic therapy, if the patient presents within hours of chest pain:

 A

6 hours

 B

12 hours

 C

18 hours

 D

24 hours

Q. 24

The treatment of a patient with myocardial infarction is thrombolytic therapy, if the patient presents within hours of chest pain:

 A

6 hours

 B

12 hours

 C

18 hours

 D

24 hours

Ans. D

Explanation:

Ans. d. 24 hours

Quiz In Between


Q. 25

Mechanism of action of transexaminic acid is

 A

Decrease vascular permeability

 B

Smooth muscle contraction

 C

Activates Plasmin formation

 D

Prevents fibrinolysis

Q. 25

Mechanism of action of transexaminic acid is

 A

Decrease vascular permeability

 B

Smooth muscle contraction

 C

Activates Plasmin formation

 D

Prevents fibrinolysis

Ans. D

Explanation:

Ans. is `d’ i.e., Prevents fibrinolysis 


Q. 26

Which prevents plasminogen activators ‑

 A

Streptokinase

 B

Aminocaproic acid

 C

Reteplase

 D

Clopidogrel

Q. 26

Which prevents plasminogen activators ‑

 A

Streptokinase

 B

Aminocaproic acid

 C

Reteplase

 D

Clopidogrel

Ans. B

Explanation:

Ans. is ‘b’ i.e., Aminocaproic acid 

Antifibrinolytics

  • These drugs inhibit plasminogen activation and dissolution of clot.
  • Examples are Epsilon amino-caproic acid (EACH), Aprotinin and Tranexaemic acid.
  • These drugs are used for overdoses of fibrinolytic agents.

Quiz In Between



Fibrinolytic Drugs

FIBRINOLYTIC DRUGS


FIBRINOLYTIC DRUGS

  • Also referred as “thrombolytics”.
  • Are drugs activating plasminogen to form plasmin & helping thrombus lysis.

MOA:

  • Insoluble fibrin molecules are broken down to soluble fragments by plasmin.
    • Plasmin is generated from plasminogen, by tissue plasminogen activator (tPA).
    • tPA selectively activates fibrin-bound plasminogen in thrombus.
  • Excess plasmin generated is inactivated by circulating antiplasmins.

Adverse effect:

  • Bleeding (major) – Due to lysis of physiological thrombi & excessive circulating plasmin.

Indication:

  • Treatment of acute myocardial infarction (Stemi)
    • Administered i.v. within 12 hours preferably within 1st 3-6 hours.          
  • In severe, life-threatening pulmonary embolism (Massive Pulmonary Embolism in Shock).

Contra-indications:

  • Mainly increased bleeding risk.
  • Based on various scenarios of bleeding risks divided into, absolute & relative.

Absolute

Relative

Absolute of hemorrhagic stroke at any time

Current use of anticoagulants (INR≥ 2)

History  of non-hemorrhagic stroke within the past year

Recent  (>2weeks) invasive or surgical procedure

Marked hypertension (systolic >180 and/or diastolic > 110mm Hg)

Prolonged (> 10 min.) cardiopulmonary resuscitation.

Suspicion of aortic dissection

Known bleeding diathesis

Active internal bleeding (excluding menses)

Pregnancy

 

Hemorrhagic ophthalmic condition (Eg. hemorrhagic diabetic retinopathy)

 

Active peptic ulcer disease

 

History  of severe hypertension (currently adequately controlled)

Fibrinolytic overdose:

  • Specific antidote: Epsilon amino caproic acid (EACA) & tranexaemic acid.

Important drugs:

  • Streptokinase, anistreplase urokinase, alteplase, reteplase & tenecteplase.
  • Streptokinase, anistreplase & urokinase – 
    • Activate bound fibrin as well as circulating plasminogen
    • Leads to systemic lytic state.
  • Reteplase, alteplase & tenecteplase – Fibrin-specific.

1. Streptokinase:

  • Obtained from β-hemolytic streptococci.
  • Activates fibrin-bound as well as circulating plasminogen.
MOA:
  • Does not directly convert plasminogen to plasmin (unlike other plasminogen activators).
  • Forms complex with plasminogen, exposing its active site.
  • Altered plasminogen acts like tPA & activates other plasminogen molecules to plasmin.
Properties:
  • Antigenic causing allergic reactions.
    • Lead to neutralizing antibody formation.
  • Less effective on repeated usage.
  • Least expensive.

2. Anistreplase:

  • Formed by combining streptokinase with Lys-plasminogen.
  • Active site of exposed plasminogen is masked with anisoyl group.
  • Non-specific for fibrin-bound plasminogen.
Properties:
  • Drug administration:
    • Via a single bolus infusion.
  • Half-life: 
    • 100 minutes.
    • Due to slow removal of anisoyl group by deacylation, on i.v. infusion.
  • Antigenic.

3. Urokinase:

  • Isolated from human urine.
  • MOA: 
    • Directly converts plasminogen to plasmin.
    • Affects both free & circulating plasmin.
    • Induces systemic lytic state.
  • Use: Used for catheter-directed lysis of thrombi in deep veins or peripheral arteries.
  • Property:
    • Not antigenic.
    • Limited availability.

4. Recombinant tPA:

  • Alteplase, reteplase & tenecteplase.
  • Non-antigenic.
  • More efficacious than streptokinase.
  • Cause hemorrhage (similar to streptokinase & urokinase).
  • Longest acting tPA:
    • Reteplase & tenecteplase.
    • Referred as “bolus fibrinolytic”.
    • Because administration does not require prolonged intravenous infusion.

Exam Important

FIBRINOLYTIC DRUGS

  • Fibrinolytic drugs are also referred as “thrombolytics”.
  • Fibrinolytic drugs are drugs activating plasminogen to form plasmin & helping thrombus lysis.
  • Plasmin is generated from plasminogen, by tissue plasminogen activator (tPA).
  • tPA selectively activates fibrin-bound plasminogen in thrombus.
  • Bleeding is the major adverse effect of fibrinolytic, mainly due to lysis of physiological thrombi & excessive circulating plasmin.
  • Fibrinolytic drugs are indicated for treatment of acute myocardial infarction (Stemi) – Administered i.v. within 12 hours preferably within 1st 3-6 hours.
  • Absolute contraindications for fibrinolytic drugs include, 
    • History of non-hemorrhagic stroke within the past year/at any time, 
    • Marked hypertension (systolic >180 and/or diastolic > 110mm Hg),
    • Active internal bleeding (excluding menses).
  • Relative contraindications for fibrinolytic drugs include, 
    • Current use of anticoagulants (INR≥ 2),
    • Recent  (>2weeks) invasive or surgical procedure,
    • Prolonged (> 10 min.) cardiopulmonary resuscitation,
    • Known bleeding diathesis,
    • Pregnancy,
    • Hemorrhagic diabetic retinopathy,
    • Active peptic ulcer disease,
    • History of severe hypertension.
  • Specific antidotes for fibrinolytic drug overdose are Epsilon aminocaproic acid (EACA) & tranexaemic acid.
  • Streptokinase, anistreplase urokinase, alteplase, reteplase & tenecteplase are some of the important fibrinolytic drugs.
  • Streptokinase, anistreplase & urokinase activate bound fibrin as well as circulating plasminogen
  • Reteplase, alteplase & tenecteplase are fibrin-specific drugs.
  • Streptokinase activates fibrin-bound as well as circulating plasminogen.
  • Unlike other plasminogen activators, streptokinase does not directly convert plasminogen to plasmin instead forms complex with plasminogen.
  • Streptokinase is antigenic in nature, causing allergic reactions.
  • Anistreplase is formed by combining streptokinase with Lys-plasminogen.
  • Urokinase directly converts plasminogen to plasmin.
  • Streptokinase & Urokinase are contraindicated in intracranial malignancy.
  • Fibrinolytic drug affecting both free & circulating plasmin is urokinase.
  • Alteplase, reteplase & tenecteplase are recombinant tPA.
  • Recombinant tPA is more efficacious than streptokinase.
  • Reteplase & tenecteplase are longest acting tPA & are referred asbolus fibrinolytic”.
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