fibrinolytics-drugs, uses, adverse affects,

1. Fibrinolytics
Meena Yadav
M.Pharm (1st semester Department of pharmacology)
INDO-SOVIET FRIENDSHIP COLLEGE OF PHARMACY MOGA,
(PUNJAB)
1

2. Contents :
• Introduction.
• Mechanism of action.
• Types of fibrinolytics.
• Uses.
• Contraindications.
• References.
2

3. Introduction :
• Fibrinolytics are the drugs which activate plasminogen to form
plasmin and thus help in lysis of thrombus.
• They are therapeutic rather than prophylactic and work by activating
the natural fibrinolytic system.
• These drugs can cause bleeding as the major adverse effects due to
lysis of physiological thrombi as well as due to excessive amount of
plasmin generated in the circulation.
3

4. 4

5. Types of fibrinolytics:
• Non fibrin-specific agents: These agents bind equally to circulating and
non-circulating plasminogen. It produces breakdown of clot and circulating
fibrinogen.
e.g. Urokinase, Streptokinase, Anistreplase.
• Fibrin-specific agents: These are tissue plasminogen activators and are
selective in action. These agents bind preferentially to non-circulating
plasminogen. The activity of these agents is enhanced upon binding to
fibrin. These are also called as tissue plasminogen activators (t-PA).
e.g. Alteplase, Reteplase, Tenecteplase.
5

6. Uses of thrombolytics:
• Acute myocardial infarction.
• Acute ischaemic stroke.
• Peripheral artery occlusion.
• Pulmonary embolism.
• Deep venous thrombosis.
6

7. Contraindications:
• Active internal bleeding.
• Cerebral haemorrhagic stroke.
• Cerebrovascular disease.
• Active peptic ulcer.
• Diabetic retinopathy.
• Pregnancy.
7

8. Streptokinase:
• It is obtained from beta-haemolytic streptococci.
• It activates fibrin bound as well as circulating plasminogen.
• This is antigenic and can lead to allergic reaction.
• It can also lead to formation of neutralizing antibodies, thus it is less
effective if given repeatedly.
• It is least expensive.
• It is used for venous or arterial thrombosis and life threatening
pulmonary embolism.
8

9. Side effects of streptokinase
• Bleeding due to activation of circulating plasminogen
• Allergic reaction like rashes, fever, hypotension.
9

10. Urokinase
• It is an human enzyme obtained from human urine, commercially
prepared from cultured human kidney cells.
• It acts directly to convert plasminogen to plasmin.
• It is nonantigenic.
• It is used for the lyses of acute massive pulmonary emboli.
Disadvantages:
• Minimal fibrin specificity
• Systemic lysis
Advantages:
Not antigenic.
10

11. Anistreplase
• It is a prodrug, de-acylated in circulation into the active plasminogen-
streptokinase complex.
Advantages:
• longer duration of action.
• More thrombolytic activity.
• Greater clot sensitivity.
Disadvantages:
• Antigenicity.
• Minimal fibrin specificity.
• Systemic lysis.
11

12. Alteplase :
• It is a recombinant form of human t-PA.
• It is tissue specific thrombolytic and also interferes with circulating
plasminogen.
• It has short half life.
• It is nonantigenic.
Side effects:
• Nausea, mild hypotension and fever may occur.
12

13. Reteplase:
• It is a variant of recombinant t-PA.
• It has longer duration than alteplase (15min).
• It has enhanced fibrin specificity.
Uses:
• Pulmonary embolism.
• To reduce incidence of CHF.
• To improve ventricular function.
13

14. Tenecteplase:
• It is another genetically modified human t-PA.
• It is more fibrin-specific & longer duration than alteplase.
• It has half life more than 30 min.
• It is used in acute myocardial infarction.
14

15. Antifibrinolytics:
• These are a class of medication that are inhibitors of fibrinolysis.
• Examples include aminocaproic acid (ε-aminocaproic acid)
and tranexamic acid.
• These lysine-like drugs interfere with the formation of the fibrinolytic
enzyme plasmin from its precursor plasminogen by plasminogen
activators which takes place mainly in lysine rich areas on the surface
of fibrin.
• These drugs block the binding sites of the enzymes or plasminogen
respectively and thus stop plasmin formation.
15

16. Epsilon Amino-Caproic Acid (EACA):
• It is analogue of lysine
• It binds to lysine binding site of plasminogen and plasmin so that the
latter is not able to bind to fibrin and lyse it.
Uses:
• Overdose of fibrinolytics.
• To prevent recurrence of G.I & subarachnoid haemorrhage.
• In certain traumatic & surgical bleedings like prostatectomy.
• In abruption placentae & menorrhagia.
16

17. Adverse effects:
• Hematuria.
• Intravascular thrombosis.
• Hypotension, bradycardia, arrhythmia.
• Myopathy.
17

18. Tranexamic Acid:
• It is a synthetic analogue of the amino acid lysine.
• Tranexamic acid is a medication used to treat or prevent excessive
blood loss from major trauma, postpartum bleeding, surgery, tooth
removal , nosebleeds and heavy menstruation.
• It is also used for hereditary angioedema.
Mechanism of action:
It reversibly bind to lysine receptor sites on plasminogen and prevent
plasmin from binding to and degrading fibrin.
18

19. Adverse effects:
• Headache.
• Backache.
• Abdominal pain.
• Diarrhea.
• Fatigue.
• Anemia.
19

20. Uses:
• Trauma
• Vaginal bleeding
• Child birth
• Dentistry
• Surgery
• Hematology
20

21. References:
• Tripathi, K.D., 2013. Essentials of Medical Pharmacology, 7th
edition. JP Medical Ltd. pp- 625-628.
• Mohan, H., 2005. Textbook of Pathology, 7th edition. New Delhi:
Jaypee brothers medical publishers, pp-380-382.
21

22. Thank You
22