thrombolytics drugs ppt presetation by Xarshad Danish

2.  Thrombosis is the formation of a clot.
 A thrombus may form in any vessel, artery, or
vein when blood flow is impeded.
 For example, a venous thrombus can develop as
the result of venous stasis (decreased blood
flow), injury to the vessel wall, or altered blood
coagulation.
 Arterial thrombosis can occur because of
atherosclerosis or arrhythmias.

3.  The thrombus may begin small, but fibrin (also
called Factor Ia) , platelets, and red blood cells
attach to the thrombus, increasing its size and
shape.
 When a thrombus detaches itself from the wall
of the vessel and is carried along through the
bloodstream, it becomes an embolus.
 The embolus travels until it reaches a vessel that
is too small to permit its passage.
 The anticoagulant drugs are use
prophylactically in patients who are at high risk
for clot formation.

4.  Coronory thrombi cause mycardial infarctions.
 Cerebrovascular thrombi produce strokes
 Pulmonary thrombi can lead to respiratory and
cardiac death.
 So it is important to rapidly diagnose and treat
the blood clot.

6.  Thrombolytics are a group of drugs used to dissolve
certain types of blood clots and reopen blood vessels after
they have been occluded.
Examples of thrombolytics
 Streptokinase Rx (Streptase)
 Urokinase Rx (Abbokinase).
 Antistreplase
Tissue plasminogen Activator (t-PA)
 Alteplase Rx (Activase)
 Reteplase Rx (Retavase)
 Tenecteplase Rx (TNKase)

7.  Before these drugs are used, their potential benefits
 must be carefully weighed against the potential dangers
 of bleeding.

11. source
 It is a protein produced by beta hemolytic strptococci .
 It has no intrinsic enzymatic activity.
MOA
 It combines with proactivator plasminogen to form a
complex.
 This complex catalyzes the conversion of plasminogen to
active plasmin.
 So rapid lysis of the clot by plasmin.
 This complex also catalyzes the clotting factor V and VII

14. Dose
 Lysis of coronary artery thrombosis 20,000 U directly
into vein , PE,DVT, embolism 250,000 IU IV over 30
mints followed by 100,000 IU for 24—72 h.
Interactions
Drug-drug. Aminocaproic acid: Inhibits streptokinase
effects on plasminogen activation. Don’t use together.
Anticoagulants: May cause hemorrhage. It may also be
necessary to reverse effects of oral anticoagulants before
beginning therapy.
Aspirin, indomethacin, phenylbutazone, or other drugs that
affect platelet activity: Increases risk of bleeding.
Drug-herb. Dong quai, feverfew, garlic, ginger, horse
chestnut, red clover: Increases risk of bleeding. Discourage
use together

17.  Lysis of coronary artery thrombi, IV catheter
clearance.
Dose
 PE: 4400 IU/kg IV over 10 min, followed by
4400 U/kg/hr for 12 h; lysis of thrombi 6000
IU/min IV for 2 h; IV catheter clearance.
Adverse effects
 Minor bleeding (superficial and surface) and major
bleeding (internal and severe)

18. Pregnancy and lactation
 There are no adequate data from the use of
urokinase in pregnant women. The potential risk for
humans is unknown. However, low-molecular
urokinase fragments and active plasmin cross the
placenta.
 Urokinase should not be used during pregnancy or
in the immediate post-partum period unless clearly
necessary.
 It is unknown whether urokinase is excreted into
human breast milk. Breast-feeding should be
avoided during treatment with urokinase

19. Interaction medicinal products and other forms of
interactions
 Anticoagulants
 Oral anticoagulants or heparin may increase the risk
of haemorrhage and should not be used concomitantly
with urokinase.
 Active substances affecting platelet function
 Due to increased risk of haemorrhage, concomitant
use of urokinase and active substances that affect
platelet function (e.g., acetylsalicylic acid, other non-
steroidal anti-inflammatory agents, dipyridamole,
dextrans) should be avoided.
 Contrast agents
 Contrast agents may delay fibrinolysis.

24. Dose
 AMI: total dose of 100 mg IV given as 60 mg
1st h, 20 mg 2nd h and 20 mg over 3rd h;
 for patients < 65 kg,decrease dose to1.25 mg/kg

25. is a recombinant form of human tPA.
It has very short half life (~5 min)
It is usually administered as an intravenous
bolus followed by an infusion.
(60 mg i.v. bolus + 40 mg infusion over 2 h).
Clinical Uses
 Acute ischemic stroke.
In ST-elevation myocardial infarction (STEMI)
Pulmonary embolism.

26. Adverse effects
 Bleeding (GU, gingival,retroperitoneal), and
epistaxis, ecchymosis.
Dose
 AMI: total dose of 100 mg IV given as 60 mg 1st h, 20
mg 2nd hand 20 mg over 3rd h;
 for patients < 65 kg, decrease dose to 1.25 mg/kg.

27. A variant of recombinant tPA
It has longer duration than alteplase (15min.)
Has enhanced fibrin specificity
Given as two I.V. bolus injections of 10 U each
Clinical Uses
In ST-elevation myocardial infarction (STEMI)
Pulmonary embolism.

28. Dose
 10 plus 10 U double bolus IV over 2 min each
with the 2nd bolus given 30 min after the 1st
Adverse effects
 Bleeding (GI, GU, or at injection site),
intracranial hemorrhage, Anemia.

29. Is another modified human t-PA.
It prepared by recombinant technology
 it has half life of more than 30 min.
It can be administered as a single IV bolus.
It is more fibrin-specific & longer duration
than alteplase.

30. Clinical uses
 It is only approved for use in acute myocardial
infarction.
Dose
 Dosage based on weight, not to exceed 50 mg IV
Adverse Effects
 Bleeding (GI, GU, or at injection site),
intracranial hemorrhage, Anemia.

31. Active internal bleeding
Recent intracranial trauma or neoplasm
Cerebral hemorrhagic stroke
Cerebrovascular disease
Major surgery within two weeks
Active peptic ulcer
Severe uncontrolled hypertension

32.  inhibit plasminogen activation and thus
inhibit fibrinolysis and promote clot
stabilization.
 Aminocaproic Acid & tranexamic cid
 acts by competitive inhibition of plasminogen
activation
 ِِِGiven orally
 Aprotinin
 It inhibits fibrinolysis by blocking plasmin
 Gien orally or i.v.

33.  Adjuvant therapy in hemophilia
 Fibrinolytic therapy-induced bleeding
(antidote).
 Postsurgical bleeding
 These drugs work like antidotes for fibrinolytic
drugs. Similar to Protamine (Antidote of the
anticoagulant, heparin) or Vitamin K (Antidote
of the oral anticoagulant warfarin)

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Xarshad Danish
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