Thrombolytics, also known as fibrinolytics, are drugs used to dissolve blood clots and recanalize blocked blood vessels. The main thrombolytics discussed are streptokinase, urokinase, alteplase, reteplase, and tenecteplase. They work by activating plasminogen to form plasmin, which breaks down fibrin in clots. Newer agents like alteplase and tenecteplase are more fibrin-specific, causing less bleeding than earlier streptokinase. Tenecteplase has a longer duration and can be given as a single bolus dose to quickly treat heart attacks. Thrombolytics are used for heart attacks

1. Thrombolytics
By
Dr. Dinesh Kumar G
Pharm. D

2. FIBRINOLYTICS (Thrombolytics)
• These are drugs used to lyse thrombi/clot to recanalize occluded blood
vessels (mainly coronary artery). They are therapeutic rather than
prophylactic and work by activating the natural fibrinolytic system
• In general, venous thrombi are lysed more easily by fibrinolytics than
arterial, and recent thrombi respond better. They have little effect on
thrombi > 3 days old. The clinically important fibrinolytics are:
Streptokinase
Alteplase (rt-PA)
Urokinase
Reteplase
Tenecteplase

4. Streptokinase
• Obtained from hemolytic Streptococci group C, it is the first fibrinolytic
drug to be used clinically but is not employed now except for considerations
of cost.
• Streptokinase is inactive as such; combines with circulating plasminogen
molecules to form an activator complex which then causes limited
proteolysis of other plasminogen molecules to generate the active enzyme
plasmin.
• It is non-fibrin specific, i.e., activates both circulating as well as fibrin
bound plasminogen.
• Therefore, it depletes circulating fibrinogen and predisposes to bleeding.
• Compared to newer more fibrin-specific tissue plasminogen activators
(alteplase, etc.) it is less effective in opening occluded coronary arteries and
causes less reduction in MI related mortality.

5. Streptokinase
• There are several other disadvantages as well with streptokinase.
• Antistreptococcal antibodies due to past infections inactivate considerable
fraction of the initial dose of Stk. A loading dose therefore is necessary.
• Plasma t½ is estimated to be 30–80 min.
• Stk is antigenic—can cause hypersensitivity reactions; anaphylaxis occurs
in1–2% patients.
• It cannot be used second time due to neutralization by antibodies generated
in response to the earlier dose.
• Fever, hypotension and arrhythmias are reported.
• However, being less expensive, it is still used in resource poor areas, but
not in Europe or USA.

6. Urokinase
• It is an enzyme isolated from human urine; but commercially prepared
from cultured human kidney cells.
• It activates plasminogen directly and has a plasma t½ of 10–15 min.
• It is non-antigenic.
• Fever occurs during treatment, but hypotension and allergic
phenomena are rare.
• Urokinase is indicated in patients in whom streptokinase has been
given for an earlier episode.

7. Alteplase
(recombinant tissue plasminogen activator (rt-PA):
• It is produced by recombinant DNA technology from human tissue
culture, it is moderately specific for fibrin-bound plasminogen, so that
circulating fibrinogen is lowered only by ~ 50%.
• It is rapidly cleared by liver and inactivated by plasminogen activator
inhibitor-1 (PAI-1). The plasma t½ is 4–8 min.
• Because of the short t½, it needs to be given by slow i.v. infusion and
often requires heparin co-administration.
• It is non-antigenic, but nausea, mild hypotension and fever may occur.
• It is expensive.

8. Tenecteplase
• This genetically engineered substitution mutant of native t-PA has higher
fibrin selectivity, slower plasma clearance (longer duration of action) and
resistance to inhibition by PAI-1.
• It is the only fibrinolytic agent that can be injected i.v. as a single bolus dose
over 10 sec, while alteplase requires 90 min infusion.
• This feature makes it possible to institute fibrinolytic therapy immediately
on diagnosis of ST segment elevation myocardial infarction (STEMI), even
during transport of the patient to the hospital.
• Several randomized multicentric trials have assessed its efficacy in STEMI
and found it to be at least equally efficacious to alteplase. Risk of
noncerebral bleeding may be lower with tenecteplase, but cranial bleeding
incidence is similar.

9. Uses of fibrinolytics
• Acute myocardial infarction
• Deep vein thrombosis
• Pulmonary embolism
• Peripheral arterial occlusion
• Stroke
Contraindications to thrombolytic therapy
1. H/o Intracranial hemorrhage
2. H/o Ischemic stroke in past 3 months
3. H/o Head injury in past 3 months
4. Intracranial tumor/vascular abnormality/aneurysms
5. Active bleeding/bleeding disorders
6. Peptic ulcer, esophageal varices
7. Any wound or recent fracture or tooth extraction
8. H/o major surgery within 3 weeks
9. Uncontrolled hypertension
10. Pregnancy

10. THROMBOLYTICS
DRUG NAME Streptokinase, Urokinase, alteplase, reteplase, tenecteplase
MECHANISM OF
ACTION
Directly bind to fibrin proteins in the clot and preferentially act on fibrin-bound plasminogen; convert
plasminogen into its active form, plasmin, which cuts the fibrin into smaller pieces and dissolves the clot
INDICATIONS
•Myocardial infarction
•Pulmonary embolism
•Ischemic stroke
•Thrombosis of prosthetic heart valves and stents
ROA IV
SIDE EFFECTS
•Bleeding; e.g., bleeding from the injection site, gastrointestinal bleeds, hemorrhagic stroke
•Reperfusion arrhythmia
•Hypersensitivity reactions like anaphylaxis
•Nausea, Vomiting, Fever
CONTRA
INDICATIONS
AND CAUTIONS
•Before major surgeries, After recent trauma, Active internal bleeding
•History of intracranial hemorrhage or ischemic stroke
•Coagulopathies
•Severe hypertension
•Older than 75 y.o.
•Active peptic ulcer
•Diabetic retinopathy
•Hepatic disease, Anticoagulants (heparin and warfarin)
•Pregnancy and breastfeeding

11. THROMBOLYTICS
ASSESSMENT AND
MONITORING
Vital signs, and cardiac and neurological status
•Laboratory test results
• CBC, Hematocrit
• Coagulation studies: PT, aPTT, INR
• Renal and hepatic function
• MI: cardiac enzymes
• PE: ABGs
•Signs and symptoms of active bleeding
•Neurological and cardiac status
•Coagulation studies
•Avoid any unnecessary venipuncture, arterial sticks, IM injections
• Manage puncture site bleeding with pressure dressing
• For active bleeding - Stop thrombolytic administration
• Notify the healthcare provider
• Prepare to administer aminocaproic acid, blood products
•Evaluate for evidence of clot dissolution and reperfusion, absence of side effects, and a
return to normal hemodynamic status
CLIENT EDUCATION
•Purpose of medication
•Discharge teaching
• Minimize bleeding and bruising
• Self-monitoring for bleeding
• Recognize symptoms of clot formation