Chapter 11: Thrombolytic Drugs

Thrombolytic is also known as brinolytic used to dissolve already been

formed thrombus, as in conditions such as acute myocardial infarction,
acute stroke, deep vein thrombosis, and acute pulmonary embolism.
Thrombolytics are also known as brinolytics.

Pharmacological action
Blood clots are dissolved by the action of the brinolytic system.
• Facilitate conversion of plasminogen to plasmin that subsequently
hydrolyzes brin to dissolve clots.
• Recombinant DNA derivatives of tissue plasminogen activator (tPA).
• They contain 527 and 355 amino acids of natural tPA.
• tPA catalyzes the conversion of plasminogen to plasmin.

Alteplase and Reteplase are Tissue plasminogen activators (tPAs)

These drugs promote brinolysis by converting plasminogen into plasmin,
which dissolves brin clots.

Therapeutic use: Acute Ischemic stroke and myocardial infarction.

Time is critical for thrombolytic therapy, with maximum bene ts seen when
administered as early as possible:
• Stroke: Ideally within 3 hours (up to 4.5 hours for selected patients).
• MI: Ideally within 6 hours (up to 12 hours in some cases).

Mechanism of Action:
• tPAs have a high a nity for plasminogen bound to brin in the
thrombus, leading to localized brinolysis.
• Streptokinase and Urokinase: These older agents lack brin speci city.
Act on free plasminogen, leading to a generalized thrombolytic state,
increasing the risk of systemic bleeding.
• Alteplase Speci city: Alteplase has a greater ability to dissolve older clots
compared to newer clots because older clots have a higher density of brin.

Contraindications:
Absolute Contraindications: Relative Contraindications:

•Cerebral bleeding (hemorrhagic stroke). Active peptic ulcer

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 Absolute Contraindications: Relative Contraindications:

•Severe uncontrolled hypertension (e.g., Diabetic

>185/110 mmHg).

•Active internal bleeding. Blood pressure

•Recent head trauma or neurosurgery (within 3 Pregnancy

months).

Time Window: Not used for acute stroke >4.5

hours from onset (speci c conditions apply for
the extended window). Not used for myocardial
infarction >6 hours after onset.

Streptokinase
Category Details

Mechanism - Streptokinase is an enzyme produced by Streptococcus bacteria (group C

beta-hemolytic streptococci). - Activates plasminogen, which dissolves
brin clots in blood vessels.

Therapeutic Use - Acute coronary syndrome (e.g., myocardial infarction).

- Ischemic stroke (cerebrovascular events).
- Deep vein thrombosis (DVT).
- Pulmonary embolism (PE).

Drug-Drug - Increased risk of bleeding when combined with anticoagulants (e.g.,

Interactions warfarin, heparin) or antiplatelet agents (e.g., aspirin, clopidogrel).

Side E ects - Allergic reactions (e.g., urticaria, rash, bronchospasm, angioneurotic

edema).
- Bleeding complications, especially at the site of catheter insertion or
internally.
- Headache.
Precautions for - Allergic reactions are more common with streptokinase than with
Allergies urokinase.
- Pre-treatment with antihistamines may reduce allergic response.
Monitoring - Avoid repeat administration of streptokinase within 6 months to prevent
hypersensitivity reactions or reduced e cacy due to antibody formation.

Urokinase
Category Details

Mechanism - Urokinase is a two-chain serine protease enzyme obtained from cultured

human kidney cells.
- Directly degrades brin and brinogen, promoting brinolysis.
Therapeutic - Used for thrombolysis in: - Coronary artery thrombosis. - Pulmonary
Use embolism (PE).

Side E ects - Allergic reactions, including: - Bronchospasm - Skin rash

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 Anistreplase
Category Details

Type - Prodrug of streptokinase. - Known as APSAC (Anisoylated Plasminogen

Streptokinase Activator Complex).

Mechanism - A complex of human lys-plasminogen and streptokinase. - The anisoyl group

blocks the catalytic site, prolonging activation and improving
pharmacokinetics.

Therapeutic Use - Acute Myocardial Infarction (AMI): Promotes clot lysis to restore coronary
artery blood ow. - Coronary artery embolism: E ective in clot resolution.

Drug Fibrin Systemic Intracrania Therapeutic Indication

Speci city Bleeding Risk l Bleeding
Risk

Tenecteplase ++++ (High brin + (Low) ++ - Acute myocardial infarction

speci city) (Moderate) (preferred for its ease of
administration).
- Longer half life

Alteplase ++++ (Selective +++ (Moderate) ++ - Pulmonary embolism (PE). -

for brin; more (Moderate) Acute ischemic stroke (within
potent) 3–4.5 hours). - Clearance of
occluded AV catheters.
- Very short half life 5-30 min

Reteplase ++ (Moderate ++ (Moderate) ++ - Acute myocardial infarction.

brin speci city) (Moderate)

Streptokinase + (Low brin +++ (High) + (Low) - Pulmonary embolism (PE). -

speci city; Deep vein thrombosis (DVT).
indirect action) - Clearance of occluded AV
catheters. -
- Not used for MI or stroke
due to lack of brin
speci city.

Aminocaproic acid antidote for a life-threatening situation caused by

thrombolytic.

Questions:
• Thrombolytic drugs dissolve blood clots by activating? Plasminogen
• Plasmin is a proteolytic enzyme that is capable of dissolving? Fibrin
molecules.
• The most common side e ect of thrombolytics? Hemorrhage or
bleeding.

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