Pharmacology
Cardiovascular
Regarding streptokinase, which of the following statement is CORRECT:
Answer:
Streptokinase (SK) is a single chain polypeptide, derived from beta-haemolytic streptococci. Its lack of fibrin specificity makes it a less desirable thrombolytic drug than tPA compounds because it produces more fibrinogenolysis. Streptokinase is antigenic, and so should not be given to patients who have already been exposed, due to the development of antibodies (after about 4 - 5 days). Prolonged persistence of antibodies to streptokinase can reduce the effectiveness of subsequent treatment; therefore, streptokinase should not be used again beyond 4 days of first administration of streptokinase. Minor allergic reactions may occur in up to 10% of patients - anaphylaxis occurs in less than 0.5% of cases. Hypotension may occur during infusion which usually responds to fluids or slowing of the infusion.Fibrinolytics
Pharmacology / Cardiovascular
Last Updated: 17th April 2019
The value of thrombolytic drugs for the treatment of myocardial infarction has been established. Streptokinase and alteplase have been shown to reduce mortality. Reteplase and tenecteplase are also licensed for acute myocardial infarction. Fibrinolytic therapy carries a risk of bleeding, including cerebral haemorrhage, and not all patients can be given this treatment safely.
Mechanism of Action
Fibrinolytic drugs act as thrombolytics by activating plasminogen to form plasmin, which degrades fibrin and so breaks up thrombi.
Alteplase should be given within 6 – 12 hours of symptom onset, reteplase and streptokinase within 12 hours of symptom onset, but ideally all should be given within 1 hour; use after 12 hours requires specialist advice.
Contraindications
- Absolute
- Previous haemorrhagic stroke
- Ischaemic stroke during the previous 6 months
- Central nervous system damage or neoplasm
- Recent (within 3 weeks) major surgery, head injury or other major trauma
- Active internal bleeding or gastrointestinal bleeding within the past month
- Known bleeding disorder
- Relative
- Refractory hypertension (SBP > 180 mmHg)
- Transient ischaemic attack during the previous 6 months
- Oral anticoagulant treatment
- Pregnancy or less than 1 week postpartum
- Traumatic CPR
- Non-compressive vascular puncture
- Active peptic ulcer disease
- Advanced liver disease
- Infective endocarditis
- Previous allergic reaction to fibrinolytic drug to be used
Side Effects
- Bleeding (serious bleeding calls for discontinuation of the thrombolytic and may require administration of coagulation factors and antifibrinolytic drugs)
- Nausea and vomiting
- Further embolism (either due to clots that break away from the original thrombus or to cholesterol crystal emboli)
- Hypotension
- Hypersensitivity reactions
Streptokinase
Streptokinase (SK) is a single chain polypeptide, derived from beta-haemolytic streptococci. Its lack of fibrin specificity makes it a less desirable thrombolytic drug than tPA compounds because it produces more fibrinogenolysis. Streptokinase is antigenic, and so should not be given to patients who have already been exposed, due to the development of antibodies (after about 4 - 5 days). Prolonged persistence of antibodies to streptokinase can reduce the effectiveness of subsequent treatment; therefore, streptokinase should not be used again beyond 4 days of first administration of streptokinase. Minor allergic reactions may occur in up to 10% of patients - anaphylaxis occurs in less than 0.5% of cases. Hypotension may occur during infusion which usually responds to fluids or slowing of the infusion.
Alteplase
Alteplase is a recombinant tissue-type plasminogen activator (tPA), a naturally occurring fibrin-specific enzyme that has selectivity for activation of fibrin-bound plasminogen. It has a short half-life of 3 - 4 minutes and must be given by continuous intravenous infusion but is not associated with antigenic or hypotensive effects, and can be used in patients when recent streptococcal infections or recent use of streptokinase contraindicates the use of streptokinase.
Reteplase and Tenecteplase
Reteplase and tenecteplase are genetically engineered forms of human tPA and have a longer half-life, higher specificity for fibrin, and greater resistance to plasminogen activator inhibitor-1 than native tPA. The increase in half-life permits administration as a bolus rather than by continuous infusion.
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
