Parnaparin - General Information:

Parnaparin, a highly sulfated glycosaminoglycan is widely used as an injectable anticoagulant. It has the highest negative charge density of any known biological molecule. Parnaparin acts as an anticoagulant, preventing the formation of clots and extension of existing clots within the blood. While heparin does not break down clots that have already formed, it allows the body's natural clot lysis mechanisms to work normally to break down clots that have already formed. Parnaparin binds to and accelerates the activity of antithrombin III. By activating antithrombin III, heparin preferentially potentiates the inhibition of coagulation factors Xa and IIa. Factor Xa catalyzes the conversion of prothrombin to thrombin, so heparin s inhibition of this process results in decreased thrombin and ultimately the prevention of fibrin clot formation.

Pharmacology:

Parnaparin is a highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Parnaparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Parnaparin is a well known and commonly used anticoagulant which has antithrombotic properties. Parnaparin is indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism, and also for the prophylaxis of ischemic complications of unstable angina and non-Q-wave myocardial infarction, when concurrently administered with aspirin. Parnaparin inhibits reactions that lead to the clotting of blood and the formation of fibrin clots both in vitro and in vivo. Parnaparin acts at multiple sites in the normal coagulation system. Small amounts of Parnaparin in combination with antithrombin III (Parnaparin cofactor) can inhibit thrombosis by inactivating activated Factor X and inhibiting the conversion of prothrombin to thrombin. Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Parnaparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor.

Parnaparin for patients

Parnaparin Interactions

Drug Interactions:

a. Drugs Enhancing Heparin Effect:
Oral anticoagulants: Heparin sodium may prolong the one-stage prothrombin time. Therefore, when heparin sodium is given with dicumarol or warfarin sodium, a period of at least 5 hours after the last intravenous dose or 24 hours after the last subcutaneous dose should elapse before blood is drawn if a valid prothrombin time is to be obtained.

Platelet inhibitors: Drugs such as acetylsalicylic acid, dextran, phenylbutazone, ibuprofen, indomethacin, dipyridamole, hydroxychloroquine and others that interfere with platelet-aggregation reactions (the main hemostatic defense of heparinized patients) may induce bleeding and should be used with caution in patients receiving heparin sodium.

The anticoagulant effect of heparin is enhanced by concurrent treatment with antithrombin III (human) in patients with hereditary antithrombin III deficiency. Thus in order to avoid bleeding, reduced dosage of heparin is recommended during treatment with antithrombin III (human).

b. Drugs Decreasing Heparin Effect:
Digitalis, tetracyclines, nicotine, or antihistamines may partially counteract the anticoagulant action of heparin sodium. Heparin Sodium Injection should not be mixed with doxorubicin, droperidol, ciprofloxacin, or mitoxantrone, since it has been reported that these drugs are incompatible with heparin and a precipitate may form.

Drug/ Laboratory Tests Interactions

Hyperaminotransferasemia: Significant elevations of aminotransferase (SGOT [S-AST] and SGPT [S-ALT]) levels have occurred in a high percentage of patients (and healthy subjects) who have received heparin sodium. Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease and pulmonary emboli, rises that might be caused by drugs (heparin sodium) should be interpreted with caution.

Parnaparin Contraindications

Heparin sodium should not be used in patients:

  • With severe thrombocytopenia.
  • In whom suitable blood coagulation tests e.g. the whole-blood clotting time, partial thromboplastin time, etc. cannot be performed at appropriate intervals (this contraindication refers to full-dose heparin; there is usually no need to monitor coagulation parameters in patients receiving low-dose heparin sodium).
  • With an uncontrollable active bleeding state, except when this is due to disseminated intravascular coagulation.

Additional information about Parnaparin

Parnaparin Indication: For anticoagulant therapy in prophylaxis and treatment of venous thrombosis and its extension, for prevention of post-operative deep venous thrombosis and pulmonary embolism and for the prevention of clotting in arterial and cardiac surgery.
Mechanism Of Action: The mechanism of action of heparin is antithrombin-dependent. It acts mainly by accelerating the rate of the neutralization of certain activated coagulation factors by antithrombin, but other mechanisms may also be involved. The antithrombotic effect of heparin is well correlated to the inhibition of factor Xa. Parnaparin interacts with antithrombin III, prothrombin and factor X.
Drug Interactions: Aspirin Association of ASA/Parnaparin increases risk of bleeding
Drospirenone Increased risk of hyperkaliemia
Food Interactions: Adequate calcium intake is recommended, needs increased with long term use, supplement recommended.
Generic Name: Heparin
Synonyms: Alpha-Heparin; Heparin sodium; Heparin sodium preservative Free; Heparin sodium salt; Heparin sulfate; Heparinate; Heparinic acid; Low molecular weight heparin sodium; Sodium heparin
Drug Category: Fibrinolytic Agents; Anticoagulants; Heparins
Drug Type: Small Molecule; Approved; Investigational
Other Brand Names containing Heparin: Ariven; Arteven; Bemiparin; Calcilean; Calciparine; Certoparin; Clexane; Clivarin; Clivarine; Dalteparin; Depo-Heparin; Eparina [DCIT]; Fluxum; Fragmin A; Fragmin B; Fraxiparin; Hed-Heparin; Hepalean; Heparin Cy 216; Heparin Leo; Heparin Lock Flush; Hepathrom; Leparan; Lipo-Hepin; Liquaemin; Liquaemin Sodium; Liquemin; Multiparin; Novoheparin; Pabyrin; Parnaparin; Parvoparin; Pularin; Reviparin; Sandoparin; Sublingula; Thromboliquine; Vetren; Vitrum AB;
Absorption: Some oral absorption but lack of anticoagulant effect. Rapidly taken up by endothelial cells with remainder bound to plasma proteins.
Toxicity (Overdose): Heparin sodium - Mouse, median lethal dose greater than 5000 mg/kg. Another side effect is heparin induced thrombocytopenia (HIT syndrome). HIT is caused by an immunological reaction that makes platelets form clots within the blood vessels, thereby using up coagulation factors
Protein Binding: Very high, mostly to low-density lipoproteins
Biotransformation: Liver and the reticulo-endothelial system are the sites of biotransformation.
Half Life: 1.5 hours
Dosage Forms of Parnaparin: Solution Intravenous
Liquid Irrigation
Solution Subcutaneous
Liquid Intravenous
Solution Intraperitoneal
Chemical IUPAC Name: 6-[5-acetamido-4,6-dihydroxy-2-(sulfooxymethyl)oxan-3-yl]oxy-3-[5-(6-carboxy-4,5-dihydroxy-3-sulfooxyoxan-2-yl)oxy-6-(hydroxymethyl)-3-(sulfoamino)-4-sulfooxyoxan-2-yl]oxy-4-hydroxy-5-sulfooxyoxane-2-carboxylic acid
Chemical Formula: C26H42N2O37S5
Heparin on Wikipedia: http://en.wikipedia.org/wiki/Heparin
Organisms Affected: Humans and other mammals

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