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Goodman & Gilman's The Pharmacological Basis of Therapeutics, 11e
| XI. Drugs Acting on the Blood and the Blood-Forming Organs > |
Parenteral Anticoagulants
Sections: Heparin, Biochemistry, Heparan Sulfate, Source, Mechanism of
Action, Miscellaneous
Pharmacological Effects, Clinical Use, Absorption and
Pharmacokinetics, Administration
and Monitoring, Low-Molecular-Weight
Heparin Preparations, Synthetic Heparin
Derivatives, Heparin Resistance, Toxicities, Bleeding, Heparin-Induced
Thrombocytopenia, Other Toxicities, Other Parenteral
Anticoagulants, Lepirudin, Bivalirudin, Argatroban, Danaparoid, Drotrecogin
Alfa.
Topics Discussed: argatroban; bivalirudin; blood coagulation; chemistry of anticoagulants; coagulation disorders; danaparoid; fondaparinux; hematologic disorders, drug-induced; hemostatic function; heparin; heparin resistance; heparitin sulfate; lepirudin; low-molecular-weight heparin; parenteral anticoagulants; pharmacotherapy of hematologic disorders; thrombocytopenia, heparin-induced; thromboembolism; venous thromboembolism.
Excerpt:
"Heparin is a glycosaminoglycan found in the secretory granules of mast cells. It is synthesized from UDP-sugar precursors as a polymer of alternating D-glucuronic acid and N-acetyl-D-glucosamine residues (Figure 54–4) (Sugahara and Kitagawa, 2002). About 10 to 15 glycosaminoglycan chains, each containing 200 to 300 monosaccharide units, are attached to a core protein and yield a proteoglycan with a molecular mass of 750,000 to 1,000,000 daltons. The glycosaminoglycan then undergoes a series of modifications, which include the following: N-deacetylation and N-sulfation of glucosamine residues, epimerization of D-glucuronic acid to L-iduronic acid, O-sulfation of iduronic and glucuronic acid residues at the C2 position, and O-sulfation of glucosamine residues at the C3 and C6 positions. Each of these modifications is incomplete, yielding a variety of oligosaccharide structures. After the heparin proteoglycan has been transported to the mast cell granule, an endo- -D-glucuronidase degrades..."
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