MEDICINAL CHEMISTRY

pentaerythritol, and is supplied diluted with an inert substance such as lactose. The
action of pentaerythritol tetranitrate is similar to glyceryl trinitrate but its duration of
action is more prolonged. It is used in angina pectoris, usually in oral doses of 10 to
40 mg three or four times daily. It is given as tablets. Pentaerythritol trinitrate is an
active metabolite of pentaerythritol tetranitrate which has been used clinically.
Preparation: Pentaerythritol Tetranitrate Tablets, B.P., I.P. Proprietary Names:
CARDIOCAP; MYOCARDOL; PERITRATE; PERITRATE-SA
Diluted Isosorbide Dinitrate, B.P., I.P.
Isosorbide dinitrate is 1, 4:3, 6-dianhydro-D-glucitol 2, 5-dinitrate. It is a white
crystalline powder; slightly soluble in water. Diluted isosorbide dinitrate is a dry mixture
of isosorbide dinitrate with lactose, mannitol or any other suitable inert excipient, which
permits safe handling.
Isosorbide dinitrate is readily absorbed from the oral mucosa and gastrointestinal tract. Its
major metabolites are isosorbide 2-mononitrate and isosorbide 5-mononitrate, both of
which possess vasodilatory activity and may contribute to the activity of the parent compound.
Isosorbide dinitrate is also absorbed through the skin from an ointment base.
Isosorbide dinitrate is suitable for sublingual as well as oral administration. The
usual dose in acute angina is 2.5 to 10 mg sublingually. The oral dosage is 30 to
120 mg daily in divided doses; preparations for sustained-release are available. It has
been given in certain states by intravenous infusion. It has also been applied
topically.
Preparation: Isosorbide Dinitrate Tablets, B.P., I.P. Proprietary Names: CARDICAP-
TR; CEDOCARD; ISODRIL; SORBICHEW; SORBITRATE; VASCARDIN
2. Anticoagulants
Introduction
The phenomenon of blood coagulation is very complex. Thrombin and several blood
clotting factors present in plasma and calcium ions are involved in the coagulation. The
factors are precursor proteins or zymogens, and at each stage, a zymogen gets converted
to an active protease (activated factor). The protease zymogens involved in coagulation
include factor II (prothrombin). VII, IX, X, XI, and XII, and prekallikrein. In addition,
there are nonenzymatic protein cofactors such as factor V and VIII. Thrombin cleaves
factors V and VIII to yield activated factors (Va and VIIIa) that have at least fifty times
the coagulant activity of the precursor form. Factors Va and VIIIa have no enzymatic
activity themselves but serve as cofactors that increase the proteolytic efficiency of Xa
and IXa, respectively (Fig. 2).
Another nonenzymatic cofactor is tissue factor, a lipoprotein that greatly enhances the
proteolytic efficiency of VII and VIIa. High molecular weight kininogen is a plasma
protein, which serves as a cofactor for XIIa when clotting is initiated in vitro. In the
process of coagulation fibrinogen, a soluble plasma protein, gets converted to insoluble