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Recombinant activated factor VII (rFVIIa) was originally developed for the treatment of hemophilic patients with inhibitors and then used successfully for treating hemorrhages in patients with acquired hemophilia. In the last few years, along with the improvement in the knowledge of its mechanisms of action, rFVIIa has also been used with benefit as a “universal hemostatic agent” in many other nonhemophilic bleeding situations, including congenital FVII deficiencies, quantitative and qualitative platelet disorders, hepatic failure, liver transplantation, major surgery and trauma [1]. This review briefly analyzes the uses of rFVIIa in treatment and focuses particularly on the newer uses, for which there are only a few randomized, controlled clinical trials. Table 1 summarizes the current approved and “off-label” clinical applications of rFVIIa. Table 1 Approved and potential clinical applications of recombinant activated factor VII Mechanisms of Action and Pharmacokinetics Recombinant activated factor VII is an important contributor to the initiation of hemostasis [2]. According to a cell-based model of coagulation, tissue factor (TF) is exposed to circulating blood following injury to the vessel wall and TF-FVIIa complexes are formed on the TF-bearing cells, where they activate factor X (FX) to produce activated FX (FXa), leading to the conversion of prothrombin to thrombin (Fig. 1). The limited amount of thrombin formed activates FV, FVIII, and FXI, as well as platelets, which in turn change shape and expose negatively charged phospholipids, such as phosphatidylserine. These activated platelets provide the template for further FX activation and full thrombin generation with a positive feedback on FV, FVIII, and FXI. The extra formation of thrombin results in the activation of thrombin-activatable fibrinolysis inhibitor (TAFI), which protects the fibrin clot from premature lysis by down-regulating fibrinolysis. The direct activation of FIX on activated platelets in the absence of TF, resulting in improved thrombin generation, may also explain the mechanism of rFVIIa action in acquired coagulopathy following trauma, surgery. Moreover, the binding of rFVIIa to activated platelets may explain why rFVIIa is localized only to the site of bleeding. The rapid decrease of rFVIIa level in vivo means that this drug must be given as frequent bolus injections (every 2–4 hours) or as a continuous infusion [2]. All published studies show that treatment with rFVIIa can be effective at doses between 35 and 120 µg/kg. Effective doses are independent of the inhibitor titer, with the standard recommended dose being 90 µg/kg given as a bolus and repeated after two hours. When more than two doses are necessary to ensure and maintain hemostasis in uncomplicated bleeding episodes, the dose interval may be prolonged to every four hours for 1 to 2 days and then every six hours until discontinuation, depending on the size and severity of the bleed. [1]. Fig. 1 Role of rFVIIa in causing thrombin burst Use in Hemophilic Patients Hemophilia A and B is treatable with highly purified plasma-derived and recombinant DNA- derived factor VIII and factor IX concentrates. However, a well recognized and potentially life-threatening complication of hemophilia is the development of neutralizing antibodies against the missing factor. Up to 25 % of patients develop an inhibitor to factor VIII, and 3–5% to factor IX. To date, therapeutic interventions in these situations have included large doses of factor VIII and activated/non-activated prothrombin complex concentrates and porcine FVIII. All these have significant drawbacks including high cost, unpredictability of response, transmission of blood-derived infections, thromboembolic complications and in the case of porcine FVIII, development of anti-porcine antibodies. All these existing therapeutic caveats led to the development of rFVIIa as a potential solution for treating hemophilia patents with inhibitors and in acquired hemophilia [3]. The standard (and approved) intravenous (IV) dose of rFVIIa in hemophilia patients with an inhibitor is 90 µg per kg until hemostasis is achieved; for surgical patients, repeated doses are given every two hours until hemostasis is achieved and less frequently thereafter[4].

Visceral leishmaniasis (VL) or kala-azar is caused by Leishmania donovani and transmitted to humans by female phlebotomine sandflies. Leishmaniasis is distributed worldwide infecting 12 million people, with about 1.5 million new cases each year. Along with Brazil, Sudan and Bangladesh, India contributes to 90% of the global burden of VL [1]. Soon National Leishmaniasis Control Programme in India may have a new drug to fight VL - miltefosine. Miltefosine (Impavido™) is the first oral drug for leishmaniasis, giving cure rates of 98%. The drug can be administered orally and has the potential to be used at the community level and even during an epidemic [2].

Acute decompensation is the most common reason for hospitalization of patients with congestive heart failure due to left ventricular systolic dysfunction [1]. Such patients are treated with intravenous diuretics, vasodilators such as nitroglycerin and nitroprusside, inotropes such as dobutamine and inodilators like miltrinone. All these are associated with limitations like arrhythmias with milrinone, electrolyte disturbances with diuretics, hypotension with nitroprusside and tolerance with nitrates [2, 3]. Nesiritide, a synthetic recombinant human B-type natriuretic peptide, has recently been introduced as short-term infusion in patients with congestive heart failure to improve volume overload and cardiac decompensation. This therapy represents a novel approach to ‘physiologic’ management of heart failure, enhancing naturally occurring protective mechanisms [4].

Remifentanil hydrochloride is a recent addition to the group of narcotic analgesics [1]. It is structurally unique as it has an ester linkage that renders it susceptible to hydrolysis by nonspecific plasma and tissue esterases to inactive metabolites. This pathway of metabolism is responsible for its uniquely evanescent effect. Thus, the side effects for which opioids are much maligned are extremely transient when remifentanil is used.

Problem of male erectile dysfunction has been better defined, recognised and being treated in the recent times. However, the intracavernosal injection of vaso-active materials and penile prosthesis implantation were only the viable options available. Sildenafil, which is a specific phosphodiesterase type V inhibitor, enhances erection on sexual arousal by increasing the quantity of cyclic guanosine monophosphate in the corpora cavernosa. This has revolutionized the treatment of erectile dysfunction. Though the drug appears very promising with little side effects, many questions regarding efficacy, safety, misuse and overuse need to be addressed.

Emerging drug resistance and intolerance to standard agents such as chloroquine, sulfadoxine/pyrimethamine and mefloquine has highlighted the need for new antimalarials. Although chloroquine remains the treatment of choice, a fixed dose combination of atovaquone/proguanil may be considered as the most promising alternative for prevention and treatment of malaria in chloroquine resistant areas. The combination has been found to be highly effective with a good tolerance and safety profile [1].

No abstract available Keywords: Beta tricalcium phosphate; Hydroxyapatite; Synthetic bone substitute.