A novel approach in treatment of rheumatoid arthritis: Janus kinase inhibitors.

Janus kinase (JAK) inhibitors are a new class of drugs that inhibit JAK enzymes, which are the main signal transducers for the majority of cytokines, growth factors, and interferons. These drugs work from inside the cell and are unique in a way that their action interrupts the signaling involved in the infl ammation. They include drugs like ruxolitinib, tofacitinib, both of which have been US Food and Drug Administration (USFDA) approved, and many others which are currently under trials. Tofacitinib was approved by USFDA in November 2012 for oral use in patients suffering with moderate to severe rheumatoid arthritis and do not respond to methotrexate.

Antiplatelet therapy: present status and its future directions.

Anti-platelets drugs play an important role in the prevention or treatment of cardiovascular diseases e.g. coronary artery disease, stroke, etc., which cause high mortality and morbidity in the present day world. These drugs either inhibit the platelet activation, aggregation or other signaling pathways, thereby inhibiting the clot formation. The anti-platelet drugs currently used are aspirin, ADP receptor inhibitors (ticlopidine and clopidogrel)and glycoprotein (GP)IIb/IIIa inhibitors (abciximab, tirofi ban and eptifi batide). Aspirin was and still continues to be the main anti-platelet therapy. A combination regimen of aspirin and clopidogrel is commonly used for the prevention of platelet activation, thrombosis and stroke. However, many of the current anti-platelet drugs face limitations due to narrow therapeutic window and limited effi cacy. The four possible targets for novel anti-platelet action are: Inhibition of agonist generation, receptor inhibition, G protein inhibition and inhibition of enzymatic cascades. Newer P2Y12 antagonists e.g. prasugrel, ticagrelor, cangrelor, etc., have better effi cacy and low bleeding risk. The thrombin receptor (PAR1 and 4) inhibitors are said to decrease the hemorrhagic complications. Drugs which inhibit TXA2 Synthase or TXA2 receptor are also promising in their anti-platelet action. Another novel group is of collagen receptor antagonists such as GPVI antagonists, GPIb receptor antagonists, etc. The other targets being explored are von Willebrand Factor antagonists, platelet Gq antagonists, etc. However, there still lies a bundle of unresolved issues regarding the effi cacy and safety, optimal dosage, administration requirements, combination therapy, clinical evaluation, cost-effectiveness, and the resistance phenomena of these drugs.

Revacept: Collagen GP VI receptor inhibitor, a new & a formidable target for antiplatelet action.

Antiplatelet drugs play an important role in the prevention as well as treatment of cardiovascular diseases like coronary artery disease and stroke. Many of the currently available antiplatelet drugs face limitations due to safety and efficacy issues. A new antiplatelet drug, revacept i.e. a collagen receptor antagonist, has been shown to reduce platelet adhesion by blocking GP VI-dependent pathways without increasing the risk of bleeding complications and without affecting the general hemostasis.