Q 1 WRITE A NOTE ON ORAL THERAPIES AND THEIR COMPLICATIONS IN PATIENTS WITH MULTIPLE SCLEROSIS ?
A 1 INTRODUCTION
1 Treatment for MULTIPLE SCLEROSIS has undergone a revolution over the past 2 decades Since , its introduction in 1993 IFN beta 1 b ( IFN B 1 b ) the 1st therapeutic drug for MS
2 Classical MS treatment using 1st line injectible drugs , although widely accepted remain of concern in terms of therapeutic adherence and efficacy such as -
A ) IFN s , 1st and most commonly used drugs for MS have been associated with injection site reactions , flu like symptoms and liver dysfunction
B ) GLATIARMER ACETATE is associated with local injection site reactions and transient systemic post injection reactions which may diminish patient adherence to treatment
3 So , overall in addition these injectables only reduce the relapse rate by 30 %
THE NEW ORALLY ADMINISTERED DRUGS ( ORAL DRUGS ) are approved for MS treatment and represent significant therapeutic response
CLINICAL SIGNIFICANCE
The new orally administered drugs promotes patient satisfaction and increases therapeutic compliance
ORAL DRUGS
1 Are Currently 3 in number - Fingolimod , Terifluonomide and DimethylFuroate
2 2 are in Phase III trials - Cladribine , Laquinimod
DISCUSSION ( IN DETAIL )
1 FINGOLIMOD -
A ) Also called FTY 720 or Gilenya
B ) Is a derivative of Myriocin , a metabolite of ascomycetes fungus Isaria Synclarii and is used in oriental medicine
MECHANISM OF ACTION
A ) Is Phosphorylated in the bloodstream to resemble ENDOGENOUS SIP ( Lysophospholipid sphingosine 1 phosphate ) for which 5 receptor exists
B ) In particular SIP 1 binds with receptors expressed on lymphocytes and regulates the normal eggress of lymphocytes from lymphoid tissue
On the other hand in CNS , it modulates neurogenesis , neural function and migration
C ) Fingolimod , acts as a receptor superagonist inducing aberrant internalisation - This inhibits the eggress of T and B cells from lymph nodes reducing the number of circulating memory T cells by 70 %
D ) Is lipophillic , easily enters the CNS , where drug can bind to various SIP receptors