In this video we can discuss about pharmacology of immunosuppressants here we will discuss the definition classification mechanism of action the reaction and uses of immunosuppressants let’s start with the definition of immunosuppressants immunosuppressants are the drugs which will inhibit cellular or humoral or both type of immune response so these treks are mainly
Used in organ transplantation as well as auto immune diseases now immunosuppressants are mainly classified into five calcium urine inhibitors like cyclosporine and tacronimus m tau inhibitors like xerolimus and abrolimus then antiproliferative drugs or cytotoxic drugs like acetobrin methotrexate cyclophosphamide and chlorambusil and mycophenolate morphetyl then
Glucocorticoids like pernicillon and other glucocorticoids like medial prednisone hydrocortisone etc and biological agents like tumor necrosis factor alpha inhibitors like endara sebs inflexima then interleukin-1 receptor underground is like anakinra interlocking two receptor underground is like tachyclysoma and bacilluximab and the cd3 antibody like moro monap
And polygonal antibody lake and the thymocete and d body and rhod immunoglobulins so this is the classification of immunosuppressants now before going to the pharmacology of each drugs first we have to understand how the immunosuppression will occur in kabab body so there is two type of immune response in our body humeral immune response and cell mediated immune
Response in case of humeral immune response this will start when antigen come in contact with the beta lymphocyte cells so when it will it contact with the beta lymphocyte cell this beta lymphocyte cell will be proliferated and differentiated to form plasma cell and this plasma cell will produce antibody and this antibody produced from the plasma cell will bind
With the antigen and it will get neutralized and in some antigen it may bind with the macrophages like antigen processing cell like macrophages when it is combined with the major stock compatibility cell so that it will differentiate whether the antigen is self or non-self so our body will consider anything that will come outside the body and the mhc molecules
Will find whether this self or known cell according to the differentiation of cell which is formed from the fluorine potential which is formed during the fertilization during the consumption time when the ovum and sperm come and fuse to form fertilizer cycle and this cycle cell are known as fluoride potential so uh the property of fluorine potential is it can
Be differentiated into different kind of tissues like cardiac cells bone etc so whether the cell is originated from the pluripotent cell according to that it can be differentiated so after finding uh with the mhc whether it is non-self it will release some uh mediators like hinder looking one so by the release of interlocking one it will activate the cd4 helper
Cell so this helper cell will activate the helper t cells and the helper t cells will start producing cytokines and cytokines may enhance the proliferation of beta lymphocyte cell and it can cause differentiation to form plasma cell and produce antibody also and the same cytokine also can mediate the cell mediated immune response so the cell mediated immune
Response is uh from the precursor cell or that is known as cytotoxic lymphocyte cell so when an antigen bind with the cytotoxic lymphocyte cell it will also produce interleukin-2 so that in the look into sorry it will activate the activated cytotoxic lymphocyte cell and this will differentiate it into mature cytotoxic lymphocyte cell and this will produce and
This will bind with the antigen and it will lies the foreign body so this is the major immune response pathway in our body now uh by understanding this we can understand the mechanism of action of immunosuppressant so first we can discuss about the glucocorticoids this glucocorticoid will inhibit the major histocompatibility expression as well as it will inhibit
The production of interleukin-1 as well as interleukin-2 which will uh responds to activate the cytokines and cytokines have major 2 oxygen it will activate the beta lymphocyte cell as well as activated cytotoxic lymphocytes and so all this process will be inhibited so the immune response will be suppressed and in case of cytotoxic tracts like acetopron they
Will act at the clonal proliferation and differentiate the version of beta lymphocyte cell as well as uh activated cytotoxic lymphocyte cell also and the cyclosporine and tacrolimus and xerolimus they will inhibit the antigen stimulated activation as well as proliferation of the t cells and expression of interleukin and cytokine also will be inhibited so they
Will act here on the cd4 helper cell and they will inhibit the immune response by inhibiting in the look into as well as by inhibiting the proliferation of helper t cells now coming to the antibodies antibodies like neuron neuromonops cd3 as well as and the thymocyte globulin specifically bind with the help for t cells so that it will inhibit the secretion of
Interleukin as well as it will inhibit the secretion of cytokines so as we mentioned before cytokine have three effects it will uh stimulate the proliferation of beta lymphocytes as well as it will stimulate the activation of cytotoxic lymphocyte cells also so this is the immunosuppressant action in general now we can consider one by one first classification
Of anti-im sorry immunosuppressants is calcium urine inhibitors or specific t cell inhibitors like cyclosporine so this is a cyclops peptide with 11 amino acid which is obtained from a fungus and this calcinomarine inhibitors like cyclosporine will act by inhibiting antigen stimulated activation as well as proliferation of alpha t cells as well as the expression
Of interleukin and other cytokines will be inhibited without affecting the suppressor t cell so this will affect on the helper t cell so thereby it will inhibit the uh release of interleukin as well as it will inhibit the release of uh cytokines also now what are the adverse reactions of cyclosporine the important reduced reactions are nephrotoxicity as well as
It will impair the liver function and there will be a sustained rising blood pressure and it may precipitate diabetics anorexia and lethargy it may cause hyperkalemia and hyperuricemia and there will be a chance for opportunity infection since the cyclosporine will suppress both the t as well as v lymphocyte immuno response then it may produce your suit issue
Then gum hyperplasia and trauma and seizures are the different advanced reactions of cyclosporine now coming to the drug interaction as we mentioned before in adverse drug reactions cyclosporine will cause neptune toxicity so if you are combining cyclosporine with other nephrotoxic drugs like aminoglycoside vancomycin and amphotericin b which are antimicrobial
Agent which may enhances the nephrotoxic action of cyclosporine and cyclosporine will depress the renal function so it can reduce the excretion of many drugs and it may cause toxicity of that kind of stress and some enzyme inducers like phenytoid phenobarbiton rupambasin these enzyme induces will increases the metabolism of cyclosporine thereby it will lower its
Blood concentration of cyclosporine so it makes it it may cause rejection of transplantation and uh cyclosporine is an uh enzyme inhibitor so it will inhibit the metabolism of many drugs like erythromys in ketoconazole and other related drugs so it will increases the bioavailability of this kind of drug and it may cause toxicity of that drugs and the potassium
Supplements and potassium sparing diuretic when if you are using along with the cyclosporine it may leads to hyperkalemia in patient on cyclosporine now what are the uses of cyclosporine it is mainly used in renal hepatic cardia bone marrow and other transplantation for the uh immunosuppression in case of this kind of transplantation we have to start the
Cyclosporine orally 12 hour before the transplantation and we have to continue for as long as we needed and it is a second line in many autoimmune diseases like rheumatoid arthritis you why it is bronchial asthma inflammatory bowel diseases and dermatologists as well as psoriasis and cyclosporine along with the corticosteroid or methotrexate it will give good
Result when obtaining a plastic anemia iso so that is all about the cyclosporine now coming to another calcium urine inhibitors like tacrolimus it will act uh by inhibiting same mechanism as that of cyclosporine it will inhibit the antigen stimulated activation as well as proliferation of helper t cells as well as it will inhibit the expression of interleukin
And other cytokines why ah without any affecting in the suppressor and what is the advantage of a tracholimus over cyclosporine it is 100 times more potent than cyclosporine and that tachrolimus is administered orally as well as by iv infusion oral absorption may be variable and decreased by food now this is the site of action of tacrolimus it will inhibit
The cd4 helper t cells so that it will inhibit the eye in the lokin as well as cytokine actions now coming to the adverse duct reaction of that polymers it may precipitate diabetes may cause nephrotoxicity sorry neurotoxicity alopecia and diarrhea and dose limiting toxicity in renal and these are mainly used in patient for the craft rejection or the transplant
Rejection which are not suppressed by cyclosporine usually we will prefer cyclosporine if the immunosuppression is not occurred during cyclosporine we have to use tacrolimus and this is particularly valuable in case of liver transplantation because its absorption do not depend on the bite and it can be also used in fistulating chronic diseases also coming to
Next class of immunosuppressant that is m tauren inhibitors like serolemus this is a new and potent immunosuppressant which is a macrolide antibiotic like tachromelimus which was early named as raphamycin and the mechanism of action this rapamycin or xerolimus will bind with the same immunophiline fk binding protein as that of the acrylimus and but the ceromos
Fkb fk bpp complex will inhibit another kinase which is known as mammalian target of rapamycin which in short we can call it as m tau and it will not uh do not interact with the calcium so this m tauran is an important link in cascade for signaling pathway which will lead to the proliferation and differentiation of the cell activated by interleukin as well as
Other cytokines so they will act at the same mechanism as that of tachrolimus but uh on different uh receptor different kinase enzyme that is the mammalian target of rapamycin in the here also this is the responsible for the differentiation of cd4 cells now coming to the adverse drug reaction it is not nephrotoxic ah when compared with the other tacrolimus so
Ah ceromos is not nephrotoxic but it will suppress bone marrow suppression and it may cause thrombocytopenia it may rise serum lipid in common it may cause diarrhea liver damage and pneumonia to the uh uses of ceromos it is used for prophylaxis and therapy of graft projection a reaction cerebrus can be used alone but in generally it is combined with the lower
Dose of cyclosporine tacrolimus or corticosteroid cerebellums quarter stents are been used to reduce the incidence of coronary artery the stenosis by inhibiting endothelial proliferation at the site so these are the uses of serolimus
Transcribed from video
IMMUNOSUPPRESSANTS Part 1: Pharmacology: Cyclosporine: Sirolimus By AsHiF’s Pharma Classes
