IMMUNOSUPPRESSIVE

DRUG THERAPY

BY
Abhishek S. Sharma
 Immune Response
Immune response is a highly sophisticated
defense mechanism of the body which is
composed of Cell mediated and Humoral
immunity (Nossel 1987) . Both of these
response have a high level of specificity
directed to antigenic epitopes expressed
on molecular components of infectious
agents , foreign (Grafts) or transformed
(Malignants) , or even autologous cells
(autoimmunity).
Cells participating in the immune
response
 General principles of
Immunosuppression
Immunosuppression:-Immunosuppression is a process of
inhibiting the immune response at different steps .

Principles governing Immunosuppression:-

Primary immune response can be more effectively suppressed

then secondary response .

If immunologic memory has been established immunosuppressive

therapy will have modest effects.

Immunosuppressive therapy is most effective before generation of

immune response.

But ironically autoimmune disease like Rheumatoid arthritis are

treated after the response is generated
 Sites of action of specific
immunosuppressive drugs on various
stages of immune response
 Pharmacological Classification
of Immunosuppressant
 Glucocorticoids:
Immunosuppressive mechanism
Anti – inflammatory effects
 Cytostatics:
Alkylating agents
Antimetabolites
Cytotoxic drugs
 Antibodies:
Polyclonal antibodies
Monoclonal antibodies
 Drugs acting of immunophilins
Cyclosporine, Tacrolimus , Sirolimus
 Miscellaneous
Interferons, Mycophenolate mofetil,
TNF
binding proteins
 Mechanism of
Immunosuppressants
Glucocorticoids:- These drugs prevent the
conversion of APCs to CD4 Helper cells by
inhibiting the production of IL-1

Eg:-Prednisolone,Hydrocortisone, etc.

Cytostatics:-These drugs inhibit the conversion of

CD8 cells to Cytotoxic T cells
and B cells to plasma cells and memory cells by
inhibition of purine synthesis.

Eg:- Azathioprine , Mercaptopurine

Antibodies:- They are used generally in cases
where steroid resistence occurs , they act as
antigens and suppress the cell mediated
responses and are generally T cell directed

Eg.:- OKT3,Anti Thymocyte Globulin(ATG)

Drugs acting on Immunophilins:- They are also

called calcineurin inhibitors as they inhibit
calceneurin which is responsible for production of
IL-2 .
Eg.:- Cyclosporine , Tacrolimus , Sirolimus
 Cyclosporine

Description:-
Was discovered in 1972
Isolated from fungi
Available as I.V , Caps , Tabs
, Sol.

Mechanism Of Action:-
1. Binds with cyclophilin of T-
lymphocytes.
2. Inhibits calcineurin which
induces the transcription of
IL-2.
Adverse drug reactions:-
High blood pressure
Unusual hair growth
Nephrotoxicity
Drug-drug interactions:-
Enzyme inducers:
Carbamazepine,Phenobarbitone.
Enzyme inhibitor:
Acyclovir,antifungals.
Drug-food interactions: Grape fruit juices should
be avoided,vaccination should not be done.
 Tacrolimus

Description:-
• Odourless and tasteless
white crystalline powder.
• Isolated from cultures of
Streptomyces
tsukubaensis, strain no.
9993

MOA:-
• Inhibits T – lymphocyte
activation by forming
complex with an
intracellular protein FKBP -
12
• The complex formed
inhibits calcineurin.
 ADR:-
Hyperglycaemia
Myocardial Hypertrophy
Hypomagnesia , Hyperkalemia

Drug-Drug interaction:-
Enzyme inducers: Anticonvulsants,Rifabutin ,
Rifampin

Enzyme Inhibitors:-
Anti fungals , Macrolides
 Azathioprine
Description:-
Immunosuppressive
metabolite

MOA:-
Non enzymatically
cleaved in
mercaptopurine which
acts as a purine
analogue and inhibitor
of DNA synthesis
 Azathioprine
ADR:-
Hematological and gastrointestinal problems

Drug-Drug interactions:-
Usual dosage of azathioprine should be reduced
when used in conjunction with allopurinol.
Use with other leukocyte enhancer like
cotrimoxazole may increase leukopenia in kidney
transplant patients
Use with ACE inhibitor may lead to leukopenia
 Mycophenolate Mofetil

 Description:-
Newer variety of
immunosuppressant
derieved from penicillium
culture.

MOA:-
Mycophenolic acid inhibits
lymphocyte purine
synthesis by non
competitive inhibition of
enzyme Inosine
Monophosphate
Dehydrogenase.
 ADR:-
Diarrhoea , nausea , vomiting , infections ,
anemia.

Drug-Drug Interactions:-
Enzyme Inducer:-
Antacids with Mg and Al hydroxides
Cholestyramine

Enzyme Inhibitor:-
Acyclovir
Renal Transplant Operation
 Drug Regime Post Kidney
Transplant
 Immunosuppressants

 Antibiotics in order to prevent infection on

surgical wounds & protection against nosocomial
infections.

 Corticosteroids are given to in order to increase

the effect of antibiotics and as anti inflammatory

 Inj. Erythropoetin is given for a couple of weaks

in order to initiate the production of newer R.B.Cs
 Role of the Transplant Pharmacist

 Disease state management

– Hypertension
– Diabetes Mellitus
– Osteoporosis
– Hyperlipidemia
– Electrolyte abnormalities
 Patient understanding and adherence to the drug
regimen
 Pharmacokinetic drug level monitoring
 Drug interactions (esp. with immunosuppressants)
 Adverse drug reaction monitoring
 Research Abstracts
 Mcdonald J.W et.al. at Medicine LHSC – UC , A-LL132,339
Windermere Road, London,Ontario,Canada,N6A 5A5.
john.mcdonald@lhsc.on.ca have proved “Cyclosporine for induction
of remission in Crohn’s disease” in Cochrane Database Syst Rev.
2005 Apr 18;(2)CD000297(10)

 J Grinyo et. Al. from dept. of nephrology and urology ,Hospital de

Bellvitge , CSUB, University of Barcelona , C.Fexia
Llarga,Barcelona,Spain. Have proved that “Primary
immunosuppression with mycophenolate mofetil; and
antithymocyte globulin for kidney transplant recipients of a
suboptimalgraft.” In Nephrology Dialysis Transplantation , Vol 13 ,
issue 10 2601 – 2604 , copyright 1998 by Oxford university.(11)
 Research Articles

 Gabardi s et. al. from the Dept. of Pharmacy Services ,

Brigham and Women’s Hospital , Boston , MA 02115-6110 ,
USA . sgabardi@partners.org have proved the
significance of enteric Mycophenolate sodium tablet
over Mycophenolate mofetil tablet in Ann Pharmacother
2003 nov ; 37 (11) : 1685 – 93(!2)

 Quang Hieu De Tran, Elizabeth Guay et al have proved the

use of “Tacrolimus ointment in dermatitis and
pyoderma gangreonosm” in Journal of Cutaneous
Medicine and Surgery : Incorporating Medical and Surgical
Dermatology vol. 5 , number 4 /August 2001 pg no. 329 –
335 published by Springer New York(!3).
 CONCLUSIONS
 The success rate of Renal Transplantation should be
supported with best possible medical facilities to the
nephrologists and best possible hospital facilities.

 Immunosuppressant drug therapy is a long term

treatment for acceptance of grafts especially renal
transplants.

 Post transplant care is to be monitored very keenly

by the Pharmacist & Family for post operative case.
 CONCLUSIONS
 Renal Transplant patients are prone to secondary and nosocomial
infections like Tuberculosis, URTI, LRTI, UTI, Meningitis etc.
hence proper care for Food and Hygiene should be maintained by
Nutritionist and Dietetics and Cleaning staff of the hospital.

 Cost of combination therapy which includes

immunosuppressants ,Broad spectrum antibiotics, Erythropoetin
and related injections, multi vitamins etc. is very high and hence
should be made feasible to underdeveloped countries.

 DPCO(Drug Price Control) 1985 act for life saving drugs of this
class should be taken into deep consideration.
 BIBLIOGRAPHY
 ( Ref : - Goodman & Gilman’s The pharmacological basis of theraputics , 9th edition , by
Hardman Joel . G , Limbird Lee E , published by McGraw Hill, int edition 1996 , pg no. 1291 –
1296)
 http://en.wikipedia.org/wiki/Immunosuppressant#immunosuppressive
 http://www.answers.com/topic/cyclosporine-1
 http://www.emcure.co.in/html/vingraf.htm
 http://www.rxlist.com/cgi/generic/azathioprine_ad.htm
 6)http://gsm.about.com/compact/showmono.asp?monotype=&cpnum=419&r=6078&match=F
 Reference:- Smith’s general urology, 13th edition , year of publication :-1992, b
Tanagho Emil .A MD (University of California. San Francisco) McAninch Jack W MD
(University of California….San Francisco)Pg no. 556-562 Book provided by Dr. Sunil Agrawal MS
, Sanjeevani Hospital, Malad(E)
 http://www.aakp.org/aakp-library/Transplant-Drugs/
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