This document discusses the effects of immunosuppression on various body systems and endocrine function. It begins by classifying different types of immunosuppressants and describing their mechanisms of action. The document then examines how immunosuppression can lead to hyperglycemia, reproductive dysfunction, decreased bone density, muscle weakness, kidney damage, gastrointestinal issues, increased risk of infection and cancer, adrenal gland effects, neurological and psychiatric side effects, eye problems, heart issues, and liver toxicity. In conclusion, the widespread effects of immunosuppression throughout the body are summarized.

1. 1
P. E. Society’s Modern College of Pharmacy, Moshi Pune - 44
Presented by:
Pallavi kakade
Assistant Professor
Pharmacology
Immunosuppression and
Endocrine Dysfunction

2. CONTENTS
INTRODUCTION
AIMAND OBJECTIVES
REVIEWANDLITERATURE
SUMMARY
CONCLUSION
REFERANCES

3. General Principle of Immunosuppression
 Primary immune responses are more easily repressed
than secondary (memory)
 Suppression is more likely to be achieved if therapy is
begun before exposure to the immunogen
 Different immunosuppressants have different effects
on different immune reactions and mediators
 Immunosuppression involves an act that reduces the
activation or efficacy of the immune system

4. Aim and objectives
 Advances in transplant immunosuppression
Have contributed to the-
 Decrease in the frequency of acute rejection.
 Increase in graft survival .
 longevity for renal allograft recipients.
 Longevity for renal allograft recipients
 For the treatment of auto-immune diseases such
as rheumatoid arthritis or crohn’s disease.

5. Classification of immunosuppressants
1.T-cell inhibitors-
cyclosporine,tacrolimus,sirolimus,mycophenolate
mofetil.
2.Cytotoxic drugs -
Azathioprine,methotrexate,cyclophosphamide,
chlorambucil.
3.Glucocorticoids.
4.Antibody reagents--Muromonab cd3,antithymocyte
globulin.

6. Type of immunosuppression
• Deliberately induced
• Non-deliberate induced

7. Endocrine dysfunction

8. Immunosuppression and Hyperglycemia
 Decreased insulin secretion and insulin sensitivity.
 Decreased glucokinase activity and reduced insulin
gene expression .
 Decreases Akt (also known as protein kinase B)
phosphorylation in the liver, which is a key step in
insulin signal transduction.
 Proliferation of beta cells .
 Apoptosis human islets.
 Hypertriglyceridemia.

9. Immunosuppression and Hyperglycemia
 To characterize this complication, including random
blood glucose ≥ 200 mg/dl, fasting blood glucose ≥
140 mg/dl.
 Which leads to increase blood glucose level and cause
diabetic mellitus.
 It is major effect of immunosuppressant.

10. Immunosuppression and Reproductive
Dysfunction
 Female reproductive system-
 Increases fertility.
 Hypogonadism .
 Amenorrhea.
 Male reproductive system-
 Hypogonadism .
 Reduced sperm count.
 Decreased motility.

11. Immunosuppression and Bone Density
 Decreased bone density.
 Hypophosphatemia.
 Calcineurins.
 Impair healing bone fracture.
 Osteoporosis.

12. Bone disorders
How?

13. Bone disorders
Multiple causes of poor bone density
Weak
bones
Hypogonadism
Low Vitamin
D &
parathyroid
gland failure
Iron overload
? Low Growth hormone Diabetes mellitus
Glucocorticoids

14. Immunosuppression and Muscle
 Decreases muscle function.
 Decreases co-ordination between different types of
muscle fibres to contract and relax .
 Decreases adaptability of fibres.
 Tingling of the hands and feet, hand tremors.
 Decrease muscle protein production and decrease the
ability of the muscle to produce muscle energy in an
effective manner.
 Muscle weakness.

15. Immunosuppression and Kidney
 Causes nephrotoxicity .
 Causes small arteries branches to constrict or smaller
causing high blood pressure .
 Causes high levels of potassium and low levels of
magnesium in the blood.
 Renal failure.

16. Immunosuppression and Kidney

17. Immunosuppression and GIT
 Enhances the secretion of gastric acid and pepsin.
 Due to that GIT disturbances occurs.
 Increases enzyme level in GIT and it disturb
metabolic process.
 Causes various symptoms like -----

18. Immunosuppression and GIT
Esophaggitis
Increased
appetite
Weight
gain
Stomach
irritation
Stomach ulcers
and pain
Nausea
Diarrhea

19. Immunosuppression and GIT
Gastritis
Vomiting
Abdominal pain
Peptic ulcer
Anxiety
Mouth
sores
Reduced
intestinal
flora

20. Immunosuppression and Infection
Weaken the immune system
Less body resistance to infection
Difficult to treat infection
Decreases platelet count
Decreases red and white blood count

21. Immunosuppression and Cancer
 Immunosuppressant drugs are also associated with a
slightly increased risk of cancer.
 Bladder cancer, also thought to be due to
accumulation in bladder
 The immune system also plays a role in protecting the
body against some forms of cancer.
 For example, long-term use of immunosuppressant
drugs carries an increased risk of developing skin
cancer as a result of the combination of the drugs and
exposure to sunlight.

22. Immunosuppression and Adrenal gland
 Long term administration immunosuppressant
causes-
 Cushing’s syndrom(excessive levels of cortisol in
the blood) symptom -moon face, buffalo hump,
thinning of skin.

23. Immunosuppression and CNS
 It cross links DNA, interferes with RNA synthesis and
inhibits the enzyme topoisomerase II.
 Ii is used for reducing neurologic disability.
 Interferes in purine nucleotide synthesis and
metabolism
 Inhibits the enzyme inosine monophosphate
dehydrogenase, and as a consequence, it decreases de
novo guanosine nucleotide synthesis.

24. Immunosuppression and CNS
Headache Tremors Depression
Insomnia Anxiety Mania

25. Immunosuppression and CNS
 Difficulty controlling emotion.
 Difficulty in maintaining train of thought psychosis,
or other psychiatric symptoms.
 Unusual fatigue or weakness.
 Mental confusion/ indecisiveness

26. Immunosuppression and Eye
 Cataract and blurry vision.(increases intraocular
pressure )
 Glaucoma

27. Immunosuppression and Heart
 Hypercholesterolemia.
 Hypertriglyceridemia.
 Hypertension.
 Heart failure.
 Myocardial infraction.
 Stroke and ischemic attack.
 Artrities

28. Immunosuppression and Heart
 Reduce capillary permeability thereby reducing fluid
exudation causes positive inotropic effect prolong use
causes hypertension.
 Change tone of arterioles causes artrities.
 They interact with s1p3 receptor results in slowing of
the sinoatrial node and reactivation of g-protein-
activated potassium channels 1 and 4.
 It has similar effects on the atrioventricular (AV)
node bradycardia and results AV block.
 Causes heart failure.

29. Immunosuppression and liver
 Direct damage to hepatocytes.
 Enhance infection of hepatitis b and hepatitis c virus .
 Hepatotoxicity due to elevation of -------
 Serum alkaline phosphatase
 Bilirubin
 Serum transaminases .

30. Summary
 Immunosupressant are drugs which inhibit immunity.
 It is necessary to suppress immune reaction in organ
transplantation.
 It is necessary to suppress immune reaction
autoimmune disorders.
 Effect of immunosupresent on endocrine and other
organ of body.

31. Conclusion
 Immunosuppressant causes hyperglycemia .
 It causes hypertension ,nephrotoxicity, bone density.
 It causes endocrine disturbance.
 Study of effect on CNS ,reproductive dysfunction ,
susceptibility to infection .
 Risk of causes cancer.

32. References –
1. Vincenti f, friman s, scheuermann e, rostaing l, jenssen t, et
al. (2007) results of an international, randomized trial
comparing glucose metabolism disorders and outcome with
cyclosporine versus tacrolimus. Am J transplant 7: 1506-
1514.
2. Hjelmesaeth j, hartmann a, leivestad t, holdaas h, sagedal s, et
al. (2006) the impact of early-diagnosed new-onset post-
transplantation diabetes mellitus on survival and major
cardiac events. Kidney int 69: 588-595. 2.
3. Kasiske bl, snyder jj, gilbertson d, matas aj (2003) diabetes
mellitus after kidney transplantation in the united states. Am J
transplant 3: 178-185.
4. 3. John PR, Thuluvath PJ (2002) Outcome of patients with
new-onset diabetes mellitus after liver transplantation
compared with those without diabetes mellitus.

33. References
5 Yates CJ, Fourlanos S, Hjelmesaeth J, Colman PG, Cohney
SJ (2011) New- Onset Diabetes After Kidney
Transplantation-Changes and Challenges. Am J Transplant.
6 Davidson J, Wilkinson A, Dantal J, Dotta F, Haller H, et al.
(2003) New-onset diabetes after transplantation: 2003
International consensus guidelines. Proceedings of an
international expert panel meeting. Barcelona, Spain, 19
February 2003. Transplantation 75: SS3-SS24.7 Montori VM,
7 Basu A, Erwin PJ, Velosa JA, Gabriel SE, et al. (2002)
Posttransplantation diabetes: a systematic review of the
literature. Diabetes Care 25: 583-592. 7.
8 Sulanc E, Lane JT, Puumala SE, Groggel GC, Wrenshall LE,
et al. (2005) New- onset diabetes after kidney transplantation:
an application of 2003 International Guidelines.
Transplantation 80: 945-952.

34. References
9 Reynolds NJ, aldaraji WI (2002) calcineurin inhibitors and
sirolimus: mechanisms of action and applications in
dermatology Clin exp dermatol 27: 555-561.
10 Halloran pf (2001) mechanism of action of the calcineurin
inhibitors. Transplant proc 33: 3067-3069.
11 Bierer be, mattila ps, standaert rf, herzenberg la, burakoff sj,
et al. (1990) two distinct signal transmission pathways in T
lymphocytes are inhibited by complexes formed between an
immunophilin and either FK506 or rapamycin. Proc natl acad
sci U S A 87: 9231-9235.
12 Halloran pf (2000) sirolimus and cyclosporin for renal
transplantation. Lancet 356: 179-180.

35. THANK YOU
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