Cyclosporin

Both acute and chronic rejection may result in hypertension. The former causes acute fluid retention and plugging of peritubular capillaries with inflammatory cells. This may progress to intimal swelling and medial necrosis and eventuate in ischemia secondary to endothelial proliferation and obliteration of small vessels. Chronic rejection, thought to be related to protracted humoral injury, results in obliteration of capillaries via the development of intimal hyperplasia. Cyclosporine has a vasoconstrictive effect which, through activation of the renin-angiotensin system, may lead to hypertension. RTAS is responsible for hypertension in 4% to 12% of renal allograft recipients. It responds well to percutaneous angioplasty. A careful trial of angiotensin-converting enzyme inhibitors may be diagnostic of RTAS. Recurrent disease such as membranoproliferative glomerulonephritis and focal glomerular sclerosis may result in significant hypertension in renal allograft recipients.

The most important adverse effects of cyclosporin are renal dysfunction leading to hyperuricemia, hyperkalemia, hypomagnesemia, hypertension, GIT side effects, gingival hyperplasia, hyperlipidemia, head ache and tremor.

Cyclosporine binds to intracellular cyclophilin, and this complex interacts with calcineurin.

Calcineurin is crucial for normal lymphokine gene activation, and its inhibition by cyclosporine consequently interferes with the production of interleukins-2, -3, and -4 (IL-2, IL-3, and IL-4), tumor necrosis factor-alpha (TNF-), and other important mediators of inflammation. In turn, specific and potent inhibition of T-cell activation (especially CD4 cells) is achieved. 

Ans. is ‘b’ i.e., IL2

• Cyclosporine enters target cells and bind to cyclophilin (an immunophilin).
• This cyclosporine-cyclophilin complex inactivates calcineurin 
• IL-2 trascripitan and proliferation of T cells.

Ans. is ‘c’ i.e., Multiple myeloma

o Cyclosporine is used in organ transplant (to prevent rejection) and autoimmune disorders (RA, psoriasis).

Ans. is ‘a’ i.e., Hypertension; ‘c’ i.e., Hirsutism

o Cyclosporin can cause nephrotoxicity (major side effect), hypertension, precipitation of diabetes (hyperglycemia), hirsutism, gum hyperplasia, hyperkalemia, hyperuricemia, heperlipedmia, hepatotoxicity and neurotoxicity.

Ans. is ‘a’ i.e., Amphotericin B

o All nephrotoxic drugs like aminoglycosides, Vancomycin, amphotericin B and NSAIDs enhance toxicity of cyclosporine.

Ans. is ‘d’ i.e., Cyclosporine A

Ans. is ‘c’ i.e., In India, organ harvesting from brain dead patients is not permitted by law

First, the type of grafts.

Allograft                      –>       An organ or tissue transplanted from one individual to the other.

Isograft                                  A transplant between identical twins.

Orthotopic graft         –              A transplant placed in its normal anatomic site e.g. Liver

Heterotopic graft –>                 A transplant placed in a site defferent from where the organ is normally located.

Renal transplant is a heterotopic graft because the transplanted kidney is not placed in its normal anatomic position, but is placed in the iliac fossa in the retroperitoneal position leaving the native kidney in situ.

• Types of Donor
• Donors are of three types

i)           Living donor

ii)         Braindead, heart beating cadaveric donors

iii)       Non heart beating (asystolic donors)

• “In India for organ harvesting from brain stem dead patient the relatives are formally asked to sign a prescribed form, in contrast to U.K. where transplant co-ordinators and nurse just write and sign in the file about the consent given”. – A.S.I. Surgery 2003 p. 244
• Organ procurement ‑

– In a brainstem dead donor, the organ to be procured should be preserved to maintain its functional integrity. For this purpose the organ should be perfused with organ preservative solution twice before it is transplanted to the recipient.

The first perfusion is done just after the abdomen is opened at laporotomy and the second perfusion is done just after the organ has been removed from the donor.

Commonly used preservative solutions include UW solution (University of wisconsin) and Eurocollins solution.

After removal from the donor, the organ is placed in two sterile bags and stored at 0-4°C by immersion in ice while they are transported to the recipient centre.

• Immunosuppressive drug in renal transplant.

– Cakineurin blockers are especially useful in renal transplant patients. These include cyclosporine and Tacrolimus.