# Immunosuppressive Drugs > Immunosuppressive drugs for NEET-PG Medicine: azathioprine, mycophenolate, calcineurin and mTOR inhibitors with mechanisms, toxicities and drug interactions. - Canonical URL: https://prepelephant.com/topics/neet-pg/medicine/immunosuppressive-drugs - Exam / course: NEET-PG · Subject: Medicine - Publisher: PrepElephant (https://prepelephant.com) — Prepared and reviewed by the PrepElephant Academic Review Team - First published: 2026-10-08 - Last updated: 2026-10-08 - Reference basis: Katzung's Basic and Clinical Pharmacology; Goodman and Gilman's The Pharmacological Basis of Therapeutics; Harrison's Principles of Internal Medicine - How to cite: "Immunosuppressive Drugs", PrepElephant, https://prepelephant.com/topics/neet-pg/medicine/immunosuppressive-drugs ## Direct answer Immunosuppressive drugs act on lymphocyte activation and proliferation, using different molecular targets to reduce rejection and autoimmunity. Azathioprine and mycophenolate block purine synthesis, calcineurin inhibitors such as ciclosporin and tacrolimus block T-cell signalling, and mTOR inhibitors such as sirolimus and everolimus halt cell-cycle progression. Each class carries characteristic toxicities, from myelosuppression and nephrotoxicity to mouth ulceration and hyperlipidaemia. ## What you must remember - **Azathioprine:** Prodrug of mercaptopurine that inhibits de novo purine synthesis; TPMT and NUDT15 deficiency causes severe myelosuppression, so testing guides dosing. - **Allopurinol interaction:** Allopurinol inhibits xanthine oxidase, which breaks down thiopurines, so the azathioprine dose is substantially reduced when the two are combined. - **Mycophenolate:** Inhibits inosine monophosphate dehydrogenase, depleting guanine nucleotides in lymphocytes; causes diarrhoea and leucopenia and is teratogenic. - **Calcineurin inhibitors:** Ciclosporin and tacrolimus block calcineurin, reducing NFAT-driven IL-2 transcription; nephrotoxicity, hypertension, hyperkalaemia and hypomagnesaemia are typical. - **Specific toxicities:** Ciclosporin causes gingival hyperplasia and hirsutism; tacrolimus causes post-transplant diabetes and neurotoxicity. - **mTOR inhibitors:** Sirolimus and everolimus bind FKBP-12 and inhibit mTOR; they cause mouth ulcers, hyperlipidaemia, delayed wound healing, thrombocytopenia and pneumonitis. - **Interactions:** Azoles, macrolides and grapefruit raise calcineurin inhibitor and sirolimus levels through CYP3A4 and P-glycoprotein inhibition; rifampicin lowers them. ## A transplant patient whose creatinine climbs A 38-year-old man, three months after a living-donor kidney transplant, takes tacrolimus, mycophenolate and prednisolone. His creatinine has risen from 110 to 180 micromol per litre over two weeks, and then he develops a fungal infection for which the team starts an azole. 1. **Recognise the interaction:** Azoles inhibit CYP3A4, so tacrolimus levels rise. High calcineurin inhibitor exposure causes afferent arteriolar vasoconstriction and nephrotoxicity. 2. **Check the trough:** A trough tacrolimus level is the first step, with blood pressure, potassium and magnesium checked. 3. **Reduce the dose:** The dose is reduced to bring the trough into the target range. 4. **Exclude rejection:** Acute rejection must still be considered, because calcineurin inhibitor toxicity and rejection produce a similar creatinine rise. A biopsy distinguishes calcineurin toxicity from rejection, and that result drives treatment. 5. **Adjust mycophenolate:** If diarrhoea develops from mycophenolate, the dose is reduced rather than stopped abruptly, and the full blood count is checked for leucopenia. 6. **Review new prescriptions:** If the team later considers azathioprine for another reason, TPMT genotype or enzyme activity is checked first, and any allopurinol co-prescription is reviewed. The lesson is that every new prescription in a transplant patient is an interaction question. ## Where the exam tries to catch you Examiners test the same few confusions about toxicity and interactions. - **Trap:** assuming all immunosuppressants are nephrotoxic — **Correct:** sirolimus does not cause the same afferent arteriolar vasoconstriction as calcineurin inhibitors, which is why it appears in some renal transplant regimens, though its own toxicities include proteinuria and impaired wound healing. - **Trap:** ignoring the competition between sirolimus and tacrolimus — **Correct:** sirolimus and tacrolimus compete for FKBP-12, so combining them needs care. - **Trap:** missing the azathioprine and allopurinol combination — **Correct:** it is the classic combination the exam expects candidates to name, and missing it means treating an avoidable toxicity as bad luck. - **Trap:** forgetting the long-term risks of these drugs — **Correct:** all of them raise the risk of malignancy and opportunistic infection, including progressive multifocal leukoencephalopathy, which candidates should mention when asked about long-term risks. ## Frequently asked questions ### What is the mechanism of action of mycophenolate? Mycophenolate inhibits inosine monophosphate dehydrogenase, reducing the guanine nucleotide synthesis that lymphocytes depend on for proliferation. Its effect is relatively selective for T and B cells, and it is combined with calcineurin inhibitors or steroids in transplant and autoimmune disease. ### Why is TPMT testing done before starting azathioprine? TPMT testing identifies patients with low thiopurine methyltransferase activity, who convert azathioprine into toxic thioguanine nucleotides and risk severe myelosuppression. Patients with low activity need major dose reduction or an alternative drug, and NUDT15 testing adds protection in some populations. ### Which drug interaction increases azathioprine toxicity? Allopurinol inhibits xanthine oxidase, the enzyme that breaks down thiopurines, so combining it with azathioprine raises levels of toxic metabolites. The azathioprine dose is typically reduced substantially when the two drugs are used together, and blood counts are monitored closely. ### Which calcineurin inhibitor causes gingival hyperplasia and hirsutism? Ciclosporin causes gingival hyperplasia and hirsutism as characteristic adverse effects, alongside nephrotoxicity, hypertension and hyperkalaemia. Trough levels and renal function are therefore monitored closely, since calcineurin inhibitors have a narrow therapeutic window. ### Why does sirolimus cause mouth ulcers and hyperlipidaemia? Sirolimus binds FKBP-12 and inhibits mTOR, which affects cell growth and lipid metabolism, producing mouth ulcers, hyperlipidaemia, delayed wound healing and thrombocytopenia. It does not cause the same afferent arteriolar vasoconstriction as calcineurin inhibitors, which is one reason it is used in some renal transplant regimens.