Transplant and Immunosuppressives

Question 1

What are two calineurin inhibitors and their side effects?

Answer 1

> cylcosporin and tacrolimus
-reduces production of IL-2 via inhibition of NFAT (most other ISTs are cell cycle inhibitors)
-TDM: good evidence that levels correlate = useful
SE
-nephrotoxicity (dose limiting),
-hypertension (CCB 1st line for CNI mediated HTN),
-neurological (seizures, neuropathy, tremor),
=>CyA - hirsutism, gingival hyperplasia;
=>Tac - diabetes
-Dyslipidaemia
-Major interactions with CYP450 3A4

Question 2

What are two mTORi, their advantages and side effects?

Answer 2

> sirolimus, everolimus; Rapamycin
- Arrests cell proliferation, Anti-angiogenesis + other anti-proliferative effects ∴ anti-cancer
Adgs: Low malignancy (RCC/ prostate/ breast)/ viral infections/ no neurotoxicity/ no hypertension
SE: myelosuppression, GI - stomatitis/mouth ulcers/diarrhoea, DM, Hyperlipidaemia, Pneumonitis (rapidly fatal if untreated Dx: HRCT), poor wound healing
- avoid in poor GFR, proteinuria

Question 3

What are side effects of azathioprine?

Answer 3

> Mechanism: cell cycle inhibitor - purine analog toxic to proliferating cells
- Check TPMT prior to starting
SE
- marrow suppression - 1-2 weeks, often dose-limiting
- liver toxicity
- pancreatitis
Safe in pregnancy

Question 4

What are side effects of mycophenolate?

Answer 4

>Mechanism
- inhibit de novo IMPD synthesis used by lymphocytes
- Unclear role of levels/TDM at present
>SE (No CV or renal side effects)
- nausea/vomiting
- abdo pain 
- marrow suppression

Question 5

What are the side effects of MTX?

Answer 5

> Mechanism
-DHFR dihydrofolate reductase inhibitor- anti-folate, interferes with purine synthesis
SEs
- hepatotoxicity, ILD, BM suppression,
- Contraindicated in pregnancy/ conception

Question 6

What are the side effects of Leflunomide?

Answer 6

> Mechanism
-DHODH Dihydro-orotate dehydrogenase inhibitor - interferes with pyrimidine synthesis
SEs
- hepatic reactions (raised transaminases) - may need cholestyramine washout, stomatitis, mouth ulcers, ILD, BM suppression

Question 7

What are side effects of TNF-inhibitors?

Answer 7

> Before starting treatment
-Check HBV/ HCV/ TB status
-Consider testing: HIV/ VZV/ ANA/ Anti-DsDNA
-Update immunisations/ pap smears
SEs:
- Infusion reactions, neutropaenia, infections, Hepatosplenic T cell Lymphoma (HTCL), demyelination, heart failure, Psoriasis like skin rash
- Probably safe in pregnancy

Question 8

What are acute SEs of Steroids?

Answer 8

• Neuropsychiatric - insomnia, aggression, delirium
• Fluid retention
• BSLs
• Appetite and weight gain
• Dyspepsia
• Delayed wound healing

Question 9

What are chronic SEs of Steroids?

Answer 9

• Osteopaenia and osteoporosis
• Myopathy
• Fat distribution (Cushingoid appearance)
• Skin atrophy
• Infection
• Avascular necrosis