19 Immunosuppressants Flashcards
How do corticosteroids eg prednisolone work?
- Decrease prostanoids production
- reduced expression of COX-2
- Decrease cytokine generation
- Decrease nitric oxide generation
- Decrease mediator release from basophils and mast cells eg histamine
- Decrease IgG production
What are the long term side effects that are caused by taking corticosteroids?
Think CUSHINGS (proteolysis)
- Weight gain
- Thin skin
- High blood sugar
- Proximal muscle weakness
Osteoporosis
Immunosuppression
Glaucoma
Name 4 (systemic) corticosteroids (not inhaled).
- Prednisolone
- Betamethasone
- Dexamethasone
- Hydrocortisone
Inhaled:
- Beclomethasone
- Budesonide
- Fluticasone
What are DMARDs?
Disease modifying anti-rheumatic drugs
Give some examples of DMARDs: (disease modifying anti-rhuematic drugs)
Azathioprine
How does azathioprine work? (DMARD)
= an antimetabolite
Azathioprine–> 6-mercaptopurine
-purine synthesis inhibitor
What are the indiications for azathioprine?
- Organ transplant eg renal
- IBD
- Rheumatoid arthritis
- SLE
What are the 2 main adverse effects of the drug azathioprine?
Adverse effects=
- Bone marrow suppression
- Thrombocytopenia
What are the indications for the drugs:
- Cyclosporin
- Tacrolimus
- Organ transplants
- Dermatomyositis
- Crohn’s disease
- Rheumatoid artiritis
- Psoriasis
How do the following drugs work?:
- Cyclosporin
- Tacrolimus
- Active against T-cells
- Inhibit calcineurin- prevent production of IL-2
What are some of the adverse effects of ciclosporin?
- Eye discomfort
- Nephrotoxicity
- Hepatitis
- Gingival hyperplasia (gums)
What are the indications for cyclophosphamide? (2)
SLE nephritis
Systemic vasculitis
Why do you need to test for TPMT (thiopurine methyltransferase) activity before prescribing azathioprine?
6-mercaptopurine (active metabolite of azthioprine)= metabolised by TPMT
TPMT= highly polymorphic
Low/absent TPMT- risk myelosuppression if given azathioprine
What is the main active metabolite of cyclophosphamide?
Main active metabolite= 4-hydroxycyclophosphamide
Other metabolites=
- Phosphoramide mustard
- Acrolein
Why do we sometimes give Mesna (drug) with cyclophosphamide?
Acrolein (metabolite of cyclophosphamide) = toxic to bladder
Can cause haemorrhagic cystitis
To prevent this:
- Give mesna
- Aggressive hydration
Useful diagram for chemotherapy toxicities:
How does methotrexate work?
Competitively and reversibly
Inhibits DHFR (dihydrofolate reductase) - required to make nucleotides
What are the indications for methotrexate? (= immunosuppressant and chemotherapy) (4)
- Rhuematoid arthritis
- Ectopic if it hasn’t ruptured (+ abortions)
- Crohn’s disease
- Psoriatic arthritis
- Cancer: breast cancer, leukemia, lung cancer, lymphoma, and osteosarcoma
(Should only be given weekly)
Give 3 adverse effects of methotrexate:
- Inflammation of membranes
- Pneumonitis
- Stomatitis (sore or inflammation inside of the mouth)
- Hepatitis
How does mycophenolate mofetil work?
Inhibits inosine monophosphate dehydrogenase
Stops DNA synthesis essentially
(= Antiproliferative immunosupressant)
What are the indications for mycophenolate mofetil?
Primary organ transplantation
SLE nephritis
What are some of the adversr effects of mycophenolate mofetil?
Increase risk of skin malignancy
Nausea, vomiting, diarrhoea
Myelosuppression
Sulfasalazine is a DMARD. What are some of its indications?
(5—aminosalicylic acid donor in RA as a DMARD)
- Rheumatoid arthritis
- Ankylosing spondylitis
- IBD
Give some of the adverse effects of sulphasalazine.
- Nausea +/- vomiting
- Leucopenia
- Dizzyness
- Arthralgia
How do each of the following work as immunosuppressants?
- infliximab
- adalinumab
- rituximab
- tocilizumab
When should we consider using disease modifying antirheumatic drugs in combination?
In severe rheumatoid disease
