DMARDs (6.1) Flashcards
What is the first choice treatment for Rheumatoid Arthritis?
Methotrexate
What is the mode of action of Methotrexate in non malignant disease?
Increase intracellular Adenosine causing a decrease in T cell proliferation
Inhibits T cell activation
What is the mode of action of Methotrexate in treating malignant disease?
Folic acid antagonist so decreases purine synthesis preventing DNA synthesis
What are some of the ADRs of Methotrexate?
Mucositis Myelosuppression Teratogenic Abortifacient Hepatitis Cirrhosis
What drugs interact with Methotrexate treatment?
NSAIDS cause displacement of Methotrexate from plasma proteins causing an increase in free drug and therefore more ADRs
What group of patients need to monitored closely when taking Methotrexate?
Those with renal impairment as the drug is excreted renally - More likely to have ADRs
How is Methotrexare administered?
Once a week Intra-Muscularly as the metabolites (Polyglutamates) have long half lives
What is an alternative drug used for RA in pregnant women?
Sulfasalazine
What is Sulfasalazine?
Combination of Salicylate (Anti inflammatory) and an antibiotic (Sulfapyridine)
What is the mode of action of Sulfasalazine?
Decreases proliferation of T cells via apoptosis/Decreased IL-2 production
Reduces chemotaxis of neutrophils
What are some ADRs of Sulfasalazine?
Diarrhoea (Due to the antibiotic)
Hepatitis
Rash
Myelosuppression
Why is Sulfasalazine effective at treating Inflammatory bowel disease?
It is cleaved and sits in the large bowel
What is the mode of action of Anti-TNF agents?
Act on VEGF and IL-8 to reduce inflammation and angiogenesis.
What are some of the ADRs of Anti-TNF agents?
Increased risk of infections
Reactivation of latent TB
Expensive
Why do patients need a TB screening before initiating Anti-TNF treatment?
TNF helps to enclose TB in granulomas making it latent. Anti-TNF agents cause reactivation of TB so all patients should be screened for TB before beginning treatment
What is Rituximab?
A monoclonal antibody to CD20 which causes apoptosis of B cells Often used in combination with Methotrexate
What is the mode of action of Prednisone?
Corticosteroid - lipophillic
Binds glucocorticoid receptor inside cell - complex goes to nucleus and alters transcription of pro-inflammatory proteases
Name some of the ADRs of Prednisone?
Stimulates appetite
Aggressive mood changes
Long term high does can cause Cushing’s syndrome
Why do patients need to be taken off Prednisone slowly?
It is a corticosteroid so takes over the role of the Adrenal cortex (Which becomes insufficient to meet the body’s demands)
If drug stopped suddenly then the Adrenal cortex cannot meet the needs of the body and an Addisonian crisis may occur = low BP causing low perfusion
What is Mycophenolate Mefetil?
A prodrug that inhibits inosine monophosphate dehydrogenase which is needed for guanine synthesis. (Guanine is used in B&T cell proliferation)
Spares rapidly dividing cells as they have a guanine salvage pathway
What are the ADRs of Mycophenolate Mefetil?
Myelosuppression Increased risk of infection Risk of birth defects and miscarriage Increases blood cholesterol Excreted renally so can become toxic in those with renal issues
What are the most appropriate uses for Mycophenolate Mefetil?
Systemic lupus erythematosus
Vasculitis
Crohn’s disease
Transplants
What is Cyclophosphamide?
An alykylating agent that cross links DNA so it cannot replicate
Suppresses B&T cell activity
Given as a prodrug
What are the ADRs of Cyclophosphamide?
Targets rapidly dividing cells meaning there is a high risk of infertility
Haemorrhagic cystitis
How can Cyclophosphamide increase the risk of Haemorrhagic cystitis?
A metabolite (Acrolin) is toxic to the epithelium of the bladder The risk can be decreased by ensuring the patient is well hydrated
What are the most appropriate uses for Cyclophosphamide?
Lymphoma
Leukaemia
Systemic lupus erythematosus
Vasculitis
What is Azathioprine?
A drug that is cleaved to 6-mercaptophrine which is an antimetabolite that decreases DNA & RNA synthesis
Why are some patients more at risk of developing myelosuppression when being treated with Azathioprine?
6-mercaptophrine is metabolised by Thiopurine methyltransferase which can vary between patients (low levels of the enzyme = higher risk of myelosuppression)
What are the ADRs of Azathioprine?
Myelosuppression
Increased risk of malignancy
Increased risk of infection
Hepatitis
What are the main uses of Azathoprine?
Inflammatory Bowel Disease
Atopic dermatitis
What is Ciclosporin?
A Calcineurin inhibitor that binds to cyclophilin protein on T helper cells
Prevents IL-2 production
What is Tacrolimus?
A Calcineurin inhibitor that binds to tacrolimus binding protein on T helper cells
Prevents IL-2 production
What are the ADRs of Calcineurin inhibitors?
Nephrotoxic
Vomiting
Diarrhoea
What group of patients are Calcineurin inhibitors particularly useful for?
Those with Rheumatoid arthritis and Cytopenias as it does not affect the bone marrow
What are Calcineurin inhibitors mainly used for?
Transplants
Psoriasis
Atopic dermatitis
Patients with Rheumatoid arthritis and Cytopenias
