RA DRUGS & TOXICITIES:
MILD RA
1) SULFASALAZINE
Anti-inflammatory and Antibiotic (acetylsalicylic acid and sulfapyridine)
Cleaved in the colon by bacterial enzymes to release acetylsalicylic acid and
sulfapyridine
ADVERSE
Inhibits absorption of folate  folate deficiency
mild gastrointestinal disturbances (nausea, vomiting, loss of appetite, diarrhoea)
skin rash and pruritus
Headache, dizziness or depression
oligospermia with impaired motility
leucopenia, bone marrow depression
haemolytic anaemia (G6PD)
abnormal liver function tests, hepatitis and abdominal pain
2) HYDROXYCHLOROQUINE
Nausea, dizziness, rash (must cease)
MAIN RISK: RETINAL TOXICITY
Haemolysis in G6PD
Routine bloods not required
(can do FBE after 1 week to check for haemolysis)
Baseline then yearly Ophthalmology r/v
MILD-MOD RA:
1) METHOTREXATE
MUST CO-ADMINISTER FOLIC ACID – different day of week
Folic acid analogue, binds to DHF-reductase and antagonises folic acid.
Folic acid = essential for DNA synthesis
Methotrexate impairs cell division. It is cytotoxic at high doses.
Very long half-life, for noncancer indications, is given on one day per week.
ADVERSE:
Nausea and mouth ulcers
Hepatotoxicity: fibrosis of increasing severity, culminating in cirrhosis
Leucopenia, thrombocytopenia and anaemia
Rash, menorrhagia, pneumonitis, fatigue, alopecia and depression
TERATOGENIC (cease 3 months before conception)
 Dose in CRF, CI in severe RF
Interactions
Other drugs that inhibit folic acid synthesis  BM depression
trimethoprim+sulfamethoxazole (cotrimoxazole),
OR
Trimethoprim alone
 Levels with renal-affecting drugs (eg NSAIDS, Probenecid, Penicillin)
BUT: At the doses used in rheumatology there is no clinically significant interaction
with NSAIDs, and many patients are successfully managed on this combination
MONITORING:
FBE, U&E, LFT’s
Monthly for 1st 6 months, then 1-2 monthly
Abnormal LFT’s  biopsy
OTHER USES:
PSORIASIS
CROHN’S
SEVERE RA: ALL 3 TOGETHER!
More effective, and not more toxic, than methotrexate alone, or combinations of any 2
drugs.
OR ADD:
LEFLUNOMIDE
In combination with Methotrexate: increased risk of leucopenia, pneumonitis and
abnormal liver function
CYCLOSPORIN
With methotrexate: combination is more effective than either therapy alone, with
adverse effects similar to that of either drug alone
Inhibits cytokine release from activated T cells
Adverse:
MAIN ONES: Reversible renal impairment and hypertension
(Co-administration with fish oil can reduce the nephrotoxicity and hypertension)
Other: hirsutism, gingival hyperplasia, gastrointestinal disturbances, pancreatitis,
weight gain, oedema, hepatic dysfunction, hyperlipidaemia, anaemia and other
haematological abnormalities, central nervous system disturbances (eg tremor,
fatigue, headache), and a burning sensation in the hands and feet. Hyperkalaemia,
hypomagnesaemia and hyperuricaemia can occur. An increased rate of malignancies
and infections has been reported
BIOLOGICAL DMARDS (bDMARD)
= Ab’s or cytokine receptors:
ETANERCEPT: soluble TNF receptor (once/twice weekly SC injection)
NB: vulnerability of patients taking biological DMARDs, or other significant
immunosuppressants, to infectious diseases such as atypical pneumonia, listeriosis,
and tuberculosis. Patients should be asked to report unusual symptoms, including
fever or persistent cough