IBD Flashcards
Sulfasalazine (an aminosalicylate) is a combination of _____________ and _______________
5- aminosalicylic acid (5-ASA)
Sulfapyridine (acts only as a carrier to the colonic site of action but still causes side effects; associated sulfonamide side effects are avoided in mesalazine and other newer aminosalicylates)
In the newer aminosalicylates, mesalazine (5-aminosalicylic acid), balsalazide sodium (a pro-drug of 5-aminosalicylic acid) and olsalazine sodium (a dimer of 5-aminosalicylic acid which cleaves in the lower bowel), the sulfonamide-related side-effects of sulfasalazine are avoided, but 5-aminosalicylic acid alone can still cause side-effects including ______________ and _____________ syndrome also seen with sulfasalazine.
blood disorders
lupus-like
Which drugs are used in the management of IBD? (3)
- Aminosalicylates (sulfasalazine and mesalazine); Acute attacks and maintenance of remission in UC and Crohn’s
- MTX (with folic acid); acute and maintenance of remission in Crohn’s
- Monoclonal antibodies, infliximab, adalimumab, and golimumab (used under specialist supervision)
How often is MTX administered?
Weekly
Patients taking MTX are warned to report immediately the onset of any features of _______________, _______________, and _______________
blood disorders (e.g. sore throat, bruising, and mouth ulcers)
liver toxicity (e.g. nausea, vomiting, abdominal discomfort, and dark urine
respiratory effects (e.g. shortness of breath)
Methotrexate should be taken ____________ in autoimmune conditions and, less commonly, in some cancer therapy regimens. A European review highlighted continued reports of inadvertent overdose due to more frequent dosing (including daily administration), which has resulted in some _______________.
once a week
Fatalities
True or false: MTX should be taken daily
False; may result in fatal overdose if taken more frequently than once a week
What are the contraindications to using MTX? (4)
- Active infection
- Ascites
- Immunodeficiency syndrome
- Significant pleural effusion
What is the mechanism of action of MTX?
Immunosuppressant that works by inhibiting enzymes responsible for nucleotide synthesis, thereby preventing cell division and leading to anti-inflammatory action (also leads to dangerous side effects such as bone marrow suppression)
MTX should be used with caution in which patients? (7)
Patents with:
- Psoriasis lesions (ulceration reported)
- Dehydration (increased risk of toxicity)
- Diarrhea
- Blood disorders
- Peptic ulceration or ulcerative stomatitis
- Risk of pleural effusion or ascites
- Ulcerative colitis
In patients taking MTX, _______________ can occur abruptly; factors likely to increase toxicity include advanced age, renal impairment, and concomitant use with another anti-folate drug (e.g. trimethoprim)
Bone marrow suppression
In patients taking MTX, bone marrow suppression can occur abruptly; factors likely to increase toxicity include _______________, _______________, and ________________
advanced age
renal impairment
concomitant use with another anti-folate drug (e.g. trimethoprim)
Manufacturer advises a clinically significant drop in ______________ or ______________ calls for immediate withdrawal of methotrexate and introduction of supportive therapy.
white cell count
platelet count
Manufacturer advises a clinically significant drop in white cell count or platelet count calls for ___________________ of methotrexate and introduction of _________________.
immediate withdrawal
supportive therapy
Manufacturer advises withdraw treatment with MTX if _____________ or ____________ develops—may be first sign of gastro-intestinal toxicity
stomatitis
diarrhoea
Manufacturer advises withdraw treatment of MTX if stomatitis or diarrhoea develops—may be first sign of ________________
gastro-intestinal toxicity
In addition to causing bone marrow suppression, MTX has been associated with ____________, ____________, and ____________ toxicity
GI
Liver
Pulmonary
______________ has been reported in patients taking MTX. Manufacturer advises treatment should not be started or should be discontinued if any abnormality of liver function or liver biopsy is present or develops during therapy.
Liver cirrhosis
Can patients’ liver function return to normal after stopping MTX therapy?
Yes, abnormalities can return to normal within 2 weeks after which treatment may be recommenced if judged appropriate
Liver function abnormalities can return to normal within 2 weeks of withdrawing MTX after which treatment may be recommenced if judged appropriate. However, ___________________ may necessitate dose reduction or discontinuation.
Persistent increases in liver transaminases
For patients taking MTX, advise patients to seek medical attention if dyspnea, cough, or fever develop; discontinue if ______________ is suspected
Pneumonitis
Coprescription of MTX with which drugs requires increased monitoring or avoidance? (4)
- NSAIDs due to increased risk of MTX toxicity
- Live vaccines due to risk of generalized infection (AVOID)
- Other immunosuppressants
- Penicillins due to increased risk of toxicity
What are the common or very common side effects associated with MTX use? (8)
- Necrotizing demyelination leukoencephalopathy (with intrathecal use)
- Neurotoxicity (with intrathecal use)
- Anemia, fatigue
- Diarrhea, vomiting, decreased appetite
- Headache
- Increased risk of infection
- Respiratory disorders, dyspnea
- Skin reactions
_______________ decreases mucosal and gastrointestinal side-effects of methotrexate and may prevent hepatotoxicity; there is no evidence of a reduction in haematological side-effects
Folic acid
Folic acid decreases _______________ side-effects of methotrexate and may prevent ______________; there is no evidence of a reduction in ______________ side-effects
mucosal and gastrointestinal
hepatotoxicity
haematological
Treatment with _______________ may be required in acute MTX toxicity.
folinic acid (as calcium folinate)
Manufacturer advises effective contraception during and for at least _____________ after treatment with MTX in men and women.
6 months
Is MTX safe to use in pregnancy and/or breastfeeding?
No teratogenic; fertility may be reduced during therapy but this may be reversible (discontinue 6 months before trying to conceive)
Discontinue if breast-feeding
Is MTX safe to use in hepatic and/or renal impairment?
When used for malignancy, avoid in severe hepatic impairment—consult local treatment protocol for details.
Avoid with hepatic impairment in non-malignant conditions—dose-related toxicity.
Risk of nephrotoxicity at high doses.
Use with caution and reduce dose; avoid in severe impairment.
What pre-treatment screening is necessary before starting MTX? (2)
- Exclude pregnancy
- FBC, renal, and liver function tests
(NOT PFTs)
What are the monitoring requirements for patients taking MTX? (2)
- FBC and renal and LFTs repeated every 1-2 weeks until therapy is stabilized, then monitoring every 2-3 months
- Be advised to report all symptoms and signs suggestive of infection, especially sore throat
Patients taking MTX should be advised to avoid self-medication with _____________ or _____________.
over-the-counter aspirin
ibuprofen
What is the dose of folate given to patients to prevent MTX-induced side effects?
5mg once weekly; dose to be taken on a different day to MTX
Folate should never be given alone for the treatment of _______________ or other ___________________
Pernicious anemia
megaloblastic anaemias caused by vitamin B12 deficiency (may precipitate subacute combined degeneration of the spinal cord)
What are the side effects of folate? (5)
- Abdominal distension
- Decreased appetite
- Flatulence
- Nausea
- Vit B12 deficiency exacerbated
