CH1: GASTRO DRUGS Flashcards
Azathioprine (indications, drug class, moa, eliminated and metabolised by?)
- Drug class: Anti-metabolite, immunosuppressant, pro-drug of 6-mercaptopurine.
- Indications
1. Add on treatment with corticosteroid/budesonide to induce remission of Crohns & UC if pt had >2 flare ups in 12 months period.
2. Rheumatoid arthritis
3. Prevent transplant rejection - MOA; inhibits DNA & RNA replication of purinase
- Is metabolised and eliminated by xanthine oxidase and TPMT (thiopurine methyltransinase)
Counter-indication of Azathioprine
CI: Low TPMT (thiopurine methyltransferase activity) or absent TPMT
Pt is required to take TPMT phenotyping prior to tx initiation.
If taken in pts with low/absent TPMT = reduced elimination of azathioprine = toxicity
Discuss the use of azathioprine in renal/hepatic impairment and pregnant women
Renal/hepatic impairment
- reduce dose
Pregnant women
- Tetrogenic
- Continue taking if started before pregnancy, if benefit> risk .e.g transplant recipient
Side effects of Azathioprine
- Bone marrow supression= increased risk of infections = thrombocytopenia (low neutrophils) and leukopenia
<may>
- Nausea (resolves after a few weeks) can be taken in divided doses to relieve this.
- Hypersensitivity reactions (malaise, rash, hypotension, pancreatitis, diarrhoea, vomiting, myalgia) - immediate withdrawal
</may>
Drug interactions between Azathioprine + Allopurinol and febuxostat
Allopurinol & Febuxostat
- are xanthines inhibitors = reduces elimination of azathiopurine= increases plasma conc of azathioprine =toxicity
- Reduce the dose of azathiopurine to 1/4th of the usual dose
State other drug interactions of azathioprine excluding xanthine oxidase inhibitors.
- Trimethoprim = increases risk of myeosupression, increases risk of leukopenia = increases risk of infection
- Warfarin = reduces anticoag effect = increased risk of clots = CVD events
monitoring requirements of azathiopurine
FBCs
- weekly for the 1st 4 weeks of initiation or dose alteration
- then 3 monthly
Aminosalicylates
E.g. Sulfasalasine, mesalazine, balasalazine and olsalazine.
MOA- limiting the inflammation in the lining of the gastrointestinal tract
Counter-indications of aminosalicylates
Salicylate hypersensitivity
a reaction that happens when you come in contact with salicylates, salicylic acid, or related chemicals. Salicylates are found in plants. They’re a natural ingredient in many fruits, vegetables, and spices.
Monitoring parameters for aminosalicylates
Monitoring = Naked Hot Bodies (NHB)
- Nephrotoxicity = Renal function before, 3 mo, annually of treatment
- Hepatotoxic = montly for first 3 mo
- Blood disorders = FBC
Use of aminosalicylates in pregnancy and BF
Pregnancy = AVOID in 3rd trimester = increases risk of neonatal hemolysis
BF= present in milk - monitor for infant diarrhoea
Counselling patients taking aminosalicylates
- Avoid lenses = cause staining
- Report any unexplained bleeding or bruises = may indicate blood disorder
- Can cause ORANGE- YELLOW URINE
Prucalopride
- Class: selective HT4 agonist
- CI: UC/Crohns
- Renal impairment = reduce dose if eGFR is less than 30
Naloxegol
- An opioid receptor antagonist
- Reducing the constipating effects of opioids without altering their central analgesic effects.
- Renal impairment-> reduce dose
- Caution -> CVD, HF, Crohns, recent history of MI within 6 months
Loperamide (counselling, antidote and MHRA alert)
- OTC >12 years
- Px > 4 years
- Counselling: take 1-2 doses at first then 1 with every loose stool (max 8 doses/day)
- Overdose: treat with naloxone
- MHRA loperamide: serious cardiac reaction (QT prolongation) with high doses
