Lecture 8 IBD Part 2 Flashcards
Aminosalicylates for IBD tx (Drugs, onset, Indication/role, AE)
Drugs: Azo - Sulfasalazine (CD), Olsalazine (UC > CD),, Mesalamines (UC > CD) - pH dependent 5-ASA products with varied coatings: Asacol delayed release, Salofalk EC,, Time Released 5-ASA: Pentasa SR
Delayed + ER: Mezavant
Onset: 3-4 weeks, assess response in 2-4 months
can also be 2-4 weeks sx remission by 12 weeks
Indication/Roles: induction tx for mild-moderate active UC > CD (colon disease only, sulfasalazine only)
maintenance of remission (usually low dose) in UC (CD: sulfasalazine only)
AE: diarrhea, interstitial nephritis, hypersensitivity
What are AEs of sulfasalazine?
Common (dose-related): nausea, dyspepsia, anorexia, diarrhea, H/A, dizziness
Non-Common (non-dose related): hypersensitivity (rash), pericarditis, hepatitis, pneumonitis, pancreatitis, hemolytic anemia, oligospermia
What are AEs of 5-ASA?
Common: flatulence, ab pain, nausea, diarrhea - olsalazine up to 30% will experience diarrhea (start slow and take with food)
H/A, malaise, rash, thrombocytopenia
Less Common: hypersensitivity - potential cross allergy with ASA allergy (can be desensitized)
Corticosteroids for IBD tx (Drugs, routes of admin, onset, Indication/role)
Drugs: Prednisone - initial 40-60 mg QD x 2-4 weeks (reassess), taper ASAP (ex. by 5 mg QW or 5 mg Q2-3D)
Budesonide - ex. Entocort is controlled ileal release preparation, deposits mainly in ileum and ascending colon ⇒ indicated for mild-moderate active CD (up to 3 months)
ex. CortimentMMX has EC tablet core delaying disintegration allowing for time-dependent release throughout colon ⇒ indicated for mild-moderate UC (reassess 4-8 weeks)
Onset: if oral within 1-2 weeks
Routes: if oral use prednisone in moderate-severe,, IV - active severe disease when pt fails oral prednisone and/or hospitalized, switch to oral once satisfactory response
What AEs of corticosteroids?
Short Term (dose-dependent): dyspepsia, acne, elevated mood, insomnia, fluid and electrolyte disturbances, hyperglycemia, increased susceptibility to infections
Long Term/Higher Dose: HPA axis suppression, osteoporosis, cataracts, muscle wasting, skin thinning, Cushing’s, depression, PUD, impaired wound healing, avascular necrosis
Thiopurine for IBD tx (Drugs, dose, onset, indication/role, AE)
Drugs: Azathioprine (AZA) - 2-2.5 mg/kg QD ⇒ in UC 50-100 mg QD, in CD 150 mg QD
6-mercaptopurine - 1-1.5 mg/kg QD
Onset: 2-6 months
Indication/Role: moderate-severe active UC ⇒ in combo with steroids only (ineffective alone)
maintenance tx in UC and CD
AE: Dose-Related: nausea, stomatitis, diarrhea, bone marrow suppression (neutropenia, thrombocytopenia), liver enzyme elevation (rare)
Non-Dose Related: hypersensitivity, sun sensitivity/nonmelanoma skin cancer, pancreatitis (3%), hepatitis (rare), hepatosplenic T-cell lymphoma (rare)
Regarding thiopurine what are things to consider ⇒ pharmacogenomics, drug intx, contras?
PGx: AZA/6-MP metabolized by thiopurine-S-methyltransferase (TPMT) to inactive metabolites - poor metabolizers (0.1% population) have increased risk of bone marrow suppression
Drug Intx: drugs that inhibit xanthine oxidase (allopurinol, febuxostat) increase active metabolites - risk severe AEs
Contra: cancer: lymphoma, skin cancer
immunodeficiency, blood disorders/severe leukopenia or thrombocytopenia, liver failure
officially labelled as contra in pregnancy but AZA often used
Methotrexate for IBD tx (Dose, onset, indication/role, AE, Drug intx)
Dose: 15-25 mg WEEKLY
initiate as SC or IM or PO (unpredictable oral bioavailability over 15 mg), reduce dose by 50% if CrCl 10-50 mL/min (some say avoid if <30)
Onset: 2-4 weeks, assess in 12-16 weeks for sx response
Indication/Role: moderate-severe steroid-dependent/resistant CD
maintenance - similar to AZA/6-MP in CD - role in UC only in combo with biologic tx to reduce antidrug antibodies
AE: Common - mouth/nose ulcers (3-10%), N/V, loss of appetite (>10%), fatigue, malaise, difficulty concentrating 1-2 days after dose
Less Common - photosensitivity, rash, hair loss, ALT/AST elevation, neutropenia, thrombocytopenia (1%),, Rare - pneumonitis, cancer
What are ways in which we can manage AEs of methotrexate?
Folic Acid: works as rescue agent for cells that are rapidly dividing and thus affected by MTX inhibition of dihydrofolate reductase - Dose: 1-10 mg QD to weekly, don’t need to skip the day of MTX dosing but ok to do
helps reduce mouth/nose ulcers, N/V, loss of appetite, hair loss, ALT/AST elevation, neutropenia, thrombocytopenia
can also use Vit B12 for these AEs (hair loss)
Dextromethorphan: blocks neurostimulation of homocysteine (increased due to MTX) at NMDA receptors which lead to H/A, lethargy, malaise, memory impairment/fogginess - Dose: 10 mL BID on day of and day after MTX dose,, may help with fatigue, malaise, difficulty concentrating
What are contraindications for MTX as well as drug intx?
Contra: avoid binge drinking and consuming alcohol within 24 hours of dose
contra in pregnancy and lactation - stop 3 months prior to conception
Drug Intx: NSAIDs, penicillins, PPIs - generally safe, may reduce renal excretion of MTX, risk hematological AEs
Trimethoprim - avoid concomitant use, both agents cause similar hematological AEs, may decrease renal excretion of MTX
