GI Flashcards
Describe the features of crohn’s disease
Inflammation - skip lesions/cobblestones, transmural (deep)
Rectal involvement is less likely
Diarrhoea, nausea and vomiting are common
Abdominal pain may be more severe and continuous
Fistulas, fissures, granulomas and strictures may be more common
Surgery and 5-ASAs less effective
Smoking potentiates symptoms
Describe the features of ulcerative colitis
Inflammation - continuous, mucosal (shallow)
Rectal involvement more likely
Bloody diarrhea and mucus very common
Abdominal pain may be intermittent and relate to bowel movements
5-ASAs effective
Surgery can reduce symptoms
How is IBD diagnosed?
Flexible sigmoidoscopy Colonoscopy Small bowel MRI Bloods - FBC, U&Es, CRP/ESR Stool - infection or inflammation
Which class of drug is given during an IBD flare?
Steroids
What is an IBD flare?
Bloody diarrhea Frequency Urgency Mucous Change in bloods Nocturnal symptoms
Describe the use of steroids in IBD
Ensure cause is not infective
Prednisolone PO 40mg OD and reducing regime
Prednisolone rectal foam
Budesonide 9mg OM8/52 and decreased 2/52
Describe steroid dependence
Provide good effect - short term cure
Concern if >2 courses/year
What does 5-ASA stand for?
5-aminosalicylic acid
What class of drugs are effective in UC?
5-ASA
Name some 5-ASAs and state their maintenance dosing
Asacol, Mezavant, Octasa 2.4g daily
Salofalk 1.5g daily
Pentasa 2g daily
What is the maximum dose of 5-ASAs?
Maximum dosing is double the maintenance dose
Describe the mechanism of action of 5-ASAs
Act locally on colonic mucosa
Reduces inflammation through a variety of anti inflammatory mechanisms
What are the contraindications of 5-ASAs
Blood clotting abnormalities
Salicylate hypersensitivy
What are the cautions of 5-ASAs?
Pulmonary disease
Elderly
Describe the interactions of 5-ASAs?
Decreased stool pH from drugs such as lactulose may decrease 5-ASA release
What are the side effects of 5-ASAs?
Arthralgia Cough Diarrhoea Dizziness Fever GI discomfort Headache Leukopenia N&V Skin reactions
What monitoring is required while on 5-ASAs?
Renal function
Describe the use of 5-ASAs in pregnancy and breast feeding
Negligible across placenta
Causes diarrhea in infant breastfeeding
Describe thiopurines
Immunomodulators/immunosuppressants
Name two thiopurines
Azathioprine
6MP
What workup is required before starting a thiopurine?
FBC
Viral
TB
TPMT (Thiopurine methyltransferase)
What is a normal TPMT?
68-150
At what TPMT are thiopurines contraindicated?
<10
Give the dose of Azathioprine
2-2.5mg/Kg
Give the dose of 6MP
1-1.5mg/Kg
Describe the monitoring of patients on thiopurines
2 weekly for a minimum of 12 weeks
Describe the mechanism of action of thiopurines
Intracellular purine analogue and alkylation
Decreased nucleic acid synthesis - DNA damage
List the contraindications of thiopurines
Hypersensitivity
Active infection
Live vaccines
BM impairment
Give the cautions of thiopurines
Renal/hepatic impairment
Splenecotmy
Decreased TPMT/ increased 6MMPN
Cancer
List the side effects of thiopurines
Dizziness Flu like N&V Myelosuppression Pancreatitis
List the interactions of thiopurines
Allopurinol
Immunosuppressants
Warfarin
ACEi, co-trimoxazole, cimetidine increase risk of myelosuppression
What monitoring is required for patients on thiopurines
Renal and hepatic
List the biologics given in CD
1st line - Infliximab or adalimumab
2nd line - Vedolizumab or Ustenkinumab
3rd line - Any that havent been tried
List the biologics given in UC
1st line - Infliximab or adalimumab
2nd line - Vedolizumab or Golimumab
3rd line - Any that havent been tried
4th line - Tofacitinib
What workup needs to be done before prescribing biologics?
TPMT FBC Viral TB CXR
What does Tofacitinib work on?
JAK 1,2 and 3
How is infliximab given?
IV
How is Adalimumab given?
SC
How is Vedolizumab given?
IV
How is ustekinumab given?
IV
How is Golimumab given?
SC
How is Tofacitinib given?
PO
What is the dose of Tofacitinib?
Loading dose 10mg BD (2-4 months)
Maintenance 5mg BD
What is the dose of golimumab?
Wk 0 = 200mg 2 = 100mg 6 = 50-100mg (response dependent*) 4 wkly = 50-100mg (response dependent*) *>80kg = 100mg
What is the dose of Ustekinumab?
≈6mg/kg
8 wkly
What is the dose of Vedolizumab?
300mg
At wk 0, 2, 6 - 8 wkly
What is the dose of adalimumab?
Wk 0 = 160mg
2 = 80mg
6 = 40mg
- 8 wkly = 40mg
What is the dose of infliximab?
5mg/kg
At wk 0, 2, 6 - 8 wkly
Acute
How are biologics monitored?
Pre infusion bloods
General wellness
IFX and ADA levels
Biosimilar switching
List some predictive features for biologics and relapse
Male Absence of surgical resection WBC >6 Hb <145 CRP >5 FCPL >300
<2 risk factors - relapse rate 14-16%
Describe the benefits of biologics and thiopurines
Better symptoms control
Describe the risks of biologics and thiopurines
Increased cancer and infection risks
Describe the effects of IBD on pregnancy?
Less likely to conceive
Safer to not be flaring during pregnancy
IBD medications during pregnancy produce similar outcomes to mothers not taking IBD medications
Which cancer is more likely in crohn’s disease?
Lymphoma - NHL
Which cancer is more likely in ulcerative colitis?
Leukemia
Which cancers are more likely in IBD?
SCC/BCC
What scoring system is used to assess severity of liver disease
Child Pugh Scoring system
How can we assess liver function?
Albumin Clotting screen - PT, INR Bilirubin Gamma-glutamyl transferase Alkaline phosphate Transaminase (ALT and AST)
What does INR tell us about drug handling?
Dose adjustment if PT >130%
Increased INR indicates reduced synthetic function
Lowe dose with close monitoring required
What does albumin tell us about drug handling?
Decreased albumin represents decreased protein binding
Many drugs - clinical consequences insignificant
Highly protein bound drugs - increase drug free and available to act and hence increased clinical effect. Eg. Phenytoin
Decreased albumin reduces synthetic liver function
What does bilirubin tell us about drug handling?
Drug absorption for highly lipophilic drugs - possible reduced absorption
Biliary clearance reduced
Competition for binding sites - potential to displace drug, enhancing effect
What do transglutaminases tell us about drug handling?
Transaminase enzymes - drug induced
Alkaline phosphate and GGT - certain drugs cause cholestasis, cholestasis may reduce drug absorption, certain drugs cause elevations in GGT
Describe LFT results of hepatic disease
Increased hepatic enzymes AST, ALT - indicate liver damage
Decrease in concentration of albumin and protein indicate a reduction of synthetic capacity
None directly reflects the metabolic function of the liver
