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Clinical pharmacology and therapeutics > GI > Flashcards

GI Flashcards

1
Q

Describe the features of crohn’s disease

A

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

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2
Q

Describe the features of ulcerative colitis

A

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

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3
Q

How is IBD diagnosed?

A 
Flexible sigmoidoscopy
Colonoscopy
Small bowel MRI
Bloods - FBC, U&Es, CRP/ESR
Stool - infection or inflammation
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4
Q

Which class of drug is given during an IBD flare?

A

Steroids

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5
Q

What is an IBD flare?

A 
Bloody diarrhea
Frequency
Urgency
Mucous 
Change in bloods
Nocturnal symptoms
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6
Q

Describe the use of steroids in IBD

A

Ensure cause is not infective
Prednisolone PO 40mg OD and reducing regime
Prednisolone rectal foam

Budesonide 9mg OM8/52 and decreased 2/52

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7
Q

Describe steroid dependence

A

Provide good effect - short term cure

Concern if >2 courses/year

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8
Q

What does 5-ASA stand for?

A

5-aminosalicylic acid

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9
Q

What class of drugs are effective in UC?

A

5-ASA

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10
Q

Name some 5-ASAs and state their maintenance dosing

A

Asacol, Mezavant, Octasa 2.4g daily
Salofalk 1.5g daily
Pentasa 2g daily

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11
Q

What is the maximum dose of 5-ASAs?

A

Maximum dosing is double the maintenance dose

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12
Q

Describe the mechanism of action of 5-ASAs

A

Act locally on colonic mucosa

Reduces inflammation through a variety of anti inflammatory mechanisms

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13
Q

What are the contraindications of 5-ASAs

A

Blood clotting abnormalities

Salicylate hypersensitivy

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14
Q

What are the cautions of 5-ASAs?

A

Pulmonary disease

Elderly

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15
Q

Describe the interactions of 5-ASAs?

A

Decreased stool pH from drugs such as lactulose may decrease 5-ASA release

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16
Q

What are the side effects of 5-ASAs?

A 
Arthralgia
Cough
Diarrhoea
Dizziness
Fever
GI discomfort 
Headache 
Leukopenia
N&V
Skin reactions
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17
Q

What monitoring is required while on 5-ASAs?

A

Renal function

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18
Q

Describe the use of 5-ASAs in pregnancy and breast feeding

A

Negligible across placenta

Causes diarrhea in infant breastfeeding

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19
Q

Describe thiopurines

A

Immunomodulators/immunosuppressants

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20
Q

Name two thiopurines

A

Azathioprine

6MP

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21
Q

What workup is required before starting a thiopurine?

A

FBC
Viral
TB
TPMT (Thiopurine methyltransferase)

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22
Q

What is a normal TPMT?

A

68-150

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23
Q

At what TPMT are thiopurines contraindicated?

A

<10

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24
Q

Give the dose of Azathioprine

A

2-2.5mg/Kg

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25
Q

Give the dose of 6MP

A

1-1.5mg/Kg

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26
Q

Describe the monitoring of patients on thiopurines

A

2 weekly for a minimum of 12 weeks

27
Q

Describe the mechanism of action of thiopurines

A

Intracellular purine analogue and alkylation

Decreased nucleic acid synthesis - DNA damage

28
Q

List the contraindications of thiopurines

A

Hypersensitivity
Active infection
Live vaccines
BM impairment

29
Q

Give the cautions of thiopurines

A

Renal/hepatic impairment
Splenecotmy
Decreased TPMT/ increased 6MMPN
Cancer

30
Q

List the side effects of thiopurines

A 
Dizziness
Flu like
N&amp;V
Myelosuppression
Pancreatitis
31
Q

List the interactions of thiopurines

A

Allopurinol
Immunosuppressants
Warfarin
ACEi, co-trimoxazole, cimetidine increase risk of myelosuppression

32
Q

What monitoring is required for patients on thiopurines

A

Renal and hepatic

33
Q

List the biologics given in CD

A

1st line - Infliximab or adalimumab
2nd line - Vedolizumab or Ustenkinumab
3rd line - Any that havent been tried

34
Q

List the biologics given in UC

A

1st line - Infliximab or adalimumab
2nd line - Vedolizumab or Golimumab
3rd line - Any that havent been tried
4th line - Tofacitinib

35
Q

What workup needs to be done before prescribing biologics?

A 
TPMT
FBC
Viral
TB
CXR
36
Q

What does Tofacitinib work on?

A

JAK 1,2 and 3

37
Q

How is infliximab given?

A

IV

38
Q

How is Adalimumab given?

A

SC

39
Q

How is Vedolizumab given?

A

IV

40
Q

How is ustekinumab given?

A

IV

41
Q

How is Golimumab given?

A

SC

42
Q

How is Tofacitinib given?

A

PO

43
Q

What is the dose of Tofacitinib?

A

Loading dose 10mg BD (2-4 months)

Maintenance 5mg BD

44
Q

What is the dose of golimumab?

A 
Wk 0 = 200mg
2 = 100mg
6 = 50-100mg (response dependent*)
4 wkly = 50-100mg (response dependent*)
*>80kg = 100mg
45
Q

What is the dose of Ustekinumab?

A

≈6mg/kg

8 wkly

46
Q

What is the dose of Vedolizumab?

A

300mg

At wk 0, 2, 6 - 8 wkly

47
Q

What is the dose of adalimumab?

A

Wk 0 = 160mg
2 = 80mg
6 = 40mg
- 8 wkly = 40mg

48
Q

What is the dose of infliximab?

A

5mg/kg
At wk 0, 2, 6 - 8 wkly
Acute

49
Q

How are biologics monitored?

A

Pre infusion bloods
General wellness
IFX and ADA levels
Biosimilar switching

50
Q

List some predictive features for biologics and relapse

A 
Male 
Absence of surgical resection 
WBC >6 
Hb <145
CRP >5
FCPL >300

<2 risk factors - relapse rate 14-16%

51
Q

Describe the benefits of biologics and thiopurines

A

Better symptoms control

52
Q

Describe the risks of biologics and thiopurines

A

Increased cancer and infection risks

53
Q

Describe the effects of IBD on pregnancy?

A

Less likely to conceive
Safer to not be flaring during pregnancy
IBD medications during pregnancy produce similar outcomes to mothers not taking IBD medications

54
Q

Which cancer is more likely in crohn’s disease?

A

Lymphoma - NHL

55
Q

Which cancer is more likely in ulcerative colitis?

A

Leukemia

56
Q

Which cancers are more likely in IBD?

A

SCC/BCC

57
Q

What scoring system is used to assess severity of liver disease

A

Child Pugh Scoring system

58
Q

How can we assess liver function?

A 
Albumin
Clotting screen - PT, INR
Bilirubin 
Gamma-glutamyl transferase 
Alkaline phosphate 
Transaminase (ALT and AST)
59
Q

What does INR tell us about drug handling?

A

Dose adjustment if PT >130%
Increased INR indicates reduced synthetic function
Lowe dose with close monitoring required

60
Q

What does albumin tell us about drug handling?

A

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

61
Q

What does bilirubin tell us about drug handling?

A

Drug absorption for highly lipophilic drugs - possible reduced absorption
Biliary clearance reduced
Competition for binding sites - potential to displace drug, enhancing effect

62
Q

What do transglutaminases tell us about drug handling?

A

Transaminase enzymes - drug induced
Alkaline phosphate and GGT - certain drugs cause cholestasis, cholestasis may reduce drug absorption, certain drugs cause elevations in GGT

63
Q

Describe LFT results of hepatic disease

A

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

Clinical pharmacology and therapeutics (27 decks)

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