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Clinical pharmacology and therapeutics > GI > Flashcards

GI Flashcards

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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
Give the dose of 6MP
1-1.5mg/Kg
26
Describe the monitoring of patients on thiopurines
2 weekly for a minimum of 12 weeks
27
Describe the mechanism of action of thiopurines
Intracellular purine analogue and alkylation | Decreased nucleic acid synthesis - DNA damage
28
List the contraindications of thiopurines
Hypersensitivity Active infection Live vaccines BM impairment
29
Give the cautions of thiopurines
Renal/hepatic impairment Splenecotmy Decreased TPMT/ increased 6MMPN Cancer
30
List the side effects of thiopurines
``` Dizziness Flu like N&V Myelosuppression Pancreatitis ```
31
List the interactions of thiopurines
Allopurinol Immunosuppressants Warfarin ACEi, co-trimoxazole, cimetidine increase risk of myelosuppression
32
What monitoring is required for patients on thiopurines
Renal and hepatic
33
List the biologics given in CD
1st line - Infliximab or adalimumab 2nd line - Vedolizumab or Ustenkinumab 3rd line - Any that havent been tried
34
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
35
What workup needs to be done before prescribing biologics?
``` TPMT FBC Viral TB CXR ```
36
What does Tofacitinib work on?
JAK 1,2 and 3
37
How is infliximab given?
IV
38
How is Adalimumab given?
SC
39
How is Vedolizumab given?
IV
40
How is ustekinumab given?
IV
41
How is Golimumab given?
SC
42
How is Tofacitinib given?
PO
43
What is the dose of Tofacitinib?
Loading dose 10mg BD (2-4 months) | Maintenance 5mg BD
44
What is the dose of golimumab?
``` Wk 0 = 200mg 2 = 100mg 6 = 50-100mg (response dependent*) 4 wkly = 50-100mg (response dependent*) *>80kg = 100mg ```
45
What is the dose of Ustekinumab?
≈6mg/kg | 8 wkly
46
What is the dose of Vedolizumab?
300mg | At wk 0, 2, 6 - 8 wkly
47
What is the dose of adalimumab?
Wk 0 = 160mg 2 = 80mg 6 = 40mg - 8 wkly = 40mg
48
What is the dose of infliximab?
5mg/kg At wk 0, 2, 6 - 8 wkly Acute
49
How are biologics monitored?
Pre infusion bloods General wellness IFX and ADA levels Biosimilar switching
50
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%
51
Describe the benefits of biologics and thiopurines
Better symptoms control
52
Describe the risks of biologics and thiopurines
Increased cancer and infection risks
53
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
54
Which cancer is more likely in crohn's disease?
Lymphoma - NHL
55
Which cancer is more likely in ulcerative colitis?
Leukemia
56
Which cancers are more likely in IBD?
SCC/BCC
57
What scoring system is used to assess severity of liver disease
Child Pugh Scoring system
58
How can we assess liver function?
``` Albumin Clotting screen - PT, INR Bilirubin Gamma-glutamyl transferase Alkaline phosphate Transaminase (ALT and AST) ```
59
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
60
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
61
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
62
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
63
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

Clinical pharmacology and therapeutics (27 decks)

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