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imed3004 COPY > Drug Management of IBD > Flashcards

Drug Management of IBD Flashcards

1
Q

What are the similarities between Ulcerative Colitis (UC) and Crohn’s disease (CD)?

A

Both are autoimmune conditions resulting from inappropriate inflammatory responses to environmental and/or self targets.

True aetiology is unknown however, likely response to environmental triggers in genetically susceptible individuals.

Clinical: They are both chronic with acute exacerbations that arise over time.

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2
Q

What is the main idea behind treating both UC and CD?

A

Suppression of inflammation is the mainstay of therapy.

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3
Q

What are the differences between UC and CD?

A

UC mucosal inflammation, CD is transmural.

Responses to drug therapy are slightly different

UC higher risk of colorectal cancer and Primary Sclerosing Cholangitis (PSC)

CD more likely to cause fistulas and strictures

CD has skip lesions that can affect any part of the bowel with predilection for terminal ilium.

UC starts distal large bowel and usually is confluent moving proximally allows for PR drug administration.

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4
Q

What are the therapeutic goals when treating IBD?

A

Manage acute exacerbations swiftly (Achieve remission)

Suppress chronic inflammation (maintain remission)

Surveillance for complications

Manage GIT complications as well as extra-intestinal disease

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5
Q

What non-pharmacological considerations should be made regarding IBD?

A

Stop smoking: reduces recurrence risk in CD

Drug management of diarrhoea

Psychological support

Manage extra-GIT manifestations

Surgery for localised complications (Crohn’s mainly)

Possible utility for probiotics and faecal transplantation

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6
Q

What do aminosalicylates do for IBD?

A

Main role is maintaining remission in UC (can also be used for mild flares). Limited use in CD. (Sulfsalazine, mesalazine)

Exact mechanism of action is unknown.

Available as enemas and suppositories

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7
Q

What are the adverse effects of aminosalicylates?

A

Headache, nausea, diarrhoea, epigastric pain

Rarely for sulfasalazine: serious (rare and idiosyncratic): StevenJohnsonSyndrome, pancreatitis, agranulocytosis

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8
Q

What kind of drug is sulfasalazine? What does this mean?

A

In addition to being an aminosalicylate it is considered a sulfonamide. Should not be used in some combinations as it can result in rash -> severe skin reaction -> anaphylaxis.

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9
Q

When are corticosteroids used for IBD? How are they administered?

A

They are used for moderate-severe relapses of both UC and CD. Short term therapy with gradual weaning dose

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10
Q

Which corticosteroids are administered for IBD?

A

IV hydrocortisone

PO prednisolone/budesonide

PR Hydrocortisone / budesonide (almost entirely metabolised on first pass making it safer to take as an enema)

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11
Q

What are the adverse effects of corticosteroid use?

A

Short term: Increased blood sugar levels, hunger, increased BP

Neuropsychiatric: Irritability and psychosis

Long term: Osteoporosis, steroid induced diabetes mellitus, proximal myopathy, thin skin

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12
Q

What happens when thiopurines are administered?

A

Result in immunomodulation via induction of T cell apoptosis by modulating cell (Rac-1) signalling.

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13
Q

How are thiopurines administered?

A

Oral agents

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14
Q

What are the most commonly used thiopurines?

A

Azathiopurine

6-mercaptopurine

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15
Q

What are the adverse effects of taking thiopurines?

A

Antiproliferative actions: bone marrow failure

Hepatotoxicity

Allergic skin rash

Teratogenicity risk

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16
Q

How are thiopurines metabolised?

A

To 6-MMPR this pathway is associated with myotoxicity and hepatotoxicity.

6-TGN this pathway is what is required but leads to immunosuppression and myelotoxicity but also leads to inhibition of Rac-1 which is required effect.

17
Q

What happens when there is low TPMT activity?

A

This leads to increased concentrations of 6-TGN which leads to increased risk of myelosuppression (bone marrow suppression) depending on extent of reduction either reduce dose or avoid thiopurines.

18
Q

What does undetectable 6-TGN and 6-MMP levels indicate?

A

Non-compliance

19
Q

What does low 6-TGN and 6-MMP levels indicate?

A

Under-dosing

20
Q

What does Low 6-TGN and high 6-MMP levels indicate?

A

Ultra-methylator (high TPMT)

Should not be given with allopurinol because it inhibits xanthine oxidase. However, sometimes it can be a good idea by flipping ratio of 6-TGN and 6-MMP

21
Q

What does high 6-TGN and high 6-MMP levels indicate?

A

Thiopurine refractory or overdosing

22
Q

What does high 6-TGN and low/normal 6-MMP levels indicate?

A

Possible overdosing with risk of myelotoxicity

23
Q

What are anti-TNF-alpha antibodies effective against?

A

Efficacy proven for both UC and CD.

24
Q

How are TNF-alpha antibodies administered?

A

Intravenously (infliximab)

Subcutaneously (adalimumab)

25
Q

What are the adverse effects of using anti-TNF-alpha antibodies?

A

Immune suppression (infections especially from oppotunistic organisms and TB)

Increased malignancy rate

Drug induced lupus

26
Q

How are anti-TNF-slpha antibodies made?

A

In-vitro cell culture (chinese hamster ovary cells)

Infliximab is chimeric mouse/human antibody whereas adalimumab is fully human.

27
Q

Why are anti-integrin antibodies used for IBD?

A

Integrin mediated adhesions allow leukocytes to attach to capillaries and enter into tissues. They use the alpha4beta7 integrin to bind to madcow1 which allows it to enter into the intestinal cells.

These antibodies target alpha4beta7 integrin which is specific to leukocytes that can enter the gut tissues

28
Q

What are the adverse effects of anti-integrin antibodies?

A

Nasopharyngitis

Arthraligia

Fever

URTI

29
Q

How are anti-integrin antibodies administered?

A

Intravenous infusion.

30
Q

Name the anti-integrin antibody drug?

A

Vedolizumab

31
Q

What are anti IL-12/23 used for?

A

IL-12 promotes Th1 response

IL-23 promotes Th17 response

Both cytokines have a p40 subunit and this is targetted by ustekinumab

32
Q

What is the name of the commonly used anti IL-12/23 antibodies?

A

Ustekinumab

33
Q

What other condition besides IBD can anti IL-12/23 be used for?

A

Psoriasis

34
Q

What are the side effects of anti-IL12/23?

A

Infections:

Nasopharyngitis

Vulvovaginal candidiasis/mycotic infection

Bronchitis

UTI

Sinusitis

Potential malignancy risk (non-melanoma skin cancer)

Hypersensitivity reaction/injection site reactions/infusion reactions.

imed3004 COPY (50 decks)

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