- mucosa and submucosa - starts in rectum, spreads proximally - always continuous - surgery can be curative

IBD Flashcards by Stephanie Dunn

what are the 2 major forms of IBD?

ulcerative colitis

- Chron’s disease

How well did you know this?

Not at all

Perfectly

whata re the risk factors of IBD?

genetic predisposition
environmental factors (smoking, diet, obesity, gut microbiome)
obesity (only for CD)

How well did you know this?

Not at all

Perfectly

what is the pathogenesis of IBD?

defective interactions b/ mucosal immune system and gut flora
leads to disrupted innate immunity
physical damage

How well did you know this?

Not at all

Perfectly

what immune cytokines are involved in UC?

Th2 mediated

- dependant on IL-5 and IL-13 cytokines

How well did you know this?

Not at all

Perfectly

what does UC affect?

mucosa and submucosa
starts in rectum, spreads proximally
always continuous
surgery can be curative

How well did you know this?

Not at all

Perfectly

what cytokines are involved in Chron’s?

Th1 mediated (worst inflammatory response)

- dependant on TNF-alpha

How well did you know this?

Not at all

Perfectly

what does Chron’s affect?

penetrates all of gut wall
affects any point of GIT
causes patchy inflammation
abscesses, fissures and fistula

How well did you know this?

Not at all

Perfectly

what are the clinical features of IBD?

R iliac fossa pain
skin rash
diarrhoea, blood, mucus
weight loss
arthritis, athralgia
abdo pain
anaemia

How well did you know this?

Not at all

Perfectly

what are the supportive therapies for IBD?

fluid/ electrolyte replacement
blood transfusion
nutritional support

How well did you know this?

Not at all

Perfectly

what are the classic symptomatic treatments?

glucocorticoids e.g. prednisolone
aminosalicylates e.g. mesalazine
immunosuppressives e.g. azathioprine

How well did you know this?

Not at all

Perfectly

what are the potentially curative treatments?

manipulation of microbiome
anti-TNF alpha
anti-alpha-4-integrins

How well did you know this?

Not at all

Perfectly

give 2 aminosalicylates and what are they?

mesalazine
olsalazine
anti-inflammatory drugs

How well did you know this?

Not at all

Perfectly

are aminosalicylates used in UC and CD treatment?

UC: 1st line in inducing and maintaining remission

- CD: not effective in active disease

How well did you know this?

Not at all

Perfectly

what is the MoA of aminosalicylates?

inhibition of IL-1, TNF-alpha, PAF
dec. antibody secretion
non-specific cytokine inhibition
reduce cell migration
localized inhibition of immune responses

How well did you know this?

Not at all

Perfectly

describe the metabolism of mesalazine?

does not need to be metabolised

- absorbed by small bowel and colon

How well did you know this?

Not at all

Perfectly

describe the metabolism of olsalazine

metabolised by gut flora

- absorbed by colon

give examples of glucorticoids

prednisolone
flucticasone
budesonide

are GC used in UC and CD?

UC: use in decline

- CD: drug of choice for inducing remission

give general info about glucocorticoids

powerful anti-inflammatories and immunosuppressives

- activate intracellular GC receptors –> +/- TF

what are the pharmacokinetics for glucocorticoids?

have long term side effects
administer topically
use low dose in combo with another drug

give examples of immunosuppressives

azathioprine
methotrexate
cyclosporine

what is azathioprine used for?

CD: used to maintain remission
UC: useful for maintaining remission in some
slow onset of action (3-4 months treatment before clinical benefits seen)

what does methotrexate do?

efficacy in some IBD pt
folate antagonist
reduces synthesis of thymidine and other purines
significant side effects

what is the MoA of azathioprine?

Aza is pro-drug activated by gut flora to 6MP

- 6MP is purine antagonist (interferes with DNA synthesis and cell replication)

what does azathioprine impair?

- humoral and innate immune responses - lymphocyte proliferation - mononuclear cell infiltration - synthesis of antibodies

what does azathioprine promote?

T cell apoptosis

what side effects are azathioprine associated with?

- pancreatitis - bone marrow suppression - hepatotoxicity - x4 inc. risk of lymphoma and skin cancer

what are the 3 main routes of metabolism of 6MP?

- HRPT: beneficial but causes myelosuppression - TPMT: hepatotoxic metabolites - XO: inert metabolites (ideal and main pathway)

are nutrition based therapies useful?

CD: no evidence UC: evidence for probiotics in induction and maintenance of remission

is antibiotic treatment (Rifaximin) useful?

- CD: induces and sustains remission in moderate cases | - UC: may be beneficial, interferes with bacterial transcription by binding to RNA polymerase

give an example of biological therapy

Anti-TNF-alpha e.g. infliximab

is anti-TNF alpha successful?

CD - successful, potentially curative, 60% responsive within 6 weeks UC: some, UC is not TNF alpha mediated, mainly IL mediated

what is the MoA of this biological therapy?

- reduces activation of TNF-alpha receptors in gut - down regulated other cytokines and infiltration of leukocytes - induces cytolysis of cells expressing TNF-alpha

what are the pharmacokinetics of this?

- very long half life (9.5 days) - benefits last for 30 weeks after infusion - pt relapse after 8-12 weeks

what are the adverse effects of this biological therapy?

- consequences of knocking out key cytokine inflammatory cascades - x5 incidence of TB - inc. risk of septicaemia (downregulated inflammation) - worsening of HF - can be immunogenic

what are other targets in biological therapy?

- alpha-4 integrin (cell adhesion molecule) - IL-13 (esp in UC) - Janus kinases 1,2,3 (block signally of IL-2,4,9,15,21 and INF-gamma)