Pharmaceutical Care of Gastrointestinal patients 2 UC and Crohn's

Question 1

Inflammatory bowel disease (IBD) is a term mainly used to describe two conditions. list these two conditions

Answer 1

ulcerative colitis and Crohn’s disease

Question 2

what is Ulcerative Colitis?

• causes?
• which part of the GI tract becomes inflamed?
• does it go away?

Answer 2

1) Ulcerative Colitis is a condition that causes inflammation and ulceration of the inner lining of the rectum and colon
2) Small ulcers develop on the surface of the intestinal lining and these may bleed and produce pus
3) Only the surface of the intestine becomes inflamed
4) UC is sometimes described as a chronic condition
5) Long periods of good health (remission) as well as relapses or flare-ups
6) Cause: unknown, but environmental, genetic and bacterial may play a role

Question 3

what is Crohn’s Disease?

• can it spread?
• can it be cured?
• which part of the body does it affect?

Answer 3

1) Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract
2) Inflammation extends all the way through the intestinal wall from mucosa to serosa
3) Crohn’s disease is a relapsing and remitting disease
4) Initially only a small segment of the gastrointestinal tract may be involved, but Crohn’s disease can progress
5) Smoking and genetic predisposition are two important factors that are likely to play a role
6) Although surgical resection of inflamed segments may temporarily arrest symptoms, subsequent inflammation is likely to recur. Resection is not curative in Crohn’s disease, which is in contrast to ulcerative colitis

Question 4

what are the symptoms of Crohn’s Disease?

• when is pain exacerbated?
• list some non GI symptoms

Answer 4

1) Patients present with diarrhoea and insidious abdominal pain
2) Pain is often exacerbated after feeding
3) Diarrhoea is usually non-bloody (helps differentiate from ulcerative colitis)
4) Patients can frequently have fever and weight loss
5) Non-intestinal manifestations can include: mouth ulcers (immune response), arthritis, erythema nodosum (inflammation of fat cells under skin)

Question 5

compare the anatomy of crohn’s disease vs ulcerative colitis. is there a difference in where each disease is typically present?

Answer 5

1) Crohn’s Disease: mainly on the ascending colon and parts of the ilium
2) Ulcerative Colitis: mainly on the descending colon

Question 6

the main difference between Crohn’s and Ulcerative Colitis is the type of inflammation. compare the difference in the type of inflammation

Answer 6

1) in Crohn’s the inflammation goes all the way through the wall
- All Layers of Bowel Inflamed
2) in ulcerative colitis: inflammation is on the surface
- Only Lining of Bowel Inflamed

Question 7

describe the differences in the appearance of the intestines in crohn’s disease vs ulcerative colitis

Answer 7

1) ulcerative colitis: ulceration, crypt distortion, pseudopolyps (surviving mucosa)
2) crohn’s disease: cobble stoning, thickened wall , fissure all may be present

Question 8

compare the majour differences in the symptoms of Crohn’s Disease & Ulcerative colitis

Answer 8

1) rectal bleeding: usual in Ulcerative Colitis only sometimes in Crohn’s Disease
2) cigarette smoking: not usually involved in ulcerative colitis but common in crohn’s disease.
3) discrete ulcers are rare in ulcerative colitis but common in crohns
4) aphthoid ulcers are rare but common in crohns
5) cobble stone lesions never occur in ulcerative colitis but are common in crohns

Question 9

what is Proctosigmoiditis?

Answer 9

Proctosigmoiditis is a form of ulcerative colitis and affects the rectum and sigmoid colon (the S-shaped last part of the large intestine, leading into the rectum).

Question 10

what is Proctitis?

Answer 10

inflammation of the anus (the opening) and lining of the rectum (lower part of the intestine leading to the anus)

Question 11

list the tests conducted to diagnose Inflammatory Bowel Disease

Answer 11

1) full blood count (FBC)
2) CT bowel
3) Sigmoidoscopy or colonoscopy
4) CRP
5) Stool sample (rule out c.diff)
6) Liver function tests (LFTs)
7) Temperature
8) Faecal calprotectin

Question 12

what is Faecal calprotectin and what two conditions does it help differentiate between?

Answer 12

1) released into the intestines in excess when there is any inflammation there. Its presence can mean a person has an inflammatory bowel disease such as Crohn’s disease or ulcerative colitis.
2) Help with differential diagnosis of IBD and IBS as symptoms are can be similar

Question 13

outline some complications that can occur as a result of Crohn’s Disease.

Answer 13

1) Strictures
2) Perforations
3) Fistulae- Uncommon in UC

Question 14

what is the Harvey-Bradshaw Index for Crohn’s?

Answer 14

1) The tool is used to quantify the stage of disease
2) This helps determine treatments options, as the disease has a variety of symptoms that effect QoL
3) Treatment options vary depending on the stage of disease or ‘flare’

Question 15

describe the mild, moderate and severe scores for ucerative Colitis

Answer 15

1) Mild: fewer than four stools daily, no more than small amounts of blood in stools, no anaemia, pulse rate not above 90, no fever and normal ESR and CRP.
2) Moderate: four to six stools a day with more blood in stools than for mild disease. No anaemia, pulse rate not above 90, no fever and normal ESR and CRP.
3) Severe: six or more stools per day, visible blood in stools and at least one feature of systemic upset (temperature above 37.8°C, pulse rate greater than 90, anaemia, ESR above 30).

Question 16

for each of the following parts of the GI system state what is absorbed:

1) colon
2) duodenum
3) jejunum
4) ileum

Answer 16

1) Colon – site of water absorption
2) Duodenum – iron and calcium ions
3) Jejunum – folic acid
4) Ileum – fat and vitamin B12 absorption

Question 17

describe the WHO analgesic pain ladder

Answer 17

1) step 1 mild : Non-opioid + Optional adjuvant If pain persists or increases, go to step 2
2) step 2 moderate: Weak opioid + Non-opioid + Optional adjuvant If pain persists or increases, go to step 3.
3) step 3 severe: Strong opioid + Non-opioid + Optional adjuvant Freedom from pain.

Question 18

Discuss the use of Steroids in UC and crohns.

• when are they used?
• risk of long term use?
• what is the dose?

Answer 18

1) Indication: both Crohn’s and UC in mod-severe relapse
2) No role in maintenance
- 40mg OD prednisolone reduced slowly 2/52
-

Question 19

for each of the following Rectal preparations state the site of action:

1) Suppository
2) Foam
3) enema

Answer 19

1) Suppository: Rectum, Proctitis
2) Foam: Sigmoid Colon, Procto-sigmoiditis
3) enema: Descending colon to splenic flexure, Left sided colitis

Question 20

what dose of 5-aminosalicylic acid (Mesalazine) should be used in crohns and UC

Answer 20

1) Crohn’s – no evidence for doses >4g
2) UC –Induction of remissions ≥ 4g/day
- Maintenance of remission ≥ 2g/day
3) Rectal preparations (PINCE) : 15% past splenic flexure: 2g bd oral + 1g OD rectal (64% remission at week 8 vs 43% oral) - this is a combined oral and rectal

Question 21

how do you optimise the use of steroids

Answer 21

1) Correct dose: Start at 40mg and slow reduction
2) Correct formulation- Know where the disease is located
3) Prevent osteoporosis
4) Consider infection risk
5) rectal steroids Only for patient not responding to rectal mesalazine

Question 22

where is mesalazine normally absorbed, what is its method of action and why are MR preparations used?

Answer 22

1) Mesalazine - orally would be extensively absorbed from the upper GIT, with little of the drug reaching the colon.
2) MR preparations used - release the drug in the terminal ileum and colon (local action)
3) Mesalazine is an anti-inflammatory drug structurally related to the salicylates
4) Mesalazine is the active moiety of sulfasalazine, which is metabolized to sulfapyridine and mesalazine.
5) Inhibits prostaglandin and leukotriene synthesis, release of reactive oxygen species and other actions

Question 23

outline the active moiety of Sulfasalazine

Answer 23

1) prodrug- not active in its ingested form. It is broken down by bacteria in the colon into its two components, 5-aminosalicylic acid (5-ASA), and sulfapyridine.
2) 5-ASA (mesalazine) →poorly absorbed →induced remission in UC by :
- inbibiting COX, PAF, cytokines
- inhibiting IL-1 and TNF α
3) sulfapyridine is rapidly absorbed in the colon → acetylated in the liver → excreted in urine → no therapeutic action in UC

Question 24

list the different formulations of mesalazine available and state their site of action

Answer 24

1) Asacol MR- EC therefore delayed release pH>7
- Site: terminal ileum + large bowel
2) Octasa MR– EC therefore delayed release pH>7
- Site: Terminal ileum and colon
3) pentasa- Ethylcellulose coated microgranules to allow slow continuous release – diffusion through semi-permeable membrane
- Site: Duodenum to rectum
4) Sulfasalazine and other azo-bonded:- cleaved by intestinal bacteria – azoreductase pH >7.
- Site: colon

Question 25

what other things do you need to consider for UC and crohns patients with regards to their treatment ?
- what needs to be monitored what is recommended?

Answer 25

1) Osteoporosis risk
2) Nutrition
3) anaemia
4) Opportunistic infections - vaccines
5) Side effects
6) DVT risk

Question 26

discuss how tablet size and frequency can lead to adherence problems in patients . how can pharmacists help?

Answer 26

1) Tablet size can be a particular problem especially when the patient is acutely unwell
2) Swallowing a large tablet or a number of large tablets can feel overwhelming
3) Talk to your patient to aid adherence and compliance to their treatment regimens
4) Does the frequency of tablets affect
- their daily life?
- what is their work/life pattern?

Question 27

what are Thiopurines?

Answer 27

Thiopurines are a class of drugs that are used to suppress the normal activity of the body's immune system. Examples of thiopurine drugs include azathioprine
29
discuss the use of Thiopurines in IBD.
- what test should be conducted first?
- which enzyme is tested for?

Question 28

Thiopurines are a class of drugs that are used to suppress the normal activity of the body's immune system. Examples of thiopurine drugs include azathioprine
29
discuss the use of Thiopurines in IBD.
- what test should be conducted first?
- which enzyme is tested for?

Answer 28

1) A TPMT test is used to check whether a person is at risk of developing severe side effects after taking a type of medication called thiopurine
2) Assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine.
3) Do not offer azathioprine or mercaptopurine if TPMT activity is deficient (very low or absent).
4) Consider azathioprine or mercaptopurine at a lower dose if TPMT activity is below normal but not deficient

Question 29

outline the Mechanism of Action of thiopurines in particular Azathioprine.

• what is its most severe side effect
• can it be given in conjunction with purine analogues?

Answer 29

1) Azathioprine is an immunosuppressive drug
2) Class of agents is purine analogues
3) Prodrug for mercaptopurine (active metabolite)
4) Azathioprine acts to inhibit purine synthesis
5) Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol

Question 30

outline the use of Methotrexate in IBD

• what is the dose?
• what should be monitored
• how often should it be administered
• what other drug should it be taken with

Answer 30

1) Used in active and relapsing Crohn’s
2) 25mg/week PO or IV/SC
3) Monitor FBC and LFTs
4) Maintenance dose to prevent remission
5) ONCE weekly dosing
6) Concomitant folic acid
- give patient methotrexate dosage record booklet

Question 31

what is Ciclosporin used to treat ?

• how should it be administered?
• what dose?
• what should be monitored?

Answer 31

1) Therapy for acute severe ulcerative colitis
2) Consider adding intravenous ciclosporin to intravenous corticosteroids or consider surgery for people:
- who have little or no improvement within 72 hours of starting intravenous corticosteroids or
- whose symptoms worsen at any time despite corticosteroid treatment.
3) Take into account the person’s preferences when choosing treatment
4) 2mg/kg PO/IV
5) Baseline BP, FBC, cholesterol, LFTS, GFR, Mg2+

Question 32

if there is an inadequate response to oral prednisolone after 2–4 weeks in Mild-moderate UC, what other drug can be added to the regime to induce remission?

Answer 32

1) Consider adding oral tacrolimus to oral prednisolone to induce remission
2) Mild to moderate ulcerative colitis if there is an inadequate response to oral prednisolone after 2–4 weeks.

Question 33

discuss the use of Monoclonal antibodies (MABs) for the treatment of IBD.

• name a brand of MAB
• when should MAB’s be considered?
• how long is the planned treatment course?
• when are they not recommended?

Answer 33

1) Infliximab is licensed for the management of severe active Crohn’s disease and severe UC
2) Not responded adequately to treatment with corticosteroid and a conventional drug that affects the immune response/intolerant
3) Planned course of treatment for 12 months or until treatment failure
4) Not recommended for treatment of subacute manifestations of moderate-severe active UC that would be managed in OP setting
5) Acute exacerbations of UC when ciclosporin is C/I

Question 34

Describe the mechanism of action of Infliximab

Answer 34

1) TNF-α has been implicated in numerous autoimmune diseases
2) Regulates inflammation
3) Infliximab is a chimeric monoclonal antibody that targets and binds to TNF-α.
4) By inactivating TNF-α, the inflammatory process is significantly diminished

Question 35

Suppository advice

Answer 35

read instructions on PIl
Use it near a toilet
take off wrapping and push gently into bottom
sit still to allow it dissolve
avoid exercise and lots of movement for 1 hour
store in cool dry pace and prevent from melting

Question 36

Heterocyclic Aromatic Compounds?

Answer 36

For a compound (or ion) to be considered aromatic, the molecule must be cyclic, planar, and must have 4n + 2 electrons in a conjugated system of p orbitals (usually on sp2-hybridized atoms. This is known as Hückel’s rule.

Question 37

What is the mechanism of action of omeprazole?

Answer 37

Enzyme inhibitor
It suppresses stomach acid secretion by specific inhibition of the H+/K+-ATPase system found at the secretory surface of gastric parietal cells. Because this enzyme system is regarded as the acid (proton, or H+) pump within the gastric mucosa, omeprazole inhibits the final step of acid production.

Question 38

PPI MoA

Answer 38

Proton pump inhibitors (PPIs) effectively block gastric acid secretion by irreversibly binding to and inhibiting the hydrogen-potassium ATPase pump that resides on the luminal surface of the parietal cell membrane.

Question 39

What is the difference in mechanism of action between a PPI and an H2 blocker?

Answer 39

“H2 blockers work by blocking the histamine receptors in parietal cells to decrease the amount of acid produced (although there are other stimuli so that some acid is still produced).” PPIs work by “shutting down the proton pumps in these cells and preventing the acid from being secreted into the stomach.”