Gastrointestinal workshop

Question 1

what is a pro drug

Answer 1

A prodrug is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug.

Question 2

is omeprazole a pro drug

Answer 2

yes

Question 3

BRIEFLY explain the mechanisms involved in pentagastrin stimulated acid secretion.

Answer 3

Pentagastrin is a longer acting (~2h) derivative of gastrin. Gastrin stimulates acid secretion directly via activation of a CCKB receptor on parietal cells and via the release of histamine from ECL cells also via a CCKB receptor.

Question 4

ii) In the space provided suggest the most likely cause of the gastric disorder patients B is suffering from.

.
• B patient suffering from epigastric pain, dyspepsia and anaemia.

Answer 4

Patient B is hyperchlorhydric with both elevated basal and stimulated rates of acid secretion. The likely cause is Zollinger-Ellison Syndrome although hyperchlorhydria can also be associated with type B gastritis or type C gastritis. Further diagnostic tests are required to confirm the diagnosis.

Question 5

In the space provided suggest the most likely cause of the gastric disorder patients C is suffering from

C patient suffering from anaemia

Answer 5

Patient C is hypochlorhydric and almost achlorhydric with a very low basal and stimulated rate of acid secretion. Combined with the observation that this patient is also suffering from anaemia, it is likely that this patient is suffering from Type A (autoimmune) gastritis. However, those with an untreated H.pylori infection can also develop atrophic gastritis, so this would also need to be ruled out.

Question 6

In the space provided suggest the most likely cause of the gastric disorder patients D is suffering from

D patient suffering with dyspepsia (heart burn

Answer 6

Patient D is normo-chlorhydric and since they are only presenting with heart burn are most likely suffering from gastrooesophageal reflux disease.

Question 7

What further diagnostic tests would be of value in confirming your suspicions for patient B

B patient suffering from epigastric pain, dyspepsia and anaemia.

Answer 7

Patient B: Barium meal (not very useful), test for H. Pylori (either mucosal biopsy, plasma antibodies or 13C-urea breath test), secretin test (greatly elevated plasma gastrin concentrations suggests ZES), measure resting plasma gastrin, endoscopy with biopsy (look for parietal cell hyperplasia indicative of ZES), test for possible anaemia due to poor absorption of IF/B12 complex due to low pH in distal ileum.

Question 8

What further diagnostic tests would be of value in confirming your suspicions for patient C

C patient suffering from anaemia

Answer 8

Patient C: Barium meal (coarse gastric mucosal folds indicating type A), measure plasma [gastrin] (elevated), antibody titre (for proton pump antibodies), Schillings’ Test (for absorption of vitamin B12; measure either plasma, urinary excretion or faecal egestion of B12), measure ratio of serum pepsinogen I to pepsinogen II (low pepsinogen I ratio, indicating type A), endoscopy with biopsy (histologically identify parietal cell loss).

Question 9

What further diagnostic tests would be of value in confirming your suspicions for patient D

D patient suffering with dyspepsia (heart burn

Answer 9

Endoscopy to rule out Barrett’s oesophagus, but if this is the first presentation and depending upon their age this is unlikely.

Question 10

In the space below, describe the most appropriate pharmacological treatment and describe it’s mechanism of action for Patient B

Answer 10

Remove non-islet tumor of the pancreas, octreotide may help suppress gastrin release, or proglumide will act as a gastrin receptor antagonist. H2 receptor antagonists to inhibit the histamine secretory component of gastrin. Most effective therapy to alleviate hyperchlorhydria is a proton pump inhibitor. If gastritis is due to H. Pylori, treat with PPI & clarithromycin & metronidazole (triple therapy) to iradicate bacterium.

Question 11

In the space below, describe the most appropriate pharmacological treatment and describe it’s mechanism of action for Patient C

Answer 11

Patient C: Conflicitng opinions exist as to the ability of drug therapies to reverse atrophic gastritis. If the atrophic gastritis is due to H. Pylori infection (which it can be), then eradication of the bacteria may be helpful. Some clinicians feel immunosuppression with steroids such as prednisolone to reduce inflammation, followed by cyclosporin to reduce antibody titre, and hydroxocobalamin (s.c.) to treat pernicious anaemia may be a long term solution.

Question 12

In the space below, describe the most appropriate pharmacological treatment and describe it’s mechanism of action for patient D

Answer 12

Patient D: Gaviscon, Rennies or other antacids may initially be helpful although H2 antagonists and short term PPI’s could also be recommended. If persists, refer to GP who should then refer to hospital for possible endoscopy.

Question 13

Describe the different methods for detecting H.Pylori. Outline the advice that you would give someone who was going for a breath test, regarding their medication?

Answer 13

A: Breath test, swallow radiolabelled urea and burp CO2

Endoscope

Should not do breath tests within 4 weeks of antibiotic or 2 weeks of acid suppressant

Question 14

what is patient B possible diagnosis?

Answer 14

Zollinger-Ellison syndrome or type B gastritis

Question 15

What counselling would you provide with this regimen?

Answer 15

What is it for / how does it work

How to take it

Any warnings? Penicillin, metronidazole?

Common side effects

Discuss the need to complete the course

Question 16

how does helicobacter pylori cause stomach ulcers?

Answer 16

The H. pylori bacteria weakens the protective mucous coating of the stomach and duodenum, thus allowing acid to get through to the sensitive lining beneath. Both the acid and the bacteria irritate the lining and cause a sore, or ulcer.

Question 17

Which regimen would be preferable in someone who is breastfeeding or pregnant?

Answer 17

Metronidazole unsafe!

Neither clarithromycin nor metronidazole recommended therefore treat with PPI until condition resolved then eradicate.

Question 18

If a patient presented with worsening GORD symptoms and was prescribed Lansoprazole 15mg a day, what would you recommend until they could see their doctor?

Answer 18

Should double dose, step up / step down approach used in GORD i.e. manage symptoms then lower dose until they reappear

Question 19

If a patient was prescribed Omeprazole 40mg daily for 3 months with GORD and had no symptoms what should they do?

Answer 19

Step down to 20 mg daily

Question 20

In ZES testing what are the important thing to consider when taking a Blood sample collected following overnight fast and then frozen?

Answer 20

Important that no

antacids

H2 antagonists or

PPI’s are being taken.

Question 21

what is the normal basal acid output?

Answer 21

1.5 mEg/h

Question 22

list 2 ways that H. pylori, can raise plasma gastri.

Answer 22

antral predominant Helicobacter Pylori infection and H. pyloriassociated chronic atrophic gastritis.

Question 23

list the stages of antral predominantHelicobacter pyloriinfection.

Answer 23

H. pylori causes a decrease in somatostatin which causes an increase in plasma gastrin which causes an increase in gastric acid, which then causes possible duodenal ulcer

Question 24

list the stages of H. pyloriassociated chronic atrophic gastritis

Answer 24

causes corpus gastritis—–hypochlorhydria——G cell hyperplasia—–an increase in gastrin—–possible ECL-cell hyperplasia.

Question 25

what are the further diagnostic tests given to patient B?

Answer 25

13C Urea breath test

Resting fasted plasma
gastrin

Endoscopy

Schilling’s test

Question 26

what is Patient C possible diagnosis?

Answer 26

Type A gastritis and Type B gastritis

Question 27

what is Patient C possible diagnosis?

Answer 27

Type A gastritis and Type B gastritis

Question 28

what is Patient D possible diagnosis?

Answer 28

GORD

Question 29

what

Answer 29

-Check the fasting gastrin level. Measure at least 3 fasting levels of gastrin on different days.

-Perform gastric acid secretory studies.
A BAO value of greater than 15 mEq/h or a gastric volume of greater than 140 mL and pH of less than 2.0 are highly suggestive of gastrinoma.

-Perform a provocative test.
The secretin stimulation test is the preferred test. 2U/Kg iv, measure serum gastrin at 0, 2, 5, 10 & 15 min. Serum gastrin at 200pg/ml.

• Perform somatostatin receptor scintigraphy (SRS).
• Perform imaging studies to stage and localize the gastrinoma.
• Determine if patient is a surgical candidate for tumour resection.

Question 30

list 4 H. pylori tests.

Answer 30

Plasma immunoglobulins (IgG)

Stool sample test for antigen (H. pylori)

Biopsy urease test

13Urea breath test INFAI Test for H. pylori

Question 31

what is used to analyse the 13 Urea breath test?

Answer 31

mass spectroscopy.

Question 32

describe the chilling test

Answer 32

firstly give them oral radio labelled vitamin B12 + intramuscular injected unlabelled B12.
the oral radio labelled

Question 33

describe the chilling test

Answer 33

firstly give them oral radio labelled vitamin B12 + intramuscular injected unlabelled B12.
the oral radio labelled is for metabolization by the stomach, and the intramuscular B12 is for saturating the B12 receptors in the liver to avoid the radio labelled B12 from being metabolized in the liver.

Question 34

describe the schilling test stage I

Answer 34

Stage I:

Oral radiolabelled vitamin B12

1 h later 1mg i/m vitamin B12 (saturate hepatic binding sites)

Collect urine over 24 h

If abnormal, stage 2.

(Normal = 8-40% eliminated in urine over 24h)

Question 35

describe the schilling test stage II

Answer 35

Stage II
Oral radiolabelled vitamin B12 + IF
If abnormal, stage III

Question 36

describe the schilling test stage III

Answer 36

Stage III

Repeat stage I after antibiotics for 2 weeks

Question 37

describe the schilling test stage IV

Answer 37

Stage IV

Take pancreatic enzymes for 3 days and repeat stage I

Question 38

In schilling test, Abnormal results from
stage I may suggest that the patient has ________

list 4

Answer 38

ZES,
 autoimmune gastritis (Type A), 

coeliac disease (gluten brush border),

Crohn’s disease.

Question 39

In schilling test, Abnormal results from
stage II may suggest that the patient has ________

list 5

Answer 39

ZES,

coeliac disease,

Crohn’s disease
Hepatic or pancreatic disease

Fish tapeworm infestation

Question 40

In schilling test, Abnormal results from
stage III may suggest that the patient has ________

list 4

Answer 40

Bacterial overgrowth syndrome

Question 41

In schilling test, Abnormal results from

stage IV may suggest that the patient has ________

Answer 41

Pancreatitis

Question 42

why is smoking a cause of dyspepsia?

Answer 42

nicotine stimulates nicotinic cholinergic receptors in the CNS which will then activate the vagus nerve which causes the rrrrelease causes the

Question 43

why is smoking a cause of dyspepsia?

Answer 43

nicotine stimulates nicotinic cholinergic receptors in the CNS which will then activate the vagus nerve which causes the release causes the release of Ach which switches on acid secretion

Question 44

why is smoking a cause of ulcer?

Answer 44

nicotine stimulates nicotinic cholinergic receptors in the CNS which will then activate the vagus nerve which causes the release causes the release of Ach which switches on acid secretion or switch on histamine which causes acid secretion.

Question 45

why is alcohol a cause of ulcer?

Answer 45

it dissolves the mucus coating of the stomach and also dissolve the lipids found in the epithelial cells, which then causes erosion and ulceration

Question 46

why is caffeine a cause of high acid output?

Answer 46

it inhibits the breakdown of Camp which causes a hyper activation of the protein kinase A and a hyper activation of the proton pump.

Question 47

Why did his symptoms return?

Answer 47

This man could have non-ulcer dyspepsia or peptic ulceration. Ranitidine for only two weeks of treatment is available without prescription; if it had been continued the symptoms would probably have been suppressed for longer.
If he is H. pylori positive and has non-ulcer dyspepsia, it is likely that he will develop peptic ulcer disease in the future. If he is H. pylori positive and has peptic ulceration, failure to eradicate H. pylori is likely to result in a recurrence of peptic ulcer within a year.

Question 48

B. This man could have non-ulcer dyspepsia or peptic ulceration. Ranitidine for only two weeks of treatment is available without prescription; if it had been continued the symptoms would probably have been suppressed for longer.
If he is H. pylori positive and has non-ulcer dyspepsia, it is likely that he will develop peptic ulcer disease in the future. If he is H. pylori positive and has peptic ulceration, failure to eradicate H. pylori is likely to result in a recurrence of peptic ulcer within a year.

Answer 48

If H. pylori is present, the symptoms will still recur in a high percentage of individuals.

Question 49

Why did his symptoms return?

see slide 38-50 for case study

Answer 49

This man could have non-ulcer dyspepsia or peptic ulceration. Ranitidine for only two weeks of treatment is available without prescription; if it had been continued the symptoms would probably have been suppressed for longer.
If he is H. pylori positive and has non-ulcer dyspepsia, it is likely that he will develop peptic ulcer disease in the future. If he is H. pylori positive and has peptic ulceration, failure to eradicate H. pylori is likely to result in a recurrence of peptic ulcer within a year.

Question 50

Would his symptoms have been less likely to return following a short course of a proton pump inhibitor?

see slide 38-50 for case study

Answer 50

If H. pylori is present, the symptoms will still recur in a high percentage of individuals.

Question 51

What should be the GPs course of action? An endoscopic examination revealed a duodenal ulcer.

see slide 38-50 for case study

Answer 51

It is recommended that:
any person over 45 years of age should be referred for endoscopic examination.

H. pylori infection can be detected

non-invasively using a blood test (Antibody to urease),

a stool antigen test or

a radiolabelled (13C) urea breath test.

In a gastric antral biopsy, it can be detected using bacterial culture, histopathology or rapid urease (CLO) test.

Use of NSAID’s tobacco and alcohol should be assessed, as these are strong contributors to ulcer disease.

Question 52

Why do some people infected with H. pylori develop gastric ulcer and some duodenal ulcer?

see slide 38-50 for case study

Answer 52

The reasons why some people develop gastric ulcer and others developed duodenal ulcer are imperfectly understood.

If there is only antral inflammation and H. pylori is present, more gastrin and therefore excess acid is produced, resulting in duodenal ulcers.

If a pan-gastritis exists, it is associated with corporal atrophy lower levels of acid secretion, and gastric ulcers.

Question 53

What eradication therapy for H. pylori should be given and is a proton pump inhibitor beneficial when given with antibacterial therapy?

see slide 38-50 for case study

Answer 53

Numerous treatment regimens have been evaluated.

Seven days therapy with
a proton pump inhibitor or ranitidine if tolerant

plus two antimicrobials
clarithromycin and

either metronidazole or amoxicillin,

in a combination dictated by local sensitivities results in a 70-90% eradication rate.

Question 54

What were the possible reasons for the return of the symptoms?

see slide 38-50 for case study

Answer 54

It is possible that the strain of H. pylori was resistant to the antibiotics used. In some places, clarithromycin resistance is 17% and metronidazole resistance is 47%.

Tests should be carried out to see whether H. pylori is still present after treatment. If necessary, quadruple therapy or longer treatment periods should be used.

Question 55

What treatment could be given for H. pylori?

see slide 38-50 for case study

Answer 55

Culture sensitivities of the H. pylori in a biopsy specimen could be sought. Quadruple therapy which has 93-98% success, could be used; for example a proton pump inhibitor or ranitidine plus bismuth salts plus metronidazole plus tetracycline.