Ulcer and Inflammation + Laxatives

Question 1

what is a peptic ulcer

Answer 1

erosion of small patch of the lining of stomach (gastric ulcer) or duodenum (duodenal ulcer)

Question 2

how do NSAIDS cause ulcers

Answer 2

less prostaglandins so less cytoprotection of gastric antrum

Question 3

State Factors that attack the gastric and duodenal mucosae

Answer 3

1. Acid and pepsin
2. H.pylori
3. Bile reflux and delayed gastric emptying – autonomic system dysfunction
4. Absence of protective prostaglandins (NSAID side effect – inhibit production of PGI2)
5. Microvascular vasoconstriction
6. Failure of epithelial regeneration – anticancer drugs, cytotoxic drug
7. Presence of stress and other risk factors - e.g. alcohol, smoking, aspirin

Question 4

Worldwide diarrhoeal diseases

Answer 4

cholera or rotaviral infections

Question 5

why take glucose with electrolytes and rice water

Answer 5

to optimise absorption of electrolytes into the blood from GIT

Question 6

What is Dexamethszone? When used?

Answer 6

an Anti-emetic corticosteroid. Used in Post-Operative or Cancer associated vomiting.

Question 7

name protective mechanisms of the stomach

Answer 7

Mucus layer - good mucosal blood flow - HC03 buffer - cytoprotective prostaglandins that inhibit acid release - epithelial regeneration

Question 8

Histamine is often known as:

Answer 8

the ‘final common mediator’, although Ach and gastrin can both activate the paritetal cell directly.

Question 9

State the three acid stimulators that cause release from acid from the parietal cell

Answer 9

Histamine, Gastrin and Acetylcholine

Question 10

Stimulant laxative indication and action

Answer 10

Bisacodyl (synthetic drug, based on active principle of senna); acts in about 8hr, take the night before; stimulates enteric nerves to cause peristalsis. Suppository acts quicker. ‘Abuse’ –> cramps: not suitable for repeated use.

Glycerol suppositories; act as a rectal stimulant (mild irritant)

Question 11

Crohns Disease and Ulcerative Colitis are both..

Answer 11

manifestations of IBD

Question 12

what is a natural alternative to ORS?

Answer 12

Rice water with electrolytes - boil rice water and use the starchy water produced. add salt.

Question 13

How does Misoprostol work?

Answer 13

it’s a PG analogue that mimics PGE2 which works by increasing Mucus and HCO3 secretion + Vasodilation

Question 14

name the two classes of drugs for IBD

Answer 14

Anti-inflammatories (Corticosteroids, Aminosalicylates) Anti-cytokine agents (infliximab)

Question 15

how does PGE₂ work?

Answer 15

It inhibits the ATP-dependent proton pump within parietal cells

Question 16

what’s the most common type of ulcer

Answer 16

Duodenal Ulcer

Question 17

benefits of dietary fibre?

Answer 17

• gives bulk, enhances mechanical efficiency of intestine
• speeds up transit (reduces exposure to toxins ),
• Adsorbs water (keeps stools soft but bulky),
• Promotes regular bowel habit

Question 18

Describe the Biosynthesis of Prostaglandins

Answer 18

Question 19

H2 Antagonists (block histamine’s effect E.g Cimetidine) - PPI’s (irreversible inhibition E.g Omeprazole, Lansoprazole) Prostaglandin Analogues (Misoprostol)

Answer 19

Acid-Modifying drug examples

Question 20

what does IBD stand for

Answer 20

Inflammatory Bowel Disease

Question 21

What should we NOT do in patients with diarrhoea

Answer 21

Do not employ bulk-forming agents with anti-spasmodics as this could lead to intestinal obstruction

Question 22

Domperidone is a

Answer 22

D2 receptor antagonist at the CTZ

Question 23

what does bismuth sulfate do

Answer 23

improve mucosal defence

Question 24

List the Key Treatments of IBS

Answer 24

reassurance

anxiolytics

anti-spasmodics

dietary improvement

Question 25

General causes of diarrhoea

Answer 25

(a) too rapid transit through colon - hypermotility, or (b) failure of colonic water reabsorption; or both

Question 26

For radiation and cancer sickness/emesis, give..

Answer 26

**Ondansetron**, dolasetron (5HT3 antags) very effective against severe nausea/vomiting esp. post anticancer chemotherapy (i.v. plus oral dexamethazone) * Aprepitant (first of the NK1 antagonists) * Nabilone (synthetic cannabinoid, given if patient is refractory to above drugs, or significant side effects) * **Dexamethasone** – **anti-emetic corticosteroid** * Domperidone – short term only (D2 antag, less sedating)

Question 27

what drugs can inhibit the vomiting centre?

Answer 27

Hyoscine and Promethazine

Question 28

What is PGF2-Alpha?

Answer 28

bronchiconstrictor

Question 29

Define IBS

Answer 29

Abnormal bowel activity, alternating episodes of diarrhoea & constipation assoc. with colic and pain. Patients are often anxious.

Question 30

Side effects of H2 Antagonists

Answer 30

Highly sedative

Question 31

What is the best treatment for Diarrhoea in healthy people? What do we check for in at-risk groups?

Answer 31

The best treatment of mild diarrhoea in healthy people is to abstain from food and drink plenty of clear fluids • In infants, children and the elderly check that fluid intake is adequate • Check patient’s diet : increasing the amount of fibre may help in the longer term

Question 32

Osmotic laxative indication and action

Answer 32

Osmotic laxatives attract water. E.g lactulose (non-absorbed disaccharide) acts in 24-48 hours. Suitable for chronic constipation. Macrogols (intert polymers of ethylene gylcol) Side effects; abdominal distension, pain, nausea

Question 33

What is the presenting symptoms of peptic ulcer

Answer 33

inflammation and pain. Gastric irritation. Vomiting, loss of appetite and poor sleep

Question 34

Bulk forming laxatives: Indication and action etc

Answer 34

E.g Ispagula husk, sterculia- theyre **Indigestible** materials, **attracts water & swells** in colon, increasing peristalsis and **promoting soft stool.** *Takes several days to work.* e,g of BFL: Methylcellulose, Bran, High Fibre diets - similar principle. Take plenty of water with all these. Can cause abdominal swelling

Question 35

General treatment strategies to peptic ulcer

Answer 35

1. Relieve **pain** e.g Antacids 2. Allow **healing**, e.g antisecretory agents and mucosal strengtheners. 3. Prevent **relapse**, e.g maintenance therapy 4. Avoidance of **risk factors** Stop smoking

Question 36

Anti-spasmodics used in IBS and how they work

Answer 36

peppermint oil capsules, mebeverine (both relax the smooth muscle & reduce pain)

Question 37

How do the acid stimulators work?

Answer 37

Act on the parietal cell to activate ATP-dependent 'proton pump' which exchanges H+ for K+

Question 39

Lubiprostone. Whats it for?

Answer 39

stimulates colonic fluid secretion, used to treat chronic idiopathic constipation in adults. Can be used in IBS

Question 40

Generally speaking, whats given for motion, pegnancy, vertigo and post-op nausea, give..

Answer 40

1. Motion sickness: hyoscine 2. Pregnancy-associated sickness (only in severe cases): promethazine (sedating H1 antagonist, use with caution) 3. Vertigo & other vestibular disorders: cinnarizine or cyclizine (H1 antags, less sedating than promethazine) 4. Post-operative nausea and vomiting: effective drugs are 5HT3 & H1 antags, and dexamethazone, some phenothiazines

Question 41

State the four types of Laxatives

Answer 41

1. Bulk Forming Laxatives 2. Osmotic Laxatives 3. Stimulant Laxatives 4. Lubrican Laxatives

Question 42

Acid-Modifying drug examples

Answer 42

H2 Antagonists (block histamine's effect E.g Cimetidine) - PPI's (irreversible inhibition E.g Omeprazole, Lansoprazole) **Prostaglandin Analogues** (**Misoprostol**)

Question 43

What does a Thrombotic do?

Answer 43

Promotes platelet aggregation

Question 44

Indication for PG Analogue

Answer 44

Prophylaxis in the frail elderly whose use of NSAIDS cannot be withdrawn

Question 45

lubricant laxative indication and action

Answer 45

Useful in management of haemorroids and anal fissure. • Arachis (peanut/ground nut) oil - warmed enema of 130 ml used to soften impacted faeces, promote bowel movement. Glycerol - as a suppository in infants

Question 46

name an example of an Anti-cytokine agent for IBD. What else can it be used to treat?

Answer 46

infliximab, used elsewhere in Rheumatoid Arthritis

Question 47

What is Colic?

Answer 47

Episodes of crying for more than three hours

Question 48

Treatment of IBD

Answer 48

A - Corticosteroid (inhibit PLA2 activity and AA-PG cascade) e.g Prednisolone, Hydrocortisone, Budesonide (as adjunct to aminosalicylates) B - Immunosuppressants (ciclosporin) C - Monoclonal TNFα Antibodies (infliximab inhibits TNFα actions D - Aminosalicylates - Maintain remission in ulcerative colitis

Question 49

Main stimulant laxatives available otc and side effects

Answer 49

Bisacodyl or senna are the main OTC therapies currently with limiting side effects, e.g. abdominal cramping, diarrhoea, dehydration.

Question 50

Traditional remedies for Diarrhoea

Answer 50

charcoal, kaolin (china clay) are helpful for mild infective diarrhoea (BUT - will also help absorb toxins if not a mild infection).

Question 51

Vomiting can be triggered by activation of the CTZ - what does that stand for?

Answer 51

Chemoreceptor Triggering Zone

Question 52

What is peppermint oil

Answer 52

a direct acting antispasmodic which relaxes the smooth muscle and reduces pain

Question 53

What is loperamide

Answer 53

an antumotility drug

Question 54

Key Differences between IBS and IBD

Answer 54

Irritable bowel syndrome (IBS) is a non-inflammatory condition, while inflammatory bowel disease (IBD) causes chronic swelling (or inflammation). Both conditions can lead to abdominal pain, constipation, or urgent bowel movements, but IBD can also cause extreme fatigue or rectal bleeding.

Question 55

The cAMP induced pathway in acid secretion is switched on by

Answer 55

Histamine.

Question 56

what is acid rebound? why is it bad?

Answer 56

when bicarbonates neutralise the acid, more acid is produced to counteract. hence pain returns!

Question 57

name 2 highly selective antagonists

Answer 57

Ranitidine and Cimetidine

Question 59

How does cancer and other cytotoxic drugs cause ulcers

Answer 59

they interfere with regeneration of epithelial cells that line the gastric Antrum

Question 60

Main treatment to peptic ulcers

Answer 60

1.Avoid risk factors, stress, smoking, alcohol, aspirin 2.Neutralise acid (antacids) or reduce its secretion Mg carbonate, Al(OH)3; NaHCO3 in indigestion remedies 3.Encourage healing with H2 antagonists, or 4.Eliminate H.pylori (after positive urease test) antibiotics 5 Improve mucosal defence

Question 61

state the triple therapy to eradicate H.Pylori

Answer 61

Omeprazole Clarithromycin Metronidazole

Question 62

Bicarbonate pros and cons in gastric ulcer treatment

Answer 62

Rapid relief as acid is neutralised chemically. Cons of Acid rebound, and cannot be used for weeks

Question 63

H Pylori Eradicaiton Regime. How long is this therapy? what side effects?

Answer 63

Omeprazole 20mg BD (S/E - Nausea) Amoxicillin 1g BD (S/E - Rash) Clarithromycin 500mg BD (insomnia) Metronidazole 400mmg TDS (darkening urine) Last seven days

Question 64

if we cant give a penicillin, what do we give?

Answer 64

Tetracycline 500mg QDS

Question 65

risk factors of PUD?

Answer 65

Age (\>65) - Previous peptic ulcer or GI bleed - Combining anti-inflammatories - Concurrent warfarin - Smoking - Alcohol

Question 66

* Anti-cholinergic drug (M antagonist), e.g. hyoscine * Sedating anti-histamines (H1 antagonists) e.g. promethazine, cinnarizine – useful against motion sickness etc. * Phenothiazines (D2 antagonists), e.g. prochlorperazine * More D2 antagonists, e.g. droperidol, domperidone ] * 5HT3 antagonists, e.g. granisetron, ondansetron * Neurokinin (NK)1 antagonists, e.g. aprepitant, fosaprepitant * Dexamethazone, has anti-emetic effects useful against vomiting assoc. with chemotherapy (mechanism not clear)