upper GI drugs

Question 1

how can peptic ulcers form (2)

Answer 1

1. too much damage to the gastric mucoss
2. weak mucosa (=> easily damaged)

Question 2

what 3 factors is the parietal cell secretion under the control of

Answer 2

1. vagus nerve (Ach)
2. gastrin
3. histamine

Question 3

6 ways to reduced gastric acid secretion and exaamples of these drugs

Answer 3

1. H2 receptor ANTagonist - cimetidine, famotidine, nizatidine;
2. gastrin anatagonist - none clinically available
3. muscarinic anatgonist (have many other side effects) - atropine, pirenzepine
4. H+ secretion mechanism blocker - PPI
5. parietal cell inhibition physiologically - misprostol, somatostain
6. neutralisation - antacids e.g. gaviscon

Question 4

what are antacids used for

Answer 4

symptomatic relief of GORD, dyspepsia etc -> they hv rapid onset but are only transient so generally used for symptom relief

Question 5

what metals do anatacids commonly contain and what side effect do they produce

Answer 5

1. magnesium - constipation;
2. calcium
3. Sodium - HTN
4. aluminium - diahorrea

=> give aluminium for constipationa nd magnesium for diahorrea

Question 6

what is milk-alkali syndrome

Answer 6

systemic alkalosis due to high doses of antacids, characterized by a triad of elevated calcium levels, metabolic alkalosis, and acute kidney injury

Question 7

what medications can aluminium not be given alongside (2)

Answer 7

1. levodopa
2. tetracyclines

Al chelates to them

Question 8

side effects of carbonate containing antacids

Answer 8

CO2 release leading to burping and stomach distension

Question 9

H2 receptor antagonist MOA

Answer 9

reversible, competitive, inhibitors of H2 receptors -> reduced histamine release leading to reduced parietal cell activation => reduced basal and stimulated acide secretion, reduced pepsin secretion (from chief cells)

Question 10

what non-GI condition might H2 antagonists be used in

Answer 10

Heart failure - has significant negative iontropic and chronotropic effects

Question 11

H2R antagonist side effects

Answer 11

side effects are uncommon
1. diahorrea
2. headache
3. elderly confusion
4. gynaecomastia (cimetidine specifically, it binds to androgen receptors)
5. interacts with warfarin, throphylline etc. (enhances their effect as inhibits P450 - cimetidine)

Question 12

PPI MOA

Answer 12

irreversibly binding (covalently bonds to receptor) to and inhibiting the hydrogen-potassium ATPase pump that resides on the luminal surface of the parietal cell membrane

Question 13

what enatiomer of esomeprazole is used (R,S)

Answer 13

S - more potent as it is broken down slower, so acid suppression is prolonged

Question 14

side effects of PPI

Answer 14

1. headaches
2. diahorrea (due to bacterial overgrowth, microscopic colitis etc.)
3. infectious gastroenteritis
4. hypergastrinaemia
5. imparied Ca and Mg absorption -> increase in osteoporotic fractures

Question 15

step up vs step down GORD mgx

Answer 15

step up - start on a lower dose and build up
step down - start on a high dose and work down to lowest dose needed

Question 16

what does parenteral mean

Answer 16

administered or occurring elsewhere in the body than the mouth and alimentary canal

Question 17

indications for pareneteral therapy (5)

Answer 17

1. prevention of aspiration during anesthesia
2. stress ulcer prophylaxis in certain critically ill patients
3. peptic disease and inability to take oral mgx for 5days
4. post endoscopic mgx in selected GI haemorrhage pts
5. non-responsive ZE syndrome

Question 18

what is the importance of CYP450 in PPI use

Answer 18

All PPIs are metabolized to varying degrees by hepatic P450 cytochromes in the liver

Question 19

what antiplatelet might PPIs interact with

Answer 19

clipidogrel - may inhibit its action

Question 20

upper GI vs lower GI bleed blood results

Answer 20

upper GI - high urea, low Hb
lower GI - low Hb, urea normal

Question 21

red flag features for dyspepsia (6)

Answer 21

1. dysphagia
2. anoerxia
3. anaemia
4. recurrent vomiting
5. mass
6. loss of weight

Question 22

misoprostol MOA

Answer 22

1. a synthetic prostaglandin E1 analog that stimulates prostaglandin E1 receptors on parietal cells in the stomach to reduce gastric acid secretion
2. EP3 agonist -> inhibitory effect on proton pump of the parietal cell

=> acid secretion inhibited, duodenal HCO3- increased, gastric mucous increase, mucosal blood flow increased

Question 23

what is the effect of misoprostol on peptic ulcers

Answer 23

helps them heal and reduces further complications from NSAID use

Question 24

misoprostol adverse effects (3)

Answer 24

1. diarrhoea
2. uterine contractions (induced labour/termination of pregnancy)
3. menorrhagia/post menopausal bleeding

Question 25

sucralfate MOA

Answer 25

1. sucralfate forms a complex that binds to protein-rich exudate found on the surface of ulcers -> barrier to H+ ions
2. increase FGF leading to increased PGE secretion

Question 26

bismuth moa

Answer 26

bismuth subsalicylate hydrolyzes in the stomach into bismuth oxychloride, which is minimally absorbed into the bloodstream, and salicylic acid, which is almost completely absorbed -> Bismuth interacts with other anions and compounds, such as hydrochloric acid, bicarbonate, phosphate, and hydrogen sulfide, in the gastrointestinal tract to form bismuth salts -> Bismuth salts possess bactericidal and antimicrobial activity, mainly by preventing bacteria from binding and growing on the mucosal cells of the stomach (esp. H.Pylori!)

Question 27

bismuth adverse effects

Answer 27

1. black stools
2. black tongue
3. minimal absoption -> could lead to accumulation, so 6-8wks is max treatment

Question 28

Mesenteric ischaemia triad

Answer 28

triad of CVD, high lactate and soft but tender abdomen