CPTP 2.11 Drugs and the GI tract

Question 1

Two types of peptic ulcer?

Answer 1

Gastric ulcer and duodenal ulcer

Question 2

What protects mucosa?

Answer 2

prostaglandin
mucus
bicarbonate
mucosal blood flow

Question 3

what damages mucosa?

Answer 3

acid
pepsin
NSAIDs
H.pylori

Question 4

What stimulates gastric acid secretion?

Answer 4

histamine (binds to H2 receptor)
gastrin (binds to CCK B receptor and trigger histamine release)
ACh (triggers histamine release)

They all induce insertion of K+/H+ ATPase

Question 5

Five types of drugs used in peptic ulcer disease

Answer 5

antimicrobial drugs
PPIs
H2 receptor antagonist
prostaglandins
antacid

Question 6

Antimicrobial agents

Answer 6

• combination of antimicrobial drugs required

- current treatment (triple therapy); PPI + Clarithromycin + Amoxicillin/metamidazole

Question 7

what is PPI?

Answer 7

Proton pump inhibitor

e.g. Omeprazole

Question 8

Mechanism of PPIs?

Answer 8

Administered as a prodrug with an enteric coating to prevent degradation by the stomach acid. Prodrugs passes into the acidic canaliculus

The coating is removed in the alkali environment in the duodenum and become active, sulfenamide form.

Sulfenamide forms covalent bond with H+/K+ ATPase irreversibly

Metabolised by the CYP enzymes in the liver and then excreted

Question 9

H2 receptor antagonist

Answer 9

rantidine

Question 10

pharmacodynamics of

H2 receptor antagonist

Answer 10

competitive antagonist

administration orally

kidney exrete parent drugs and metabolites by filtration and renal tubular secretion

Question 11

antacid

Answer 11

weak bases that react with gastric acid to form water and a salt to diminish gastric acidity

aluminium hydroxide Al(OH)3
Magnesium carbonate

administered as liquid/oral tablets

for quick relief

Question 12

Antimotility drugs

Answer 12

Opioid e.g. Loperimide
Oral or liquid administration

act on opioid receptors to inhibit ACh release and reduce motility

control diarrhoea

Question 13

adsorbent

Answer 13

e.g. methylcellulose

absorb intestinal microorganisms (when used as an adsorbent)

absorb water and increase stool bulk (when used as anti-constipation drug)

Question 14

Agents that modify fluid transport

Answer 14

e.g. bismuth subsalicylate
stimulates absorption of fluids and electrolytes by the intestinal wall (anti-secretory action)
reduces hypermotility of the stomach

Question 15

Drugs to treat diarrhoea

Answer 15

antimotility drugs
absorbents
agents that modify fluid transport

Question 16

type of drug used to treat constipation?

Answer 16

Laxative

Question 17

Four types of Laxatives

Answer 17

Bulk-forming drugs e.g. ispaghula husk
Osmotic laxatives e.g. lactulose
faecal softeners e.g. liquid paraffin
Stimulant laxatives e.g. senna

Question 18

Bulk-forming drugs

Answer 18

e.g. ispaghula husk
absorb water and increase stool bulk -> increase intestinal distension, thereby increasing peristaltic activity

colonic bacteria use the hydrated material as a metabolic substrate -> increase in the bacterial cell mass with a consequential softening of the faeces

takes 1-3 days

Question 19

Osmotic laxatives

Answer 19

e.g. lactulose
Non absorbable compounds that hold water in the intestines by osmosis. This distends the bowel, increasing intestinal activity

take up to 24 hours to act

Question 20

Faecal softneners

Answer 20

e.g. liquid paraffin

agents become emulsified with the stool and soften/lubricate it for easy passage

Question 21

Stimulant laxatives

Answer 21

e.g. senna

administered in an innocuous form

converted to their active forms by bacteria in the colon

They irritate the mucosa, inducing low grade inflammation, which stimulates peristalsis and promotes accumulation of water and electrolytes

Question 22

How is gut motility controlled?

Answer 22

ENS

Submucosal (Meissner) plexus controls ion and fluid transport

Myenteric (Auerbach) plexus control motility

Question 23

How the sympathetic and parasympathetic nervous system modulate the ENS in the gut

Answer 23

Para- releases ACh that stimulate ENS to release ACh for gut SM constraction

Sym- release noradrenaline that inhibits ENS, so no ACh release. Inhibitory.

Question 24

Drug used to treat IBS

Answer 24

Antispasmodics

e.g. hyoscine and mebeverine

Question 25

Antimuscarinics

Answer 25

e. g. Hyoscine
- competitively antagonise action of ACh in enteric plexus
- side effects: dry mouth, blurred vision and cardiac arrhythmia

e. g. mebeverine
- act directly on SM to relax it

Question 26

Drugs for inflammatory bowel disease (IBD)

Answer 26

anti-inflammatory drugs

immunosuppressive drugs

Question 27

Aminosalicylates

Answer 27

anti-inflammatory drugs e.g. mesalazine

treat mild to moderate ulcerative colitis and maintain remission

Oral tablets with coating
absorbed in large intestine

Question 28

corticosteroids

Answer 28

anti-inflammatory and immunosupressive drugs e..g prednisolone

inhibits synthesis of inflammatory mediators such as prostaglandin and leukotriene

used to treat moderate to severe UC and Crohn’s disease

Question 29

Antibodies to tumour necrosis factor (TNF)

Answer 29

TNF causes activation of immune cells and release of inflammatory mediators

its antibodies e.g. infliximab induce remission in 1/3 patients with Crohn’s