F2 Pharmacological treatment of the upper GIT Flashcards
1
Q
where is HCl produced and secreted into?
A
- produced by parietal cells
- secreted into their canaliculi
2
Q
how are the proton for HCl formation formed?
A
from dissociating from carbonate ions
3
Q
how are the Cl- ions obtained for the formation of HCl?
A
- bicarbonate is pumped out of parietal cells in exchange for chloride ions
- (because protons have dissociated from carbonate) there is now protons and Cl- in the parietal cell
- they get secreted as hydrochloric acid
4
Q
how can parietal cell acid output be directly or indirectly controlled?
A
- acetylcholine
- histamine
- gastrin
- prostaglandins
- somatostatin
5
Q
what is acetylcholine?
A
a stimulatory neurotransmitter
6
Q
what is histamine?
A
a stimulatory local hormone
7
Q
what is gastrin?
A
a stimulatory peptide hormone
8
Q
what are prostaglandins E2 and I2?
A
inhibitory local hormones
9
Q
what is somatostatin?
A
an inhibitory peptide hormone
10
Q
which of the 5 molecules that control parietal cell acid output cause the output to increase / cause secretion?
A
- acetylcholine
- histamine
- gastrin
11
Q
which of the 5 molecules that control parietal cell acid output cause the output to decrease / stop acid secretion?
A
- prostaglandins E2 and I2
- somatostatin
12
Q
annotate this image to add stimulatory and inhibitory signals
A
13
Q
what is dyspepsia? state some conditions that are included under this umbrella term
A
- a group of symptoms that arise from the upper GIT, such as heartburn, abdominal pain or discomfort, fullness, bloating, early satiety, belching and nausea
non-ulcer dyspepsia
GORD
gastritis
peptic ulcer disease
Zollinger-Ellison syndrome
14
Q
what is GORD?
A
stomach acid continuously refluxes into the oesophagus causing pain, heartburn and inflammation
15
Q
what is GORD caused and exacerbated by?
A
- increased intra-abdominal pressure (obesity, pregnancy, big meals, tight clothing)
- reduced lower oesophageal sphincter tone
16
Q
what may cause reduced lower oesophageal sphincter tone?
A
hiatus hernia
tricyclic antidepressants
opioids
calcium channel blockers
anticholinergic drugs
17
Q
what is gastritis?
A
inflammation of the gastric mucosa
18
Q
causes of gastritis
A
- alcohol
- smoking
- prolonged use of NSAIDs
- infection (H. pylori)
19
Q
what is peptic ulcer disease?
A
a lesion extending through the mucosa and submucosa into deeper structures of the wall of the GIT
20
Q
describe gastric ulcers
A
- commonly found on the lesser curvature between the corpus and antrum of the stomach
- breakdown of the mucosal barrier (mucus and HCO3-)
- due to increased secretions of protons or pepsin
21
Q
describe duodenal ulcer including where they develop and the main causes
A
- most common ulcers
- develop in the first part of the small intestine
main causes:
- Helicobacter pylori
- NSAID therapy
22
Q
what percentage of both gastric and duodenal ulcers are cause by H. pylori infection?
A
70% gastric
90% duodenal
23
Q
how does NSAID therapy cause duodenal ulcer formation?
A
interference with the synthesis of cytoprotective prostanoids via COX1 inhibition
24
Q
what is Zollinger-Ellison syndrome? describe the ulcers and symptoms
A
- rare condition caused by gastrin-secreting pancreatic adenomas (tumour) that lead to multiple ulcers in the stomach and duodenum (sometimes called gastrinoma)
- ulcers are frequently drug resistant and are accompanied by diarrhoea and steatorrhea and usual peptic ulcer symptoms
25
usual peptic ulcer symptoms
burning abdominal discomfort
heartburn
nausea
vomiting
weight loss
26
2 main goals of treatments for dyspepsia?
- symptomatic relief
- cure
27
describe symptomatic relief treatment of dyspepsia
lifestyle changes
- avoidance of causative drugs
- avoidance of causative foods
- smoking cessation
- GORD: propping up bed, removing belts
neutralising acid
suppression of acid release or activity
mucosal protection
28
describe treatments to cure dyspepsia
- suppression of acid release to allow natural healing
- eradication of H. pylori infection (reduces the chance of developing gastric carcinomas, as H. pylori is regarded as a carcinogen)
29
what is an antacid?
weak bases able to partially neutralise gastric acid and inhibit pepsin activity both directly and by increasing pH, thus protecting the stomach mucosa
30
what are the 2 types of antacids?
systemic
non-systemic
31
how do systemic antacids work?
- they are absorbed into the systemic circulation
- they have a cationic group that doesn't form insoluble basic compounds with HCO3-
- thus, the HCO3- can be absorbed producing a metabolic alkalosis
32
how do non-systemic antacids work?
- not absorbed into the systemic circulation
- their anionic group neutralises the protons in gastric acid
- this releases their cationic group which combines with HCO3- from the pancreas to form an insoluble basic compound that is excreted in faeces
33
nowadays, which kinds of antacids are relied on?
- non-systemic
- this is because they are not absorbed and won't cause any systemic issues
34
give 2 examples of non-systemic antacids
- magnesium hydroxide (milk of magnesia)
- aluminium hydroxide
35
describe magnesium hydroxide as an antacid
- non-systemic
- Mg2+ salts act as both antacids and laxative agents
- the laxative effect is lessened by concomitant use with calcium carbonate or aluminium hydroxide
36
describe aluminium hydroxide as an antacid
- non-systemic
- reacts with HCl to form aluminium chloride
- this in turn reacts with intestinal secretions to produce insoluble salts, especially phosphate
- could cause constipation, osteomalacia (by interfering with PO4 3- absorption)
37
describe sodium bicarbonate as an antacid
- systemic
- reacts with acid and relieves pain within minutes
- it is absorbed and causes a metabolic alkalosis
- it can release sufficient carbon dioxide in the stomach to cause discomfort and belching
- severe distension of the stomach by carbon dioxide gas may be dangerous if a gastric ulcer that could perforate is present
38
describe calcium carbonate as an antacid
- systemic
- acts by neutralising HCl in gastric secretions
- also inhibits the action of pepsin by increasing the pH and via adsorption
- cytoprotective effects may occur through increases in bicarbonate ion and prostaglandins
- neutralisation of hydrochloric acid results in the formation of calcium chloride, carbon dioxide and water
39
how does alginic acid work?
- by forming a protective layer that floats on top of the contents of your stomach
- this stops stomach acid escaping up into your food pipe
- forms a sort of raft which covers lining of stomach and oesophagus so it protects the irritated area to allow if to heal and recover
40
what do all proprietary preparations have combined within them?
an antacid
alginic acid
41
state 4 examples of proton pump inhibitors
omeprazole
esomeprazole
lansoprazole
pantoprazole
42
despite the half-life of weak, lipophilic bases being about 1 hour, how long does a single daily dose affect acid secretion for?
- 2-3 days
- they protonate proton pump and inhibit it
- parietal cell must synthesise new proton pump which takes a while as it is a protein
43
describe the characteristics of proton pump inhibitors and what do they do?
- weak, lipophilic bases
- diffuse into the parietal cell canaliculi
- here they become protonated and concentrated more than 1000-fold
- here they undergo conversion to compounds that irreversibly inactivate the parietal cell H+/K+ ATPase
44
adverse effects of PPIs
- headache
- diarrhoea
- rashes
45
what is acid-suppression with PPIs associated with?
- increased risk of Clostridium difficile diarrhoea due to alteration of gut microbiota
- particularly in patients who are immunosuppressed or have been receiving antibiotics
46
what may PPIs decrease in relation to vitamins and certain drugs?
- oral bio-availability of vitamin B12 and certain drugs that require acidity for their GI absorption
- eg. digoxin, ketoconazole
47
who should PPIs be used in with caution?
- patients with liver disease
- women who are pregnant or breastfeeding
48
simply describe what histamine H2 antagonists are and their effect
pharmacological blockade of histamine H2 receptors (reduced cAMP)
49
what are the 4 histamine H2 receptor antagonists that are available OTC?
cimetidine (the prototype)
ranitidine
famotidine
nizatidine
50
effects of histamine H2 antagonists on duodenal ulcers
- reduce nocturnal acid secretion
- accelerate healing
- prevent recurrences
51
effects of histamine H2 antagonists on gastric ulcers
- effective in accelerating healing
- effective in preventing recurrences
52
what are intravenous H2 blockers useful for?
preventing gastric erosions and haemorrhage in intensive care units
53
describe cimetidine as an H2 antagonist
- potent inhibitor of CYP450 hepatic drug-metabolising enzymes
- therefore it inhibits the metabolism of other drugs (oral anti-coagulants)
54
what is the most effective treatment for ulcers caused by H. pylori infection?
- eradication
- most effective treatment for long term cure of ulcers with low relapse rates
55
what is included in 'triple therapy'?
2 of the 3 antibiotics below:
- clarithromycin
- amoxicillin
- metronidazole
plus a PPI and / or H2 antagonist
56
what time course of treatment is used in triple therapy?
- triple therapy for 1 week
- then PPI alone
57
what is triple therapy used to do?
eradicate H. pylori
58
describe quadruple therapy: what is included and describe its effectiveness
- bismuth sub citrate potassium
- metronidazole
- tetracycline
- omeprazole
- very effective, especially when there is antibiotic resistance
59
what kinds of drugs are associated with peptic damage / ulceration?
- commonly NSAIDs
- less commonly corticosteroids
60
state 4 NSAIDs
aspirin
ibuprofen
diclofenac
naproxen
61
describe how NSAIDs affect prostaglandins and the overall effect of this
- prostaglandins can inhibit gastric acid secretion
- NSAIDs can block prostaglandins
- overall, NSAIDs cause increased gastric acid secretion
62
how can GI damage by NSAIDs by minimised?
- prophylaxis with PPI
- give in combination with misopristol (a stable PGE1 analogue)
- don't prescribe NSAID is the patient has an active ulcer
- H2 antagonists less or ineffective (famotidine has been shown to be effective)
63
why is 'take with food' probably an ineffective piece of advice for minimising GI damage by NSAIDs?
- painkillers will induce ulcer systemically by stimulating prostaglandins
- even topical applications can be bad for ulcers
- food does not limit the chance of inducing a peptic ulcer in these patients
64
what does misopristol mimic? what is it prescribed to do?
- mimics endogenous prostaglandin
- prescribed to limit prevalence of inducing peptic ulcer in individuals
