Lecture 13: Pharmacology of Upper and Lower GIT Drug Treatment Flashcards
what is dyspepsia
indigestion e.g. heartburn, bloating, gas etc
what is dysphagia
difficulty swallowing
what is the target cell for drugs treating gastric inflammation/ulceration
parietal cell
describe the physiological control of acid secretion in the GIT
vagal nerve (parasympathetic system) –> acetylcholine –> +ve signal promoting acid secretion by H+/K+ ATPase dependent (proton) pump
- histamine also stimulates acid signal through H2 receptor
- gastrin responds to dietary intake signalling gastric acid secretion
name the 3 main influencers promoting gastric acid secretion via the proton pump
- acetylcholine
- gastrin
- histamine
what hormone has a negative signal to acid secretion
- prostaglandin 2 (PGE2)
what is a peptic ulcer
defect in the gastric or duodenal mucosa due to imbalance in the peptic acid secretion and gastroduodenal mucosal defence
which patient suffering from peptic ulcer requires investigation
those at increased risk of gastric carcinoma
especially older patients
why is it important to investigate patients at increased risk of gastric carcinoma before PUD therapy
treatment may mask early symptoms of the gastric carcinoma
- pain could be that of could be stomach cancer
what type of pain is more typical of a peptic ulcer
epigastric pain
- sometimes no pain experienced in duodenal
what is the first step in PUD treatment
remove the irritants
- especially NSAIDs
- helicobacter pylori if present
name some of the treatment options for PUD
- antacids
- proton pump inhibitor
- H2 receptor antagonist
- antibiotics
how do NSAIDs affect prostaglandin production
inhibitory effect on prostaglandin formation enzymes COX 1 and COX 2
how does COX 1 affect acid secretion
- COX 1 –> PGE2 prostaglandin signal to reduce acid secretion
what other drugs are aetiological factors in PUD
- aspirin/corticosteroids
- bisphosphonates
- nicotine
- alcohol
- caffeine
how do antacids produce symptomatic relief in PUD
alkali based (Al and Mg) salts that raise gastric pH and reduce proteolytic activity
why are aluminium and magnesium salt antacids most commonly used for PUD treatment
- they aren’t as easily absorbed so not as likely to affect blood pH
why is sodium bicarbonate typically not used as an antacid
it is easily absorbed into the blood which affects blood pH and can cause…
- metabolic alkalosis
- Na and H2O retention
- renal stone formation
why is antacid use limited (not long term)
parietal cells will continue to secrete HCl acid so imbalance between acid over-production and irritation of stomach lining continues after alkali has been absorbed
how can you typically recognise proton pump inhibitors
names end with -prazole/-azole e.g. omeprazole
CAUTION -prazole ending can be used for a wide range of drug types
MoA of proton pump inhibitor
inhibits K+/H+ ATPase pump of parietal cell
MoA of proton pump inhibitor
inhibits K+/H+ ATPase pump of parietal cell –> irreversible
omeprazole MoA
targeted irreversible proton pump inhibitor
- irreversible –> will last a bit longer (until parietal cell replaced)
- very effective and well tolerated by patients
clinical indications of omeprazole
- dyspepsia
- PUD
- reflux oesophagitis (GORD)
common ADRs of PPI
- GI disturbance
- headache
important ADRs of PPI
- increased risk of C. diff.
- hyponatraemia, hypomagnesaemia
- hepatitis, interstitial nephritis, blood disorders
- risk of community acquired pneumonia
- risk of developing CKD
interactions of PPI
(slight variation between diff PPIs)
- Warfarin –> weak CYP450 enz inhibitors –> increase anticoagulant effect
- clopidogrel (hepatic pro drug) –> reduce anti platelet effect
why should you not take PPIs for more than 8 weeks
rebound acid hypertension syndrome (RAHS)
how can you typically recognise H2 receptor antagonists
end in -tidine e.g. cimetidine
role of H2 receptor antagonists in PUD treatment
competitive antagonist at H2 receptor thus reducing gastric acid secretion
- reduce basal and stimulated acid output (90%)
clinical indications of cimetidine
2nd line agent for PUD and reflux oesophagitis
cimetidine ADRs
- diarrhoea
- confusion
- gynaecomastia
cimetidine interactions
potent inhibitor of cytochrome p450 dependent metabolism
- any other drugs being hepatically processed would produce side-effects
MoA for ranitidine
competitive antagonist at H2 receptor in gastric parietal cells
clinical indications for ranitidine
2nd line agent for PUD and reflux oesophagitis
ranitidine ARDs
diarrhoea
fewer than cimetidine
what type of bacteria is helicobacter pylori
gram negative bacillus
what bacteria is a common cause of ulcer disease
helicobacter pylori
what other conditions can helicobacter pylori be assc w/
- mucosa-assc lymphoid tissue (MALT) lymphoma
- gastric cancer
why is ranitidine not really used anymore
carcinogenic effects
how does helicobacter pylori cause PUD
- secretes inflammatory proteins and toxins in mucus layer
- urease producing –> urea to NH4+ and CO2- –> undermines mucosal protection system
describe the helicobacter pylori eradication regimen
- PPI (or H2RA)
- clarithromycin
- amoxicillin (or metronidazole if penicillin allergic)
- triple therapy 7 days
- if ulcer large or complicated (by haemorrhage or perforation) continue PPI (or H2RA) for 3 more weeks
- use different antibiotic if needing second treatment course
how is helicobacter pylori initially detected
- Carbon-13 urea breath test
- upper GI endoscopy with biopsy and rapid urease test
- serology (IgG) though inadequate performance so not recommended
when is an urgent upper GI endoscopy required
- acute bleeding suspected
- chronic bleeding/ Fe def anaemia
- weight loss
- dysphagia
- persistent vomiting
- unexplained, persistent dyspepsia (especially if elderly)
how is constipation most commonly treated
non-pharmalogical interventions:
- ^ fluid uptake
- improve mobility
- ^ fibre uptake (unless d/t opioids)
- stop constipating drugs
- exclude underlying pathology
causes of constipation
- drugs –> esp opioids and anti-muscarinics –> slow peristaltic movement
- local pain e.g. anal fissure, peri-anal access
- benign colorectal disease
- endocrine/metabolic e.g. hypercalcaemia, hypothyroidism
- malignancy
name some types of laxatives and MoA for each
- bulk laxatives e.g. fybogel –> binding agent for water to make stools big and easy to pass; swells and distends colon
- osmotic laxatives e.g. macrogols –> pulls water into lumen to bind with bulking agent
- faecal softener e.g. decussate –> ^ intestinal fluid secretion
- stimulant laxatives e.g. bisacodyl, Senna –> stimulate enteric NS to promote peristalsis
constipation management
- put everyone at risk (e.g. patients on opioids) on laxatives
- treat reversible causes
- adjust any constipating medication
- advise ^ dietary uptake, ^ fluid uptake, exercise
- offer oral laxatives if dietary measure ineffective
constipation management for patient with opined-induced constipation
- AVOID bulking laxatives
- use osmotic laxative AND stimulant
