MP322 week 6 Flashcards
functional dyspepsia
non-ulcer dyspepsia
no or unknown underlying reason for symptoms
stomach protection (from acid)
- alkaline mucous gel
– both the protein content and alkalinity neutralise the hydrochloric acid in the immediate area of the epithelium
– the mucous forms a chemical barrier between the highly acidic contents of the lumen and cell surface - tight junctions between epithelial cells
– tight junctions between epithelial cells lining of the stomach limit the diffusion of hydrogen ions(H+) into underlying tissues - rapid turnover of epithelial cells (replacement of damaged cells every few days)
– replaced every few days by new cells arising by the division of cells within the gastric pits
gastric and duodenal cells secrete bicarbonate which aids in buffering acids that lies near the mucosa - PGE (prostaglandins of the E type) is important as it increases the production of both bicarbonate and the mucous layer
perforation of an ulcer
this sore can erode all the way through the stomach- this is called a perforated ulcer which is a surgical emergency
- with a perforated ulcer bacteria are able to leave the stomach and enter the peritoneum (this is called peritonitis), this bacterial infection can spread into the blood (causing sepsis) and cause organ failure and eventually death
the first sign of a perforated ulcer is sudden, intense, steady abdominal pain
- about 15% of patients die
ulcer formation
involves breaking down the mucosal barrier and exposing the underlying tissue to the corrosive action if acid and pepsin - not always clear what causes the initial damage to the barrier
acid is essential for ulcer formation- not always primary factor, many patients have normal or even sub-normal acid secretion rates
causes of ulcers include
H. pylori, NSAIDs, Pepsin, Smoking, Alcohol, Bile acids, Steroids, Stress, Changes in gastric mucin consistency (may be genetically determined)
- these can alter the mucosal defence by allowing back diffusion of hydrogen ions and subsequent epithelial cell injury
H.pylori
gram negative bacteria
first linked to gastritis in 1983 , since then research has shown it is major contributor to peptic ulcer disease, along with acid and pepsin
uses its flagella to burrow into the mucus (where the pH is more neutral)
also it neutralises the acid in it’d environment by producing large amounts of urease (an enzyme which breaks down urea present in the stomach) this breaks down urea into ammonia and carbon dioxide
causes inflammation of the gastric mucosa
infects the lower part of the stomach
40% of people are infected with h. pylori
increases gastrin release and thereby acid secretion
also causes direct damage to mucosa thus furthering disruption the physiological balance
95% of patients with gastric ulcer and 80% of those with duodenal ulcer have a h.pylori infection
almost all patients with duodenal ulcer and most with gastric ulcer have H. pylori infection
epithelial cells
- secrete mucous in response to irritation of epithelial lining and as a result of cholinergic stimulation
NSAIDs
impair mucosal resistance but do not alter acid secretion
prostaglandin
inhibition of endogenous prostaglandin synthesis leads to a decrease in epithelial mucus, bicarbonate secretion, mucosal blood flow, epithelial proliferation and mucous resistance to injury
protective factors
bicarbonate layer
mucous
blood flow
cell renewal
prostaglandins
phospholipids
damaging factors
acid, pepsin, bile salts, NSAIDs, H.pylori
symptoms of a peptic ulcer
abdominal discomfort, pain or nausea
pain is located in the epigastrium and usually does not radiate
pain may be described as burning, gnawing or as hunger pains
classically gastric ulcer pain is aggravated by meals, whereas that os a duodenal ulcer is relieved
symptoms of a peptic ulcer
abdominal discomfort, pain or nausea
pain is located in the epigastrium and usually does not radiate
pain may be described as burning, gnawing or as hunger pains
classically gastric ulcer pain is aggravated by meals, whereas that os a duodenal ulcer is relieved
diagnosis of a peptic ulcer
endoscopy
- only really done if over 55, signs of bleeding or pain when swallowing
can apply local treatments and take a sample (biopsy)
diagnostic testing for H. pylori
urea breath test (UBT) based on principle that h. pylori contains large amounts of the enzyme urease which converts urea to NH3 (ammonia) and co2 (carbon dioxide)
if h. pylori is present them co2 produced is absorbed the lining of the stomach into the blood- samples of breath are collected and the isotopic carbon (carbon 13) is measured
also stool antigen test (SAT)- this cannot determine if an infection is current or previous
who discovered propranolol and cimetidine
James black
the stomach
fundus
- upper part of stomach
- thin walled
- secretes mucus, pepsinogen and acid
antrum
-lower part of stomach
- thicker layer of smooth muscle
- responsible for mixing and grinding food
- glands here secrete little acid but contain endocrine cells which secrete gastrin
- also contain enterochomafin-like cells which release histamine
- contain D cells which release somatostatin
- both histamine and somatostatin regulate acid secretion
glands
- cells at opening secrete mucus
- lining walls of the glands are parietal cells ( which secrete acid and intrinsic factor ) and chef cells (which secret pepsinogen)
acid secretion
When parietal cells are activated by acetylcholine or gastrin, there is an increase in the intracellular Ca2+ concentration, which in turn stimulates acid secretion from the H+/K+ ATPase (proton pump) on the canalicular surface
in close proximity to the parietal cells are gut endocrine cells called enterochromaffin-like cells, which also have receptors for gastrin and acetylcholine, which stimulate histamine release. Histamine binds to the H2 receptor on the parietal cell, resulting in the activation of adenylyl cyclase, which increases cAMP and activates protein kinases stimulates acid secretion from the H+/K+ ATPase (proton pump). Neural (acetylcholine), endocrine (gastrin), paracrine (histamine) mediated stimulation of acid secretion
parietal cells are stimulated to secrete acid by gastrin (acting on gastrin/cck-B receptor), acetylcholine (m3 receptor) and histamine (h2 receptor)
acid is secreted across the parietal cell canalicular membrane by the h+/K+ ATPase proton pump into gastric lumen
gastrin
secreted by astral G cells into blood vessels in response to intraluminal dietary peptides
within the gastric body gastrin passes from blood vessels into submucosal tissue of fundic glands where it binds to gastrin-cck-b receptors on parietal cells and ECL cells
the vagus nerve stimulates postganglionic neurone of the enteric nervous system to release acetylcholine which binds to m3 receptors on parietal cells and ECL cells
stimulation of ECL cells by gastrin (cck receptor) or acetylcholine (m3 receptor) stimulates release of histamine
astral D cells are stimulated to release somatostatin by the rise in intraluminal h+ concentration and by cck that is released into the bloodstream by duodenal I cells in response to proteins and fats
binding of somatostatin to receptors on adjacent antral G cells inhibits further gastrin release
acid secretion in the stomach
- carbonic anhydrase produces HCO3- and H+
- HCO3- is exchanged for CL-
- CL- diffuses into lumen
- H+ is pumped into lumen by H+/K+ ATPase
- carbonic anhydrase catalyses the reaction between CO2 and H2) to produce carbonic acid
drugs for treating peptic ulcer disease
Antacids
Antisecretory agents
Raising gastric pH (above 3) for a few hours/day promotes healing
Duration of acid suppression determines the rate of healing
Rapid healing requires suppression for 18-20 hours/day
Eradication of H. pylori infection
Pharmacological treatments
histamine receptor (h2) antagonists
H2 antagonists: cimetidine, ranitidine, nizatidine, famotidine
Act competitively on H2 receptors on gastric parietal cells
Reduce basal acid secretion and prevent the increase that occurs in response to a number of secretory stimuli
Reduce acid secretion by ~60%
Can treat both duodenal and gastric ulcers; BUT relapse is common after treatment stops
adverse effects of H2 antagonists
- diarrhoea
- headache
- confusion in elderly
- gynaecomastoa (with cimetidine because of an anti-androgen effect)
-cimetidine inhibits cytochrome P450 system (potential interactions with warfarin, phenytoin and theophylline)
PPIs
PPIs: omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole
Inhibition of the pump almost completely blocks acid secretion
PPIs are irreversible
Return of acid secretion is dependent on synthesis of new enzymes (H+/K+ ATPase)
Acid secretion is inhibited by ~90% for ~24 h with a single dose
adverse effects of PPIs
Gastrointestinal upset (e.g. epigastric discomfort, nausea and vomiting, diarrhoea)
Headache
Skin rashes
Omeprazole has both stimulatory and inhibitory effects on cytochrome P450 system
Long-term use may cause gastric atrophy (or stomach cancer-possibly)
eradication of H.pylori infection
patients with peptic ulcer disease and positive test for h.pylori
triple therapy- PPI, amoxicillin and clarythromycin or metronidazole
- if penicillin allergic give both clarythromycin and metronidazole with PPI
twice daily for 7 days
cytoproctective agents
Prostaglandin analogue: misoprostol
Methyl analogue of prostaglandin E1
Enhanced duodenal bicarbonate secretion
Weak inhibition of gastric acid secretion, through activation of prostaglandin receptor on parietal cells
Increased mucosal blood flow
Must not be used during pregnancy
Zollinger- Ellison syndrome
Rare disorder that can cause gastric or duodenal ulcers (usually multiple), as well as in the jejunum
Massive gastric acid hypersecretion
Due to gastrin secreting tumour in the pancreas or duodenum (gastrinoma) that stimulates acid secretion in stomach
Patients likely to have intractable ulcer disease
Treatment must control the hypersecretion and the gastrinoma
GORD
can be called GERD too
Amount of acid secretion is normal
Functionally incompetent lower oesophageal sphincter
Allows reflux of gastric contents (containing acid and pepsin into oesophagus)
Symptoms - restrosternal burning
treatment
Antacids and antacid/alginate combinations
Drugs that inhibit gastric acid secretion (H2 receptor antagonists and proton pump inhibitors)
Drugs that act on oesophageal and/or gastric motility
barret’s oesophagus
Commonly diagnosed in patients with long-term GORD
Replacement of normal stratified squamous epithelium by columnar epithelium with goblet cells
Can lead to oesophageal adenocarcinoma (>85% mortality)
a patient comes into the pharmacy to request Peptac suspension as treatment for acid reflux symptoms. Examining the patient’s medication record (PMR) you see that they are currently prescribed omeprazole 10mg gastro/resistant capsules, one to be taken in the morning
can we give peptac?
any other qs
- yes can give peptac - however not within 2 hours of omeprazole
- how long have they been on omeprazole?- it can take a few days to work
Scenario 2- a patient comes into the pharmacy with a prescription for Arcoxia (etoricoxib) 90mg, one tablet to be taken in the morning. The doctor has chosen this medication as it is less likely to cause GI irritation than other non-steroidal anti-inflammatory drugs (NSAID). While the patient is waiting for their prescription you over hear them requesting treatment for a mouth ulcer from the medicine counter assistant.
oral ulceration if a very common side effect
if ulcer caused by this medication it will not be self limiting - needs to come off meds
is this the first prescription/ first time in a while- ulcer won’t be caused by the medication
this is a cox 2 inhibitor- meaning it doesn’t cause GI irritation but still have analgesic effect
a patient requests a supply of ibuprofen to treat epicondylitis. On examining the patient’s Patient Medication Record (PMR) you see that that they have been prescribed ranitidine 150mg tablets, one to be taken twice a day
- Epicondylitis- a painful condition that occurs when tendons in the elbow are overloaded – usually by repetitive motions ie tennis elbow
ranitadine- used for gastric ulceration and GORD
- if they have GI issues they shouldn’t use NSAIDs
should recommend a non NSAID like paracetamol for pain management
a patient requests a supply of lactulose to treat constipation. On examining the patient’s PMR you see that that they have been prescribed co-codamol 15/500 tablets, two to be taken four times a day.
- constipation is a side effect of pain killers
- ask how long she’s been taking the co-codamol and how long she has been constipated- could be completely unrelated
- safe to give lactulose- drink plenty fluids and remind them it b=may take 2-3 days to work
can you supply a CD to a doctor in an emergency without a prescription
yes
when you supply a CD to a doctor in an emergency without a prescription, how long do they have to provide a prescription
24 hours
What is the legal limit on the number of Paracetamol tablets / capsules you can you sell?
No more than 100 non effervescent tablets
No legal limit on effervescent just professional judgement, why would they need more?
What are the licensing restrictions for OTC sales of codeine and dihydrocodeine?
Short term use only (3 days), max pack size 32, can cause addiction on packaging, acute pain that is not relived by paracetamol, ibuprofen or aspirin alone
What are the different means by which you can help people who have run out of their medication in Scotland?
Unscheduled care PGD
Emergency supply
Cant give schedule 1, 2 or 3 through these- only phenobarbital (when indicated for epilepsy)
