PUD and GORD Flashcards
Describe the regulation of acid secretion
- Parietal cells secrete isotonic solution of HCl via proton pump
- pH <1
- Mediators that act directly or indirectly on control of parietal cell acid output include:
- Histamine (stimulatory local hormone)
- Gastrin (stimulatory peptide hormone)
- Acetylcholine (stimulatory neurotransmitter)
- Prostaglandins E2 and I2 (local hormones that inhibit acid secretion)
- Somatostatin (inhibitory peptide hormone)
-
Mucus-secreting cells are also found in gastric mucosa
- Bicarbonate ions are secreted and trapped in mucus ->form gel like protective barrier ->keeps pH of mucosal surface at 6-7
- Disturbances in secretory & protective mechanisms is involved in pathogenesis of:PUD and GORD
Describe the MoA of PPIs
- irreeversibly inactivate theHK ATPase system or proton pump, on parietal cells
- termainal step in acid secretory pathway (suppression is more complete than H2 receptor antagonists)
- suppressing both stimulated and basal acid secretion (regardless of stimulus - histamine, gastrin, Ach)
- when PPIs are stopped, acid secretion is restored by synthesis of new HK ATPase
PPIs are pro-drugs converted to active metabolites by acids in the canaliculus ofthe gastric parietal cell
Descrube the adverse effects of PPIs
- generally well tolerated
- serious toxicity rare but includes; anaphylaxis, hepatitisandinterstitial nephritis
- Possible increased risk (associated with prolonged therapy):
- C. difficile-associated colitis
- community-acquired pneumonia
- hip fracture (high doses > 1 y)
- decrease vitamin/mineral absorption such as B12 and Mg
Describe H2 antagonists MoA
- Competitively inhibit histamine action on H2-receptors on parietal cells
- Inhibition results in:
- Inhibition of histamine- and gastrin- stimulated acid secretions
- ↓ pepsin secretion
- ↓ volume of gastric juice
Describe adverse effcts of H2 antags
- diarrhoea
- dizziness
- muscle pains
- alopecia
- transient rashes
- confusion in the elderly
- hypergastrinaemia
- May accumulate in renal impairment
- Many available without prescription
Describe antacids
Symptomatic based relief of excessive gastric acid secretion (directly neutralise acid)
Most antacids use a combination of magnesium and aluminium salts
- Magnesium salts cause diarrhoea
- Aluminium salts cause constipation
Antacids are faster acting when given in a fasting state
Liquid and powder dosing forms tend to be more effective than tablets
Antacids can reduce the effect of a number of other medicines taken by mouth. The best way to avoid a problem is to separate taking antacids and other medicines by at least 2hours
Most available without prescription (and even in the supermarket)
Describe some examples of antacids
- MgOH
- forms magnesium chloride in stomach
- no systemic effects as Mg2+ is poorly absorbed from the gut .˙. local action
- diarrhoea
- AlOH
- Forms aluminium chloride in stomach
- Raises gastric juice pH to ~4
- constipation
- Alginates
- sometimes added to antacids
- ↑ viscosity and adherence to mucus
- forms protective barrier
- Simethicone
- sometimes added to antacids
- anti-foaming agent
- relieves bloating and flatulence
Describe mucosal protective agents
Rarely used in practice
Sucralfate: aluminium salt – forms protective barrier at ulcer site resistant to acid, bile and pepsin
Misoprostol: prostaglandin E1 (PGE1) analogue; stimulates secretion of gastric mucus and bicarbonate in the duodenum and decrease in gastric acid secretion by parietal cells
Bismuth subcitrate: no longer marketed in Australia. Forms an acid‑ and pepsin-resistant protective coating at the ulcer site; also has an antibacterial effect against_H.pylori_
List and briefly describe some medications linked with peptic ulceration
-
aspirin:
- 1 in 10 have ulcer on endoscopy (many asymptomatic)
- lower risk with lower doses, i.e. 100 mg a day ie lowering dose helps
- risk is not reduced by enteric-coated formulations ie does not help
- primary PPI prophylaxis is usually reserved for high-risk patients (see below) ie may help
- NSAIDs due to COX-1 inhibition (and to a lesser extent COX 2 inhibitors): see below
- corticosteroids: may increase the risk of peptic ulcers
Describe NSAID induced ulcers
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NSAIDs are used commonly and their complications result in a significant disease burden and healthcare costs.
- Abdominal discomfort is reported in up to 50% of NSAID users (15-30% of whom have peptic ulceration at endoscopy).
- Peptic ulcers induced by NSAIDs are often silent and may present with complications (e.g. bleeding, perforation, obstruction due to pyloric stenosis or small bowel strictures).
The risk varies within the class and is often dose-related
- All NSAIDs can cause serious GI adverse effects.
- COX-2 inhibitors are associated with a lower risk of GI complications than non-selective agents.
- COX1 inhibition inhibits COX1 gastric mucus production, reducing this protective factor
- Of the non-selective NSAIDs, ketoprofen and piroxicam (long half-life) appear to have the highest risk of GI complications while diclofenac and ibuprofen (short half-life) appear to have the lowest.
List some RFs for increased gastrointestinal toxicity with NSAID sue
- older age
- history of upper gastrointestinal bleeding or peptic ulcer disease
- _Helicobacter pylori_infection
- NSAID treatment in the presence of_H.pylori_infection significantly increases the risk of PUD (60 fold) and its complications. Conversely, the risk of bleeding is decreased if H. pylori is eradicated.
- the concomitant use of drugs that increase the risk of upper gastrointestinal bleeding or perforation (eg. anticoagulants, antiplatelet drugs, selective serotonin reuptake inhibitors [SSRIs], serotonin and noradrenaline reuptake inhibitors [SNRIs], systemic corticosteroids)
- smoking
Importantly many NSAIDs are available without prescription and some in supermarkets
dESCRIBE Prevention fo NSAID toxicity
- Minimise NSAID use by using alternative treatment options (pharmacological and non-pharmacological)
- Use lowest dose for shortest time of a short-acting NSAID (or COX-2 if suitable)
Concomitant use of a PPI can reduce ulceration and is recommended for high-risk patients
- Use a PPI with an NSAIDin those patients at highest risk of GI adverse effects, eg. the elderly, past history of PUD (especially if complicated); continue for duration of NSAID treatment. Lifestyle risk factors should also be addressed (smoking, obesity etc).
For patients with previous ulcer should be tested and treated for H. pylori
- For secondary prevention in patients with H.pylori it should be treated and ongoing PPI (if NSAID therapy required)
- For secondary prevention in patients without H. pylori use COX-2 with/without PPI
- Avoid NSAIDs ifpossible: no strategy adequately protects against ulcer recurrence
