Lecture 19 – GI Pharmacology Flashcards
1
Q
peptic ulceration involves
A
gastric and uodenal ulcers
2
Q
symptoms of peptic ulcerations are not
A
a reliable guide to ulcer location e.g. epigastric pain
3
Q
chronic ulcers cna be
A
asymptomatic
4
Q
adverse events of peptic ulceration
A
- Bleeding, perforation, scarring and possible obstruction
5
Q
acid and peptic ulceration
A
- Acid essential for ulceration and inability of normal [acid] to inhibit further acid is a significant factor
6
Q
risk factors of peptic ulcers
A
- Early gastric emptying also risk factor
- Helicobacter pylori is a major risk factor
- NSAIDs most common cause after H. pylori
Smoking and alcohol delay healing
7
Q
How is acid produced by parietal cells
A
- Apical membrane has H+/K ATPase pump, K+ and Cl- pumps
- On the basal membranes HCO3-/Cl- antiport
- Carbonic anhydrase produces H2CO3 from water and carbon dioxide
- This dissociates to form HCO3- and H+
- H+ is pumped out of the cell on the apical membrane in exchange for potassium which comes into the cell
- Potassium conc of the lumen is replenished by the K+ transporter
- The chloride channel allows Cl- to move out of the cell into the lumen and combine with H+ à HCL
- Meanwhile the Cl- conc of the cell is maintained by the HCO3-/Cl- antiport on the basal membrane
- Influx of HCO3- into bloodstream= ALKALINE TIDE
8
Q
drugs used to treat peptic ulceration
A
- Alginates and antacids
- PPIs
- H2 receptor antagonists
- aminosalicylates
9
Q
name a drug undee the class Alginates and antacids
A
gaviscon
10
Q
gaviscon is a compound of
A
- Alginic acid (sodium alginate) +
- Antacid (aluminium hydroxide/magnesium carbonate)
11
Q
alginates and antacids (gaviscon) Uses
A
Protect the oesophageal mucosa from acid reflux
12
Q
Mode of action of gaviscon
A
- Antacids- buffer stomach acid
- Alginic acid (seaweeds)- increase stomach content viscosity and reduce reflux
13
Q
Adverse drug response of gaviscon
A
- Magnesium salts can cause diarrhoea
- Aluminium salts can cause constipation
14
Q
Contraindication gaviscon
A
- Na+ and K+ containing preparations should be used with caution in renal failure
- High [sucrose] in some preparations- hyperglycaemia in DM
15
Q
Drug-drug interactions gaviscon
A
- Can reduce absorption of many drugs so doses should be separated
- Increased urine alkalinity can increase aspirin excretion
16
Q
name 2 proton pump inhibitors
A
- Lansoprazole
- Omeprazole
17
Q
uses of PPis
A
Uses (often prescribed alongside long term NSAID or steroid)
- Relive acid reflux symptoms and GERD
- Duodenal or stomach ulcers
- Treat damage to lower oesophagus caused by acid reflux
18
Q
Mode of action of PPis
A
- Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
- Final stage in pathway therefore very significant reduction in acid secretion
19
Q
Adverse drug response PPIs
A
- GI disturbances- abdominal pain, constipation, diarrhoea
- Headache, dizziness
- Drowsiness/confusion
20
Q
Contraindication PPIs
A
- BEWARE: can mask symptoms of gastro-oesophageal cancer
- Osteoporosis – fracture risk
21
Q
Drug-drug interactions
A
- Omeprazole is CYP inhibitor- reduced clopidogrel action
- PPIs can increase effects of warfarin and phenytoin- need to monitor
- Should be given shortest effective duration at lowest effective dose
22
Q
name a h2 receptor antagonist
A
ranitidine
23
Q
Uses of ranitidine (H2 receptor antagonist)
A
- Indigestion
- Heart burn
- Acid reflux
- Protect the oesophageal mucosa from acid reflux
24
Q
Mode of action raniditine
A
- Local histamine release contributes to proton pump activation
- H2 receptor antagonists inhibit H2 receptors reducing this local histamine release –> therefore only partial reducing in acid secretion
25
**Adverse drug response** ranitidine
Generally well tolerated- diarrhoea, headache
26
**Drug-drug interactions ranitidine**
***Few DDIS***
27
cureent large scale recall of most ranitidine due to
possible carcinogenic contaiminantion
- iansoprazole typically first alternative upon pt review
28
Helicobacter pylori and peptic ulceration
- major risk fact
- gram negative bacteria
- **infection**: H. pyrlori infects lower part of the stomach antrum
- **inflammation:** inflammation of gastric mucosa (gastritis)- often asymptomatic
- **ulcer:** gastric inflammation may lead to duodenal or gastric ulcer
**- complications:** bleeding ulcer and perforated ulcer
29
% of people in UK infected
10-15% (infection from childhood)
30
consider H. pylori for all pts with
* duodenal or gastric ulcers not associated with NSAID or unresponsive to lifestyle PPI and antacids
31
confirmation of H.pylori infection
* Urea breath test
* Gastric urea= C12 isotopes (99%) and C13 isotopes= 1%
* Pts ingest urea with enriched C13
* H. pyrloi should convert this to ammonia and CO2
* Can detect C13 in exhaled CO2
* Stool antigen test
* Endoscopy with biopsy
32
treatment of H pylori
* One week **triple** therapy
* PPI + two antibacterial agents
* Lansoprazole + clarithromycin + amoxicillin **OR**
* Lansoprazole + clarithromycin + *metronidazole (where allergic to amoxicillin )*
* Some evidence of local metronidazole resistance
* **Compliance with full course important for effectiveness and minimise risk of bacterial resistance**
33
name a drug under the class aminosalicylates
mesalazine (enteric coated tablet)
34
mesalazine uses
first line treatment in UC
35
**Mode of action mesalazine**
* Release of 5-aminosalsylic acid
* Topical anti-inflammatory action at the colon (enteric coated tablets limit gastric breakdown)
* Mesalazine has no role in rheumatoid arthritis (no systemic effect)
* Sulfasalazine has more side effects so used infrequently for UC but sulfa group good for rheumatoid arthritis
36
**Adverse drug response mesalazine**
* GI disturbance- nausea, dyspepsia
* Leukopenia- rare
37
**Contraindication mesalazine**
Salicylates like aspirin- similar hypersensitivity
38
**Drug-drug interactions** mesalazine
Enteric coated tablets may break down quicker in presence of PPI (because of increase pH)
