Pharmacology
Gastrointestinal
Question 157 of 180
Regarding proton pump inhibitors, which of the following statements is CORRECT:
Answer:
PPIs are associated with an increased risk of gastrointestinal infection (including C. diff infection). PPIs act by inhibiting the proton pump on gastric parietal cells. Post-endoscopic treatment of severe peptic ulcer bleeding typically includes an intravenous high dose PPI which reduces risk of rebleeding and the need for surgery. PPIs are associated with an increased risk of gastric malignancy, and may mask symptoms of malignancy. Long term PPI use is associated with an increased risk of fractures thus is not protective against osteoporosis.Proton Pump Inhibitors
Pharmacology / Gastrointestinal
Last Updated: 26th March 2019
Mechanism of Action
Proton pump inhibitors act by directly inhibiting the H+/K+ ATPase (proton) pump on gastric parietal cell luminal membranes and thus inhibiting acid secretion.
Indications
Proton pump inhibitors may be indicated for:
- treatment of gastric and duodenal ulcers
- eradication of Helicobacter pylori in combination with antibacterials
- treatment of dyspepsia and GORD
- post-endoscopic treatment of severe peptic ulcer bleeding (an intravenous high dose PPI reduces risk of rebleeding and the need for surgery)
- treatment and prevention of NSAID-associated ulcers
- cystic fibrosis (reduces degradation of pancreatic enzyme supplements)
- Zollinger-Ellison syndrome (controls excessive gastric acid secretion)
Cautions
Proton pump inhibitors:
- can increase the risk of fractures (particularly when used at high doses for over a year in the elderly or used in those at risk of osteoporosis)
- may increase the risk of gastrointestinal infections (including Clostridium difficile infection)
- may mask the symptoms of gastric cancer (in patients with 'alarm features', gastric malignancy should be ruled out before starting treatment)
- can cause false negative H. pylori test results (and should be stopped at least 2 weeks before testing)
Side Effects
Common side effects (usually mild and reversible) include:
- abdominal pain
- constipation
- diarrhoea
- flatulence
- headache
- nausea
- vomiting
- dizziness
- skin rashes
Possible adverse effects of long-term PPI treatment:
- Hypomagnesaemia (measurement of serum magnesium concentrations should be considered before and during prolonged treatment with a PPI, especially when used with other drugs that cause hypomagnesaemia or with digoxin)
- Rebound acid hypersecretion and protracted dyspepsia after stopping prolonged treatment
- Interstitial nephritis
- Vitamin B12 deficiency
Administration
Omeprazole:
- H. pylori eradication regimen dose: 20 mg od
- Healing peptic ulcer: 20 mg od (40 mg od may be used in severe or recurrent cases)
- Healing NSAID-associated ulcer: 20 mg od
- Prophylaxis for NSAID-associated ulcer: 20 mg od
- Major peptic ulcer bleeding (following endoscopic treatment): Initially 80 mg, to be given over 40–60 minutes, then (by continuous intravenous infusion) 8 mg/hour for 72 hours, subsequent dose then changed to oral therapy
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
