19.2 Gastrointestinal drugs Flashcards
Which first line medication is used to treat gastro-oesophageal reflux disease?
Proton pump inhibitors e.g. omperazole, lansoprazole
Give examples of drugs used to treat GORD, dyspepsia, peptic ulcers and upper gastrointestinal haemorrhages.
- Alkali alginate mixtures e.g. gaviscon
- H2 receptor antagonists e.g. ranitidine, cimetidine
- PPIs e.g. omeprazole
Describe the action of H2 receptor antagonists.
- Antagonise (block) the H2 receptor on the gastric parietal cells
- Reduces gastric acid secretion
- Less effective than PPIs
- Preferable for long term use
Do H2 receptor inhibitors interact with other drugs?
Yes, they interfere with a range of drugs.
E.g. Cimetidine interacts with warfarin, erythromycin, antifungals, carbamazepine
Give examples of proton pump inhibitors.
- Esomeprazole
- Lansoprazole
- Omperazole
- Pantoprazole
- Rabeprazole
How do H2 receptor antagonists act on the gastric parietal cells?
They block histamine 2 from binding to the H2 receptor of the parietal cell, thus preventing the production of cAMP and therefore preventing the function of the proton pump.
How do proton pump inhibitors act on gastric parietal cells?
Irreversibly inhibit the proton pump H/K-ATPase thus preventing acid secretion.
Describe the main features of PPIs.
- Prodrugs which require gastric acid for their conversion
- Good oral bioavailability
- Short plasma half life, approx.1 hour
- Duration of action is longer than 1 hour as they covalently bond causing irreversible inhibition of the proton pump - duration of acid suppression = 48 hours
Which enzymes metabolise PPIs?
- CYP2C19
- 3A4
What are the possible adverse side effects of PPIs?
- Hyponatraemia (low sodium)
- Fractures
- C.difficile infection
- Hypomagnesaemia
- Gastric cancers
- B12 deficiency
- Acute intestinal nephritis
- Pneumonia
- Cardiovascular disease
Which drug does omeprazole interact with?
Omeprazole interacts with clopidogrel, reducing its antiplatelet effects
What is H. pylori?
Helicobacter Pylori is a bacteria which infects the stomach, it is a major risk factor for peptic ulcers and stomach cancer.
How can we test for H. pylori?
- Carbon-13 urea breath test
- Stool antigen test
How is H. pylori treated?
- 7 day, twice daily course of treatment with: a PPI, amoxicillin and clarithomycin or metronidazole
- Pencillin allergy: 7-day, twice daily course of treatment with a PPI and clarithromycin and metronidazole
How should patients take PPIs?
- Prescribe the lowest effective dose for the minimum period of time
- Advise patients to take them 30-60 minutes before breakfast
- Risk of rebound hypersecretion on discontinuation for possibly 2-4 weeks after
Name 6 anti-emetics.
- Histamine-1 receptor antagonists
- Dopamine-2 receptor antagonists
- Muscarinic cholinergic receptor antagonists
- 5HT-3 receptor antagonists
- Neurokinin receptor antagonists
- Cannabinoids
Give examples of histamine-1 receptor antagonists.
- Cyclizine
- Cinnarizine
Give examples of dopamine-2 receptor antagonists.
- Metoclopramide
- Phenothiazines
Give an example of a muscarinic cholinergic receptor antagonist.
Hyoscine (anti-motion sickness)
Give an example of a 5HT-3 receptor antagonist.
Ondansetron (for severely emetogenic chemotherapy), risk of cleft lip/palate in pregnancy.
Give an example of a neurokinin receptor antagonist.
Aprepitant
Give an example of a cannabinoid.
Nabilone
What are the 3 major modes of actions for medicines used on the GI tract to manage constipation and diarrhoea?
- Laxatives and purgatives: affect fluid absorption and secretion
- Drugs that increase gastric motility: increase smooth muscle motility
- Drugs that decrease gastric motility: decrease smooth muscle motility
Non-drug management of constipation.
- Increase dietary fibre
- Adequate fluid intake
What are the main medicines used for the management of constipation?
- Bulk forming laxatives e.g. methylcellulose
- Stimulants e.g. senna, bisacodyl
- Faecal softeners
- Osmotic laxatives e.g. lactulose, macrogol, magnesium hydroxide
- Bowel cleansing for colonoscopy or bowel radiology investigation
Describe diarrhoea.
- Frequent passage of loose stools
- Increased GI motility
- Increased secretions
- Reduced absorption
What are the possible causes of diarrhoea?
- Infection e.g. norovirus, campylobacter, salmonella
- Toxins
- Drugs
- Anxiety
How is diarrhoea managed?
- Fluids and electrolyte replacement e.g. dioralyte
- Cautious use of anti-motility agents
- Possible antimicrobial treatments
What agents decrease GI motility?
- Opiates: increase tone but diminish propulsive activity, act on pyloric, ileocecal and anal sphincters e.g. codeine, loperamide
- Adsorbants: absorb toxic substances that cause infective diarrhoea e.g. Kaolin, pectin
Describe irritable bowel syndrome.
- Has no demonstratable pathology
- Could be associated with depression and anxiety
How is IBS managed?
- Anti-motility drugs for diarrhoea
- Laxatives for constipation (avoid lactulose)
- Antispasmodics and peppermint oil for pain and diarrhoea
What diseases does IBD cover?
Crohn’s disease and ulcerative colitis
Give examples of steroids used to treat IBD.
- Budesonide
- Beclometasone
Give examples of aminosalicylates used to treat IBD.
- Mesalazine
- Sulfasalazine
Give examples of drugs used to treat IBD which affect the immune response.
- Methotrexate
- Azathioprine
- Cytokine modulators: inflixamab and adalimumab
What precautions need to be taken if a patient is prescribed infliximab or adalimumab?
- Pre-treatment screening for TB
- Regular blood tests
- Patients provided with an alert card
What are the risk factors for gall stones?
- Female, especially if they have had children or are on high dose oestrogen
- Over 40
- Raised BMI
- Rapid weight loss
- Crohn’s/IBS
- Cirrhosis / Primary sclerosing cholangitis / Obstetric choletstasis
- Family history
What is cholecystitis?
Inflammation of the gall bladder, usually caused by a gallstone blocking the cystic duct. Can also be caused by a bacterial infection.
Treated with antibiotics (if caused by infection) and elective surgery.
What is biliary colic?
Pain in the abdomen as a result of obstruction in the cystic duct or common bile duct.
Managed with pethidine (an opioid).
