Clinical Pharmacology of Alimentary System Flashcards
3 targets for gastric acid suppression drugs?
H2 (histamine) receptors on gastric cell membranes (H2 antagonists)
Proton pump (PPI)
H+ in the stomach lumen (antacids)
How do antacids suppress gastric acid?
Contain Mg or Al to neutralize gastric acid
taken when symptoms occur
How do alginates work? Example drug?
They form a viscous gel that floats on stomach contents and prevents reflux
Eg. Gaviscon
How do H2 receptor antagonists work? When are they indicated? Admission route?
Block histamine receptors in parietal cells, reduce acid secretion
Indicated in GORD/peptic ulcer disease
Oral/IV
When are proton pump inhibitors indicated? Route of administration?
Example?
Indicated in GORD/peptic ulcer disease
Oral/IV
Omeprazole
Common issues with PPI’s?
GI upset
c. difficile infection
Hypomagnesaemia
B12 deficiency
What do prokinetic agents do for gut motility? When are they indicated?
Increase gut motility and gastric emptying
Gastroparesis (can’t empty stomach)
GORD
Anti-emetics (anti-vomiting)
What is the mechanism by which drugs decreasing GI motility work? Drug example?
Act on opiate receptors in the GI tract to reduce ACh release
Loperamide (immodium)
What effect do anti-spasmodics have on GI motility?
Relax the smooth muscle in the gut wall - reduces symptoms due to IBS
How do laxatives work?
Route of administration?
Increase faecal bulk or draw fluid into the gut
Route of administration can depend on what’s causing the constipation - either oral or rectal
What are aminosalicylates used to treat? What is their action?
Examples?
Used to treat IBD
Anti-inflammatory action
Mesalazine, olsalazine
route of administration for aminosalicylates? Contraindications?
Oral or rectal
Salicylate allergy
Renal impairment
When are corticosteroids indicated?
Route of administration?
Concerns/contraindications?
Indicated in IBD - anti-inflammatory effect
Orally, IV or rectally
Osteoporosis,
cushings features
May become susceptible to infection
Addisonian crisis with abrupt withdrawal
Main immunosuppressant drug for IBD? Mechanism?
Azathioprine
Prevents purine formation required for DNA synthesis - reduces immune cell proliferation
Concerns/contraindications for azathioprine?
Bone marrow suppression
Azathioprine hypersensitivity
Organ damage (lung, liver, pancreas)
How do biologics treat IBD?
Examples?
They are largely antibodies to cytokines involved in the inflammatory response - stop inflammation
Infliximab
Certolizumab, adalimumab etc.
Which cytokine is infliximab an antibody to? How was infliximab made?
The TNF alpha cytokine
Infliximab is a mouse-human chimera
Cautions/Contraindications for infliximab?
Adverse effects?
Current TB/other serious infection
MS
Pregnancy/breast feeding
Adverse effects: Infection risk, infusion reaction (fever, itch) Anaemia Demyelination (can cause MS) Malignancy
Drug classes used to treat IBD?
Biologics
Aminosalicylates
Immunosuppressants
Corticosteroids
What does cholestyramine treat? Mechanism?
Treats pruritis from biliary cause
Binds bile salts in the gut and then excretes as an insoluble complex
What does Ursodeoxycholic acid treat? Mechanism?
Gallstones and primary biliary cirrhosis (PBC)
Inhibits enzyme involved in cholesterol formation - altering the amount in bile and slowly dissolving non-calcified stones
What drug properties can be affected by GI or liver disease?
Absorption
Distribution
Metabolism
Excretion
How can liver disease affect drug distribution?
Low albumin results in decreased binding and higher free drug concentration
How can liver disease affect drug metabolism?
Fewer liver enzymes - less detoxification
How can liver disease affect drug excretion?
Less excretion if hepatobiliary disease - more toxicity
What is the major consequence of NSAID abuse?
Mucosal injury and bleeding
Via prostaglandins (?)
What can drug induced liver injury do to the gut?
Change the bacterial flora - reduced vitamin K absorption & overgrowth of pathogenic bacteria
How do we classify the severity of liver disease?
Child - Pugh classification
< 7 - A
7-9 - B
>9 - C
Which drugs should be prescribed with care to patients with liver disease?
Drugs which may become toxic due to changes in
- Liver metabolism
- Biliary excretion
&
- Drugs that are hepatotoxic
- Drugs that may worsen non-liver aspects of liver disease (encephalopathy)
Particular drugs to be cautious of in liver diseased patients?
- Warfarin/anti-coagulants (clotting factors already low in liver disease)
- Aspirin/NSAIDS (can increase bleeding time/worsen ascites)
- Opiates/benzodiazepines (precipitate encephalopathy)
