Clinical Pharmacology of Alimentary Flashcards
What are the drugs of the alimentary system for?
Acid suppression
Drugs affecting GI motility
Laxitives
Drugs for inflammatory bowel disease
Drugs affecting intestinal secretions
What are the ways to reduce acidity?
Antacids
Alginates
H2 receptor antagonists
Proton pump inhibitors
What do antacids contain?
Magnesium or aluminium - neutralises gastric acid
Taken when symptoms occur
Give an example of an antacid
Example: Maalox
How do alginates work?
–Form a viscous gel that floats on stomach contents and reduces reflux
Give an example of an alginate
Gaviscon
What does the H2 receptor antagonist block?
The effects of histamine: Increases the rate of the hydrogen potassium carrier
Give an example of a H2 receptor antagonist and when you would use it
Ranitidine
Indicated in GORD/Peptic Ulcer disease
What are the routes of administration for ranitidine?
Orally or intravenously
Name a proton pump inhibitor
Omeprazole
How do proton pump inhibitors reduce acid secretion?
Block the proton pump
When are proton pump inhibitors indicated?
–GORD/peptic ulcer disease
–Triple therapy for treatment of PU/DU associated with H pylori
What is the route of administration for omeprazole?
Oral or IV
What is the effect of prokinetics?
Increase gut motility and gastric emptying
What is the effect of an anti-emitic drug?
Effective against vomiting and nausea
What are Prokinetics used for?
Gastroparesis
GORD?
Give examples of prokinetic agents
Metoclopramide
Domperidone
What is the mechanism of prokinetics?
•Mechanism of action is not clear but involves parasympathetic nervous system control of smooth muscle and sphincter tone (via ACh)
What is the action of domperidone?
Probably acts by blocking dopamine receptors which inhibit post-synaptic cholinergic neurones
What is the purpose of drugs which decrease motility?
Anti- diarrhoea
Can cause constipation
Give examples of drugs which decrease GI motility
Loperamide (immodium) and Opioids
What is the mechanism of action in drugs which decrease motility?
•Mechanism of action is via opiate receptors in GI tract to decrease ACh release
Reduced smooth muscle contraction
Increased anal sphincter tone
What are antispasmotics used for?
Reduce symptoms of IBS, renal colic
Define what is meant by colic pain
Starts and stops abruptly
What are the three mechanisms of anti-spasmodics
–Anti-cholinergic muscarinic antagonists (hyoscine buscopan, mebeverine)
•inhibit smooth muscle constriction in the gut wall, producing muscle relaxation and reduction spasm.
–Direct smooth muscle relaxants
–Calcium-channel blockers (peppermint oil) reduce calcium required for smooth muscle contraction
What are the 4 types of laxitives?
How do they work?
–Bulk (e.g. Isphagula)
–Osmotic (e.g. Lactulose)
–Stimulant (e.g. Senna)
–Softeners (e.g. Arachis oil)
–Work by increasing bulk or drawing fluid into gut
What is the route of administration for laxitives?
Oral or rectal
What is the prerequisite for osmotic laxitives?
Water, they will ont work without adequate fluid intake
What are the drugs for IBD?
Aminosalicylates
Corticosteroids
Immunosuppressants
Biologics
Give an example of an aminosalicylate
Mesalazine, Olsalazine
What is the method of action of aminosalicylates?
Anti - inflammatory
What is the route of admission of aminosalicylates?
Oral
Rectal
What are the adverse effects of aminosalicylates?
GI upset, blood dyscrasias, renal impairment
What are the effects of corticosteroids on IBD?
Anti - inflammatory
What are the long term effects of steroids?
Osteoporosis
Cushingoid features including weight gain
Increased susceptibility to infection
Addisonian crisis with abrupt withdrawal
What is the effect of immuno suppressants on IBD?
–Prevents the formation of purines required for DNA synthesis so reduces immune cell proliferation
Name an immunosuppressant drug
Azathioprine
What are the adverse effects of immunosuppressants?
–Adverse effects mainly relate to bone marrow suppression but also azathioprine hypersensitivity and organ damage (lung, liver, pancreatitis)
–Numerous drug interactions
What is the mechanism of action for bioloics in inflammatory bowel disease?
Prevents action of TNF alpha - major cytokine in inflammatory response
Give an example of a biologic agent
Infliximab
What other conditions are biologic agents used for?
Psoriasis, Rheumatoid Arthritis
What are the cautions / contraindications for infliximab?
–Current TB or other serious infection
–Multiple sclerosis
–Pregnancy/breast feeding
What are the adverse effects of infliximab?
–Risk of infection, particularly TB so all patients should be screened
–Infusion reaction (fever, itch)
–Anaemia, thrombocytopenia, neutropenia
–?Demyelination
–Malignancy
What is the effect of cholestyramine?
Reduces bile salts by binding with them in the gut and then excreting as insoluble complexe
What is ursodeoxycholic acid used for?
To treat gallstones and primary biliary cirrhosis
What is the mechanism of action of ursodeoxycholic acid?
–Inhibits an enzyme involved in the formation of cholesterol, altering the amount of cholesterol in bile and slowly dissolving non-calcified stones
What is the action of drugs affected in the case of GI or liver disease
Can affect the processes of drug:
–Absorption,
–Distribution,
–Metabolism
–Excretion
GI symptoms may also necessitate a change in route of administration
Why might absorption be affected?
Change in pH
Change in gut length
Change in transit time (Digoxin, warfarin)
Why might distribution be affected?
–Low albumin (decreased binding and increased free drug concentration)
•e.g. Phenytoin
Why might metabolism be affected?
–Liver enzymes (variability in effects but generally toxicity)
–Increased gut bacteria (metabolise drugs so increased dose needed)
–Gut wall metabolism (disease may reduce first pass metabolism)
•e.g. Morphine
–Liver blood flow (drugs with a high extraction ratio)
What are GI adverse effects?
Diarrhoea / constipation (–25% of drug-induced diarrhoea is due to antimicrobials)
GI Bleed / Ulceration - Low dose aspirin is the most common cause, warfarin is the third most common cause (newer agent to warfarin is called NOAC’s - lower incidence of intracranial haemorrhage)
Warfarin is used to treat DVT and PE
Changes to gut bacteria - antibiotics, reduced vitamin K absorption (increased prothrombin time), c.Diff overgrowth
Type A adverse reaction - intrinsic hepatotoxicity (predictable - dose related)
Tybe B adverse reaction - as a result of drug / active metabolite, asymptomatic increase in LFT’s, liver failure, hepatitis, cholestasis, may mimic any pattern of acute or chronic liver disease
Why is the oral contraceptive affected by antibiotics?
Relies on metablism and recirculation by gut bacteria – antibiotic stops the circulation and metabolism of the drug
When should you take care when prescribing with the context of liver disease?
care with / avoidance of
–Drugs which can be toxic due to changes in pharmacokinetics
–Drugs which are hepatotoxic (azathioprine, methotrexate) (statins?)
–Drugs which may worsen the non-liver aspects of liver disease (e.g. encephalopathy) (benzodiazapines)
What is the risk attached to warfarin / anticoagulants?
–In liver disease, clotting factors are already low
What is the risk attached to using Aspirin / NSAIDS?
–Can increase bleeding time, in combination with deficiency in clotting factors;
–NSAIDs can worsen ascites due to fluid retention
What is the risk assoicated with opiates / benzodiazepines?
–May precipitate encephalopathy by increasing sedation
