Clinical Pharmacology of the Alimentary System Flashcards
What is the most common symptom of malignancy in terms of altered bowel habit?
Diarrhoea
What are the main drug classes used in treatment of alimentary disease?
Acid suppressing Drugs affecting GI motility Laxatives Drugs for IBD Drugs affecting intestinal secretions
Give an example of a drug used for acid suppression in alimentary disease
Antacids
H2 receptor antagonists
Proton pump inhibitors
give an example of a drug used to affect GI motility in alimentary disease
Anti-emetics
Anti-muscarinics/anti-spasmodics
Anti-motility drugs
Give an example of a drug type used for IBD
Aminosalicylates
Corticosteroids
Immunosuppressants
Biologics
What do antacids contain that neutralises gastric acid?
Magnesium or aluminium
How do alginates help acid reflux?
They form a viscous gel which floats on the stomach contents and reduces reflux
What do H2 receptor antagonists block?
Histamine receptors
In what diseases are H2 receptor antagonists indicated?
GORD
Peptic ulcer disease
How can H2 receptor antagonists be administered?
Orally or intravenously
In what diseases are proton pump inhibitors indicated?
GORD
Peptic ulcer disease
How can proton pump inhibitors be administered?
Orally or intravenously
When would triple therapy including a proton pump inhibitor be indicated?
For treatment of peptic or duodenal ulcers associated with H. pylori
Proton pump inhibitors can cause a predisposition to what?
Clostridium difficile infection
Hypomagenesaemia
B12 deficiency
What do prokinetic agents increase?
Gut motility and gastric emptying
When would prokinetic agents be indicated?
GORD
Gastroparesis
(constipation)
Give an example of a prokinetic agent
Anti-emetics
Laxatives
e.g Metoclopramide, Domperidone
Give an example of a drug which can be used to treat diarrhoea i.e. which decrease motility
Loperamide
Opiates
What is the mechanism of action of drugs which decrease gut motility?
Via opiate receptors in the GI tract to decrease ACh release and smooth muscle contraction and increase anal sphincter tone
What are the mechanisms of action of anti-spasmodics?
Anti-cholinergic muscarinic antagonists
Direct smooth muscle relaxants
Calcium channel blockers
How do anti-cholinergic muscarinic antagonists work?
Inhibit smooth muscle contraction in the gut wall, producing muscle relaxation and reducing spasm
Give the different types of laxative and an example of each
Bulk - Isphagula
Osmotic - Lactulose
Stimulant - Senna
Softeners - Arachis oil
How do laxatives work?
By increasing the bulk of fluid drawn into the gut
What cause of constipation do you need to rule out before prescribing laxatives?
Obstruction - giving laxatives when constipation is due to obstruction could cause rupture, megacolon etc.
Give an example of an aminosalicylate
Mesalazine
Olzalazine
Sulfasalazine
Aminosalicylates are first line treatment in
inflammatory bowel disease
Where are aminosalicylates metabolised?
In the liver
When should aminosalicylates be avoided?
If the patient is allergic to salicylates
How can corticosteroids be administered?
Orally
Intravenously
Rectally
Give an adverse effect of corticosteroids
Diabetes Osteoporosis Hypertension Cushing's disease Increased risk of infection
If a patient on corticosteroids becomes acutely unwell, should you withdraw or increase their corticosteroid dose?
Increase (double)
How do immunosuppressants work?
Prevent formation of purines which are required for DNA synthesis, so reduces immune cell proliferation
Adverse effects of immunosuppressants mainly relate to
bone marrow suppression
How to biologics work?
Prevent action of TNF-alpha which is a key cytokine in inflammatory response
What are the contra-indications for immunosuppressant use?
Current TB, or other serious infection
Multiple sclerosis
Pregnancy or breast feeding
Give an adverse effect of immunosuppressants
Increased risk of infection, particularly TB
Infusion reaction causing fever and itch
Anaemia
Thrombocytopenia
Neutropenia
Malignancy
Give an example of a drug affecting biliary secretion
Cholestyramine
Ursodeoxycholic acid
How does cholestyramine work?
Reduces bile salts by binding with them in the gut and then excreting them as an insoluble complex
Other than bile salts, what might cholestyramine affect?
Absorption of other drugs (should be taken separately)
Fat soluble vitamin absorption
Ursodeoxycholic acid is used to treat
gallstones and primary biliary cirrhosis
Gastrointestinal or liver disease can affect the processes of drug;
Absorption
Distribution
Metabolism
Excretion
Drug absorption is affected by
pH
gut length
transit time
The rate of drug absorption in GI/liver disease is more affected than
the total drug absorption
Drug distribution can be affected by
low albumin levels
Drug metabolism is affected by;
liver enzyme concentration
gut wall metabolism
What percentage of adverse drug reactions does GI upset account for?
20-40%
What drugs are commonly responsible for diarrhoea/constipation?
Cholinergics NSAIDs Antimicrobials Opiates Anticholinergics Opiates
Give an example of a mechanism affected by drugs causing diarrhoea/constipation
Osmotic
Secretory
Transit time
Protein absorption
25% of drug induced diarrhoea is due to
antimicrobials
GI bleeding/ulceration accounts for what percentage of hospital admissions due to adverse drug reactions?
6.5%
What drugs, taken by a high percentage of the elderly population, are common causes of GI bleeding/ulceration?
Low dose aspirin
NSAIDs
Warfarin
Changes to gut bacteria is mainly due to
antibiotics
Give an adverse effect of changes in gut bacteria due to antibiotics
Loss of OCP activity
Reduced vitamin K absorption
Overgrowth of pathogenic bacteria
What are the features of intrinsic hepatotoxicity (type A ADR)?
Predictable
Dose dependent
Acute
e.g. paracetamol overdose
What are the features of idiosyncratic hepatotoxicity (type B ADR)?
Unpredictable
Not dose dependent
Can occur at any time
May be part of a hypersensitivity reaction
Can be due to the drug itself or an active metabolite
What are the most common types of drug induced liver injury?
Hepatitis
Cholestasis
What are the risk factors for drug induced liver injury?
Age Female Alcohol consumption Genetic Malnourishment
When prescribing for a patient with liver disease, what needs to be considered?
Risk factors of drug induced liver injury
Severity of liver disease
What classification can be used to assess the severity of liver disease in a patient?
Child-Pugh classification
The Child-Pugh score separates liver disease into what three classifications, and which has the worst prognosis?
A - score < 7
B - score 7-9
C - score > 9
C has the worst prognosis
In prescribing for a patient with liver disease, care should be taken to avoid drugs which;
Can be toxic due to changes in pharmacokinetics
Are hepatotoxic
May worsen non-liver aspects of disease e.g. ascites
Drugs prescribed to patients with liver disease should have what kind of therapeutic index?
Wide therapeutic index
Give an example of a drug which should be avoided in patients with liver disease
Methotrexate
Azathioprine
Bensodiazepines
Caution should be taken when prescribing what kind of drugs to patients with liver disease?
Warfarin/anticoagulants Aspirin NSAIDs Opiates Benzodiazepines
When can you find information about risks with specific drugs in liver disease?
British National Formulary (BNF)
