Clinical pharmacology - Alimentary Flashcards
What things do drugs target for alimentary disease
Acid suppression
GI motility
Constipation
Which drugs act to suppress excess acid in GI system
Antacids
H2-receptor antagonists
Proton pump inhibitors
What types of drugs affect GI motility
Anti-emetics - work against vomiting and nausea
Anti-muscarinics/other anti-spasmodics
Anti-motility
Which drugs are used for inflammatory bowel disease
Aminosalicylates
Corticosteroids
Immunosuppressants
Biologics
which drugs affect intestinal secretions
Bile acid sequestrants and ursodeoxycholic acid
How does histamine contribute to acid production?
acts on parietal cells which then secrete hydrochloric acid and intrinsic factor
How does Gastrin contribute to acid production?
stimulates proton pump which in turn triggers release of gastric acid
How do antacids work? when are they taken?
Give an example
they contain magnesium or aluminium which work to neutralise gastric acid
take when symptoms occur
Maalox
How do alginates like Gaviscon work to reduce effects of stomach acid?
form a viscous gel that floats on stomach contents and reduces reflux
How do H2 receptor antagonists reduce stomach acid? how are they taken? Reasons why a patient might take these?
Block histamine receptor thereby reducing acid secretion
orally or intravenously
Indicated in GORD/Peptic ulcer disease
Proton pump inhibitors:-
- How do they work to reduce acid?
- How are they administered?
- Give an example of a commonly used PPI.
Block proton pump and thereby reduce acid secretion
Give in GORD/peptic ulcer disease - orally or IV
Omeprazole
Complications with proton pump inhibitors
Problems with GI upset and predisposition to c. difficile infection, hypomagnesaemia, B12 deficiency
How do PPIs result in vitamin B12 deficiencyt
since gastric acidity is required for vitamin B12absorption, acid suppression may lead to malabsorption and ultimatelydeficiency
What do prokinetics do ?
Prokinetic agents increase gut motility and gastric emptying
Give 2 examples of diseases that may need treated with prokinetics
gastroparesis - abnormal gastric emptying
GORD
Give 2 examples of some anti-emetic drugs
Metoclopramide - increases the movements or contractions of the stomach and intestines. Also increases the tone of the lower esophageal sphincter - GORD
Domperidone - probably acts by blocking dopamine receptors which inhibit post-synaptic cholinergic neurones
Both act on parasympathetic NS and alter control of smooth muscle and sphincter tone
Where is the vomiting centre in the brain?
in the medulla
Which drugs target the vomiting centre?
Anti-muscarinics & Anti-histamines
Motion sickness affects what part of the brainstem? and which drug targets this?
pons and medulla
anti-histamines
Sickness in response to drugs, toxins affects a place in the medulla called ____ ?
Chemoreceptor Trigger Zone
Which drugs are used to help drug/toxin induced vomiting
Dopamine antagonists
5 HT3,antagonists
Cannabinoids
Vomiting caused by radiotherapy, Gastroenteritis or some drugs is detected where?
in the pharynx and GIT which then goes to the vomiting centre in the medulla
Give 1 pro and con for anti-motility drugs?
Can prevent diarrhoea
but can also cause constipation
How do drugs that decrease motility work?
work via opiate receptors in GI tract to decrease ACh release
this in turn decreases smooth muscle contraction and increases anal sphincter tone so chyme moves slower down GI tract
Why does Loperamide (Immodium) not have many central opiate effects?
it isn’t well absorbed across the blood brain barrier so it doesn’t access the CNS
What are anti-spasmoidic used for?
to reduce symptoms due to IBS, renal colic
How do anti-spasmoidic work?
Anti-cholinergic muscarinic antagonists - inhibit smooth muscle constriction in the gut wall, producing muscle relaxation and reduction spasm.
Direct smooth muscle relaxants
Calcium-channel blockers - reduce calcium required for smooth muscle contraction
What are the 4 types of laxative? Give examples
Bulk (e.g. Isphagula)
Osmotic (e.g.
Lactulose)
Stimulant (e.g. Senna)
Softeners (e.g. Arachis oil)
they either work by increasing bulk or drawing fluid into the gut
Issues with laxatives?
Obstruction
Route of administration (Oral or Rectal)
Need for other measures - Osmotic laxatives will not work without adequate fluid intake
Misuse (weight loss)
Which drugs are used for IBD?
Aminosalicylates - anti -inflammatory
Corticosteroids
Immunosuppressants (Azathioprine)
Corticosteroids: effects? administration? contraindications?
Anti-inflammatory effects
Given orally, IV or rectally
Usual concerns and contraindications:-
Osteoporosis
Cushingoid features (excess cortisol) including weight gain, DM, HT
Increased susceptibility to infection
Addisonian crisis with abrupt withdrawal
Immunosuppressants for IBD:-
How do they work?
Prevents the formation of purines required for DNA synthesis so reduces immune cell proliferation
Adverse effects mainly relate to bone marrow suppression but also azathioprine hypersensitivity and organ damage (lung, liver, pancreatitis)
Numerous drug interactions
Specialist use and close monitoring required
What sorts of things does the drug Infliximab treat? (3)
Current TB or other serious infection
Multiple sclerosis
Pregnancy/breast feeding
Adverse affects of infliximab? (type of biologic - treats a number of autoimmune diseases)
Risk of infection, particularly TB so all patients should be screened
Infusion reaction (fever, itch)
Anaemia, thrombocytopenia, neutropenia
?Demyelination - nerve deterioration
Malignancy
Types of biologics other than infliximab
Certolizumab
Adalimumab
Natalizumab
Golimumab
Vedolizumab
Which drugs affect biliary secretion? (2)
Cholestyramine
Ursodeoxycholic Acid
How does Cholestyramine work?
Reduces bile salts by binding with them in the gut and then excreting as insoluble complex
May affect absorption of other drugs so should be taken separately
May affect fat soluble vitamin absorption so may decrease vitamin K levels (affecting clotting and warfarin)
How does Ursodeoxycholic Acid
affect biliary secretion?
Used to treat Gallstones and Primary Biliary Cirrhosis (PBC)
Inhibits an enzyme involved in the formation of cholesterol, altering amount in bile and slowly dissolving non-calcified stones
What can GI or liver disease affect in regards to drug processing?
Absorption (more so rate of absorption rather than total absorption)
Distribution
Metabolism
Excretion
What does drug absorption in the gut depend on?
pH
Gut length
Transit time
e.g. Digoxin, Warfarin
How can low albumin levels reduce drug distribution
drugs that are usually bound to protein are then free
free drug conc increases and decreased binding overall
What problems can there be with drug metabolism?
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 - the organ is capable of removing all the drug presented to it, independently of plasma binding)
liver enzymes - toxicity
(has to be severe liver disease to be problematic)
GI adverse effects (
GI bleeding/ulceration
changes to gut bacteria
what are the most common drugs to cause GI bleeding or ulceration?
low dose aspirin/NSAIDs or warfarin
Give examples of some changes that can occur with gut bacteria?
Loss of Oral Contraceptive activity
Reduced vitamin K absorption (increased prothrombin time)
Overgrowth of pathogenic bacteria (e.g. Clostridium difficile)
Liver injury due to GI drug therapy
Intrinsic hepatotoxicity (predictable, dose–dependent, acute) type A ADR
Idiosyncratic hepatotoxicity (unpredictable, not dose dependent, and may occur at any time – may be part of a hypersensitivity reaction) type B ADR
May be due to the drug itself or an active metabolite
Generally hepatitis or cholestasis, but can mimic any pattern of acute or chronic liver disease
Risk factors for hepatotoxictiy? (5)
Age (elderly at risk) Sex (female at risk) Alcohol consumption Genetic factors Malnourishment
Classification tool for hepatotoxicity
Child-Pugh classification
The individual scores are summed and then grouped as:
<7 = A
7-9 = B
>9 = C
Takes into consideration things like bilirubin, albumin levels, PT, ascites adn encephalopathy
2 drugs that are hepatotoxic
methotrexate
azathioprine
Opiates may precipitate what by increasing sedation?
encephalopathy
