Clinical pharmacology - Alimentary

Question 1

What things do drugs target for alimentary disease

Answer 1

Acid suppression

GI motility

Constipation

Question 2

Which drugs act to suppress excess acid in GI system

Answer 2

Antacids
H2-receptor antagonists
Proton pump inhibitors

Question 3

What types of drugs affect GI motility

Answer 3

Anti-emetics - work against vomiting and nausea

Anti-muscarinics/other anti-spasmodics

Anti-motility

Question 4

Which drugs are used for inflammatory bowel disease

Answer 4

Aminosalicylates

Corticosteroids

Immunosuppressants

Biologics

Question 5

which drugs affect intestinal secretions

Answer 5

Bile acid sequestrants and ursodeoxycholic acid

Question 6

How does histamine contribute to acid production?

Answer 6

acts on parietal cells which then secrete hydrochloric acid and intrinsic factor

Question 7

How does Gastrin contribute to acid production?

Answer 7

stimulates proton pump which in turn triggers release of gastric acid

Question 8

How do antacids work? when are they taken?

Give an example

Answer 8

they contain magnesium or aluminium which work to neutralise gastric acid

take when symptoms occur

Maalox

Question 9

How do alginates like Gaviscon work to reduce effects of stomach acid?

Answer 9

form a viscous gel that floats on stomach contents and reduces reflux

Question 10

How do H2 receptor antagonists reduce stomach acid? how are they taken? Reasons why a patient might take these?

Answer 10

Block histamine receptor thereby reducing acid secretion

orally or intravenously

Indicated in GORD/Peptic ulcer disease

Question 11

Proton pump inhibitors:-

• How do they work to reduce acid?
• How are they administered?
• Give an example of a commonly used PPI.

Answer 11

Block proton pump and thereby reduce acid secretion

Give in GORD/peptic ulcer disease - orally or IV

Omeprazole

Question 12

Complications with proton pump inhibitors

Answer 12

Problems with GI upset and predisposition to c. difficile infection, hypomagnesaemia, B12 deficiency

Question 13

How do PPIs result in vitamin B12 deficiencyt

Answer 13

since gastric acidity is required for vitamin B12absorption, acid suppression may lead to malabsorption and ultimatelydeficiency

Question 14

What do prokinetics do ?

Answer 14

Prokinetic agents increase gut motility and gastric emptying

Question 15

Give 2 examples of diseases that may need treated with prokinetics

Answer 15

gastroparesis - abnormal gastric emptying

GORD

Question 16

Give 2 examples of some anti-emetic drugs

Answer 16

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

Question 17

Where is the vomiting centre in the brain?

Answer 17

in the medulla

Question 18

Which drugs target the vomiting centre?

Answer 18

Anti-muscarinics & Anti-histamines

Question 19

Motion sickness affects what part of the brainstem? and which drug targets this?

Answer 19

pons and medulla

anti-histamines

Question 20

Sickness in response to drugs, toxins affects a place in the medulla called ____ ?

Answer 20

Chemoreceptor Trigger Zone

Question 21

Which drugs are used to help drug/toxin induced vomiting

Answer 21

Dopamine antagonists

5 HT3,antagonists

Cannabinoids

Question 22

Vomiting caused by radiotherapy, Gastroenteritis or some drugs is detected where?

Answer 22

in the pharynx and GIT which then goes to the vomiting centre in the medulla

Question 23

Give 1 pro and con for anti-motility drugs?

Answer 23

Can prevent diarrhoea

but can also cause constipation

Question 24

How do drugs that decrease motility work?

Answer 24

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

Question 25

Why does Loperamide (Immodium) not have many central opiate effects?

Answer 25

it isn't well absorbed across the blood brain barrier so it doesn't access the CNS

Question 26

What are anti-spasmoidic used for?

Answer 26

to reduce symptoms due to IBS, renal colic

Question 27

How do anti-spasmoidic work?

Answer 27

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

Question 28

What are the 4 types of laxative? Give examples

Answer 28

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

Question 29

Issues with laxatives?

Answer 29

Obstruction Route of administration (Oral or Rectal) Need for other measures - Osmotic laxatives will not work without adequate fluid intake Misuse (weight loss)

Question 30

Which drugs are used for IBD?

Answer 30

Aminosalicylates - anti -inflammatory Corticosteroids Immunosuppressants (Azathioprine)

Question 31

Corticosteroids: effects? administration? contraindications?

Answer 31

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

Question 32

Immunosuppressants for IBD:- | How do they work?

Answer 32

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

Question 33

What sorts of things does the drug Infliximab treat? (3)

Answer 33

Current TB or other serious infection Multiple sclerosis Pregnancy/breast feeding

Question 34

Adverse affects of infliximab? (type of biologic - treats a number of autoimmune diseases)

Answer 34

Risk of infection, particularly TB so all patients should be screened Infusion reaction (fever, itch) Anaemia, thrombocytopenia, neutropenia ?Demyelination - nerve deterioration Malignancy

Question 35

Types of biologics other than infliximab

Answer 35

Certolizumab Adalimumab Natalizumab Golimumab Vedolizumab

Question 36

Which drugs affect biliary secretion? (2)

Answer 36

Cholestyramine Ursodeoxycholic Acid

Question 37

How does Cholestyramine work?

Answer 37

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)

Question 38

How does Ursodeoxycholic Acid | affect biliary secretion?

Answer 38

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

Question 39

What can GI or liver disease affect in regards to drug processing?

Answer 39

Absorption (more so rate of absorption rather than total absorption) Distribution Metabolism Excretion

Question 40

What does drug absorption in the gut depend on?

Answer 40

pH Gut length Transit time e.g. Digoxin, Warfarin

Question 41

How can low albumin levels reduce drug distribution

Answer 41

drugs that are usually bound to protein are then free free drug conc increases and decreased binding overall

Question 42

What problems can there be with drug metabolism?

Answer 42

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)

Question 43

GI adverse effects (

Answer 43

GI bleeding/ulceration changes to gut bacteria

Question 44

what are the most common drugs to cause GI bleeding or ulceration?

Answer 44

low dose aspirin/NSAIDs or warfarin

Question 45

Give examples of some changes that can occur with gut bacteria?

Answer 45

Loss of Oral Contraceptive activity Reduced vitamin K absorption (increased prothrombin time) Overgrowth of pathogenic bacteria (e.g. Clostridium difficile)

Question 46

Liver injury due to GI drug therapy

Answer 46

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

Question 47

Risk factors for hepatotoxictiy? (5)

Answer 47

``` Age (elderly at risk) Sex (female at risk) Alcohol consumption Genetic factors Malnourishment ```

Question 48

Classification tool for hepatotoxicity

Answer 48

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

Question 49

2 drugs that are hepatotoxic

Answer 49

methotrexate | azathioprine

Question 50

Opiates may precipitate what by increasing sedation?

Answer 50

encephalopathy