GI Pharmacology

Question 1

What are important GI functions from a pharmacological perspective?

Answer 1

Gastric secretion
Vomiting and nausea
Gut motility and defaecation
Formation and excretion of bile

Question 2

What are the main drug classes?

Answer 2

Acid suppression
Drugs affecting motility
Laxatives
Drugs for treating IBD
Drugs affecting biliary secretions

Question 3

Describe neural control of GI tract

Answer 3

Enteric nervous system
Coordinates contraction of muscles, transport across mucosal lining and intramural blood flow
2 intramural plexuses

Question 4

Describe the neurons in the enteric nervous system

Answer 4

Neurones in plexuses secrete ACh, NA, 5-HT, Purines and NO
Sensory neurons respond to mucosal stroking and distention

Question 5

Describe parasympathetic and sympathetic control in enteric nervous system

Answer 5

Para - fibres are preganglionic, ACh and excitatory
Symp - fibres are post-ganglionic and inhibitory
Act on blood vessels, smooth muscle and some glandular tissue

Question 6

Describe hormonal control in GI

Answer 6

Endocrine - Gastrin and CCK in blood
Paracrine - histamine and somatostatin from cells acting on nearby cells
Paracrine also function as neurotransmitters - substance P

Question 7

Describe acid secretion in GI

Answer 7

Gastric - ECL parietal axis hypothesis
Histamine acts on H2 receptors on parietal cells
Gastrin cause release of gastrin from G cells and vagal input stimulate histamine

Question 8

How can acid damage the mucosa?

Answer 8

GORD, Barret’s, peptic ulcer disease
Needs to be balance between damage and protection
Acid and H.pylori damage

Question 9

What protects the mucosa?

Answer 9

Prostaglandins (PGE2 and I2) inhibit acid and increase mucus production
Nitric Oxide is protective

Question 10

What do you do if test for H. pylori is postitive?

Answer 10

Triple therapy
PPI and 2 antibacterial agents - amoxicillin and metronidazole/ clarithromycin

Question 11

What do you do if H. pylori test is negative or patient is untested?

Answer 11

Acid suppression
Antacids - Maalox which neutralises and Alginates - Gaviscon which forms protective layer

Question 12

What are some other mucosal protectors?

Answer 12

Bismuth - insoluble salt containing salicylic acid which is antibacterial
Sucralfate - hydrolyses in acid so coats mucosa
Misoprostol - reduces acid secretion and supports mucus production

Question 13

Describe H2-receptor antagonists

Answer 13

Ranitidine - given orally or IV
Block histamine receptor reducing acid secretion
Indicated in GORD and peptic ulcer

Question 14

Describe Proton Pump Inhibitors

Answer 14

Omeprazole - orally or IV
Irreversible inhibitor of H-K-ATPase and targets parietal cells
Indicated in GORD and peptic ulcer

Question 15

What are the adverse effects of acid suppression drugs?

Answer 15

C. difficile, B12 deficiency, ECL tumours and AIN - acute interstitial nephritis

Question 16

What are the motor outputs for vomiting?

Answer 16

Somatomotor - diaphragm and abdominal muscle contraction
Autonomic - increased salivation, cold sweating, cutaneous vasoconstriction, proximal gastric relaxation and intestinal retrograde giant contraction

Question 17

What are the pharmacological options for vomiting?

Answer 17

NK1 antagonists
CB1 agonists
H1RA
Antimuscarinics
D2 antagonists
5HT3RA

Question 18

What are the side effects for drugs used for vomiting?

Answer 18

Sedation, movement, prolactin release, GI drowsiness, dizziness, dry mouth, and blurred vision

Question 19

What drug is used for late phase of cytotoxic emesis?

Answer 19

NK1 antagonists

Question 20

What is a cytotoxic drug used for vomiting?

Answer 20

CB1 agonists - nabilone

Question 21

What drugs are used for motion sickness?

Answer 21

H1RA -cyclizine
Anti-muscarinic - hyoscine

Question 22

What drug is used in pregnancy for vomiting?

Answer 22

D2 antagonists - prochlorperazine

Question 23

What is 5HR3RA drug used for?

Answer 23

Cytotoxic drugs
Radiation
Post operative
For vomiting

Question 24

What is used for management of nausea?

Answer 24

Low dose antidepressants - gabapentin and olanzapine

Question 25

What are some drugs which affect the motility of the GI tract?

Answer 25

Purgatives Agents which increase motility Anti-diarrhoeal drugs Anti-spasmatic

Question 26

What do purgatives do?

Answer 26

Accelerate the passage of food through the gut Used for treating constipation

Question 27

What do anti-spasmodic drugs do?

Answer 27

Decrease smooth muscle tone

Question 28

What are bulk laxatives?

Answer 28

Methylcellulose Bulky hydrated mass, takes several days to work but no serious adverse effects

Question 29

What are osmotic laxatives?

Answer 29

Saline, Lactulose Poorly absorbed solutes Osmotic load draws water so takes 2-3 days to work

Question 30

What can high doses of osmotic laxatives cause?

Answer 30

Electrolyte disturbances

Question 31

What are faecal softeners?

Answer 31

Docusate sodium Surface active and weak stimulant

Question 32

Explain stimulant purgatives - laxatives

Answer 32

Increase the electrolyte secretion by gut mucosa and therefor increase water secretion Adverse effects are cramps

Question 33

What are some types of stimulant purgatives?

Answer 33

Bisacodyl and glycerol - suppositories Sodium picosulfate - oral Senna and dantron - stimulate myenteric plexus

Question 34

Explain domperidone - D2 antagonist

Answer 34

Mechanism unknown Increases LOS pressure which increases gastric emptying and duodenal peristalsis

Question 35

Explain metoclopramide

Answer 35

Increases gastric motility and emptying

Question 36

What is diarrhoea caused by?

Answer 36

Increased motility, increased secretion and reduced absorption Treatment needs maintenance of fluid and electrolytes

Question 37

What is the treatment of diarrhoea?

Answer 37

Anti-infective agents, anti-diarrhoeal agents, anti-spasmodic agents Main agent to reduce motility is opioids Anti-muscarinic

Question 38

What is the main opioid used for treatment of diarrhoea and how does it work?

Answer 38

Loperamide Opioid receptors decrease ACh release reduces smooth muscle contraction and increases anal sphincter tone

Question 39

What is treatment for chronic bowel disease?

Answer 39

IBS and IBD Treatment is symptomatic May include loperamide and anti-depressants High residue diet

Question 40

What is the clinical management of IBD?

Answer 40

Corticosteroids - anti-inflammatory effects Given orally, IV or rectally

Question 41

What are the concerns and contradiction of corticosteroids?

Answer 41

Osteoporosis Cushingoid features Increased susceptibility of infection Addisonian crisis with abrupt withdrawal

Question 42

What is the chronic treatment of IBD?

Answer 42

Amino salicylates - mesalazine and olsalazine Is anti-inflammatory Oral or rectal administration Avoid if allergic and caution of renal impairment

Question 43

What are the adverse effects of amino salicylates?

Answer 43

GI upset, blood dyscrasias, renal impairment

Question 44

What are some other drugs for chronic treatment of IBD?

Answer 44

Immunosuppressants - Azathioprine, cycloprin, 6-mercaptopurine Methotrexate - anti-folate Infliximab - biologics

Question 45

Describe immunosuppressants

Answer 45

Prevents formation of purines required for DNA synthesis so reduces cell proliferation Adverse effects - bone marrow suppression and organ damage

Question 46

What is the role of TNF-alpha in IBD?

Answer 46

Inflammatory cells express TNF-alpha which is membrane bound enzyme Stimulates inflammatory response which causes gut damage and ulceration

Question 47

What are the 3 mechanisms of anti-spasmodics?

Answer 47

Used for symptom relief in IBS Anti-cholinergic muscarinic antagonists Inhibit smooth muscle constriction in gut wall Direct smooth muscle relaxants

Question 48

What drug is used for biliary secretion?

Answer 48

If not heavily calcified then Ursodeocycholic acid GTN for spasm Cholestyramine - bile acid sequestrants

Question 49

How can GI and liver disease effect ADME?

Answer 49

Absorption - pH, gut length and transit time Distribution - reduced albumin Metabolism - damaged gut wall, less first pass metabolism, infected gut wall Excretion - build up if cant be excreted by biliary

Question 50

What drugs can cause GI adverse effects?

Answer 50

Lose dose aspirin/ NSAIDs Warfarin

Question 51

How can drugs effects the liver?

Answer 51

Intrinsic hepatotoxicity - dose dependant Idiosyncratic hepatotoxicity - not dose dependant Asymptomatic increase in LFTS or liver failure

Question 52

What are some risk factors for hepatic drug response?

Answer 52

Age, gender, alcohol consumption, genetic factors and malnourishment

Question 53

What is the Child-Pugh classification?

Answer 53

Scoring for liver impairment <7 = A, 7-9 = B, >9 = C Allows sensible dosing in cases of hepatic impairment