GI Pharmacology Flashcards
What are important GI functions from a pharmacological perspective?
Gastric secretion
Vomiting and nausea
Gut motility and defaecation
Formation and excretion of bile
What are the main drug classes?
Acid suppression
Drugs affecting motility
Laxatives
Drugs for treating IBD
Drugs affecting biliary secretions
Describe neural control of GI tract
Enteric nervous system
Coordinates contraction of muscles, transport across mucosal lining and intramural blood flow
2 intramural plexuses
Describe the neurons in the enteric nervous system
Neurones in plexuses secrete ACh, NA, 5-HT, Purines and NO
Sensory neurons respond to mucosal stroking and distention
Describe parasympathetic and sympathetic control in enteric nervous system
Para - fibres are preganglionic, ACh and excitatory
Symp - fibres are post-ganglionic and inhibitory
Act on blood vessels, smooth muscle and some glandular tissue
Describe hormonal control in GI
Endocrine - Gastrin and CCK in blood
Paracrine - histamine and somatostatin from cells acting on nearby cells
Paracrine also function as neurotransmitters - substance P
Describe acid secretion in GI
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
How can acid damage the mucosa?
GORD, Barret’s, peptic ulcer disease
Needs to be balance between damage and protection
Acid and H.pylori damage
What protects the mucosa?
Prostaglandins (PGE2 and I2) inhibit acid and increase mucus production
Nitric Oxide is protective
What do you do if test for H. pylori is postitive?
Triple therapy
PPI and 2 antibacterial agents - amoxicillin and metronidazole/ clarithromycin
What do you do if H. pylori test is negative or patient is untested?
Acid suppression
Antacids - Maalox which neutralises and Alginates - Gaviscon which forms protective layer
What are some other mucosal protectors?
Bismuth - insoluble salt containing salicylic acid which is antibacterial
Sucralfate - hydrolyses in acid so coats mucosa
Misoprostol - reduces acid secretion and supports mucus production
Describe H2-receptor antagonists
Ranitidine - given orally or IV
Block histamine receptor reducing acid secretion
Indicated in GORD and peptic ulcer
Describe Proton Pump Inhibitors
Omeprazole - orally or IV
Irreversible inhibitor of H-K-ATPase and targets parietal cells
Indicated in GORD and peptic ulcer
What are the adverse effects of acid suppression drugs?
C. difficile, B12 deficiency, ECL tumours and AIN - acute interstitial nephritis
What are the motor outputs for vomiting?
Somatomotor - diaphragm and abdominal muscle contraction
Autonomic - increased salivation, cold sweating, cutaneous vasoconstriction, proximal gastric relaxation and intestinal retrograde giant contraction
What are the pharmacological options for vomiting?
NK1 antagonists
CB1 agonists
H1RA
Antimuscarinics
D2 antagonists
5HT3RA
What are the side effects for drugs used for vomiting?
Sedation, movement, prolactin release, GI drowsiness, dizziness, dry mouth, and blurred vision
What drug is used for late phase of cytotoxic emesis?
NK1 antagonists
What is a cytotoxic drug used for vomiting?
CB1 agonists - nabilone
What drugs are used for motion sickness?
H1RA -cyclizine
Anti-muscarinic - hyoscine
What drug is used in pregnancy for vomiting?
D2 antagonists - prochlorperazine
What is 5HR3RA drug used for?
Cytotoxic drugs
Radiation
Post operative
For vomiting
What is used for management of nausea?
Low dose antidepressants - gabapentin and olanzapine
What are some drugs which affect the motility of the GI tract?
Purgatives
Agents which increase motility
Anti-diarrhoeal drugs
Anti-spasmatic
What do purgatives do?
Accelerate the passage of food through the gut
Used for treating constipation
What do anti-spasmodic drugs do?
Decrease smooth muscle tone
What are bulk laxatives?
Methylcellulose
Bulky hydrated mass, takes several days to work but no serious adverse effects
What are osmotic laxatives?
Saline, Lactulose
Poorly absorbed solutes
Osmotic load draws water so takes 2-3 days to work
What can high doses of osmotic laxatives cause?
Electrolyte disturbances
What are faecal softeners?
Docusate sodium
Surface active and weak stimulant
Explain stimulant purgatives - laxatives
Increase the electrolyte secretion by gut mucosa and therefor increase water secretion
Adverse effects are cramps
What are some types of stimulant purgatives?
Bisacodyl and glycerol - suppositories
Sodium picosulfate - oral
Senna and dantron - stimulate myenteric plexus
Explain domperidone - D2 antagonist
Mechanism unknown
Increases LOS pressure which increases gastric emptying and duodenal peristalsis
Explain metoclopramide
Increases gastric motility and emptying
What is diarrhoea caused by?
Increased motility, increased secretion and reduced absorption
Treatment needs maintenance of fluid and electrolytes
What is the treatment of diarrhoea?
Anti-infective agents, anti-diarrhoeal agents, anti-spasmodic agents
Main agent to reduce motility is opioids
Anti-muscarinic
What is the main opioid used for treatment of diarrhoea and how does it work?
Loperamide
Opioid receptors decrease ACh release
reduces smooth muscle contraction and increases anal sphincter tone
What is treatment for chronic bowel disease?
IBS and IBD
Treatment is symptomatic
May include loperamide and anti-depressants
High residue diet
What is the clinical management of IBD?
Corticosteroids - anti-inflammatory effects
Given orally, IV or rectally
What are the concerns and contradiction of corticosteroids?
Osteoporosis
Cushingoid features
Increased susceptibility of infection
Addisonian crisis with abrupt withdrawal
What is the chronic treatment of IBD?
Amino salicylates - mesalazine and olsalazine
Is anti-inflammatory
Oral or rectal administration
Avoid if allergic and caution of renal impairment
What are the adverse effects of amino salicylates?
GI upset, blood dyscrasias, renal impairment
What are some other drugs for chronic treatment of IBD?
Immunosuppressants - Azathioprine, cycloprin, 6-mercaptopurine
Methotrexate - anti-folate
Infliximab - biologics
Describe immunosuppressants
Prevents formation of purines required for DNA synthesis so reduces cell proliferation
Adverse effects - bone marrow suppression and organ damage
What is the role of TNF-alpha in IBD?
Inflammatory cells express TNF-alpha which is membrane bound enzyme
Stimulates inflammatory response which causes gut damage and ulceration
What are the 3 mechanisms of anti-spasmodics?
Used for symptom relief in IBS
Anti-cholinergic muscarinic antagonists
Inhibit smooth muscle constriction in gut wall
Direct smooth muscle relaxants
What drug is used for biliary secretion?
If not heavily calcified then Ursodeocycholic acid
GTN for spasm
Cholestyramine - bile acid sequestrants
How can GI and liver disease effect ADME?
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
What drugs can cause GI adverse effects?
Lose dose aspirin/ NSAIDs
Warfarin
How can drugs effects the liver?
Intrinsic hepatotoxicity - dose dependant
Idiosyncratic hepatotoxicity - not dose dependant
Asymptomatic increase in LFTS or liver failure
What are some risk factors for hepatic drug response?
Age, gender, alcohol consumption, genetic factors and malnourishment
What is the Child-Pugh classification?
Scoring for liver impairment
<7 = A, 7-9 = B, >9 = C
Allows sensible dosing in cases of hepatic impairment
