S10: GI pharmacology & antiemetics Flashcards
Describe the mechanism of action of alginates and antacids
Antacids – buffering stomach acid
Alginic acid – increase stomach content viscosity and reduce reflux
Often taken as compound preparations (alginic acid + antacid)
Eg. Gaviscon
What are the adverse effects, warnings, contraindications & important drug interactions of alginates and antacids?
Adverse effects: magnesium salts can cause diarrhoea & aluminium salts can cause constipation
Warnings, contraindications: Na+ and K+ containing preparations should be used with caution in renal failure, high [sucrose] in some preparations (hyperglycaemia in DM)
Important drug interactions: can reduce absorption of many drugs, increased urine alkalinity can increase aspirin excretion
Describe the mechanism of action of proton pump inhibitors
Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
Final stage in the pathway -> very significant reduction in acid secretion
List examples of PPIs
Lansoprazole
Omeprazole
What are the adverse effects, warnings, contraindications & important drug interactions of PPIs?
Adverse effects: GI disturbance (abdominal pain, constipation, diarrhoea), headache, dizziness, drowsiness/confusion
Warnings, contraindications: mask symptoms of gastro-oesophageal cancer, osteoporosis – fracture risk
Important drug interactions: omeprazole CYP inhibitor – reduced clopidogrel action, can increase effects of warfarin & phenytoin
Describe the mechanism of action of H2 receptor antagonists
Inhibition of H2 receptors – local histamine release contributes to proton pump activation
Only partial reduction in acid secretion
What are the adverse effects, warnings, contraindications & important drug interactions of H2 receptor antagonists?
Adverse effects: well tolerated – diarrhoea, headache
Warnings, contraindications: mask symptoms of gastro-oesophageal cancer, renal impairment
Important drug interactions: few common DDIs
List examples of H2 receptor antagonists
Ranitidine
Current large scale recall on most ranitidine containing products -> possible carcinogenic contaminant
Describe treatment for H. pylori infection
Confirm infection by urea breath test
One week triple therapy – PPI + two antibacterial agents
Lansoprazole + clarithromycin + amoxicillin
OR lansoprazole + clarithromycin + metronidazole (where allergic to amoxicillin)
Compliance with full course important for effectiveness & minimise risk of bacterial resistance
Describe mechanism of action of aminosalicylates
Release of 5-aminosalsylic acid
Topical action at the colon – enteric coated tablets limit gastric breakdown
Used as first line treatment in ulcerative colitis
What are the adverse effects, warnings, contraindications & important drug interactions of aminosalicylates?
Adverse effects: GI disturbance (nausea, dyspepsia), leukopenia – rare
Warnings, contraindications: similar hypersensitivity (like aspirin)
Important drug interactions: enteric coated tablets may break down quicker in presence of PPI (increased pH)
List triggers which cause the vomiting centre to go
Direct triggers
Sensory afferents via midbrain
Visceral afferents from gut
Vestibular nuclei
List agents which act on the vestibular nuclei
Muscarinic receptor antagonists
H1 receptor antagonists
Describe muscarinic receptor antagonists
Hyoscine hydrobromide
Competitive blockade of muscarinic acetylcholine receptors – in vestibular nuclei & at chemoreceptor trigger zone (CTZ)
Indications: people who can’t take tablets, motion sickness & bowel obstruction
List side effects of muscarinic receptor antagonists
Sedation
Memory problems
Glaucoma
Dry mouth and constipation
Describe H1 receptor antagonists
Cyclizine
Centrally – acts on vestibular nuclei, inhibits histaminergic signals from the vestibular system to CTZ in medulla
Indications: motion sickness
Not good for: old ladies & children
List side effects of H1 receptor antagonists
Sedation
Excitation
Antimuscarinic – dry mouth, constipation, urinary retention
Cardiac toxicity – long QT interval
List agents acting on visceral afferents in the gut
5HT3 receptor antagonists
D2 receptor antagonists
Describe 5HT3 receptor antagonists
Ondansetron
Peripherally – reduces gut motility, reduces GI secretions
Centrally – acts to inhibit CTZ
Indications: almost everyone – 1st line treatment
List side effects of 5HT3 receptor antagonists
Uncommon Constipation Headache Elevated liver enzymes Long QT syndrome Extra-pyramidal effects – dystonia, parkinsonism
Describe D2 receptor antagonists (acting on visceral afferents in gut)
Metoclopramide, domperidone
Increases acetylcholine at muscarinic receptors in gut
Promotes gastric emptying – increases tone at LOS, increases tone and amplitude of gastric contractions, decreases tone of pylorus so it opens
Increases peristalsis
Indications:
- Metoclopramide: GORD, ileus
- Domperidone: improving lactation in breastfeeding mothers
List side effects of D2 receptor antagonists
Metoclopramide: galactorrhoea, extra pyramidal effects
Domperidone: sudden cardiac death (long QT and VT), galactorrhoea
List agents acting on the CTZ
5HT3 receptor antagonists H1 receptor antagonists Muscarinic receptor antagonists D2 receptor antagonists Corticosteroids Cannabinoids NK1 receptor antagonists
Describe D2 receptor antagonists (acting on CTZ)
Metoclopramide, domperidone, chlorpromazine, haloperidol
Act on the CTZ, may also block H1 and muscarinic receptors
Indications: motion sickness, vertigo, pregnancy
Haloperidol – chemotherapy & palliation
Side effects: extra-pyramidal effects, sedation, hypotension
Describe corticosteroids
Dexamethasone, methylprednisolone
Assumed to act on the CTZ, may also have properties of D2 receptor antagonists
Indications: perioperative nausea & vomiting, chemotherapy, palliation
List side effects of corticosteroids
Insomnia
Increased appetite
Increased blood sugar
Describe neurokinin-1 receptor antagonists
Aprepitant
Prevent the action of substance P at CTZ & in peripheral nerves
Boosts effects of 5HT3 receptor antagonists
Anxiolytic & antidepressant properties
Good for chemotherapy – particularly for delayed emesis
List side effects of neurokinin-1 receptor antagonists
Headache
Diarrhoea/constipation
Stevens-Johnson syndrome
Describe treatment for motion sickness
Hyoscine hydrobromide is 1st line
Cinnirazine has fewer side effects
What is hyperemesis gravidarum? What is the treatment for it?
Rapid rise in B-hCG stimulates the CTZ
More than just ‘morning sickness’ – dehydration, weight loss, electrolyte imbalance, urinary ketones
1st line: promethazine, prochlorperazine
Outline treatment for post-operative nausea
Ondansetron and/or cyclizine
Then add dexamethasone
Describe opioid receptor agonists (specific for intestine)
Loperamide, codeine phopshate
Specific to u receptors in myenteric plexus
Decreases tone of longitudinal and circular smooth muscle
Reduces peristalsis but increases segmental contractions
Decreases colonic mass movement by supressing gastrocolic reflex
List side effects of opioid receptor agonists
Paralytic ileus
Nausea and vomiting
Sedation and addiction (codeine & morphine)
Describe osmotic laxatives
Lactulose, Movicol
Increase the amount of water in the large bowel
Lactulose – draws fluid in
Movicol – retain the fluid they came with
Describe stimulant laxatives
Bisacodyl, senna, docusate sodium
Increase intestinal motility, may be given orally or per rectum
Describe bulk forming laxatives
Ispaghula husk, methylcellulose
Medicinal fibre
Describe stool softeners
Docusate sodium, glycerin suppository
Decrease surface tension of stool
Increase penetration of fluid into stool
