GI pharmacology Flashcards
peptic ulceration
• Gastric and duodenal ulcers
• Symptoms not reliable guide to ulcer location -epigastric pain
• Chronic ulcers can be asymptomatic
• Bleeding, perforation, scarring and possible obstruction
• Helicobacter pylori is a major risk factor
• NSAIDs most common cause after H. pylori
Early gastric emptying also risk factor
• Smoking and alcohol delay healing
antacids, alginates example
Gaviscon compound, has both antacid and alginate
antacid and alginates mechanism
Buffering stomach acid – antacids
increase stomach content viscosity and reduce reflux – alginic acid
antacid and alginates#, X, ^
• # Magnesium salts can cause diarrhoea and aluminium salts can cause constipation
• X Na+ and K+ containing preparations should be used with caution in renal failure
High [sucrose] in some preparations – hyperglycaemia in DM
• Δ Can reduce absorption of many drugs so doses should be separated
Increased urine alkalinity can increase aspirin excretion
Proton pump inhibitors example
Lansoprazole
Omeprazole
PPI mechanism
• Irreversibly inhibit the H+/K+ ATPase in gastric parietal cells
very significant reduction in acid secretion
• Shortest effective duration at lowest effective dose
• Often prescribed along side long term NSAID or steroid
PPI #,X,^
• #
GI – abdominal pain, constipation diarrhoea
CNS: Headache, dizziness, Drowsiness/confusion
• X Mask symptoms of gastro oesophageal cancer
Osteoporosis – fracture risk
• Δ Omeprazole CYP inhibitor – reduced clopidogrel action
PPIs can increase effects of warfarin and phenytoin - monitor
H2 inh antagonists example
Ranitidine
H2 inh antagonists mechanism
- Inhibition of H2 receptors – local histamine release contributes to proton pump activation
- Other routes to pump inhibition mean only partial reduction in acid secretion
H2 inh antagonists #,X,^
ranitidine
• # generally well tolerated - diarrhoea, headache
• X Mask symptoms of gastro-oesophageal cancer,
renal impairment
• Δ Few common DDIs – (reduced exposure to some antivirals and protein kinase inhibitors)
Helicobacter pylori
• Consider for all patients with duodenal or gastric ulcers
not associated with NSAID or unresponsive to lifestyle PPI and antacids,
urea breath test
One week triple therapy
PPI + two antibacterial agents
• Lansoprazole + clarithromycin + amoxicillin (or metronidazole if allergic to amoxicillin)
Amionsalicylates example
Mesalazine
Amionsalicylates mechanism, indication
• first line treatment in ulcerative colitis (UC)
• Release of 5-aminosalsylic acid
Topical action at the colon (enteric coated tablets limit gastric breakdown)
Amionsalicylates #,X,^
Mesalazine
• # GI disturbance – nausea, dyspepsia
leukopenia - rare
• X hypersensitivity
• Δ Enteric coated tablets may break down quicker in presence of PPI (because of ↑p
vomiting
Involuntary, forceful expulsion of gastric contents through the mouth vomiting centre in medulla signals vomit 1. nausea, salivation, sweating. 2. retrogade peristalsis 3. deep inspiration 4. closure of glottis 5. abdominal muscles contract 6. lower esophageal spinster relaxes
what makes the vomiting centre go?
sensory afferents via midbrain (sight, sell, situation)
vestibular nuclei(motion sickness)
direct triggers(drugs, hormones)
visceral afferents from gut (stretch via vagus)
TO CHEMORECEPTOR TRIGGER ZONE this is area of streamer in the floor of the fourth ventricle, on the blood side of the blood brain barrier
agents acting on vestibular nuclei
- Muscarinic receptor Antagonists
-H1 receptor antagonists
also acting on CTZ
- Muscarinic receptor Antagonists example
Hyoscine hydrobromide
- Muscarinic receptor Antagonists mechanism and indication
hyoscine hydrobromide
• Competitive blockade of muscarinic
acetylcholine receptors
• In the vestibular nuclei • Also at the CTZ
• People who can’t take tablets
• Motion sickness
• Bowel obstruction
exploiting side effects: extreme salivation
- Muscarinic receptor Antagonists #
• Sedation • Memory problems
• Glaucoma
• Dry mouth and constipation
due to blocking parasympathetic nervous system block
-H1 receptor antagonists example
Cyclizine
-H1 receptor antagonists mechanism, indication
- Acts on the vestibular nuclei
- Inhibits histaminergic signals from the vestibular system to the CTZ in medulla
- Motion sickness – long plane journeys
-H1 receptor antagonists
#,X, ^
cyclizine
• Sedation
• Excitation
• Antimuscarinic – dry mouth, constipation, urinary retention,
• Cardiac toxicity (long QTinterval)
X : Cyclizine – little old ladies and children
Agents acting on visceral afferents in the gut
- 5HT3 receptor Antagonists
- D2 receptor antagonists
also acting on CTZ
Serotonin (5HT) in the gut
ondansetron
- 95% serotonin in the body is located in the gut
- Produced by the enterochromaffin cells
- In response to parasympathetic stimulation, serotonin excites enteric neurones
- Smooth muscle contraction increases motility (except in the stomach)
- Increases gut secretions
- Regulates appetite
- 5HT3 receptor Antagonists example
Ondansetron
- 5HT3 receptor Antagonists mechanism, indication
ondansetron
- Peripherally
- Reduces GI motility
- Reduces GI secretions
- Centrally: Acts to inhibit the CTZ
- Good for: Almost everyone – it’s often the 1st line treatment
- 5HT3 receptor Antagonists #
UNCOMMON• Constipation • Headache • Elevated liver enzymes • Long QT syndrome • Extra-pyramidal effects – dystonia, parkinsonism
- D2 receptor antagonists (only some)
Metoclopramide
Domperidone
Metoclopramide mechanism, indication
- Increases acetylcholine at muscarinic receptors in the gut
- Promotes gastric emptying
- ↑ tone at lower oesophageal sphincter so it closes
- ↑ tone and amplitude of gastric contractions
- ↓ tone of pylorus so it opens
- Increases peristalsis
- Good for:-
- GORD
- Ileus (no peristalsis)
Metoclopramide #
• Galactorrhoea via prolactin release
• Extra-pyramidal effects – dystonia,
parkinsonism
Domperidone mechanism, indication, #
• Similar mechanism as metoclopramide
• Good for:-• Improving lactation in breastfeeding mothers
#: • Sudden cardiac death (long QT and VT)
• Galactorrhoea
D2 receptor antagonists
Domperidone Metoclopramide
corticosteroids examples
Dexamethasone
corticosteroids indication
dexamethasone
Good for:-
• Perioperative nausea and vomiting
• Chemotherapy
• Palliation
corticosteroids #
- Insomnia
- ↑ appetite
- ↑ blood sugar
cannabinoids example, indication, #
Nabilone
Good for chemotherapy
- used as last line
Side effects Dizziness • Drowsiness
- Neurokinin 1 receptor antagonists
example
Aprepitant
- Neurokinin 1 receptor antagonists mechanism, indication, #
aprepitant
• Anxiolytic and antidepressant properties • Good for chemotherapy Side effects • Headache • Diarrhoea/constipation • Stevens-Johnson, syndrome
Opioid receptor agonist
Loperamide: specific to µ receptors in the myentericplexus
Codeine Morphine :µ and δ receptors
Loperamide mechanism
specific to µ receptors in the myenteric
plexus
• Decreases tone of longitudinal and circular smooth muscle
• Reduces peristalsis but increases segmental contractions
• Decreases colonic mass movement by supressing gastrocolic reflex.
Imodium
start with small dose, build up people have different responses
Codeine and morphine mechanism, indication, #
- µ and δ receptors Similar effects to loperamide More often used when patients have pain Side effects • Paralytic ileus • Nausea and vomiting • Sedation Addiction (codeine and morphine)
osmotic laxatives
lactulose: draw fluid in, mild constipation
macrogol: retain the fluid they came with.
stimulant laxasives
Bisacodyl,
Docusate sodium(also acts as a stool softener),
Glycerol suppository, (rectal irritation and lubrication also acts as a stool softener)
Senna
Enhance gut motility and increase water and electrolyte transfer into the lower gut
orally, per rectum
bulk forming laxatives
Ispaghula husk, Methylcellulose
medicinal fibre
Stimulation through increased faecal bulk, hydrophilic action causing gut lumen water retention
Antipsychotics:
Haloperidol chemotherapy and palliation, sedation)
Chlorpromazine
Motion sickness, vertigo.
