GI pharmacology Flashcards
Causes of nausea
- GI irritation
- Migraine, pain
- Motion sickness, pregnancy
- Psychogenic - stress/emotional trauma
- Radiation
- Drugs
Effects of nausea
- Dehydration
- Alkalosis - excreting stomach acid
- Hypokalaemia - volume depletion
How is vomiting controlled?
- Sensory input → vomiting centre (smooth muscle contraction)
- Vestibular organ → vestibular nucleus → CTZ → vomiting centre
- CTZ screens blood fot toxins etc
- Sensory afferents from GIT via vagus nerve into NTS = vomiting centre for contractile response
Anti-emetic drugs
- H1 antagonists - target vestibular nuclei
- Muscarinic ACh antagonists - target vestibular nuclei and vomiting centre
- 5-HT3 antagonists - targets CTZ and visceral afferents
- D2 antagonists - targets CTZ
What do H1 antagonists target?
Vestibular nuclei
What do muscarinic ACh antagonists target?
Vestibular nuclei and vomiting centre
What do 5-HT3 antagonists target?
CTZ and visceral afferents
When are D2 dopamine antagonists needed, example
Post operative nausea and vomiting, metoclopramide
When are H1 histamine antagonists needed, example
Most nausea and vomiting, cyclising
When are muscarinic ACh antagonists needed, example
Motion sickness
Hyoscine
When are 5-HT3 antagonists needed, example
Post operative sickness and nausea
Ondansetron
Controlling acid secretion
- Neuronal - ACh - via vagus nerve to acts on msucarinic receptors on mast-like cells in gut (enterochromaffin cells) and parietal cells
- Parietal cells secrete acid
- Endocrine - gastrin - peptide from endocrine mucosa in duodenum - acts on mast-like cells to activate proton pumps and acid secretion
- Paracrine - histamine acts on H2 receptors in parietal cells
Pathological consequences of gastric acid
- Protective factors: NaHCO3, mucus, epithelial cell regeneration and tight junctions, blood supply
- Aggressive factors: H+, pepsin, helicobacter pylori
- Dyspepsia - discomfort due to acid production
- GORD - oesophageal sphincters are not strong - flows to oesophagus
- Gastric and duodenal ulcers - protective factors in gut overcome
Helicobacter pylori
- Gram -ve bacterium
- Risk factor for gastritis, gastric cancer, peptic ulcer
- 95% of duodenal ulcer presentations
Pharmacotherapy
- Addresses primary problems and controlling acid secretion and mucus production
- Proton pump inhibitors
- H2 antagonists
- Synthetic PGs to increase mucus production and inhibit parietal cell activation
- Antacids
- Antibiotics eradicate H.pylori - amoxicillin plus clarithromycin or metronidazole
What do H2 antagonists target?
H2R
What do NSAIDs target?
AA - PGE2 = no mucus
Function of misoprostol
Replaces PGs
When are PPIs needed, example
GAstric/duodenal ulcers, GORD
Omeprazole
When are H2 antagonists needed, example
Only if PPI contraindicated
Ranitidine
When are synthetic PGs needed, example
Gastric/duodenal ulcers/NSAID
Misoprostol
When are antacids needed, example
Ulcer dyspepsia, GORD
Aluminium hydroxide
What is constipation
Definition: small, hard stools with a frequency below pts normal function
Causes of constipation
- Dietary, fluid/electrolyte disturbance
- Misconceptions about normal bowel habit
- IBS
- Poor bowel habit
- Laxative abuse
- Pregnancy
- Endocrine disorders - hypothyroidism
- Anorectal disease - fissures and haemorrhoids
- Parkinson’s/stroke
- Mechanical obstruction
- Nerve damage
- Immobility
- Drugs
Drugs affecting GIT
- Decreasing motility: autonomic effects - atropine
- Opiates increase muscle tone, suppress peristalsis, raise sphincter tone and reduce sensitivity to rectal distension
- Increase motility - metoclopramide, osmotic effects (magnesium), fat malabsorption (orlistat), microbial proliferation (antibiotics)
Laxative function
Colon adjusts fluid and sodium balance
Bowel cleansing solutions
- Picolax - sodium picosulphate (stimulant)
- Magnesium citrate (osmotic)
What is diarrhoea?
Failure of intestinal uptake of sodium and water = watery bowel movements
Effects of diarrhoea
Dehydration and acidosis
Treatment of diarrhoea
- Symptomatic - correction of fluid and electrolyte loss
- Antimotility drugs - opioids (loperamide)
- Bulking agents - ispaghula
What do bulk laxatives do, example
Increase faecal mass
Bran/ispaghula husk
What do osmotic laxatives do, example
Increase fluid in bowel
Lactulose
What do stimulant laxatives do, example
Increased intestinal motility
Senna
What do faecal softeners do, example
Lubricate and soften
Arachis (peanut) oil
