Drugs Affecting the GIT Flashcards
How do NSAIDS promote peptic ulcer disease?
- irritate gastric mucosa
- inhibit PG synthesis by blocking COX
- PGs normally reduce gastric acid, increase mucus and bicarbonate production (cytoprotective of gastric mucosa)
- blockage promotes ulcer formation, irritates existing ulcers
What causes PUD?
- H. pylori
- NSAID use
- smoking
- caffeine
- glucocorticoid use
- alcohol
- bile
What classes of drugs are used to treat PUD?
- H+/K+ ATPase inhibitors/PPIs
- H2 receptor antagonists
- antacids
- cytoprotective agents
- spasmolytics (anticholinergics and direct)
- prostaglandin E analogues
H2 receptor antagonists block which mediators of gastric acid release?
histamine (directly)
ACh and gastrin (indirectly, preventing histamine release from ECL cells)
What is the cytoprotective effect of prostaglandins in gastric mucosa?
PGE2 and PGI2 stimulate secretion of mucus and bicarbonate, stimulate mucosal blood flow (removes stray H+ ions)
Omeprazole (Losec, Prilosec), Esomeprazole (Nexium)
H+/K+ ATPase/Proton Pump Inhibitors (PPI)
How do PPIs work?
- eg Omeprazole, Esomeprazole (greater bioavailability)
- irreversibly inhibit H+/K+ ATPase pump on lumenal surface of parietal cells
- decreses gastric acid formation
- used for ~8 wks
What are PPIs used for?
- PUD (peptic ulcer disease)
- reflux oesophagitis
- Zollinger-Ellison syndrome (gastrin-secreting tumour +acidity)
What are the side effects of PPIs?
- excessive inhibition of acid secretion (Rx for ~8wks)
Cimetidine, Ranitidine (Zantac)
H2 receptor antagonists
How do H2 receptor antagonists work?
Block H2 receptors on basolateral surface of parietal cells
Antacids
- sodium bicarbonate (systemic)
- magnesium hydroxide/carbonate/oxide/trisilicate (fast acting, cause diarrhoea)
- aluminium hydroxide (slow acting)
- calcium carbonate (fast acting)
- Gaviscon (sodium bicarbonate + calcium carbonate + sodium alginate)
What are the dangers of antacids?
- easily available, self-medication
- interactions with prescription drugs
- systemic (sodium bicarbonate) can have adverse effects:
- bicarbonate causes systemic alkalosis, sodium affects fluid retention (hypertension, renal failure)
- magnesium salts cause diarrhoea
- calcium carbonate and aluminium hydroxide cause constipation
- magnesium can anaesthetise children
- calcium salts cause rebound acidity requiring progressively increased dose
- stimulate gastrin release, which increases acid secretion
Hyoscine butylbromide
spasmolytic: anticholinergic/muscarinic receptor antagonist
What is the function of hyoscine butylbromide?
- spasmolytic muscarinic receptor antagonist
- blocks GIT muscarnic receptors from ACh to decrease motility
What is the function of prostaglandin E analogues?
increase mucus secretion, bicarbonate secretion, and mucosal blood flow (to clear H+)
decrease gastric acid secretion
Misoprostol
Misoprostol
Prostaglandin E analogue
cytoprotective agent
What are the side effects of prostaglandin E analogues?
- increased utierine motility (used in abortions)
- increased bowel motility
- causes severe colic, diarrhoea
What is commonly prescribed with long-term NSAID use?
PPIs, prostaglandin E analogues
PPIs are used in treatment of
PUD and GORD
(peptic ulcer disease and gastro-oesophageal reflux disease)
The vomiting centre is located
in the dorsolateral reticular formation in the floor of the 4th ventricle of the medulla oblongata
Where is the chemoreceptor trigger zone located?
in the medulla, outside the blood-brain barrier
The CTZ responds to
circulating toxins, cytotoxic drugs, chemotherapeutic agents,
The vomiting centre receives input from
CTZ, vestibular apparatus (ear), higher brainstem and cortical centres,
visceral afferents from the heart, testes, GIT, etc.
Vomiting that involves stimulation of the CTZ is caused by
stimulation of D2 (dopamine) and 5HT3 (serotonin) receptors
from circulating substances in the blood
What receptors are involved in motion sickness?
muscarinic and H1
Motion sickness, or vomiting due to labyrnthitis, dizziness, or vertigo, is treated with what classes of drugs?
muscarinic M1 receptor antagonists
histamine H1 receptor antagonists (older, sedative versions)
Hyoscine hydrobromide
- muscarinic receptor antagonist
- anti-emetic for motion sickness
- can cross BBB
- sedative but less so than in Travacalm, a combination with dimenhydrinate (H1 receptor antagonist)
H1 receptor antagonists
- anti-emetic drugs:
- dimenhydinate
- promethazine
- pheniramine
Promethazine (Phenergan)
- H1 receptor antagonist anti-emetic
- one of the earliest discovered (previously used to settle babies, motion sickness)
- extremely sedative
- cannot be given to children under 6
What are the side effects of drugs used to treat motion sickness?
highly sedative
What classes of drugs are used to treat vomiting induced by the CTZ?
dopamine D2 receptor antagonists and serotonin 5HT3 receptor antagonists
dopamine D2 receptor antagonists
- metoclopramide (Maxalon)
- phrochlorperazine (Stematil)
- domperidone (peripheral)
- chlorpromazine (anti-psychotic)
- haloperidol (anti-psychotic)
- droperidol (anti-psychotic)
Metoclopramide (Maxalon)
- dopamine D2 receptor antagonist anti-emetic
- increases ACh stim to gut (dopamine inhibits ACh)
- used for vomiting and nausea induced by CTZ
- has pro-motility effects (eg in gastric stasis)
- tf enhances absorption of drugs
- weak 5HT3 receptor antagonist (high doses)
- 5HT4 agonist - increases ACh stim of upper GIT (+motility)
Prochlorperazine (Stematil)
dopamine D2 recceptor antagonist anti-emetic
used for nausea and vomiting induced by the CTZ
Domperidone
dopamine D2 receptor antagonist anti-emetic
used for nausea and vomiting induced by CTZ
peripheral - although similar to metoclopramide, does not cross BBB tf less potent
What are the side effects of dopamine D2 receptor antagonists that act in the CNS?
- extrapyramidal:
- effects of Parkinson’s disease and other motor disorders
- tardive dyskinesia (can be irreversible)
- dystonias
- changes in facial movements
- muscular problems
- occur with prolonged use (especially metoclopramoide)
What are the side effects of muscarinic antagonists?
anti-SLUD
- anti: salivation, lacrimation, urination, defacation
- dry mouth, blurred vision, urinary retention, constipation
What are the side effects of seratonin 5HT3 receptor antagonists?
anti-emetic drugs
- headache
- constipation
Ondansetron
- seratonin 5HT3-R antagoist anti emetic
- widely used in hospitals
How do cytotoxic drugs trigger vomiting in the gut?
- release of 5HT (seratonin) from enterochromaffin cells stimulated by the drugs
- 5HT binds 5HT3 receptor that sends a message to CTZ to trigger vomiting
Aprepitant
neurokinin-1 R antatonist anti-emetic
used in combination with D2R antagonists and 5HT3R antagonists
Dexomethasone
glucocorticoid steroid
used in combo with other drugs for N & V
emetic drugs
- morphine, opioids, apo-morphine (D2R agonist)
- induce vomiting
- toxins
- aversion therapy
- reflex emetics via 5HT3 stimulation in the gut
- ipecacuanha (ipecac makes you yak!)
bulking agents
laxatives:
- bran
- psyllium
How do bulking agent laxatives work?
ingestable fibre that absorbs water to increase intestinal contents and stimulate normal reflex bowel activity
Docusate
- faecal softener/lubricant detergent laxative
- enhances mixture of water into faeces
- popular in combination with stimulant laxatives (eg with senna in Coloxyl)
Magnesium sulphate (Epsom salts)
- saline osmotic laxative
- causes osmotic fluid retention to increase fluid volume and stimulate defecation
stimulant laxatives
- bisacodyl, senna
- may stimulate myenteric plexuses, irritate intestinal mucosa or nerve endings to increase motility and reduce reabsorption of water and electrolytes
bisacodyl
stimulant laxative
senna
stimulant laxative
most commonly in combination with docusate (coloxyl)
Loperamide
opioid antidiarrhoeal
(does not cross BBB)
Simethicone
- defoaming polymer (coalesces gas bubles) anti-flatulent
- often combined with loperamide (anti-diarrhoeal)
- not absorbed by gut
- changes surface tension of air bubbles so that they combine
