GI Pharmacology - Acid Suppressors and Anti-Nausea Agents Flashcards
Gastrin receptor?
- CKK-receptor
Acetylcholine receptor?
- M3-receptor (muscarinic)
Histamine receptor?
- H2- receptor
Prostaglandin receptor?
- PGE-receptor
Stimulatory G-protein signalling?
Gastrin, Ach, Histamine
Inhibitory G-protein signalling?
Prostaglandin
H2-Blocker mechanism of action?
Competitive block of H2-R on parietal cells
Common H2-Blockers? (3)
- Cimetidine
- Ranitidine
- Famotidine
Therapeutic uses of H2-Blockers? (3)
- Ulcers
- Management of Zollinger-Ellison syndrome (?)
- GERD
What type of infection are H2-blockers often associated with?
H. pylori
Mechanism of action of anticholinergics?
Block M3-receptors on parietal cells
What NT normally acts on M3 receptors? Which nerve releases this NT at the level of the viscera?
Acetylcholine - Vagus nerve
Therapeutic uses of anticholinergics?
Ulcers
PPI mechanism of action?
H+, K+-ATPase inhibition
Specific PPI medications?
- Omeprazole
- Esomeprazole
- Pantoprazole
Therapeutic uses of PPIs?
- Ulcers
- GERD
- Management of Zollinger-Ellison syndrome
Which do you think would be more effective to manage Zollinger-Ellison syndrome, H2-blockers or PPI’s? Why?
Better with PPI, as inhibits HCl from all stimulatory routes (gastrin, ACH, histamine) and not just via H2 receptors
What are prostaglandins considered?
Eicosanoids
What are the two structural categories of lipids?
- Triglycerides and phospholipids
What specific lipids are most eicosanoids derived from?
Arachodonic acid
Mechanism of action of PGE1 analogues? (2)
- Decreased proton pump activity
- Increased bicarbonate and mucous secretion
PGE1 medication analogue?
Misoprostal
Therapeutic use of PGE1 analogues?
Most common = prevention of NSAID-induced ulcer/GI bleed
What is the connection between NSAIDs and PGs including the enzymes involved?
NSAIDs block COX, which blocks production of PG’s
Why is Misoprostol contraindicated in pregnancy?
Causes uterine contractions
Agents that decrease motility?
- Diphenoxylate-atropine (Lomotil)
- Loperamide (Imodium)
Agents that increase motility?
- Laxatives
- Metoclopramide (Maxeran, Reglan)
- Domperidone (Motilium)
Diphenoxylate-atropine mechanism of action - DIPHENOXYLATE?
- Opioid receptor agonist
- Inhibits ACH release in enteric system at low doses
What does Ach usually do for gut motility?
Increases gut motility
Diphenoxylate-atropine
mechanism of action - ATROPINE?
M-blocker = Synergistic effects with diphenoxylate to decrease Ach effects on the gut
What are the side effects of anticholinergics? What does this cause?
Dry mouth - low abuse potential
Anticholinergic side effects occur before _______ effects are felt?
Euphoric opioid
Drug similar to diphenoxylate-atropine, but without the atropine?
Loperamide
Why does Loperamide lack CNS effects - therefore having an extremely low abuse potential?
Does not cross BBB
Laxative mechanisms? (4)
- Bulking agents
- Osmotic laxatives
- Chemical stimulants
- Stool softeners
Examples of Bulking laxatives?
Bran, psyllium
Non-absorbed agents that create bulkier stools and draw water into stools?
Bulking laxatives
Examples of Osmotic laxatives?
Mg sulfate, Mg hydroxide, lactulose
Osmotic laxatives are not well-absorbed from the intestinal tract, what does this cause?
Increase in osmotic pressure leading to retention of water in intestine, lumen extension, and increased bowel action
What can low dose of Mg hydroxide do?
Can neutralize stomach acid
What is lactulose?
Disaccharide that is not broken down well in the SI
=> Reaches colon, broken down by bacteria to produce lactic acid
Will lactulose increase or decrease excretion of ammonia? Why?
Increase => charged so less likely to be reabsorbed and therefore more likely to be excreted
Examples of chemical stimulant laxatives?
Emodin (active ingredient in senna, aloe, cascara)
What is the mechanism of action of chemical stimulants?
Irritate the gut to induce peristalsis and increase mucous production
Examples of stool softeners?
Mineral oil, sodium docusate
What do stool softeners use?
Water or oil to soften stool
What does mineral oil do?
Lubricates stools for easier passage
What does sodium docusate do?
Detergent that allows water to penetrate stools = prevents hard, dry stools and allows for easier passage
Metoclopramide mechanism of action for increased motility?
Block of peripheral D-receptors (dopamine is inhibitory to GIT)
What does blocking dopamine result in?
Allows Ach effects to predominate:
- Increased peristalsis
- Increased tone of LES
Metoclopramide mechanism of action for anti-nausea/vomiting?
Antiemetic action comes from block of D2-receptors in medulla (trigger zone from vomiting)
Therapeutic uses of Metaclopramide for nausea and vomiting?
- GERD
- Diabetic gastric stasis
- Nausea and vomiting with chemo
What happens when you take the peripheral effects of Metoclopramide too far?
Diarrhea
Blocking dopamine causes increased prolactin, which can cause?
Hyperprolactinemia
What is similar to metoclopramide, but less likely to cross BBB or into breast milk?
Domperidome
How can domperidone stimulate milk production in lactating mothers?
Increased prolactin
How do anticholinergics have anti-nausea effects?
Block cholinergic transmissions between vestibular and vomiting centers in the CNS
Specific anticholinergic anti-nausea agents?
- Scopolamine (M-receptor)
- Promethazine (M-blocker and H1-blocker)
