61-62: GI protectants Flashcards
Drugs that increase GI motility
-laxatives
-prokinetic drugs
Drugs affecting gastric secretion
-Antacids
-H2 histamine receptor antagonists
-Proton Pump Inhibitors
-Protectants
Drugs that reduce GI motility
-antidiarrheals
-anti-emetics
Acid-peptic disease
-non-ulcer dyspepsia (indigestion)
-gastric and duodenal ulcers
-GERD
-hypersecretory states (Zollinger syndrome)
Physiologic control of GI secretions
-slide 10-13
Antacids
-systemically absorbed: NaHCO3 and CaCO3
-minimally absorbed: Al(OH)3 and Mg(OH)2
NaHCO3
-systemic
-high efficacy
-alkalosis, fluid retention, gas)
-alkaseltzer
CaCO3
-systemic
-moderate efficacy
-hypercalcemia, nephrolithiasis, milk-alkali syndrome, CO2
-Tums and Rolaids
AlOH3
-minmally absorbed
-high efficacy
-contipation, hypophosphatemia
-encephalopathy if absorbed
-AlternaGEL and Maalox
MgOH2
-minimal absorption
-high efficacy
-diarrhea
-CNS toxicity if absorbed
-Maalox and Rolaids
AlternaGEL
-AlOH3
-antacid
-minimal absorbed
Tums
-CaCO3
-systemic
-mod efficacy
-antacid
Maalox/Mylanta
-AlOH3 and MgOH
-minimally absorbed
Rolaids
-CaCO3 and MhOH
-antacid
Alka-seltzer
-ASA and NaHCO3
Gaviscon
-sodium alginate + antacids
-viscous, weak base
-prevents reflux
-effective in GERD
Commercial antacids
-AlternaGEL
-Tums
-Maalox.Mylanta
-Rolaids
-Alka-seltzer
-Gaviscon
Histamine Receptor Antagonists
-slide 16-19
Cimetidine (tagamet)
-competative antagonist of H2
-reduce gastric secretion in response to histamine, gastrin, acetylcholine
2nd gen H2 blockers
-Rantidine (NO_
-Nizatidine
-Famotidine
Nizatidine (axid) and famotidine (pepcid
-2nd gen H2 antagonists
-reduce acid secretion in response to histamine, gastrin, acetylcholine
-longer hlaf life
-fewer CYP effects
-greater potency
-absorbed quickly to reduce parietal cell function
Proton Pump inhibitors
mech slide24-25
PPI drugs
-Benzimidazoles
-six ring next to 5 ring
-or Vonoprazan (P-CAB)
Benzimidazoles (PPI drugs)
-Esomeprazole (nexium)
-omeprazole (prilosec)
-lansoprazole (prevacid)
-rabeprazole (aciphex)
-pantoprazole (protonix)
-dexlansoprazole (dexilant)
Omeprazole (prilosec) vs eSomeprazole (nexium
-omeprazole racemic
-eSomeprazole is S enantiomer
-more potent
PPI action
-must be absorbed in SI, circulate and then be taken up by parietal cells = SLOW onset
-prodrugs activated by acidic pH in parietal cell
-irreversible inhibitor of H/K ATPase
-short plasma half-life (1 hour) but long duration of action due to covalent inhibition (>24 hours) and slow turnover of proton pumps
-hypergastrinemia occurs and may result in rebound hypersecretion of gastric acid upon drug withdrawal
Acid rebound
-inc acid secretion upon withdrawal of acid suppressing medications
-reduced gastric acid removes somatostatin’s inhibition of gastrin secretion (HYPERgastrinemia)
-tolerance to H2 antagonists can occur
PPI risks
-inc risk of infection
-vitamin b12 deficiency
-dec Ca absorption/inc bone fractures
-dementia?
-maybe bc calcium is dec and PTH is inc which takes Ca out of bone to replace blood levels
Vonoprazan
-PPI
-K-competative acid blocker (P-CAB)
-adbantages: faster acid suppresion, not prodrug, not influenced by meals, very stable in low pH
Mucosal Protective Agents
-Sucralfate (Carafate)
-Misoprostol (Cytotec)
-affect secretion
Sucralfate (carafate)
-mucosal protective agent
-al hydroxide complex of sucrose
-polymerices and forms protective barrier at ULCER site
-acidic pH activates complex
-poorly absorbed (big ugly charged molecule)
Misoprostol
-semi-synthetic prostaglandin E1 derivative
-reduce acid secretion pariteal cell
-cytoprotectant effects (enhance musuc and bicarbonate secretion)
-used in combo w chronic NSAIDs
-diarrhea, abortifacient
Ulcers
-failure of mucosal protection
-many associated w H. pylori infection (gram-neg)
H. Pylori eradication
-bismuth subsalicylate
-antibiotic (metro, tetra, amox, clar)
-H2 blocker or PPI
-combo them
Bismuth subslicylate
-converted to bismuth salts and salicylic acid in GI tract
-antibacterial/viral/secretory
-treat nausea, heartburn, indigestion, upset stomach, diarrhea
-part of multi-drug therapy for H. pylori eradication
Drugs that INCREASE GI motility
-laxative
-prokinetic drugs
Intrinsic nerve plexuses
-myenteric
-submucosal
-idk man watch the vid
Bulk and Osmotic ? Laxatives
-cellulose, agar, bran, linseed complex
-form hydrophillic mass in presence of water
-inc water in intestinal lumen by osmotic force = inc distension = inc peristalisis
Bulk and osmotic laxative
-fibers
-PEG3350 (miraLAX)
-isosmotic electrolyte solutions with PEG 3350 (GoLytely) produce similar effects
-Lactulose
-Maltitol in some sugar free gummies
Fiber laxatives
-bulk and osmotic
-psyllium (metamucil)
-methylcellulose (citrucel)
-calcium polycarbophil (fiberCon)
Types of laxatives
-bulk and osmotic
-stool softeners
-secrectory/stimulant
Lactulose
-non aborbable sugar
-osmolytic effect
-also fermeted by gut flora which inc peristalisis
Stool softener mech
-inc into stool to ease passage
-dec water absorption
-lube lower bowel
-can dec absorption of fat-soluble vitamins
Stool softeners
-docusate sodium (Colace)
-mineral oil
-glycerin
-surfactants and lubricants
Secretory/Stimulant laxatives mech
-poorly understood
-irritation of mucosa affects fluid secretion/absorption balance and induces peristalsis
Secretory/stimulant laxatives
-castor oil
-diphenylmethane derivatives (bisacodyl dulcolax)
-anthraquinones (cascara, senna, aloes)
Castor oil
-stimulant lax
-hydrolyzed in upper SI to ricinoleic acid
Common GI HYPOmotility disorders
-gastroparesis
-ileus
-opioid-induced constipation
Gastroparesis
-neuropathy during diabetes or Parkinson’s disease
Ileus
-small bowels don’t recover after surgery
Prokinetic drugs
-Metoclopramide (reglan)
-Prucalopride (motegrity)
-Tegaserod (Zelnorm)
-Tenapanor
-opioid ANTAgonists
-chloride channel activators
Metoclopramide (Reglan)
-D2 ANTAgonist
-block D2 in myenteric plexus
=inc aCH release
=anti-emetic effects
-promotes gastric emptying to facilitate small bowel intubation, post-op and diabetic gastroparesis, GERD
-can lead to acute dystonic reactions
Opioid ANTAgonists
-Central: Naloxone (Narcan), Naltrexone, nalmefene
-Peripheral: nalozegol, alvimopan, naldemedine
Prucalopride (Motegrity)
-5HT4 AGONIST
-serotonin receptor = GPCR = inc cAMP = release AcH
-treat chronic idiopathic constipation in adults
Tegaserod (Zelnorm)
-5HT4 AGONIST
-treat IBS with constipation in WOMEN UNDER 65
Chloride channel activators
-prokinetic
-inc chloride-rich fluid secretion into intestine
-treat IBS + constipation
-not systemic
-lubiprostone and linaclotide
Lubiprostone
-type 2chloride channel activator in small intestine
Linaclotide and Plecanatide
-peptide activator of guanylate cyclase C
Sodium/hydrogen exchanger inhibition
-prokinetic
-Tenapanor or enema
-dec Na absorption = inc Na in gut
-Na in gut leads to inc water, accelerating poop
Tenapanor
-Sodium/H exchanger inhibition
-prokinetic drug
-inc Na and water in gut
Slide 70
prac question
Drugs that REDUCE GI motility
-antidiarrheals
-anti-emetics
Anti-diarrheals
-slow peristalsis to inc water and electrolyte absorption
-opiates
-5HT3 ANTAgonist
Anti-diarrheal opiates
-inhibit presynaptic cholinergic nerves
-Diphenoxylate active in the CNS
-Loperamide (poorly cross BBB, act locally)
5HT3 ANTAgonist
-anti-diarrheal
-alosetron
-ondansetron, franisetron, dolasteron, palonosetron
-blocks visceral afferent pain and dec motility
-contipation, ischemic colitis side effects
Intrinsic primary
Extrinsic prim afferent neuron
-nausea, vomiting, pain
ENS neuron
-inc peristalsis
-setrons (5th3 ANTAagonists) use
-nausea, vomiting associated w chemo
-seide effects constipation
Anti-emetics
-NK1 ANTAgonists
-Antihistamines/anticholinergics
NK1 ANTAgonists
-Aprepiant
-Netupitant
-Rolapitant
-receptors in chemo trigger zone
-combined w 5-HT2 ANTAgonists
Antihistamines/anticholinergics
-H1 ANTAgonists and one muscarinic receptor antagonist
-PREVENT motion sickness
-anti-emetic
H1 ANTAgonist anti-emetics
-dimenhydraminate (dramamine
-Meclizine (antivert)
-promethazine
Scopolamine
-muscarinic receptor ANTAgonist
-PREVENT motion sickness with his H ANTAgonist buddies
Anti-emetic drugs
-antihistamines/anticholinergics
-D2 ANTAgonists
D2 ANTAgonists
-anti-emetic and sedative
-antimuscarinic and antihistamine effects
-can cause acute distonic reactions
-Metoclopramide (Reglan)
-Prochlorperazine = Compazine
-Droperidol (Inapsine)
Opioid-induced constipation can also be avoided by using a biased agonist
-activation of opioid recptors in myenteric plexus
-dec smooth musc contractin
-inc rectal sphinter tone
-dec secretion
-block B arrestin inc analgesia
