GI protectants Flashcards
two major classes of drugs affecting GI system
drugs affecting secretion: antacids, H2 histamine receptor antagonists, PPIs
drugs affecting GI motility: prokineic, anti-diarrheal/emetic
drugs affecting GI secretions are used in the treatment of:
peptic ulcers (gastric or duodenal), GERD, and hypersecretory states such as zollinger-ellison syndrome
physiologic control of GI secretions
vary depending on the area where the cell is located
secretions controlled by many receptors and singals (histamine, ACh, gastrin) - lead to activation of proton pumps and acid pumped into stomach
ulcer
a failure of mucosal protection
antacids
NaHCO3, CaCO3, Al(OH)3, Mg(OH)2
NaHCO3
high neutralizing capacity
AEs: systemic alkalosis, fluid retention
CaCO3
moderate neutralizing capacity
AEs: hypercalcemia, nephrolithiasis, milk-alkali syndrome
Al(OH)3
high neutralizing capacity
AEs: constipation**, hypophosphatemia
Mg(OH)2
high neutralizing capacity
AEs: diarrhea**, hypermagesemia
commercial antacids
alternagel - Al(OH)3
maalox, mylanta - Al(OH)3 and Mg(OH)2
tums - CaCO3
gaviscon (sodium alginate + antacids) - viscous, weak base, prevents reflux, effective in GERD
1st generation H2 receptor antagonist
cimetidine
competitive antagonist
reduce gastric acid secretion in response to histamine, gastrin, ACh
inhibits CYP 2C6 and 2D9: warfarin, phenytoin, theophylline, benzos, sulfonylureas
SE: CNS effects (delerium) with IV adin to elderly, antiandrogen (gynecomastia, impotence), inhibition of estradiol metabolism (galactorhhea), thrombocytopenia
2nd gen. H2 receptor antagonists
ranitidine, nizatidine, famotidine
competitive antagonist of H2 histamine receptor
reduce gastric acid secretion in response to histamine, gastrin, ACh
longer half life than 1st gen
increase ethanol bioavailability by reducing first-pass meabolism (not famotidine)
fewer effects on CYP
greater potency
PPI examples and actions
esomeprazole, lansoprazole, rabeprazole, pantoprazole
actions:
prodrugs: activated by acid
irreversible inhibitor of H+/K+ATPase
short t1/2 but long duration of action* due to covalent inhibition
hypergastremia occurs and may result in rebound hyper secretion of gastric acid upon withdrawal
inc in gastric pH can affect drug absorption and potentially increase risk of infections
PPI AEs
few, nausea most common, can cause vit B12 deficiency
drug interactions:
omeprazole inhibits CYP2C19: diazepam, warfarin, phenytoin levels increase, clopidogrel activity may be reduced
all PPIs: decreased absorption of digozin and ketoconazole (increased gastric pH)
H2 antagonist may be beneficial at what time of day?
they show effect at night
PPIs work around the clock
acid rebound
inc gastric acid secretion upon withdrawal of suppressing medication (most common w H2 antagonists)
reduced gastric acid removes somatostatin inhibition of gastric secretion - hypergastrinemia
sucralfate
mucosal protective aluminum hydroxide complex of sucrose polymerizes and forms protective barrier at ulcer site acidic pH activates complex poorly absorbed
misoprostol
mucosal protective agent semi-synthetic PG E1 derivative reduced acid secretion (parietal cell) cytoprotectant effects - enhanced mucus and bicarbonate secretion used in combination with chronic NSAIDs adverse effects: diarrhea, abortifacient
infection causing ulcers
H. pylori in the gastric mucosa
therapy: bismuth salt (pepto), antibiotic (metronidazole, tetracycline, amoxicillin, clarithromycin), H2 or PPI, ranitide bismuth citrate
pepto bismol
bismuth subsalicylate - converted to bismuth salts and salicylic acid in GI tract
antibacterial, antiviral and antisecretory activity
uses: treatment of mild diarhhea and part of therapy for H. pylori eradication
drugs affecting GI motility
increase motility: laxative, prokinetic
decrease motility: antidiarhheals, antiemetics
bulk and saline laxatives
psyllium, methylcellulose, bran, milk of magnesia, non-absorbable sugars
non-absorbable and form hydrophilic mass in the presence of water
inc water in the intestinal lumen by osmotic force, leading to distention and an increase in peristalsis
isosmotic electrolyte solutions with polyethylene glycol produce similar effects
stool softeners
docusate sodium (colace), mineral oil, glycerin
surfactantants and lubricants
incorporate into stool to make passage easier and decrease water absorption
lubricate lower bowel to reduce fetal impaction
can decrease absorption of fat soluble vitamins
stimulant laxatives
poorly understood mechanism
castor oil-hydrolyzed in the upper small intestine to ricinoleic acid
bisacodyl (dulcolax), cascara, senna, and aloes
stimulate peristalsis
prokinetic drugs
can act on many parts of the cholinergic motor neuron / smooth muscle system that affects bowel movements increase GI motility
metoclopramide
prokinetic drug
D2 dopamine receptor antagonist
-blockade of D2 receptors in the myenteric plexus leads to increase ACh release
-this blockade produces anti-emetic effects
-clinical uses: promotes gastric emptying to facilitate small bowel intubation, post-op and diabetic gastroparesis, GERD
side effects: sedation, EPS, hyperprolactinemia (hynecomastia, galactorrhea, breast tenderness)
Chloride Channel activators
increase motility by increasing chloride-rich fluid secretion into intestine
for treatment of IBS + constipation
not absorbed systemically (low SE)
lubiprostone (amatiza) - stimulation of type 2 chloride channel (ClC-2) activator in small intestine
linaclotide (linzess) - a peptide activator of guanylate cyclase 2
anti-diarrheals
slow peristalsis to increase water and electrolyte absorption
bismuth (pepto bismol)
bile-salt binding resins
-cholestryamine, colestipol, colesevam
-ion exhchange resins
-diseases of terminal ileum (Crohn’s)
-decrease diarrhea caused by osmotic imbalance due to excessive bile salts
decrease absorption of many drugs and fat-soluble vitamins
opiates
inhibit presynaptic cholinergic nerves
- diphenoxylate (with atropine to discourage OD; lomotil)
- loperamide (imodium)
- poorly traverse the BBB
- act locally to delay gastric emptying
- contraindicated in patients with severe ulcerative colitis and bacterially-induced diarrhea
IBS
abdominal pain and distention + altered bowel habits
alosetron (lotronex) - 5HT3 receptor antagonist
-for women with IBS + diarrhea
-blocks visceral afferent pain sensation and decreases colon motility
-GI SE: constipation, ischemic colitis (sometimes fatal)
-withdrawn and reintroduced via a restricted prescribing program in 2002
anticholinergics
dicyclomine and hyoscamine
inhibit muscarinic cholinergic receptors
antispasmodic
toxicity due to anticholinergic effects
anti-emetics
serotonin receptor antagonists
ondansetron, granisetron, dolastron, palonostron
block activity in CTZ and vagal afferents from stomach and small intestine which activate CNS emetic centers
clinical use: NV associated with chemotherapy
SE: constipation
treating NV in chemo
combine antiemetics with different properties
5HT3 + corticosteroids (enhance activity) or aprepitant (NK1 antagonist - brain receptors in chemoreceptor trigger zone)
cannabinoids
dronabinol (marinol), nabilone (Cesamet) synthetic THC treat NV associated with chemo therapy limited to patients who are refractory to other agents mechanism unclear may experience psychoactive effects
motion sickness treatment
antihistamines/anticholinergics
diphenhydramine - H1 antihistamine with ACh properties
meclizine - H1 antihistamine with minimal ACh properties
scopolamine - muscarinic receptor antagonist with significant ACh effects that are tolerated as a transdermal patch
antipsychotics as antiemetics
D2 dopamine receptor antagonists antiemetic and sedative properties prochloperazine (compazine), promethazine, thiethylperazine - also inhibit muscarinic receptors, antihistamine effects droperidol - IV metoclopramide, trimethobenzamide
