Pharmacology of Digestive System

treatment approaches of PUD

eradicating H.P
reducing gastric acid
mucosal protective agents

quadruple therapy for PUD H.P

bismuth, metronidazole, tetracycline, PPi

triple therapy for PUD H.P

PPi, amoxicillin, clarithromycin

while quadruple therapy is first line, when is triple therapy preferred for PUD

low resistance/exposure to atb

endings of H2-r antagonists

"tidine"

______ was the first H2-r antagonist but use is limited due to SE + DD interactions

cimetidine

moa of H2-r antagonists

act selectively on H2 r in stomach, competitive antagonists + reversible

cli of h2-r antagonists

PUD, acute stress ulcers (IV), GERD

what drugs are preferred to h2-r antagonists

ppis

pharmacokinetics of H2-r antagonists

distribute widely (milk + placenta), excreted in urine

which h2-r antagonists are available iv and require dosage adjustments in renal dysfxn

cimetidine, ranitidine, famotidine

SE h2-r antagonists

only cimetidine -> endocrine (gynecomastia + galactorrhea), CNS (confusion)

_______ inhibits cytochrome p450 and can interfere w/ warfarin, phenytoin and clopidogrel

cimetidine

PPis bind to __________ and suppresses secretion of _______ into gastric lumen

H+/k+-ATPase enzyme system
acids

ending of ppis

"prazole"

moa ppi

prodrugs w/ acid-resistant enteric coat -> removed in duodenum -> covalent bond w/ proton pump -> inhibits 90% acid secretion

an oral product containing ______ combined w/ _______ for faster absorption is available to decrease gastric acid secretion

omeprazole
sodium bicarb

cli ppi

GERD, erosive esophagitis, active duodenal ulcers, Zollinger-Ellison, prevention NSAID + stress ulcers

pharmacokinetics of ppis

orally -> taken 30-60m before breakfast or largest meal of day, excreted in urine and feces

which ppis are available iv

esomeprazole, lansoprazole, pantoprazole

se ppis

omeprazole + esomeprazole decreases clopidogrel
fractures, b12 + ca + mg deficiency, diarrhea + c. difficile colitis, pneumonia

cli prostaglandins

NSAID gastric ulcers

prostaglandins ending

"prostol"

CO misoprostol

pregnancy (uterine contractions)

SE PGs

diarrhea

_____ reduce gastric acidity + pepsin activity

antacids

when should antacids be taken

full stomach

2 antacids used

aluminum OH
magnesium OH

cli antacids

symptoms of PUD, heartburn, GERD

SE antacids

aluminum OH - constipation
magnesium OH - diarrhea

sucralfate

mucosal protective agent, aluminum OH + sucrose -> physical gel barrier

cli sucralfate

duodenal ulcers, prevention stress ulcers

why is sucralfate not used much

multiple daily dosing, DD interactions w/ PPis, H2 antagonists and antacids (needs acidic pH)

bismuth

mucosal protective agent w/ antimicrobial action + coats ulcer

which brainstem vomiting site is outside bbb

CTZ

_____ functions mainly in motion sickness

vestibular system

moa phenothiazines

block dopa r in CTZ

phenothiazines cli

emetogenic chemo drugs

__________ is a phenothiazine

prochlorperazine

ending 5-H53-r blockers

"setron"

moa 5-ht3-r blockers

block 5-ht3 r in periphery + CTZ

cli 5-ht3-r blockers

for CINV, administered as single dose before chemo

5-ht3 antagonists are metabolized by liver but only ________ need dosage requirements in hepatic insufficiency

ondansetron

SE 5-ht3-r blockers

only ondansetron + dolasetron = qt prolongation

the substituted benzamide, _______ is effective at high doses against chemo

metoclopramide

metoclopramide moa + SE

inhibition of dopa in CTZ -> extrapyramidal symptoms

metoclopramide cli

gastroparesis + CINV

moa butyrophenones

blocking dopa r

butyrophenones ending

"peridol" (droperidol + haloperidol)

cli droperidol

sedation in interventions (antiemetic)

why is droperidol last resort antiemetic

qt prolongation

benzodiazepines ending

"zepam" (lorazepam + alprazolam)

cli benzos

anticipatory vomiting

corticosteroids such as _______ are used alone for CINV

dexamethasone, methylprednisolone

substance p/neurokinin-1-r antagonists endings

"pitant"

substance P antagonists are used for _____ in combo w/ ______

delayed phase CINV
dexamethasone + 5-ht3 antagonist

substance P antagonists undergo hepatic metabolism by

CYP4A4 (many DD interactions)

SE substance P antagonists

hiccups

antiemetic combo: corticosteroids are given with

metoclopramide, phenothiazine and butyrophenone/benzo

antiemetic combo: metoclopramides are given in combo with

antihistamines (reduced extrapyramidal) or corticosteroids (reduced diarrhea)

best antiemetic combo for delayed CINV

substance P antagonist + 5-HT3 antagonist + dexamethasone

classes of antidiarrheal drugs

antimotility agents, adsorbents, drugs modifying fluid and electrolyte transport

2 antimotility agents

diphenoxylate + loperamide

moa of antimotility agents (diphenoxylate, loperamide)

opioid-like actions, activated presynaptic opioid receptors in enteric n system -> Ach inhibited -> less peristalsis

loperamide cli

acute + traveler's diarrhea

CO antimotility agent (diphenoxylate + loperamide)

children or colitis

adsorbents for diarrhea

aluminum hydroxide + methylcellulose

moa adsorbents

adsorb toxins/organisms + coat mucosa

bismuth cli for diarrhea

traveler's diarhea

SE bismuth

black tongue + stool

stimulant laxatives

senna and bisacodyl

opioid-induced constipation drug combo

senna + docusate

bisacodyl pharmokinetics

suppository or enteric-coated tablet, acts directly on n

irritant laxative

castor oil

CO castor oil

pregnancy (uterine contractions)

bulk laxatives

methylcellulose

psyllium adverse efect

reduce drug absorption (for 2h)

saline laxatives

magnesium citrate + OH

saline laxatives (magnesium citrate + OH) moa

hold water in intestines

PEG cli

colonic lavage for interventions

lactulose

osmotic laxative

cli lactulose

hepatic encephalopathy + constipation

stool softeners

docusate (Na + Ca)

cli docusate

prophylactic constipation

CO stool softeners

mineral oil

lubricant laxatives

mineral oil + glycerin suppositories

how should mineral oil be taken

upright position

Cl- channel activator

lubiprostone

moa lubiprostone

activates Cl- channels to increase fluid secretion in lumen

cli lubiprostone

chronic constipation + IBS-C

IBD mild/moderation symptoms treatment

aminosalicylates/corticosteroids

IBD chronic symptoms treatment

thiopurines, methotrexate, cyclosporin

_______ is an atb infusion for IBD

infliximab