pharm - GI drugs Flashcards
what stimulates chief cells ? result?
ACh, CCK, gastrin –> release of pepsinogen
prostaglandins in the stomach
are protective! stimulate mucous cell secretion (reduce inflammation)
vs rest of body where they cause inflammation
ECL cell secrete
histamine
major stimulatory mechanism for HCl secretion from parietal cells?
paracrine - histamine from ECL cells –> H2 receptor
imbalance between aggressive and defensive stomach mechanisms
peptic ulcer disease
antacids
neutralization of the HCl
4 –> aluminum hydroxide, magnesium hydroxide, calcium carbonate, and sodium bicarbonate
tums
sodium bicarbonate/ca carbonate
may increase gassiness and bloating due to CO2 product
antacids w effects on gastric motility
aluminum hydroxide –> DECREASE motility
magnesium hydroxide –> INCREASE motility
tums –> no effect
which antacid INCREASES gastric motility?
mg hydroxide
mucosal protective drugs
sucralfate (aluminum sucrose sulfate)
and
bismuth-subsalicylate
sucralfate
aluminum sucrose sulfate
forms a water insoluble viscous layer over ulcer tissue - maintenance therapy
**give on empty stomach!
-few side effects (constipation/dry mouth)
bismuth-subsalicylate
(pepto) does NOT neutralize acid –> binds to ulcer and
1) absorbs bile acids
2) stimulates mucous secretion
3) antibacterial effect on H pylori
* *aspirin sensitive people might be sensitive
* *turns stool black
what drug forms a viscous water insoluble layer over ulcer; non curative just maintenance
sucralfate
antimuscarinic agents?
dicyclomine and hycosamine
dicyclomine and hycosamine use?
antimuscarinic agents —-UNPLEASANT, bad side effects, rarely used to treat PUD
H2 receptor antagonists
and mechanism?
cimetidine, ranitidine
- used to treat ulcers
mech: structural analogs to histamine –> competitively inhibit histamine binding to H2 receptors - —REDUCE ACID SECRETION
Do H2 receptor antagonists have CNS side effects?
**they are hydrophilic so NO CNS side effects
H2 receptor antagonists have a ____ half life.
why is this not an issue?
short (2-3 hrs)
lack of significant side effects allow high/multiple dosages
which H2 receptor antagonist is the least ideal (most side effects)?
what are its negative effects?
cimetidine
- enhances prolactin and binds androgen receptos leading to gynecomastia, impotence and lactation issues
- inhbits cyt P450s –> prolongs half life of other drugs
PPIs
proton pump inhibitors - used to treat ulcers
omeprazole, esomeprazole, lansoprezole, pantoprazole
mech: inhibit the H K ATPase of gastric parietal cells with an irreversible covalent bond(kills the pump)
how PPIs get to the ATPase
prodrug as delayed release/enteric coated capsules–> absorbed as prodrug in duodenum –> circulation –> reaches parietal cell and is pumped into the acidic caniculi –> protonated by low pH –> active drug –> inactivates that same atpase
PPIs are most effective when…
how long is the effect?
–>taken 30-60 minbefore eating
when you are hungry the pumps begin pumping
they have half life of 1 hr, but since the ATPases are irreversibly inhibited, effect lasts days until new ones can be made
treatment of choice for zollinger ellison syndrome?
PPI
omeprazole
what is more effective for GERD: PPI or H2 antagonists?
PPI
do PPIs have CNS effects?
yes
PPIs side effects
- CNS, nausea, diarrhea
- prolonged suppression of acid secretion may increase c dificile colonization in stomach –> risk of pneumonia
- risk of spinal/hip fracture
- inhibits clopidrogel activation
Misoprostol
prostaglandin analog that inhibits gastric acid secretion and stimulates mucin secretion (protective just like PGE2)
why is misoprostol not used often?
1) PPIs are more effective and getting cheaper
2) potential abortifacient –> doesnt allow/aborts pregnancies
antimicrobial therapy for peptic ulcers
many ulcers have H pylori infection
Quadruple therapy - PPI + 2 antibiotics (tetracycline and metronidazole) + busmuth-subsalicylate
Concomittant therapy - PPI + 3 antibiotics (clarithromycin, metronadizole/tinidazole, and amoxicillin)
concommittant antimicrobial therapy
PPI + 3 antibiotics
clarithromycin. amoxicillin, and metronidazole/tinidazole
quadruple antimicrobial therapy
PPI + bismuth-subsalicylate + 2 antibiotics (tetracycline and metronidazole)
metoclopramide
increases gastric motility
D2 antagonist, 5HT3 antagonist, 5HT4 agonist
*binding to 5HT4 increases motility in 3 ways = 1) increase LES pressure, 2) increases rate of gastric emptying, and 3) decreases small bowel transit time
—-treats nausea associated with cancer treatment
why is metoclopramide not used alot?
central D2 side effects!
hyperprolactinemia, galactorrhea, parkinsonism, tardive dyskinesia
RISKY drug
cholinergic activity _____ motility
receptors?
increases
D2 antagonists
5HT3 antagonists
5HT4 agonists
adrenergic activity ____ motility
receptors?
decreases
opioid Mu receptor
5HT3 antagonists
emesis center
is the medulla - receives input from higher and lower areas and from area postrema (half in and half out of the BBB so good sensory)
receptor trigger zone has 5HT3, D2, and M1 receptors
treatment choice for cytotoxic (chemotherapy) drug emesis/nausea
1) 5HT3 antagonists are best (ondansetron or palonosetron)
2) NK1 antagonist - aprepitant
3) metoclorpramide (D2/5HT3 antagonist) - last option due to bad side effects
aprepitant
nk1 antagonist
treats CINV from cytotoxic/chemo
ondansetron vs palonosetron
both are 5HT3 antagonists
O - centrally acting - blocks peripheral and central emetic serotonin input
P - better for CINV
treatment for severe IBD?
TNF inhibitors, monoclonal Ab (-mab) –> INFLIXIMAB or etanercept
treatment for mild/moderate IBD?
salazines
they are converted to the active drug mesalamine (5-ASA)
anti-inflammatory and aspirin analog (aspirin sensitive ppl watch out!)
what is used to treat gut after antibiotic treatments?
probiotics to repopulate gut
what drugs can cause increased h pylori populatiion?
PPIs
treatment options for diarrhea?
loperamide
or
alosetron
loperamide
an opioid mu agonist (doesnt penetrate CNS so low abuse potential)
**DO NOT use with ulcerative colitis; can cause constipation and toxic megacolon
alosetron
5HT3 antagonist that blocks motility
usually 5ht3 antagonists promote motility BUT this is an exception
**ONLY use for diarrhea-predominant IBS
linaclotide
increases cGMP –> increased Cl/bicarb secretions in intestine
treats constipation predominant IBS
lubiprostone
bicyclic FA that opens Cl channel
treats opioid induced constipation
naloxegol
opioid antagonist that doesnt enter CNS
treats opioid induced constipation
two drugs to treat opioid induced constipation
lubiprostone
and
naloxegol
bulk laxatives
mild and slow acting that add fiber and water to gut
bran, psyllium, and methylcellulose
osmotically active agents
promote water retention in distal ileum/colon
sodium phosphate/bisphosphate (oral)
polyethylene glycol
stimulant laxatives
promote accumulation of water and salts in the colonic lumen and stimulate motility –> POTENT AND QUICK
(bisacodyl, senna)
