GI Drugs 1 Flashcards
what are the second generation H2 receptor antagonists?
ranitidine, famotidine and nizatidine; better than the first generation H2 receptor antagonist which is cimetidine because 2nd generation has no anti-adrenergic or CNS adverse effects
motilin in GI peristalsis ↑ GI motility by binding to ______ or _______
- binds directly to the motilin receptor on the muscularis layer
OR - binds to the enteric neuron which then releases acetylcholine that binds to the M1 receptor on the muscularis layer
triple therapy for H. Pylori eradication lasts for ______ days. what are the drugs used in triple therapy
10-14 days
clarithromycin + amoxicillin + PPI
OR
clarithromycin + metronidazole + PPI
what receptors does metoclopramide work on?
- D2 (dopamine) receptor ANTAGONIST
- vagal and central 5HT3 ANTAGONIST
- 5 HT4 agonist
effects confined to the upper digestive tract
why can’t you give misoprostol to pregnant patient?
it has abortifacient effects (cause uterine contractions)
what receptors are involved in the motion sickness cause of vomiting
H1 and muscarinic receptors in cerebellum
describe the mechanism by which prostaglandin ____ is protective
E2; it is coupled to a Gi receptor which DOWNREGULATES the adenylate cyclase activity → ↓ cAMP release → ↓ proton pump
when would you use quadruple therapy for H. pylori eradication?
what are the drugs and how long does this last?
- give quadruple therapy for patients with H. pylori infection in endemic regions where there is macrolide resistant H. pylori
- bismuth subsalicylate (antacid) + metronidazole + tetracycline + PPI
- lasts 14 days
_______ is an analog of PGE1
misoprostol
clopidogrel is converted to the active form via ________
CYP2C19
what are the complications of peptic ulcer disease
- upper GI bleeding
- gastric/duodenal perforation
- gastric outlet obstruction
what drugs are H1 antagonists? what can they be used for?
- lizine: meclisine and cycling
- diphenhydramine
can be used for motion sickness and postoperative emesis
blackening of the stool and tongue is seen with use of what drug?
bismuth subsalicylate (harmless)
are msucarinic (m1) receptor agonists good agents for ↑ GI motility?
no because they dont create a coordinated contraction; for a coordinated contraction want to use a drug that works at the level of the enteric neurons or higher
aprepitant can affect the metabolism of many drugs such as warfarin and oral contraceptives because _________
aprepitant undergoes extensive CYP3A4 metabolism
M___ receptor is repsobiblry for GI motility
M1
why do you give PPI’s as part of the triple therapy for H. pylori infection
- direct antimicrobial properties of PPI’s
- raises gastric pH thus lowers the minimal inhibitory concentrations of antibiotics needed to clear the organism because the ↑ in pH causes the organism to divide and that is when it is most susceptible to destruction
explain the triple therapy for H. Pylori eradication
2 antibiotics + 1 PPI
PPI’s ______ bind to the H/K ATPase pump
irreversibly
how do benzodiazepines help treat nausea? q
- reduce the anticipatory component of nausea and vomiting and thus works on the cerebrum
NO INTRINSIC ANTIEMETIC EFFECTS
misoprostol is an analog of _____
PGE1
all three compounds ultimately activates ______ which then increases the acid secretion into the gastric lumen by ______
protein kinase which then ↑ the activity of the K/H protein pump in the parietal cells: H+ is pumped into the gastric lumen when K is pumped into the parietal cell
how do corticosteroids help treat nausea in patients with metastatic cancer?
- suppression of peritumoral inflammation and prostaglandin production
drugs: dexamethasone and methylprednisolone
extrapyramidal effects are an AE of what drugs
promethazine and droperidol
antacids are a _______ antagonist
chemical; does NOT act on any receptor but rather converts the acid into a salt and water
what is the MOA of benzodiazepines
facilitate GABA action in the CNS by ↑ frequency of chloride channel opening
______ ulcers are alleviated by eating
duodenal
misoprostol binds to the ______ receptor and situates the ______ pathway
EP3 receptor → stimulates Gi pathway to DECREASE gastric acid secretion
antacids should NOT be co-admistered with what 4 types of drugs
tetracyclines, fluoroquinolones, itraconazole and iron therapy
______ antagonists are the DOC for prophylaxis against immediate CINV (chemotherapy induced nausea and vomitin)
5HT3 antagonists
CANNOT BE USED FOR DELAYED CINV OR MOTION SICKNESS
what would you give for triple therapy for H. pylori infection in patients with allergy to penicillin?
- carlithromycin + metronidazole + PPI
usually would give amoxicillin instead of metronidazole in non penicillin allergic patients
what three compounds lead to the release of acid in the stomach?
- histamine : activate adenylate cyclase and ↑ cAMP due to Gs
- Acetylcholine (M3 which is Gq protein) : release Calcium
- Gastrin (CCKb) : release calcium
cimetidine is a potent ______ of the CYP450 system. this can affect the concentration on which 3 drugs
INHIBITOR; can cause ↑ serum concentration of: warfarin, diazepam and phenytoin
how can blood borne emetics cause vomiting?
blood borne emetics include
the blood born emetics act on the area prostrema chemoreceptor trigger zone
receptors: 5HT3, D2, M1, CB1
and also causes irritation of the stomach and SI (receptors: 5HT3)
chemotherapy agents
can erythromycin be used for longer term therapy
NO because rapid down regulation of motilin receptor lets to early tolerance
______ is an antacid that can cause osmotic diarrhea
magnum hydroxide
what are some adverse effects of PPI’s?
- B12 deficiency
- CAP and C. difficile infection
- HYPOmagnesemia → ↓ absorption of calcium → osteopenia
________ are the most potent inhibitors of gastric acid secretion
PPI; effectively suppress basal and meal release of astray acid
-setron drugs are _______ drugs
5HT3 antagonists; ondansetron and granisetron
what are the 4 main inputs into the medulla emetic center?
- cerebrum (anticipation/fear)
- cerebellum (motion sickness, H1 receptor and Muscarinic receptor)
- area prostrema (5Ht3, D2, M1, CB1)
- solitary tract nucleus (5HT3, D2, M, H1, NK1, CB1)
of the two methods of gastric acid secretion: ______ and ______, H2RA’s strongly suppress the ________ gastric acid secretion
basal and meal stimulated;
H2RA’s strongly suppress the BASAL gastric acid secretion with moderate effect on meal stimulated release
what are the receptors on the solitary tract nucleus
5HT3, D2, M, H1, NK1, CB1
_____, _____ and ______ are PPI’s that inhibit CYP2C19 which is required for the activation of what drug?
omeprazole, esomeprazole and lansoprazole
CYP2C19 is required for the activation of the prodrug Clopidrogrel
gastrin binds to _______ receptor
CCKb
histamine works on the ____ receptors
H2; the effects of H2 antagonists are mainly upstream
what are some AE of metoclopramamide?
- extrapyramidal effects (due to the D2 receptor antagonist effect) commonly sen in kids and young adults
- galactorrhea (↑ release of prolactin due to D2 receptor antagonism)
sucralfate binds via charge interaction; it is ______ charged and the ulcers are _______ charged
negative; positive
gastric ulcers are alleviated/worsened by eating
worsened
what is the effect of metoclopramide on the LES tone?
↑ the LES tone (can be used for GERD) and stimulates antral and SI contractions
which PPI is associated with CYP450 metabolism?
omeprazole (CYP450 INHIBITOR)
drugs that will have ↑ concentration: warfarin, diazepam and phenytoin
drugs that end in _______ are PPI’s
-prazole
omeprazole, esomeprazole, lansoprazole, rabeprazole, pantoprazole
______ is a macrolide that has the highest incidence of diarrhea as a side effect. why?
erythromycin because it has agonist effects at the motilin receptor
what vitamin deficiency is an adverse effect of cimetidine use?
B12 deficiency (and myelosuppression). because cimetidine can ↑ gastric pH making it harder for pepsin to cleave off the B12 from animal products
_______ is a pro kinetic drug that is no longer prescribed due to potential to induce serious and fatal cardiac ventricular arrhythmias
cispapride; (5HT-4 receptor agonist)
promethazine and droperidol can be used in what area that causes emesis?
these are D2 receptor antagonists and this receptor can be found on the CTZ (chemoreceptor trigger zone) in the area prostrema
________ is a mucosal protective agent that binds selectively to ulcers
sucralfate; binds by charge interaction because it is negatively charged and the proteins of the ulcer are positively charged
PPI’s put people at risk for what kind of infections?
CAP and C. difficile colitis
if your patient had a recent MI and is taking clopidogrel, and now needs PPI’s because he has GERD, what are some PPI’s you can prescribe him and why?
- give pantoprazole or rabeprazole because omeprazole, esomeprazole and lansoprazole are CYP2C19 inhibitors and CYP2C19 is required to convert clopidogrel to the active form
can H2 receptor antagonists be used for long term therapy? how long does it take to work and how long do the effects last?
no cannot be used for long term therapy because build resistance and tachyphylaxis develops within 2-6 weeks
onset: 2.5 hrs
duration: 4-10 hours
what are 3 mechanisms by which misoprostol is protective
- ↓ gastric acid secretion by simulation Gi
- stimulates mucus and bicarbonate secretion
- enhances mucosal blood flow
promethazine and droperidol are use to effectively treat what symptom?
motion sickness;
NOT effective in CINV
_______ receptors are found in critical sites involved in chemotherapy induced vomiting
5HT3
______ and ______ are D2 antagonists
promethazine and droperidol
_______ is useful for treated delayed CINV
aprepitant / fosaprepitant
bismuth salicylate is contraindicated in patients with renal failure due to accumulation of ______
salcyclate
what are some adverse effects of calcium carbonate antacids?
- belching caused by carbon dioxide and can lead to alkalosis
solitary tract nucleus causes emesis by receiving input from: ___________
area prostrema and the stomach/SI irritations (vagal and sympathetic afferents)
______ is an antacid the can cause constipation
Aluminum hydroxide
NK1 antagonists (_________) are usually given in combination with ______ and ________
aprepitant/fosaprepitant
given with dexamethasone and a 5HT3 receptor antagonist
erythromycin is the DOC for what GI condition
diabetic gastroparesis
how does serotonin ↑ GI motility?
binds to 5HT-4 receptors on the enteric neuron which then releases Ach onto the M1 receptor
the most common side effect of sucralfate is _____
constipation
sucralfate should not be given with ______ antacids
aluminium containing antacids or in patients with renal failure and are at high risk for aluminum overload
