B5.048 Gastrointestinal Pharmacology Flashcards
(102 cards)
1
Q
most common GI secretory disorders
A
acid peptic disease
GERD
2
Q
lifetime prevalence of peptic ulcers
A
10%
3
Q
lifetime prevalence of GERD
A
50%
4
Q
examples of motility disorders
A
vomiting
diarrhea
constipation
5
Q
therapeutic goal of PPIs
A
inhibit gastric acid secretion
6
Q
therapeutic goal of H2 antagonists
A
inhibit gastric acid secretion
7
Q
therapeutic goal of antacids
A
neutralize gastric acid
8
Q
therapeutic goal of mucosal protective agents
A
acid barrier in necrotic tissue
9
Q
therapeutic goal of antimicrobial agents
A
eradicate H.pylori
10
Q
mechanism of PPIs
A
benzimidazole compounds that irreversibly inhibit the parietal cell proton pump (H+/K+ ATPase)
covalent chelation
11
Q
discuss the activation of PPIs
A
pro-drugs that are inactive at neutral pH
- activation requires an acidic environment (take with meals to stimulate acid secretion)
- unstable at low pH, so degradation in esophagus and stomach is prevented by enteric coating of tablets that dissolve only at alkaline pH
- enteric coating dissolves and pro-drug is absorbed in the intestines
- blood circulation carries pro-drug to parietal cells, where it accumulates in the secretory canaliculi
- finally activated at acid pH and binds to sulfhydryl groups on the H+/K+ ATPase
12
Q
how to PPIs maintain efficacy with chronic use? aka…how do they get activated when you’re stopping acid secretion
A
parietal intracellular canaliculi where pro-drug is activated is UPSTREAM from the proton pump target in luminal membrane
13
Q
names of PPIs
A
esomeprazole omeprazole lansoprazole dexlansoprazole pantoprazole rabeprazole
14
Q
why are PPIs the most effective drugs for acid secretion suppression
A
inhibit gastric response to all stimuli (neural, gastrin, histamine)
inhibitions persists after withdrawal of drug, takes time to synthesize new proton pumps to replace inhibited ones
15
Q
adverse effects of PPIs
A
generally well tolerated most common: GI effects CNS effects skin rahses diarrhea due to GI bacterial overgrowth due to removal of natural acid barrier hypergastrinemia in 5-10%
16
Q
pharmacokinetics of PPIs
A
hepatic metabolism
renal clearance
17
Q
H2 receptor agonist preparations
A
cimetidine famotidine nizatidine ranitidine all equally effective, rapidly and well absorbed orally, and well tolerated
18
Q
how do H2 receptor agonist preparations differ?
A
relative potency, dosing is different
famotidine > nizatidine = ranitidine > cimetidine
19
Q
overall effectiveness of H2RAs
A
inhibit acid secretion for < 6 hours
inhibit 60-70% of total 24 hr acid secretion
especially effective against nocturnal secretion which is largely driven by histamine
20
Q
H2RA mechanism
A
structural histamine analogs that block H2 receptors selectively to reduce gastric acid and pepsin secretion without affecting other parts of the acid secretion pathway
21
Q
clinical uses of H2RAs
A
given once daily at bedtime to suppress nocturnal acid secretion
20% failure in ulcer patients who smoke and in the elderly
use has declined since PPIs
22
Q
when should you not use H2RAs
A
in combo with PPIs
reduce efficacy of PPIs by reducing acid activation
23
Q
adverse effects of H2RAs
A
safe with minor and infrequent adverse effects
should not be given when pregnant or nursing
most common side effects: diarrhea, headaches, fatigue, myalgias, constipation, bradycardia
24
Q
when can mental changes occur with H2RA use
A
IV administration in patients who are elderly or have renal or hepatic dysfunction
25
specific adverse effects of cimetidine (longed H2RA on the market)
gynecomastia or impotence in men
galactorrhea in women
^^inhibits binding of DHT on androgen receptors
interferes with cytochrome p450 pathways for hepatic metabolism of many drugs
26
types of antacids
aluminum hydroxide
calcium carbonate
combo aluminum hydroxide and magnesium hydroxide
27
mechanism of antacids
weak bases that neutralize gastric HCl to form salt and water, and may interfere with absorption of other drugs
act by reducing gastric acidity and inactivating pepsin
may also provide mucosal protection by stimulating PG synthesis
28
why are antacids popular
low cost
| rapid action
29
what are adverse effects associated with antacids
diarrhea - magnesium
constipation- aluminum
cation absorption and systemic alkalosis in renal patients
rebound acid oversecretion
30
administration of antacids
single effective dose given 1 hr after eating neutralizes for 2 hrs
a second dose given 3 hours after eating extends the effect for 4 hours
31
common uses and contraindications for antacids
uses: esophagitis, peptic ulcer, GERD
contraindications: active peptic ulcers
32
mechanism of mucosal protective agents (MPAs)
creates a protective coating on peptic ulcers
| limits exposure to acid and pepsin
33
mechanism of action of sucralfate
binds selectively to necrotic ulcer tissue and acts as a barrier
polymerizes to produce a viscous, sticky gel that adheres strongly to epithelial cells and ulcer craters in acid environment
effective in healing duodenal ulcers
34
side effects of sucralfate
constipation
| poorly absorbed systemically, so few adverse effects
35
contraindications for sucralfate
required acid pH for activation
| do not give with PPIs, antacids, or H2RAs
36
mechanism of misoprostol
methyl analog of PGE1
binds to PG receptors on parietal cells to inhibit acid secretion
because NSAIDs inhibit PG formation, misoprostol is used to prevent NSAID induced ulcers
exact mechanism unknown
37
adverse effects of misoprostol
most frequent: diarrhea, abdominal pain
| may cause abortion by stimulating uterine contractions
38
why can misoprostol cause uterine contractions
PGE1 is a potent regulator of uterine muscle tone
39
what is bismuth subsalicylate?
Pepto-Bismol
| colloidal bismuth
40
mechanism of pepto bismol
protective coating of ulcers
| antibacterial against H.pyloru
41
pepto bismol usage
estimated 60% of American households have it
| treat dyspepsia and acute diarrhea
42
pepto bismol adverse effects
darken the tongue and stool bc the bismuth sulfide formed is a black solid
43
what are the mucosal protective agents
bismuth subsalicylate
misoprostol
sucralfate
44
treatment for H.pylori
```
triple therapy, 10-14 days
clarithromycin, 500 mg bid
amoxicillin, 1 gm bid
PPIs, bid
for pts allergic to penicillin use metronidazole 500 mg bid instead of amoxicillin
```
45
classes of laxatives
osmotically active
stimulant/irritant
bulk forming
46
what are saline laxatives
nonabsorbable salts containing magnesium cations (magnesium citrate) or phosphate anions (sodium phosphate)
47
mechanism of saline laxatives
act by osmotic force to draw water into the intestinal lumen > distended intestines > stimulation of peristalsis
48
contraindications for saline laxatives
renal insufficiency
heart disease
electrolyte imbalance
diuretic drug co-treatment
49
mechanism of glycerin
alcohol that acts in the rectum as a lubricant and hygroscopic agent > water retention > stimulate peristalsis
50
mechanism of lactulose, sorbitol, and mannitol
hydrolyzed to organic acids > acidify luminal contents > draw water into lumen > increase colonic propulsive movement
51
nondigestible sugars and alcohols laxatives
glycerin
lactulose
sorbitol
mannitol
52
mechanism of polyethylene glycol (PEG)-electrolyte solutions
poorly absorbed and retain added water by their high osmotic pressure
53
when is PEG useful?
colonoscopy prep
3-4 liters over 3-4 hours to produce watery diarrhea and remove solid waste
good for complete clearance
54
preparation of PEG
```
mixture of:
sodium sulfate
sodium bicarb
sodium choloride
potassium chloride
in isotonic solution with 60 g of PEG
```
55
mechanism of stimulant/irritant laxatives
act directly on enterocytes, enteric neurons, and muscle
induce low grade intestinal inflammation > water and electrolytes accumulate > increase intestinal motility
more useful day to day than PEG
56
classes of stimulant/irritant laxatives
diphenylmethane derivatives
anthraquinones
ricinoleic acid
57
diphenylmethane derivative laxative
bisacodyl
58
bisacodyl administration
enteric coated tablets taken at bedtime and take effect the next morning
swallow without chewing to avoid stomach irritation
59
examples of anthraquinones
aloe
cascara sagrada
senna
60
mechanism of anthraquinones
poorly absorbed in the small intestine and require activation in the colon with laxative effects 6-12 hours later
61
effects of long term anthraquinones use
melanomic pigmentation of colonic mucosa and cathartic colon (colon dilated and ahaustral)
62
mechanism of ricinoleic acid (castor oil)
local irritant that increases instestinal secretion and motility
now seldom used due to unpleasant taste and potential toxicity
63
examples of bulk forming laxatives
methylcellulose
lactulose
polycarbophil
64
function of bulk forming laxatives
add bulk and hold water to expand intestinal contents
65
requirements for bulk forming laxative use
adequate hydration
| without water and movement, can simply make the brick bigger
66
stool softeners
mineral oil
glycerin suppositories
docusate sodium
67
use of docusate sodium
prevents straining in hospitalized patients
68
major antidiarrheal drugs
loperamide
kaolin/pectin
bismuth subsalicylate
somatostatin/octreotide
69
mechanism of moperamide
Mu agonist relatively selective for intestinal opioid receptors
inhibit ACh release > decrease motility
70
administration of loperamide
acts quickly on oral admin
| peak levels 3-5 hrs after admin
71
effectiveness of loperamide
40-50 times more effective than morphine for diarrhea
effective against travelers diarrhea
relief of acute, non specific diarrhea
72
when should you discontinue loperamide
if there isn't clinical improvement in 48 hours
| few adverse effects otherwise
73
mechanism of kaolin/pectin
kaolin acts by absorbing compounds and presumably binding potential intestinal toxins
pectin increases viscosity of luminal contents
74
mechanism of pepto bismol when used for diarrhea
inhibits intestinal secretions
| management of infectious diarrhea
75
mechanism of somatostatin/octreotide
inhibits secretion of gastrin, CCK, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, VIP, and 5-HT
reduces intestinal fluid and pancreatic secretion
slows GI motility and inhibits gallbladder
reduces portal and splanchnic blood flow
76
examples of when nausea and vomiting may occur
pregnancy
motion sickness
GI obstruction
chemo
77
discuss the pathways involved in emesis
coordinated by medullary vomit center activating efferent pathways in the vagus, phrenic nerves, and spinal innervation of abdominal muscles
78
mediators of emetic signals
dopamine
serotonin
histamine
substance P
79
common anti emetic drugs
```
histamine H1 antagonists
dopamine, serotonin, and NK-1 antagonists
phenothiazines/
benzodiazepines
marijuana derivatives
```
80
histamine H1 antagonists
dimenhydrinate
diphenhydramine
cyclizine
meclizine
81
mechanism of histamine H1 antagonists
produce sedation and antimuscarinic activity
| prevent motion sickness
82
dopamine D2 antagonists
metoclopramide
| trimethobenzamine
83
serotonin 5-HT3 antagonists
ondansetron
granisetron
dolasetron
used during chemo
84
NK-1 antagonists
aprepitant
fosaprepitant
rolapitant
85
mechanism of phenothiazines/
| benzodiazepines
decrease sensory inputs that drive emesis (anxiety driven)
86
phenothiazines
chlorpromazine
| prochlorperazine
87
benzodiazepines
lorazepam
| alprazolam
88
marijuana derivatives
tetrahydrocannabinol (THC)
| dronabinol
89
dronabinol use
prophylactic in patients receiving chemo
90
adverse effects of marijuana derivatives
central sympathomimetic activity in form of marijuana like "highs"
mood changes, laughing, paranoid reaction, and thinking abnormalities
91
discuss diarrhea as an adverse drug effect
relatively frequent, accounts for 7% of all adverse drug effects
more than 700 drugs implicated
92
drugs that (more) commonly induce diarrhea
laxatives
GI meds (PIs, H2 blockers)
NSAIDS (3-9%)
SSRIs
93
important cardio drug that causes diarrhea
ACE inhib
94
important antidiabetic drug that causes diarrhea
metformin
95
important antineoplastic drugs that cause diarrhea
irinotecan
| doxorubicin
96
important immunosuppressive agent that causes diarrhea
mycophenolate mofetil (MMF)
97
drug classes that cause constipation
```
parasympatholytic agents (reduce PNS tone in the GI)
cation containing agents
OPIODS
cholestyramine
NSAIDs
vinca alkaloids
```
98
important parasympatholytic agents that cause constipation
anticholinergics
diphenhydramine
trimethaphan
99
important cation agent that causes constipation
iron supplements
100
mechanism of opioid induced constipation (OIC)
dose dependent and predictable
Mu receptor in the GI directly inhibit Ach release and motility
No tolerance develops
101
treatment of OIC
```
stepwise:
reduce or eliminate opioid use
senna+docusate
add bisocodyl
add PEG
```
102
prevention of OIC
limit opioids to short duration
start bowel maintenance with initial opioid dose
hydration, fiber, movement
