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Pharmacology Exam 1 > Gastrointestinal Drugs > Flashcards

Gastrointestinal Drugs Flashcards

1
Q

Two major classes of drugs affecting GI system

A

Drugs affecting secretion
-antacids, H2 R antags, Proton Pump Inhibs

Drugs affecting GI motility
-Prokinetic, Anti-diarrheal/emetics

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2
Q

Antacids

A

NaHCO3
CaCO3
Al(OH)3
Mg(OH)2

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3
Q

Neutralizing capcity of antacids

A

NaHCO3 - High
CaCO3 - Moderate
Al(OH)3 - High
Mg(OH)2 - High

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4
Q

adverse effects of antacids

A

NaHCO3 - systemic alkalosis, fluid retention
CaCO3 - milk-alkali syndrome: hypercalcemia, nephrolithiasis
Al(OH)3 - constipation, hypophosphatemia
Mg(OH)2 - diarrhea, hypermagnesemia

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5
Q

commercial antacids

A

alternagel - Al(OH)3
maalox, mylanta - Al(OH)3 & Mg(OH)2
tums - CaCO3

chewable tablets vs liquid suspension

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6
Q

related OTC products

A

gaviscon (sodium alginate + antacids) & mylicon, phazyme (simethicone)

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7
Q

properties of gaviscon

A

viscous, weak base
prevents reflux
effective in GERD

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8
Q

properties of mylicon, phazyme (simethicone)

A

mild surfactant

enhances release of gas

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9
Q

what is characteristic of H2 antags

A

amidazole side chain

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10
Q

functions of cimetidine

A

competitive antag of H2 R
drops gastric acid secretion in response to histamine, gastrin, ACh
Inhibits CYP 2C6 & 2D9 (warfarin phenytoin, theophylline, benzodiazepines, sulfonylureas)

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11
Q

side effects of cimetidine

A
  • CNS effets (confusion, delirium, HAs) seen with IV admin to elderly
  • antiandrogen (gynecomastia, impotence)
  • inhibition of estradiol metabolism (galactorrhea)
  • thrombocytopenia
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12
Q

2nd gen H2 blockers

A

Ranitidine (Zantac)
Nizatidine (Axid)
Famotidine (Pepcid)

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13
Q

advantages of 2nd gen H2 blockers over 1st gen

A

longer half-life
fewer effects on CYP450 system
greater potency

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14
Q

possible negative effect of 2nd gen H2 antag

A

increase ethanol bioavailability by reducing first-pass metabolism (except Famotidine)

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15
Q

examples of proton pump inhibitors

A

lansoprazole, omeprazole, raberprazole, pantoprazole

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16
Q

how does omeprazole work?

A

omeprazole picks up H+ in the canaliculi -> sulfenic acid -> loses water -> cyclic sulfenamide -> binds to proton pump to form enzyme-inhibitor complex

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17
Q

function of PPIs

A

irreversible inhibition of H+/K+-ATPase

noted to also inhibit nocturnal secretions of acid

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18
Q

half-life and duration of PPIs

A

short plasma life ~ 1 hr, but long duration (24hr)

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19
Q

possible feedback from PPI use

A

hypergastrinemia occurs -> rebound hypersecretion of gastric acids

can affect drug absorption & increase risk of infections

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20
Q

adverse effects of PPIs

A

nausea most common, few others:

vit B12 deficiency, osteoporotic fx

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21
Q

drug interactions with PPIs

A

omeprazole inhibits CYP2C19

diazpam, warfarin, phenytoin levels increase;
clopidogrel activity may be reduced

all PPIs decrease absorption of digoxin & ketoconazole

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22
Q

which is more likely to cause acid rebound: H2 antags or PPIs

A

H2 antags more commonly present with acid rebound

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23
Q

why does acid rebound occur?

A

reduced gastric acid removes somatostatin inhibition of gastrin secretion - hypergastrinemia

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24
Q

which acid secreting antagonist can develop tolerance?

A

H2 antagonists

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25
mucosal protective agents
sucralfate (carafate), misoprostol (cytotec)
26
function of sucralfate
aluminium hydroxide complex of sucrose polymerizes and forms protective barrier at ulcer site acidic pH activates complex
27
disadvantages to sucralfate
poorly absorbed | may decrease absorption of tetacycline, digoxin, phenytoin
28
function of misoprostol
semi-synthetic prostaglandin E1 derivative reduced acid secretion (parietal cell) cytoprotectant effects - enhanced mucus & bicarb secretion
29
what is misoprostol used with
used in combo with NSAIDs
30
adverse effects of misoprostol
Diarrhea, Abortifacient
31
peptic ulcers are associated with infections of gastric mucosa by what organism
Helicobacter pylori (~90%)
32
mechanism of H. pylori's cause of peptic ulcers
reduction in Delta-cell production of somatostatin -> increased secretion of gastrin
33
therapy for H. pylori would include tx combos of:
bismuth salt (PeptoBismol) Abx - Metronidazole, Tetracycline, Amoxicillin, Clarithromycin H2 blocker or PPI Ranitidine bismuth citrate (Tritec)
34
function of bismuth subsalicylate
converted to bismuth salts and salicyclic acid in the GI tract antibacterial antiviral, and antisecretory activity
35
uses of bismuth subsalicylate
treatment of mild diarrhea | part of multidrug therapy for H. pylori
36
where is 90% of the serotonin in the body?
90% of serotonin in the body is in the gut (not the brain)
37
brief summary of the enteric nervous system
afferent pathway: enterochromoffin cells sense stimuli -> release serotonin -> sends information to dorsal root or cranial nerve afferent (primary afferents are splanchnic and vagus) -> CNS reflexive sensorimotor pathway: EC cells sense stimuli -> release serotonin -> submucosal Intrinsic Primary Afferent Neuron (IPAN) transmits ACh & CGRP (?) to ENS Neuron -> motor/secretomotor/interneuron effects
38
what autonomic R is responsible for smooth muscle contraction in the gut?
binding to serotonin/motilin receptors stimulate ACh to be released to bind to M3 receptors on smooth muscle
39
prokinetic drugs
``` metoclopramide (reglan) cisapride (propulsid) 5-HT4 agonist tegaserod (zelnorm) 5-HT4 agonist prucalopride (resolor) 5-HT4 agonist erythromycin (motilin agonist) linaclotide ```
40
which of the prokinetic drugs have high cardiovascular toxicity
cisapride & tegaserod | withdrawn due to cardiovascular toxicity
41
which of the prokinetic drugs is not available in the US
prucalopride
42
which of the prokinetic drugs has a rapid tolerance
erythromycin
43
function of metoclopramide
D2 dopamine R antag blockade of D2 R in the myenteric plexus -> ups ACh release D2 R blockade also produces anti-emetic effects
44
clinical uses of metoclopramide
facilitates small bowel intubation, post-op and diabetic gastroparesis, gastro-esophageal reflux disease (GERD), and anti-emetic
45
side effects of metoclopramide
sedateion, Parkinson's-like syndrome, hyperprolactinemia (gynecomastia, galactorrhea, and breast tenderness)
46
function of linaclotide
peptide activator of guanylate cyclase 2
47
clinical use of linaclotide
treatment of IBS+constipation or idiopathic constipation taken orally 30 minutes before first meal not absorbed systemically
48
adverse effects of inaclotide
diarrhea is main adverse effect
49
examples of secretory or stimulant laxatives
castor oil bisacodyl, cascara, senna, aloes lubiprostone
50
mechanism of castor oil
hydrolyzed in upper small intestine to ricinoleic acid
51
function of secretory/stimulant laxatives (except for lubiprostone)
stimulate peristalsis | open Cl- channels in intestinal mucosa to facilitate movement of Cl-, Na+, and H2O in the intestinal lumen
52
function of lubiprostone
specific ClC-2 (chloride-channel 2) activator for chronic idiopathic constipation used in IBS with chronic constipation
53
examples of bulk and saline laxatives
psyllium, methylcellulose, bran, milk of magnesia, lactulose
54
functions of bulk&saline laxatives
non-absorbable and form hydrophilic mass in presence of water -> increase water in intestinal lumen by osmotic force -> distention-> peristalsis
55
what produces similar effects to bulk&saline laxatives
isosmotic electrolyte solution with polyethylene glycol produce similar effects
56
alternative use for lactulose
used in hepatic encephalopathy (drops ammonia)
57
stool softeners examples
docusate sodium (colace), mineral oil, glycerin
58
function of stool softeners
surfactants and lubricants incorporate into stool to make passage easier lubricate lower bowel to reduce fecal impaction
59
possible adverse effect of stool softeners
can decrease absorption of fat-soluble vitamins
60
drugs types reducing GI motility
anti-diarrheals anticholinergics opiates
61
mechanism for anti-diarrheals
2 mechs 1) slow peristalsis to up H2O & electrolyte absorption 2) adsorb (?) potential intestinal toxins and water
62
examples of anticholinergics
dicyclomine, bentyl
63
examples of anti-diarrheals
kaolin (aka attapulgite - type of clay), pectin (from fruit) | low-dose fiber
64
irritable bowel syndrome is characterized by
abdominal pain and distention + altered bowel habits
65
treatment of choice for IBS + diarrhea
alosetron (lotronex) 5HT3 R antag
66
function of alosetron
blocks visceral afferen tpain sensation and decreases colon motility
67
side effects of alosetron
GI side effects - constipation, ischemic colitis (sometimes fatal) ischemic colitis caused by constriction of blood vessels **withrdawn & reintroduced va restricted prescribing program in 2002**
68
where is the area postrema
at the level of the medulla
69
types of anti-emetics
D2 dopamine R antags anticholinergics/antihistamines serotonin R antags cannabinoids
70
examples of D2 dopamine R antagonists for anti-emetics
promethazine | prochlorperazine
71
examples of anticholinergics/antihistamines
meclizine (antivert) | scopolamine
72
5-HT3 R antag examples
odansetron (zofran) | granisetron (kytril)
73
function of serotonin R antags
block activity in CTZ and vagal afferents from stomach and small intestine which activate CNS emetic centers
74
clinical use of serotonin R antags
nausea and vomiting associated with chemotherapy | combined with aprepitant (NK1 antag) & Dexamethasone
75
examples of cannabinoids
dronabinol, nabilone, synthetic tetrahydrocannabinol (THC)
76
clinical use of cannabinoids
nausea and vomiting associated with chemotherapy | limited to patients who are refractory to other agents
77
side effects of cannabinoid use
may experience psychoactive side effects

Pharmacology Exam 1 (7 decks)

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