Gastrointestinal Disorders (Exam 3) Flashcards
1
Q
Most common GI disorder in the US
A
GERD
2
Q
major GI disorders in the US
A
GERD
IBS
Gallstones
Celiac disease
Crohn’s disease
Ulcerative colitis
Hemorrhoids
Diverticulosis
Colon cancer
3
Q
cells in the GI tract
A
pit cell
stem cell
neck cell
parietal cell
chief cell
endocrine cell
4
Q
which layer of the stomach wall does drugs typically act?
A
mucosa
5
Q
types of enzymes in the small intestine
A
pancreatic enzymes
brush border enzymes
6
Q
pancreatic enzymes
A
lipases, amylases, exopeptidase, nucleases
secreted into the intestine, in intestinal lumen
7
Q
brush border enzymes
A
embedded in the absorptive cell membranes
carry digestive work, not in lumen
8
Q
intestinal cells can absorb only
A
monosaccarhides
9
Q
digestion of proteins begins in the
A
stomach
10
Q
digestion and absorption of lipids
A
bile salts must emulsify the lipid droplets into smaller ones
11
Q
micelle
A
cholesterol
monoglyceride
fatty acid
12
Q
how does components of a micelle cross the membrane?
A
cholesterol - carrier protein
monoglycerides and fatty acids - simple diffusion
13
Q
what happens when the components of a micelle cross the membrane?
A
triglycerides reform
cholesterol, TG, proteins form chylomicrons
chylomicrons released into lacteal
14
Q
what types of drugs are used to treat GI disorders?
A
drugs that neutralize acids
drugs that decrease acid output
drugs that affect GI motility
15
Q
histamine
A
produced in enterochromaffin-like cells, mast cells, basophils and neurons
16
Q
histamine has an important role in
A
gastric secretion
17
Q
site of histamine storage is mainly in
A
mast cells
18
Q
serotonin
A
modulation of platelet function and neurotransmission
important role in the gut
19
Q
serotonin is produced in
A
enterochromaffin cells, neurons
20
Q
serotonin is not produced in _____________, only stored there
A
platelets
21
Q
precursor of serotonin
A
tryptophan
22
Q
5HT1 subtypes and where they act
A
A-F - brain
P - enteric NS
23
Q
5HT2 subtypes and where they act
A
2A - platelets, smooth muscle
2B - stomach
24
Q
where does 5HT3 act?
A
vomiting centers - CNS
stomach
25
what stimulates gastric acid secretion?
acetylcholine, histamine, gastrin
26
G cells are
gastrin producers
27
D cells are
somatostatin producers
28
somatostatins role
inhibits G cell
inhibits gastrin secretion
29
nerve involved in gastric acid secretion
vagus preganglionic nerve
30
acetylcholine is present in
D cells
ECL cells
Parietal cells
31
where is the proton pump located and what is its official name?
in parietal cells
H+K+ ATPase
32
drugs that neutralize acids
systemic antacids
nonsystematic antacids
33
systemic antacids
are soluble and reabsorbable
cause systemic alkalosis
34
example of systemic antacids
sodium bicarbonate
35
nonsystematic antacids
not absorbed into systemic circulation
do not produce systemic alkalosis
36
examples of nonsystematic antacids
aluminum containing antacids
calcium containing antacids
magnesium containing antacids
combination antacids
37
magaldrate
use to treat variety of conditions such as esophagitis, duodenal and gastric ulcers and GERD
38
mechanism of systemic antacids
in stomach: instantaneous interaction with HCl --> NaCl, water and CO2
in intestines: NaCl + HCO3 to Na+ HCO3
39
side effects of systemic antacids
hypernatremia
fluid retention
metabolic alkalosis
40
where part of the MOA of systemic antacids does absorption occur?
in intestines
NaHCO3 --> Na+ and HCO3
41
Nonsystemic antacids CaCO3 MOA
in stomach: CaCO3 + 2HCl --> CaCl2, water and CO2
in intestines: CaCl2 + HCO3 --> CaCO3 and HCl
42
CaCO3 reacts slower than
Na+ bicarbonate
43
side effects of CaCO3
hypercalcemia can trigger gastrin release --> acid rebound
44
how much of CaCO3 is absorbed (nonsystemic antacid)
about 10%
45
nonsystematic acids Mg(OH)2 and Al(OH)3 MOA
in stomach: reacts slowly with HCl --> MgCl2 and water
in intestines: MgCl2 and HCO3 --> Mg(OH)2 and HCl
46
Mg(OH)2 and Al(OH)3 are relatively
insoluble and slow neutralize acid
retention in stomach
47
side effects of Mg(OH)2
cathartic
can induce N/V
diarrhea
48
side effects of Al(OH)3
constipation
can bind to antibiotics, antifungals, iron supplements and prevent absorption
toxicity in renal insufficiency
49
nonsystemic antacids can be combined with
anticholinergic drugs to delay gastric emptying
50
common anticholinergics combined with nonsystemic antacids
pirenzepine, propantheline and mepenzolate
all act as M1 receptor antagonists
51
side effects of nonsystemic antacids with anticholinergics
blurry vision
contraindicated with glaucoma
52
potency of H2 receptor antagonists (from greatest to least)
famotidine > nizatidine = ranitidine > cimetidine
53
H2 receptor antagonists examples
cimetidine
nizatidine
famotidine
ranitidine (discontinued)
54
H2 receptor antagonists MOA
competitive H2 receptor antagonist
permissive and transmissive role of histamine
55
permissive role of histamine
presence of histamine permits action of acetylcholine and gastrin
56
transmissive role of histamine
histamine is basic and final requirement for acetylcholine and gastrin
57
how are H2 receptor antagonists metabolized?
hepatic metabolism
glomerular filtration
tubular secretion
58
H2 receptor antagonists are very effective at
inhibiting nocturnal H+ secretion
59
which H2 receptor antagonists has little first pass hepatic metabolism?
nizatidine
60
cimetidine inhibits
CYP450 hepatic drug metabolism
61
toxicity of H2 receptor antagonists from greatest to least
cimetidine > nizatidine > famotidine > ranitidine
62
toxicity of H2 receptor antagonists
inhibits dihydrotestosterone binding to androgen receptors
inhibits estradiol metabolism
increase serum prolactin levels
inhibition of hepatic alcohol metabolism
63
toxicity of H2 receptor antagonists can lead to
Gynecomastia in men
Galactorrhea in women
64
proton pump inhibitors examples
omeprazole
esomeprazole
rabeprazole
lansoprazole
pantoprazole
65
MOA of PPIs
non competitive inhibitors of the H+K+ ATPase
66
PPIs are _____________ and are activated in an _________ environment
prodrugs
acidic
67
PPIs must pass through the
stomach to be effectively absorbed
68
PPIs are absorbed in the _______ into ________________ and converted into the __________
intestine
PC vesicles
active form
69
omeprazole
Prilosec
metabolized in the liver by CYP2C19 and CYP3A4
70
CYP3A4 converts ___-omeprazole to _________________
S
3-hydroxyomeprazole
71
__ isomer of omeprazole is the conversion to _________________ by CYP______
R
5-hydroxyomperazole
CYP2C19
72
metabolites of R-omeprazole
5-hydroxyomeprazole
omeprazole sulfone
5'-O-desmethylomeprazole
3-hydroxyomeprazole
73
The S-isomer of omeprazole is converted primarily to
5'-O-desmethylomeprazole via CYP2C19
74
proton pump encodes for which 2 genes?
ATP4A and ATP4B
75
the binding of the PPI to the ATP4A/ATP4B complex prevents
acid secretion
76
PPIs enter through
PPIs exit through
diffusion
ATP4A/B transporter
77
omeprazole brand name and bioavailability
prilosec
40-65%
78
esomeprazole brand name and bioavailability
Nexium
>80%
79
lansoprazole brand name and bioavailability
Prevacid
>80%
80
pantoprazole brand name and bioavailability
protonix
77%
81
rabeprazole brand name and bioavailability
aciphex
52%
82
dexlansoprazole brand name
dexilant
83
what is the difference in effects of H2 receptor antagonists and PPIs?
H2 receptor antagonists have a marked effect on nocturnal acid but only a modest effect on meal stimulated acid
PPIs have a markedly suppress both
84
Adverse effects of PPIs
diarrhea
headache
abdominal pain (1-5%)
increased gastric biota in chronic use
85
Prostaglandin analogues
misoprostol
86
misoprostol
PGE1 analogue
EP agonist
87
Prostaglandin E2 is the most widely
produced prostanoid in the human body
88
MOA of misoprostol
protects mucus lining in two ways
increases gastric pH and enhances the mucosal barrier that protects the stomach
89
prostaglandin E receptors
found on parietal cells
when stimulated, have an inhibitory effect on the proton pump
90
PGE2 acts as a __________ on _____ receptors on parietal cells and __________ activity of the proton pump
agonist
EP3
reduces
91
PGE2 contributes to the maintenance of
the mucosal barrier, stimulating secretion of mucin and bicarbonate --> enhances mucosal blood flow
92
PGE2 is synthesized in the
COX pathway
93
NSAIDs effect on PGE2
NSAIDs inhibit COX enzymes --> reduce amount of PGE2
reduce the amount of protective mucus in the stomach
94
Misoprostol is typically given as an
adjunct in patents undergoing NSAID therapy, substituting for PGE lost by NSAID use
95
misoprostol enhances
epithelial mucus and bicarbonate secretion
96
misoprostol inhibits
histamine induced H release
gastrin release
97
adverse effects of misoprostol
diarrhea
abortive
98
bismuth compounds
non rx: bismuth subsalicylate
rx: bismuth substrate potassium
99
what is included in the formulation of bismuth substrate potassium?
metronidazole
tetracycline
100
mechanism of bismuth compounds
not clear
coats and protects stomach
antibacterial effect
101
adverse effects of bismuth compounds
blackening of the stool
102
types of laxatives
bulk
osmotic
stimulants
stool softeners
103
bulk laxatives
insoluble and non absorbable
not digestible
104
examples of bulk laxatives
psyllium
bran
methylcellulose
105
why do bulk laxatives need to be taken with lots of water?
if they don't constipation will get worse
106
bulk laxatives MOA
increase in bowel content volume triggers stretch receptors in intestinal wall
causes reflux contraction and propels contents forward
107
types of saline and osmotic laxatives
non-digestible sugars and alcohols (lactulose)
salts (milk of magnesia, epsom salt, Glauber's salt, sodium phosphates and citrate)
polyethylene glycol
108
lactulose is broken down by
bacteria to acetic and lactic acid which causes the osmotic effect
109
mechanism of polyethylene glycol
fluid is drawn into the bowel by osmotic force --> increased volume triggers peristalsis --> used to purge intestine
110
stool softeners examples
docusate sodium
liquid paraffin
glycerin suppositories
111
docusate MOA
decreases surface tension of fecal matter and allows for water to penetrate feces
112
adverse effects of stool softeners
excessive use disrupts GI epithelial cells
113
stimulants examples
Senna
bisacodyl
lubiprostone
114
lubiprostone
prostanoic acid derivative
stimulates epithelial chloride channel
increases intestinal motility
irritates GI mucosa and pulls water into lumen
115
lubiprostone is indicated for
severe constipation where rapid effect is required
116
dopamine D2 receptor antagonists examples
metoclopramide
chlorpromazine
Prochlorperazine
promethazine
haloperidol
droperidol
117
dopamine receptor antagonists MOA
block dopamine induced attenuation of pro kinetic effects of Ach
inhibition of D2-R in CTZ --> antiemetic effect
118
dopamine decreases _____________
decreases _________ release from myenteric motor neurons
peristalsis
acetylcholine
119
metoclopramide pharmacodynamics
primarily D2-R antagonist
5-HT4-R agonist
5-HT3-R antagonist
120
metoclopramide pharmacokinetics
absorbed rapidly after oral ingestion
undergoes sulfaten and glucuronidation by the liver
121
metoclopramide adverse effects
crosses BBB
extrapyramidal effects (movement disorders)
tardive dyskinesia (unusual movements of muscles of face)
122
chemoreceptor trigger zone
induces emesis
sensitive to chemical stimuli
123
emetics
agents to induce vomiting
124
emetics examples
emetine
dehydroemetine
apomorphine
125
emetine and dehydrometine are used as
second or third line of antiprotozoal therapy
126
dehydroemetine
induces emesis
direct stimulation of CTZ
127
side effects of dehydroemetine
drowsiness
diarrhea
stomach ache
128
apomorphine
dopaminergic agonist
treats off episodes in Parkinson's
129
antihistamines and anticholinergics examples
dimenhydrinates
hydroxyzine
cyclizine
meclizine
scopolamine
trimethobenzamide
130
5HT3 receptor antagonist examples
ondansetron
granisetron
dolasetron
ramosetron
tropisetron
alosetron
131
neurokinin-1 receptor antagonists
aprepitant
fosaprepitant
rolapitant
132
other anti emetic examples
cannabinoids
nabilone
dronabinol
nabiximol
dexamethasone
netupitant / palonosetron
133
5HT3 antagonists MOA
5HT3-R antagonism in both peripheral and CNS
134
ondansetron PK
metabolized in liver --> glucoronide/sulfate conjugation
135
patents with hepatic dysfunction have reduced plasma clearance of
ondansetron
136
granisetron PK
metabolized by CYP3A
inhibited by ketoconazole
137
dolasetron PK
converted by plasma enzymes to active metabolite hydrodolasetron
138
where is hydrodolasetron metabolized?
2/3 - liver
1/3 - excreted unchanged in urine
139
palonosetron PK
metabolized 1/2 in liver and 1/2 excreted unchanged in urine
140
adverse effects of 5HT3 antagonists
headache
dizziness
constipation
141
Irritable bowel disease
bowel inflammation
no causative agent
systemic manifestations (axial arthritis, eye inflammation, skin lesions)
142
Crohn disease
inflammation skips lesions
mostly in SI and colon
genetic susceptibility, distinct HLA associations
143
ulcerative colitis
continuous involvement of colon and rectum
HLA associations likely
144
what is a risk factor for IBD?
tobacco smoke
145
IBD is an exaggerated
immune response against normal flora
146
treatment for Crohn's disease and ulcerative colitis
coticosteroids
immunomodulators
biologis: HUMIRA
147
anti TNF antibodies used in IBD
infliximab
adlimumab
certolizumab
golimumab
148
what do anti-TNF antibodies do?
neutralize soluble TNF (tumor necrosis factor)
149
release of serotonin by enterochromaffin cells from _________________ stimulates ________________
gut distension
submucosal intrinsic primary afferent neurons
150
submucosal IPANs activate
the enteric neurons responsible for peristaltic and secretory reflex activity
151
stimulation of 5HT4 receptors of IPANs enhances
release of Ach and calcitonin gene related peptide, promoting reflex activity
152
5HT4 partial agonist example
tegaserod
153
azo compounds include
balsalazide
olsalazine
sulfsalazine
154
azo compounds are converted by _________________ to ____________________ which is the active therapeutic moiety
bacterial azoreductase
5-aminosalicylic acid (mesalamine)
155
sites of 5-ASA release from different formulations in the small and large intestine include the
jejunum (SI) - DR C
ileum (SI) - pH dependent release
proximal - sulfasalazine/balsalazide
colon distal - enema
rectum - suppository
156
anti emetic examples
promethazine
prochlorperazine
chlorperazine
157
anti emetics MOA
D2 receptor antagonism at the CTZ
158
anti emetics are of value in
motion sickness
159
anti emetics are weak ______________ without _______________ activity
DA antagonists
antiphsychotic activity
160
adverse effects of anti emetics
extra-pyramidal symptoms or other movement disorders
161
cannabinoids examples
cannabis sativa
cannabis indica
cannabis ruderalis
162
endocannabinoids examples
anandamide
2-arachidonyl glycerol (2-AG)
163
active compound that produces the most pharmacological effects of smoked marajuana
delta-9-tetrahydrocannabinol
164
cannabinoid receptors that have been identified and cloned
CB1 and CB2
165
the endocannabinoids for the cannabinoid receptors are
arachidonic acid derivatives
166
cannabis has been used for its
physcotropic effects (sensory perception, elation, euphoria)
medicinal properties (pain relief, nausea and vomiting)
167
the clinical potential of delta-9 THC against
chemotherapy induced nausea and vomiting (CINV)
168
synthesis of anandamide
N-arachidonyl phosphotidylethenolamine --> (PLD2) --> Anandamide
169
synthesis of 2-AG
membrane phospholipid --> PLC to Diacylglycerol (DAG) --> DAG lipase to 2-AG
170
when anandamide acts on CB1 receptor it inhibits _______________ which acts on ________________
adenylate cyclase
CNS, leukocytes, and testis
171
when anandamide acts of CB2 receptor it inhibits ________________ which acts on _______________
adenylate cyclase
spleen, tonsils, bone marrow, peripheral blood leukocytes
172
delta-9-THC anti emetic examples
dronabinol
marinol
173
pharmacodynamics of delta-9-THC
stimulation of CB1 receptors on neurons in and around the vomiting center in the brainstem
174
pharmacokinetics of delta-9-THC
highly soluble lipid compound
absorbed readily after oral administration
onset = 1 hour
175
delta-9-THC undergoes extensive _____________________ with limited ________________
first pass metabolism
systemic bioavailability
176
principle active metabolite of delta-9-THC
11-OH-delta-9-tetrahydrocannabinol
177
delta-9-THC is excreted via
biliary fecal route
178
only ____________ delta-9-THC is excreted in the ____________ and it is highly bound to _____________
10-15%
urine
plasma proteins
179
adverse effects of delta-9-THC
complex effects on the CNS
can displace other plasma protein bound drugs
