Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Pharmacology > GI Pharm Class > Flashcards

GI Pharm Class Flashcards

(423 cards)

Start Studying
1
Q

What are antacids for?

A

Short term temporary relief from mild pain and symptoms of PUD/GERD

Also used to promote headline of duodenal ulcers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Are there better drugs for PUD/GERD than antacid

A

Year with more effective, more convientnt, longer lasting effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the two types of antacids

A

Low systemic agents

High systemic agents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Name the low systemic agents

A 
Aluminum salts (aluminum hydroxide)
Calcium salts(calcium carbonate)
Magnesium salts(magnesium hydroxide/carbonate/trisilicate)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are high systemic agents antacids

A

Sodium salts (sodium bicarbonate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is a supplemental agent for antacids

A

Simethicone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do antacids work

A

They are weak bases that form a salt and water upon reaction with gastric HCl. The net result is to increase the pH and thereby reduce the acidity of the gastric contents. Furthermore, since pepsin is inactivated at pH>4, antacids may also act to decrease the peptic activity of protein breakdown. Also it has been postulated that antacids may increase the mucosal barrier of the gastric lining by stimulating prostagladin synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Side effect aluminum hydroxide

A

Constipation

Hypophosphatemia (can treat hyperphosphatemia)

Renal osteodystrophy (ESRD)
Encephalopathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Side effect magnesium hydroxide

A

Diarrhea(stool soft/laxative)

Hypermagnesemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Side effects calcium carbonate

A

Hypercalcemia; milk alkali syndrome resulting in nephropathy and metabolic alkalosis

Constipation

Hypophosphatemia (effective treatment for hyperphosphatemia)

Calcium based kidney stones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Side effects sodium bicarbonate

A

Flatulence, metabolic acidosis

Hypernatremia

Metabolic alkalosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is sucralfate

A

Compound to promote healing of duodenal ulcers. It enhances mucosal barrier through prostagladin synthsis stimulation or by acting as a physical barrier itself and thereby protecting the delicate mucosal lining from the acidic stomach contents. Since sucrlfate requires an acidic environment for activation, it should not be taken with antacids H2 blockers, or protein pump inhibitors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Do antacids reduce acid secretion or production

A

No

Can get rebound acid production

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do antacids work

A

Combine with H ions in stomach acid , capturing the loose H atoms

Forming common byproducts that depend on the antacid agent . (Water, carbon dioxide, chloride salts)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

At _ doses, antacids increase LES tone

A

High

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Calcium vs magnesium onset

A

Both rapid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Calcium vs magnesium DOA

A

Both long

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Acid neutralizing capcity of calcium and Magnesium

A

Both good (calcium a bit better)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Aluminum and sodium

A

Fair good acid neutralizing and short duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Simethicone

A

A surfactant-decreases surface tension

AIDS in expulsion of gas GAS RELIEF and given as a supplement with antacids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Why use combinations of antacids

A

Enhance efficacy and reduce side effects (use of lower doses of each and opposing side effects)
Bc side effects are dose related

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How decide which antacid/combination to use

A

What works best for patient, trial and error, and experience

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are patient factors that we have to take into account what prescribing antacids

A

Dosage form and palatability

Presence of renal or heart disease

Electrolyte status

Diseases associated with diarrhea and constipation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

If on other meds, when should you are antacids

A

1-2 hours before other medications OR 2-4 hours after other meds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What are anti-ulcer agents
H2 receptor Proton pump inhibitors Surface acting agents PGE1 analogs Bismuth compounds
26
Name H2 receptor antagonists
Cimetidine (po/iv) Famotidine (po/iv) Nizatidine (po/iv) Ranitidine (po)
27
Name proton pump inhibitors
``` Lansoprazole Dexlansoprazole Omeprazole Esmoprazole Pantoprazole Rabeprazole ```
28
Name a surface acting agent
Sucralfate
29
Name a PGE1 analog
Misoprostol
30
Name a bismuth compounds
Bismuth subsalicylate
31
How do H1 blockers work
Reversible block the binding of histamine to the H2 receptor (basolateral membrane of parietal cell) that is present not he parietal cells of the gastric mucosa. By inhibiting stimulation of the H2 receptor, cyclic AMP levels are decreased, which then eventually leads to the decreased activity of the H/K proton pump. The end result is that gastric acid secretion is decreased
32
Onset Histamine type 2 blockers
.5-2 hours (longer than antacids, shorter than PPI) QB to BID
33
Clinical use of histamine type 2 blockers
Treat GERD< peptic ulcer disease, and other diseases associated with gastric ulcers and get ulcer healing in 4-8 weeks
34
H2 blockers inhibit __% of acid production
20-50
35
Adverse effects H2 blockers
Headache (CNS) Nausea/diarrhea/constipatoin (GI) Gynecomastia Cimetidine is also associated with decreased hepatic metabolism of certain drugs (warfarin, phenytoin, diazepam) Cimetidine decreases testosterone binding to androgen receptor (weak anti androgen effects) -gynecomastia in men, galactorrhea in women Blood dyscrasias-neutropenia, thrombocytopenia
36
Cimetidine interesting
Prototypical inhibitor of several CYP450 isoenzymes Lots of drug drug interactions
37
Ranitidine interesting
Inhibits but 10% of what is with cimetidine Pregnancy only if necessary!! Contraindicated in preg
38
Name PPI
``` Omeprazole po Esomeprazole po/iv Lansoprazole po Dexlansoprazole po Pantoprazole po/iv Rabeprazole po ```
39
MOA PPI
Covalently/irreversibly bind sulfhydryl groups of HKATPas at parietal cell secretory sites, thereby inhibiting gastric acid secretion by irreversibly inhibiting functions ase pumps, suppressing gastric secretion Inhibits pump induced egress of gastric acid Takes several days to create new steady state of pump activite
40
Use of PPI
PUD, GERD, zollinger ellison syndrome, and esophagitis, and in regimen for H pylori
41
why QD dosing PPI
Effects last 24 hours
42
PPI inhibit _% of acid
50-90
43
Onset PPI
Days -longer than H2 and ulcerations heal 4-8 weeks
44
Adverse effects of PPI
CNS-headache GI-diarrhea, dyspepsia/nausea, *additional risk of Clostridium Difficile Associated Diarrhea Rash Rare-generalized myalgia, fatigue, myopathies Other-kidney disease, bone fractures, MI
45
Special omeprazole
P450 inhibition many drug drug interactions Not for preg
46
Contraindications PPI
Pregnancy, but if 1100% necessary, can try lasoprazole AVOID omeprazole
47
Sucralfate
A sulfate polysaccharide-an octasulfate of sucrose and ALOH3 added
48
MOA sucralfate
Undergoes cross linking from interaction with stomach acid, creating a viscous, sticky polymer which adheres to epithelial cells around ulcer’s crater, preventing acid access to ulcer sites May also stimulate local prostagladin and mucous productiona nd epidermal growth factor (cytoprotection) but does not affect pH
49
What use sucralfate for
DU* But also aphthous ulcers, mucositis/stomatitis Radiation procitis/ulcers (enema) Bile reflux gastropathy
50
Adverse effects sucralfate
Constipation
51
Contraindication sucralfate
Severe renal failure | Aluminum containing antacids should be avoided
52
Drug interaction sucralfate
Possible therefore take 2 hours after other meds | QID for active ulcers so plan dosing other meds accordingly if possible
53
Misoprostol
Prostagladin E1 analog that provides protective prostagladin to gastric mucosa and reduces gastric acid release from parietal cells (providing cytoprotection by increasing mucosal defenses-stimulates bicarbonate and mucous production, increases mucosal blood flow)
54
Misoprostol and acid output
Reduce basal and nocturnal acid output but lesss than H2 antagonist and PPI
55
Indication misoprostol
Prevention of NSAID induced gastric ulceration in patients at high risk of ulcerations and complications
56
Off label uses of misoprostol
With/without mifepristone (pregnancy termination) Alone for cervical ripening Post partum hemorrhaging (high dose)
57
Adverse effects misoprostol
GI-diarrhea with or without N/V and cramping CNS-related: headache/dizziness
58
Contraindications misoprostol
Pregnancy IBD
59
Bismuth compounds MOA
Not precisely delineated; but as a salicylate derivative can function similar to asprin and inhibit prostagladin synthesis
60
What was bismuth originally developed as
Antidiarrheal
61
What is bismuth most well known for
Antimicrobial actions which prevent microbial attachment to mucosa, possible inactivation of enterotoxins, and disruption of bacterial cell wall
62
OTC bismuth compounds
Alone for reflux (heartburn), indigestion and diarrhea
63
RX bismuth compounds
In combination with antibiotics and acid suppressant for H pylori
64
Adverse effects bismuth compounds
Constipation from antidiarrheal Black/dark stools but regularly formed
65
Drug interactions bismuth
LOTS take 2 hours after other meds
66
Contraindications bismuth compounds
Severe renal failure Antiplatelets and anticoagulatnts (bismuth subsalicylate)
67
Absolute contraindications bismuth
GI bleeding Salicylate hypersensitivity
68
Treat H pylori
Combination therapy-at least 2 antibiotics and an acid reducer (PPI or H blocker) 14 days of triple drug regimen (PPI, clarithromycin, and either amoxicillin or metronidazole) on BID Or ``` 10-14 days quadruple therapy PPI BID Metronidazole QID Tetracycline QID Bismuth subsalicylate QID ```
69
What drugs may lead to false negative urea breath test with h pylori
Bismuth, antimicrobials, PPI suppress H pylori Avoid the use of agents known to suppress H pylori
70
Prevpac for PUD
Amoxicillin Clarithromycin Lansoprazole
71
Omeclamox for PUD
Amoxicillin Clarithromycin Omeprazole
72
Helidac for PUD
Bismuth Metronidazole Tetracyclines Plus additional PPI
73
Pylera for PUD
Bismuth subcitrate potassium Metronidazole Tetracycline Plus addition of PPI omeprazole
74
Why consider PPI for a few/several weeks after 10-14 days h pylori combo therapy
For complete healing of ulcers
75
What do if failure to eradicate h pylori with metronidazole containing triple therapy
Follow up with non metronidazole containing quadruple therapy
76
H pylori with PCN allergy
No amoxicillin Substitute metronidazole (consider bismuth quad)
77
H pyloric ith metronidazole resistance
Substitute tetracycline | Consider quadruple therapy (with clarithromycin and amoxicillin)
78
H pylori with clarithromycin resistance
Substitute either amoxicillin or tetracycline Consider bismuth quadruple therapy
79
Pregnant patient with PUD without h pylori
Short course of antacids or sucralfate - if moderate symptoms consider ranitidin - if severe consider iansoprazole
80
PUD if nsaid at risk
If nsaid not required, consider acetaminophen and D/C NSAID If NSAID required, consider COX-2 NSAID and/or consider PPI or misoprostol
81
What are common causes of nausea and vomiting
``` Chemotherapy/radiation Post op Vestibular dysfunction Gastrointestinal obstruction/dysmotility Metabolic conditions Pregnancy Infections Intracranial lesions Non chemo medications ```
82
Receptors of nausea/vomiting
Receptors in Brain and GI stimulate, which we can use antiemetic agents in combinations since have different MOA , espicially for chemo and radiation induced N/V
83
Categories of emetic potential for chemotherapy
High (90%) Moderate (30-90%) Low(10-30%) Minimal (fewer than 10%)
84
what are the important receptors for N/V
5-HT3 Neurokinin (NK1) Histamine (H1) Dopamine(D2) Muscarinic (M1) Cannabinoid *antagonize them all except agonist cannabinoid
85
What are commonly used to treat N/V
Glucocorticosteroids Benzodiazepines
86
Name serotonin 5HT3 receptor antagonists
Dolasetron Granisetron Ondansetron Palonosetron
87
Name neurokinin receptor antagonists (NK1)
``` Aprepitant Fosaprepitant Netupitant Fosnetupitant Rolapitant ```
88
Name histamine receptor antagonists
``` Diphenhydramine Dimenhydrinate Hydroxyzine Promethazine Meclizine Cyclizine ```
89
Name dopamine receptor antagonists
Phenothiazines -chlorpromazine -perphenazine Prochlorperazine Other - metoclopramide - haloperidol, olanzapine and trimethobenzamide
90
Name muscadine M1 receptor antagonists
Scopolamine
91
Name cannabinoid receptor agonists
Dronabinol | Nabilone
92
Indication for aldosterone
IBS-D
93
Serotonin are strong antiemetic agents, what were they developed for
Chemotherapy induced N/V (CINV)
94
How do serotonin 5-HT3 receptor antagonists work
Block serotonin type-3 receptors at vagal nerve terminals and blocks signal transmission to CTZ -blocks serotonin receptor activation after serotonin release from intestinal enterochromaffin cells
95
Uses for serotonin 5-HT2 receptor antagonists
CINV RINV Post op NV (PONV) NV of pregnancy (NVP)
96
Adverse effects serotonin receptor antagonists
CNS-headache GI-constipation/diarrhea —-serotonin syndrome (IF WITH OTHER 5-HT AFFECTING DRUGS) BUT MOST WORRISOME -DOSE DEPENDENT QT PROLONGATION AND TORSADES
97
Dose dependent QT prolongation and torsades with serotonin receptor antagonsits
Extreme caution required when using with other QT-prolonging agents (anti-arrhythmatics ) or in patients with electrolyte imbalances (hypokalemia or hypomagnesmia ) -dolasetron high risk; no longer recommended for CINV prophylaxis
98
All serotonin 5-HT3 receptor antagonists have short half lives, except which one
Palonosetron and sustained release formulation of grainisetron
99
Long half life makes palonosetron and 2 branded granisetron agents effective for :
Delayed CINV as a single dose
100
Drug interactions H2 receptor antagonists
QT prolonging agents | Antiarrhythmics
101
Name neurokinin NK1 receptor antagonists
``` Aprepitant Fosaprepitant Netuputitant Fosnetupitant Rolapitant ```
102
Fosaprepitant is a prodrug of ___
Aprepitant
103
Fosnetupitant is a prodrug of __
Netupitant
104
Netupitant and fosnetupitant are in combo only.. what what
Palonosetron
105
Neurokinin1 receptor antagonist is a __ antiemetic
Moderate
106
Blockade of neurokinin receptors (subastant P) in CTZ/VC
Peripheral blockade of NK1 receptors located on vagal terminals in gut an additional hypothesized actio
107
Therapeutic uses NK1 antagonist
Chemotherapy induced NV | -most effected when used in combo with a glucocoticosteroid and 5HT3 antagonist
108
Prophylaxis NK1 antagonist
PONV | Only aprepitant given up to 3 hours prior to anesthesia induction
109
Adverse effects NK1 antagonist
GI-dyspepsia/constipation/diarrhea CNS-dizzy/fatigue/somnolence
110
Neutupitant/rolapitant
Moderate major active metabolites | Longer half lives
111
NK1 cyp450
Mild moderate inhibition
112
Name H2 receptor antagonists
``` Diphenhydramine Dimenhydroxyine Promethazine Meclizine Cyclizine ```
113
Doxylamine
Initial therapy for NVP
114
Histamine receptor antagonists are __ antiemetic agents
Weak
115
Use of histamine receptor antagonist
PONV
116
MOA histamine receptor antagonist
Block histamine type 1 receptors in VC and vestibular system | -*agents exhibitvarying levels of central anticholinergic properties at level CTZ
117
Therapeutic uses histamine receptor antagonist
``` Idiopathic mild NV Post op NV NVP (doxylamine/B6) Motion sickness/vertigo(only indication for meclizine and cyclizine) Chemotherapy-induced NV RINV ```
118
Adverse effects histamine->CLASSIC ANTICHOLINERGIC EFFECTS
``` Drowsiness Dry mouth Constipation Urinary retention Blurred vision Decreased BP ```
119
Hydroxyzine pharmacokinetics
Active metabolism=cetirizine IM route
120
Promethazine pharmacokinetics
IV administration requires dilution and lower dose (than oral)
121
Interactions histamine receptor antagonist
Other agents that also induce anticholinergic-related side effects (cumulative)
122
Name the dopamine receptor antagonists
Phenothiazines - chlorpromazine - perphenazine - prochlorperazine Other -metoclopramide
123
Dopamine receptor antagonists are ___ antiemetic agents
Weak to moderate
124
How do dopamine receptor antagonists work
Block dopamine type 2 receptors in CTZ -agents exhibit varying levels of anticholinergic properties; affect other receptors (histamine, muscarinic, adrenergic receptors)
125
Metoclopramide also stimulates _____ in GI. Doing what
Acetylcholine Enhancing GI motility (dysmotility use) and increases lower esophageal sphincter tone -no impact on GI secretions -also has weak 5HT inhibition
126
Therapeutic dopamine receptor antagonist
Idiopathic mild NV Gastroparesis/dysmotility -specifically metoclopramide Post operative NV NV of pregnancy Chemotherapy induced NV and radiation induced NV -as single agents only weak moderate antiemetic activity;olanzapine used in combination with other agents for CINV RINV
127
Adverse effects dopamine effects-classic anticholinergic effects
``` Drowsy Dry mouth Constipation Urinary retention Blurred vision Hypotension -arrhythmias and extrapyramidal SE are possible;usually seen with larger psychiatric doses ```
128
Dopamine receptor antagonists interactions
Other agents that also induce anticholinergic related side effects Antiarrhythmics, espicially QT prolonging agents Antihypertensives
129
Name muscarinic receptor antagonists
Scopolamine
130
Scopolamine transdermal scop
Worn for 73 Horus
131
Scopolamine is a _ antiemetic agent
Weak
132
What is scopolamine used for
Motion sickness | And also in end of life care foe excessive secretions
133
MOA scopolamine
Block acetylcholine stimulates muscarinic receptors in neural pathways fromt he vestibular nuclei in inner ear to brain stem and from reticular formation to VC - significant anticholinergic properties - usually put behind ear
134
Adverse effects scopolamine -classic anticholinergic effects
``` Drowsy Dry mouth Constipation Urinary retention Blurred vision ```
135
Interactions scopolamine
Other agents that also induce anticholinergic related side effects (cumulative)
136
Name cannabinoid receptor agonist
Dronabinol | Nabilone
137
What are cannabinoid
Synthetic preparations of cannabinol (THC) - synthetic cannabinoids are FDA schedules(controlled) medications - limits on quantities/refill
138
Cannabinoids are _ antiemetic agents
Strong
139
Cannabinoids are reserved for treatment of what
CINV
140
Stimulation of cannabinoid receptors stimulates what
Central (CB1) and peripheral (CB2) cannabinoid receptors in VC/CTZ This exerts signal transduction effects through G protein coupled receptors, resulting in decreased excitability of neurons -minimizing serotonin 5HT3 release from vagal afferent terminals
141
Therapeutic uses of cannabinoids
CINV Appetites stimulation in select (anorexic) patients due to severe disease (cancer or AIDS)
142
Why are cannabinoids commonly reserved for treatment resistant clinical scenarios
FDA scheduling Can be used in combination with other agents
143
Adverse effects of cannabinoids
``` Euphoria/irritability Vertigo Sedation/drowsiness Impaired cognition/memory Alterations in perception of reality Xerostomia Sympathomimetic Appetite stimulation ```
144
Pharmacokinetics dronabinol
Large first pass effect and metabolized to one active metabolite
145
Nabilone pharmacokinetics
Metabolized to several active metabolites | -both have a short time to onset of activity and a long duration of action (34-36 hours) so can use fewer doses a day
146
Interactions cannabinoids
Caution in use with other CNS depressants and cardiovascular agents and sympathomimetics
147
Acute CINV
<24 hours after chemo given
148
Chronic CINV
>24 hours after chemo given
149
Anticipatory CINV
Occurs before chemo give, customarily in non treatment naive patients
150
You should add ___ to antiemetic regimens for adults who receive high emetic risk, antineoplastic agents or who experience breakthrough nausea and vomiting
Olanzapine
151
High emetogenic regimen for CINV
NK1 receptor antagonist 5HT3 receptor antagonist Corticosteroid (dexamethasone)
152
When should the region for CINV be started
Day of (prior to therapy) and 3 days after
153
What can you add to the high emetogenic regim to make it a four drug regimen
Olanzapine (D2 antagonist) Cannabinoid in treatment resistance
154
Also provide therapy for breakthrough NV for all patients and provide therapy for anticipatory NV as needed
Ok
155
Moderate emetogenic regimen
5HT3 receptor antagonist (palonos/granis SQ) | Corticosteroid (dexamethasone)
156
When give the moderate emetogenic regimen
Day of (prior) to chemo and for 2 days after
157
What can you add to the moderate emetogenic regimen
NK1 antagonist or olanzapine May add cannabinoid in treatment resistsance (make.4 drug after 3)
158
Provide therapy breakthrough NV for all patients | Provide therapy for anticipatory NV as needed
Ok
159
Low emetogenic regimen for CINV
``` Corticosteroid (dexamethasone) Or 5HT3 receptor antagonist Or Metoclopramide Or Prochlorperazine ```
160
Same timing thing here
Ok
161
Minimal emetogenic regimen for CINV
No routine prophylaxis therapy recommended
162
Breakthrough emesis regimen
Add one agent from a different drug class to the current regimen
163
Motion sickness
Scopolamine or dimenhydrinate or meclizine
164
Vertigo
Meclizine or cyclizine
165
Diabetic gastroparesis
Metoclopramide
166
Pregnancy induced (stepped therapy)
1. Vitamin B6 or histamine antagonist w/B6 or 5 HT2 antagonist 2. Dopamine antagonist 3. Steroid or different dopamine antagonist
167
Take home points
Targeted therapy of NV by first determining cause Multiclass combination therapy appropriate for moderate to high emetogenic chemotherapy regimens Prevention is more cost effective and clinically accepted than attempting to treat after it develops
168
What groups of drugs are for diarrhea
Prostagladin inhibitors Opoid agonists Serotonin antagonists Chloride channel inhibitors
169
Name prostagladin inhibitors
Bismuth
170
Name opoid agonists
Loperamide Diphenoxylate Eluxadoline
171
Name serotonin antagonists
Alosetron
172
Name chloride channel inhibitors
Crofelemer
173
Loperamide
Chemically related to opoids but does not exhibit analgesic/opiate-like effects or appear to produce physical dependence
174
Loperamide OTC or Rex
Both
175
Misuse with loperamide
Overdose | FDA issues drug safety communication-cardiac toxicities leading to death
176
MOA loperamide
Interferes with peristalsis direct action on circular and longitudinal muscles of intestinal wall, slowing motility -the slowed motility allows for fluid/electrolyte reabsorption and increasing bulk/density of feces
177
Side effects loperamide
Dizziness, fatigue, drowsiness and urinary retention (anticholinergic) -long half life; increases with increasing dose
178
Diphenoxylate
Synthetic opiate agonist (chemically similar to meperidine) - opoid effects only seen at very high doses - small quantity of atropine added to discourage deliberate abuse/over-dosage
179
MOA diphenoxylate
Locally and centrally on GI smooth muscle cells; inhibits GI motility and slows excess GI propulasion
180
Side effects diphenoxylate
Dizzy, drowsi, urinary retention (anticholinergic; atropine)
181
Kinetics diphenoxylate
Active metabolite with long half life
182
MOA eluxadoline
Agonist at opoid mu and kappa receptors in GI tract (slows peristalsis/delays digestion) Antagonist-a delta opoid receptors in GI -stomach, pancreas, and biliary tract secretions decreased
183
Indication for eluxadoline
IBS, diarrhea predominant subtype (IBS-D)
184
Side effects eluxadoline
GI-related Hepatic /pancreatic toxicity -PANCREATITIS HI-RISK IN PTS W/O GALLBLADDER—>DEATHS HAVE OCCURED CNA-related (dizzy/fatigue/sedation/euphoria/impaired)
185
Contraindications eluxadoline
``` Biliary duct obstruction Sphincter of oddi dysfunction Alcoholism History pancreatitis Severe hepatic impairment ``` Stop therapy if severe constipation develops and lasts 4+ hours
186
MOA alosetron
Selectively blocks GI based 5HT2 receptors | -antagonism in GI modulate regulation of visceral pain, colonic transit and GI secretions
187
Alosetron indication
Chronic, severe IBS-D not responsive to other conventional therapies (women) -severe diarrhea predominant IBS includes diarrhea, and one or more of the following —frequent/severe abdominal pain —frequent bowel urgency or fecal incontinence —restriction of daily activities due to IBS ——anatomical or biochemical GI abnormalities must be excluded before prescribing
188
Alosetron side effects
GI-constipation, dyspepsia, GERD and NV Ischemic colitis (black bow warning) - no refills without a follow up exam by prescriber - physicians must enroll in prescribing program - patients and physicians must sing a risk benefit statement and agree to adhere to therapy plans - additional self training and testing by physicians to learn to appropriately diagnose IBS required
189
Alosetron contraindications
GI obstruction, perforation, stricture, adhesions, or toxic megacolon Diverticulitis, crohns, UC Impaired intestinal circulation, thrombophlebitis or hypercoagulable state Severe constipation; DC immediately if develops on alosetron therapy
190
Crofelemer
Derived from dark red sap of croton lechleri tree
191
MOA crofelemer
Inhibitis chloride ion secretion by blocking cAMP-stimulated CFTR and calcium activated chloride channels -channels regulate fluid secretion ny intestinal epithelial cells
192
Indication crofelemer
Non infectious diarrhea in HIV AIDS on antiretroviral therapy
193
Side effects crofelemer
GI -abdominal distention, elevated AST/ALT/bilirubin Infections-respiratory/urinary
194
Name antimuscarinic agents
Hyoscyamine Dicyclomine Clidinium Chlordiazepoxide
195
What are antimuscarinic for
Abdominal pain IBS
196
MOA antimuscarinic
Competitively inhibit autonomic, post ganglionic cholinergic receptors to decrease GI motility and spasms
197
Indication antimuscarinic
Abdominal pain/spasm espicially when associated with IBS
198
Side effects antimuscarinic
``` Dry mouth Urinary retention Constipation Drowsy Mental confusion Blurred vision ```
199
What do we use for constipation
Laxative and cathartic agents Peripheral opoid antagonists Guanylate cyclase C Agonists Selective chloride channel activators
200
Linaclotide MOA
Selective guanylate cyclase C agonist - binds to GC-C on luminal surface of intestinal epithelium and increases intracellular/extracellular concentrations of cGMP - stimulates secretion of chloride/bicarbonate into intestinal lumen cia activation of CFTR ion channel-results in increased intestinal fluid and accelerated transit
201
Linaclotide indication
IBS-C IBS constipation | CIC chronic idiopathic constipation
202
Side effects linaclotide
GI-diarrhea (dehydration/electrolyte imbalance), GERD/dyspepsia NV
203
Lubiprostone MOA
A bicyclist fatty acid, prostagladin E1 derivative -increases intestinal fluid secretion by activating GI specific chloride channels in luminal cells of intestinal epithelium
204
Lubiprostone indications
IBS-C CIC OIC opoid induced. Constipation
205
Side effects lubiprostone
Nausea, dyspepsia, dizziness
206
Methylnaltrexone and naloxegol and alvimopan MOA
Peripheral mu opoid receptor antagonists | -no common significant CNS penetrations/actions or induction of withdrawal/pain symptoms
207
Methylnaltrexone, naloxegol and alvimopan indications
OIC Alvimopan only for accelerating time to GI recovery following bowel resection surgery with primary anastomoses (prevention of postoperative ileus) -therapeutic doses of opoids for <7 consecutive days immediately before starting alvimopan
208
Side effects methylnaltrexone and naloxegol and alvimopan
Abdominal pain, diarrhea, nausea, flatulence, vomiting
209
Warning alvimopan
Carries risk of MI with use; REMS program requires use only in approved institutions for max of 15 doses Only for short term hospital use
210
Laxative and cathartic agents stimulants
``` Bisacodyl Castor oil Glycerin Senna Na picosulfate ```
211
Laxative and cathartic agents osmotic
Lactulose Mag citrate Polyethylene glycerol (PEG) Sorbitol (glycerin)
212
Laxative and cathartic agents saline’s
Mag. Hydroxide | Na phosphate
213
Laxative and cathartic agents bulk forming
``` Dietary (fiber/bran fruits/grains/cereal) Psyllium Methylcelluose Carboxymethylcellulose Calcium polycarbophil ```
214
Laxative and cathartic agents stool softeners
Docusate | Mineral oil
215
Dietary fiber/brain
Fruits, bran, whole grains, cereals, wheat
216
Methylcellulose/carboxymethylcellulose
Bulk forming/hydrophilic colloidal agents
217
What do bulk forming hydrophilic colloidal agents do
Work to increase bulk volume and water content thereby increasing GI motility Fiber can also support colonic bacteria, fermentation and digestion’s Efficacy seen in 2-4 days
218
Adverse effects bulk forming/hydrophilic colloidal agents
Bloating/obstruction | -drink fluids
219
Drug interactions bulk forming/hydrophilic colloidal agents
LOTS (recommendation similar to that f the bile acid sequesterants and antacids) -mainly with psyllium and cellulose
220
Stool softeners (surfactant or emollient)
Docusate salts | Mineral oil
221
Stool softeners-anionic surfactants
Soften/lubricate fecesvia reduction in surface tension Increase fluid secretion into GI tract
222
Mineral oil is a hydrocarbon
Ingestible and penetrates still thereby softening it | -may also inhibit water reabsorption from GI tract
223
When is efficacy seen with stool softeners
1-3 days
224
Stool softeners laxative
Minimal, softening mainly
225
Adverse effects stool softeners
GI-bloating/flatulence, abdominal cramps Can leak past anus in some-aspiration caution in elderly/delibitated stroke
226
Stimulants
Senna Bisacodyl Castor oilglycerin Sodium picosulfate-OSMOTIC, also has magnesium oxide/anhydrous citric acid, metabolically converted to magnesium citrate
227
MOA stimulatnts
Irritant to enterocytes, GI smooth muscle leading to inflammation -Na K ATPas inhibition and/or increase in prostagladin synthesis/secretion (via cAMP/GMP) Promote water/electrolyte accumulation in GI -castor oil is hydrolyzed to ricinoleic acid Glycerin is a tri-hydroxyl alcohol and functions as an irritant and an osmotic and lubricant agent
228
Efficacy of usual stimulants
12-36 hours
229
Adverse effects stimulants
Abdominal cramping Urine discoloration (yellow brown/red pink)-senna Fluidelectrolyte disturbances (long use)
230
Stimulants contraindications
GI obstruction/ileus/impaction
231
Caution stimulants
Several of these agents pass into break milk
232
Bisacodyl and glycerin PR route
Faster onset via this route (.5-3 hours)
233
Prepopik and large doses PEG-3350 for precolonoscopy only
Classically given evening prior; with bisacodyl
234
Magnesium/phosphate
Ions poorly absorbed Hyperosmolar solutions;osmotically retain water in GI tract Greater volume shortens transit time
235
Drug interactions saline agents
Diuretics (electrolyte balance)
236
Caution saline agents
Renal disease (electrolytes) CHF/HTN (sodium)
237
Osmotic agents
Lactulose Magnesium citrate Sorbitol Polyethylene glycol (PEG-3350)
238
Lactulose
Disaccharide of galactose and fructose which aids in retaining fluid in GI
239
Sorbitol
Non absorbable sugar hydrolyzed to short chain FA retaining fluid in GI
240
In general osmotic agents provide effects in 1-2 days with laxative doses; larger doses may provide catharsis sooner
Ok
241
Lactulose also used for what
Severe liver disease patients (hyperammonemia) changes in pH traps ammonia in GI
242
Adverse effects osmotic agents
Electrolyte disturbances;watch closely | Abdominal pain/distention/flatulence
243
Polyethylene glycol (PEG-3350)
Also used for bowel prep prior to GI scopes radiological procedures or surgery Smaller doses for constipation Isotonic solution of long chain PEGs, not absorbed which retain water in GI (osmotically)
244
PEG products can provide a large volume of fluid to consume in a short period -bloating/distension and NV Palatability
Efficacy may be seen within 1-3 hours of large volume administration -smaller, daily doses provides effects in .5-3 days
245
What drugs do we use for UC
5-ASA JAK inhibitors TNF-a inhibitors 1-4 integrins inhibitors
246
Name 5-ASA
Sulfasalazine Mesalamine Olsalazine Balsalazide
247
Name JAK inhibitors
Tofacitinib
248
Name TNF-a inhibitors
Adalimumab Golimumab Infliximab
249
Name a-4 integrin inhibitor
Vedolizumab
250
__, ______, and ___ are also used as first line therapy for UC and crohnsbut not officially indicated, and covered elsewhere...not one exam
Steroids, immune modulators, antibiotics
251
What can we use to treat CD
IL-12/23 inhibitors TNF-a inhibitors A-4 inhibitors
252
Name IL-12/23 inhibitors
Ustekinumab
253
Name TNF-a inhibtors
Adalimumab Certolizumab Infliximab
254
Name a-4 integrin inhibtors
Natalizumab | Vedolizumab
255
5-ASA MOA
Inhibit PG and LT production via arachidonic acid pathway -COX and LIPOX Inhibiton of PG and LT produciton via arachidonic acid pathway Reduction in PMN and macrophage chemotaxis -may also inhibit the activation of NFKB which regulated transcription of genes for pro inflammatory proteins
256
Name the 5-ASA agents
Sulfasalazine (sulfapyridine and 5-ASA) Mesalamine (single 5-ASA) Olsalazine (2 molecules of 5-ASA) Balasalazide (inert carrier +5-ASA)
257
The extend of disease impacts how 5-ASA are given.
Oral-make distal ileum, colon or throughout GI Rectal exam-may reach the splenic flexure, so not frequently concentrate in the rectum Rectal suppositories-reach the upper rectum
258
Side effects 5-ASA agents
``` Izzy/headache/fatigue Epigastric distress (anorexia, abdominal pain, NVD) ``` Fewer systemic SE with pure 5-ASA products and topical formulations
259
Contraindication of 5-ASA
ASA allergic paintings
260
Contraindication for sulfasalazine
Sulfonamide allergic patients
261
Indications for 5-ASA agents
Active and maintence of mild to moderate UC Olsalazine-only for maintence of remission Balasalazide-only for active disease approval in males
262
MOA TNF-a inhibitors
Binding to TNF receptors and mediating upregulation of surface adhesion molecules-VCAM-1, E-selectin, MAdCAM-1 for leukocyte adhesion Binds to and neutralized membrane-associated and soluble human TNF-a mediated proinflammatory cell signaling, ultimately blocking leukocyte migration to its of inflammation
263
Name TNF-a inhibitors
Adalimumab Infliximab Golimumab Certolizumab
264
What are TNF-a inhibitors used for
IBD
265
Side effects TNF-a inhibtors
Infections (TB testing pre therapy)
266
Adalimumab black bow
Serious warning of infection that may lead to hospitalization or death. Most who developed these infections were also taking immunosuppressants
267
When discontinue adalimumab
Serious infection or sepsis TB Closely monitor
268
Side effects TNF-a inhibtors
Infections-TB treat pre therapy recommended Liver toxicity (increased enzymes) Headache/arthralgias/fatigue Rare-but-severe - dermatological related (EM, SJS, TEN) - malignancies
269
Indications adalimumab and infliximab
UC CD
270
Indication golimumab
UC
271
Indication certolizumab
CD
272
Administration adalimumab
SQ every 2 weeks
273
Administer infliximab
IV every 8 weeks
274
Administer golimumab
SQ every 4 weeks
275
Certolizumab
SQ every 4 weeks
276
A-4 integrin MOA
Limits integrins associated cell adhesion and subsequent treansendothelial migration of leukocytes to cite of inflammation
277
Name a-4 integrin inhibitors
Natalizumab (recombinant humanized IgG4 monoclonal antibody) Vedolizumab (humanized IgG1 monoclonal antibody)
278
Side effects a-4 integrin inhibitors
Infections (only natalizumab) -PML Infusion related SE Anti medication antibodies (decrease efficacy)rare-malignancies (vedolizumab)
279
What are the 3 risk factors for PML with a-4 integrin inhibtors
Treatment over 2 years Prior immunosuppressant treatment Anti-JC virus antibodies
280
Black bow warning a-4 integrin
PML Natalizumab only available through TOUCH prescribing program (only prescribers, infusion centers, and pharmacies associated with infusion centers registered with the program are able to prescribe, distribute, or infuse)
281
How diagnose PML
Evaluation that includes a gadolinium enhanced MRI scan of brain and when indicated, CSF analysis for John Cunningham viral DNA are recommended
282
Indication a-4 inhibtors
Used after inadequate response to conventional or TNF-a therapy Vedolizumab-moderate to severe CD and UC Natalizumab-moderate to severe CD
283
What is natalizumab not requested with
Moderate to severe CD Not recommended in combination with immunosuppressants; including TNF-a agents
284
Dose natalizumab
Administration IV infusion every 4 weeks
285
Dose vedolizumab
IV every 8 weeks
286
IL-23 and 12 MOA
Bind to respective receptors on naive T cells to induce differentiation and production of pro inflammatory cytokines Bind p40 subunit of IL12 and IL23 blocking activation and differentiation of naive T cells and activation of NK cells -thereby inhibiting production of pro inflammatory cytokines; INFg (TH1), TNFa, IL17(TH12), IL21,
287
Ustekinumab
Fully human igG1k monoclonal antibody Also indicated for plaque psoriasis and psoriatic arthritis IBD
288
Side effects IL12/23
Infections-TB testing pre therapy recommendation Infusion/injection related allergic reactions Headache/arthralgias/fatigue Rare-malignancies
289
Indications IL12/23
Active and maintence CD For patients intolerant or inadequate response (resistant) to conventional immune modulators, steroids or TNFa therapy
290
Dosing ustekinumab
IV as a single infusion For induction SQ every 8 weeks for maintence
291
JAK
Intracellular enzymes that transmit signals arising from cytokine interactions on cellular membrane to influence pro inflammatory gene transcription and expression
292
MOA JAK inhibtors
Bind to and inhibit free floating and bound JAK1 and JAK3 (lesser extent JAK2) -thereby ultimately inhibiting gene transcription and more cytokine release
293
Tofacitinib
Oral jak1/3 inhibitor Also indicated for psoriatic and RA
294
Side effects JAK inhibitors
Lymphopenia/lymphocytosis Neutropenia Fatigue Increases in LDL and HDL Rare-increased risk of malignancies/serious infections -from RA indication data
295
Indication JAK inhibitors
Moderate to severe UC active and maintence Concomitant use in biologic therapies or potent immunosuppressants not recommended
296
Siding tofacitinib
PO BID
297
Indications for steroid agents
Acute and/or severe UC and CD uncontrolled by other conventional medications -not for mainance of remission unless absolutely required
298
Dosing steroid agents
Use the lowest dose for shortest duration possible
299
C diff
Gram positive spore forming anaerobic rod Antibiotic associated pseudo membranous diarrhea
300
C diff toxins
Toxin a-enterotoxin_>diarrhea Toxin b-cytotoxic->cytotoxic to the colonic cells
301
Treat C diff
Cessation antibiotic Supportive, fecal transplant Vancomycin , metronidazole Fidaxomixin
302
Vancomycin c diff | A glycoprotein
Severe or mild
303
Metronidazole for c diff | A 5 nitroimidazole
Mild If oral administation wont work
304
Fidaxomicin c diff | A macrolide
Recurrent cdi | Spares anaerobic colic flora
305
Name Protozoa
Entamoeba histolytica Giardia lamblia Cryptosporidium
306
Treat entamoeba histolytica
Metronidazole or tinidazole to eliminate trophozoites Paromomycin or iodoquinol to eradicate intestinal carriage or organism
307
How treat entamoeba histolytica asymptomatic carriage
Cysts or trophozoites without internalized RBC With amebicide
308
Why must metronidazole and tinidazole be given with a luminal amebicide
Ensure eradication of e histolytica
309
Do paromomucin and lodoquinol effect extraintestinal organisms
No
310
MOA lodoquinol
Halogenated hydrocyquinolone unknown mechanism of e histolytica
311
Pharmacokinetics lodoquinol
90% retained in the intestines and excreted in feces
312
SE lodoquinol
Diarrhea, anorexia, nausea, vomiting, abdominal pain, headache, rash pruritus
313
Paromomycin is a aminoglycosides
Ok
314
Treat giardia lamblia
Tinidazole first line Metronidazole maybe Nitazoxanide
315
Nitrazoxanide MOA
Inhibit pyruvate ferredoxin oxidoreductase enzyme essential to anaerobic energy metabolism Prodrug active metabolite is tizoxanide
316
Pharmacokinetics nitazoxanide
Rapidly absorbed, excreted in urine and feces
317
SE nitazoxanide
Nausea, anorexia, flatulence, increased appetites, enlarged salivary glands, yellow eyes, dysuria, bright yellow urging
318
Key drugs for g lamblia
Nitazoxanide 5-nitroimidazoles-metronidazole, tinidazole
319
Cryptosporidium partum
Water day care, immunocompromised severe life threatening diarrhea 4 motile sporophytes
320
Treat cryptosporidium parvum
Antidiarrheal-loperamide Fluid management Antimicrobial-nitazoxanide, paromomcin
321
Cryptosporidium treatment in HIV
Antiretroviral therapy+ nitazoxanide
322
Cryptosporidium therapy not HIV
Reduce dose of immunosuppressant and nitazoxanide
323
Main goal of treating cryptosporidium in immunocompromised
Restore immune function
324
Key drugs for c parvum
Nitazoxanide Aminoglycosides-paromomycin
325
Nematodes
Round worms need to visualize microscopic eggs in feces Elevate eosinophils
326
Necator americanus and ancylostoma duodenal (hook worms)
Penetrate skin between toes Larva to lungs To SI where worms populate and release effs into feces Diarrhea, ab pain, weight loss, anemia, itching at penetration site
327
Ascaris lumbricoides
``` Consume eggs Large penetrate intestine and travel to lung Grow and cough hp Adult worms in fertilized eggs Eggs excreted in feces Eggs hatch in soil and live ``` Ab cramping. Malnutrition, worm invasion
328
Strongyloides
Larva in soil penetrate skin to lung Mature in SI release eggs that ARE NOT PASSED IN STOOL Hatched eggs autoinfect excrete larva
329
Clinical signs and diagnosis strongyloides
Vomit, ab bloating, diarrhea, anemia, weight loss,
330
Treat stronglyoides
Prednisone and asthma
331
Diagnose strongyloides
Larva in feces, enterohepatic
332
Trichuris trichuria whip worm
Ingest in food with eggs they hatch in SI mature thousands of eggs per day for a year No large no lung, no transit, no eosinophilia, no auto infection Diagnose eggs in feces
333
Enterobius vermicularis pin worm
Eggs ingested mature, migrate o perianal area to lay eggs Severe perianal itching scotch tape test
334
Treat nematode
``` Albendazole Mebendazole Ivermectin Ivermectin Thiabendazole Pyrantel pamoate ```
335
MOA albendazole and mebendazole which are broad spectrum oral anti helmithic agents
Inhibit microtubules synthesis, paralyzes worms, Prodrug , active metabolite produced after first pass effect
336
Thiabendazole MOA
Same as albendazole and mebendazole
337
Pharmacokinetics thiabendazole
Rapidly absorbed after ingestion, largely excreted in uring, can be absorbed from the skin
338
Adverse effects thiabendazole
Toxic, dizzy, anorexia, vomit, Irreversible liver fail and SJS
339
Ivermectin MOA
Intensifies GABA mediated transmission of signals in peripheral nerves of the nematode
340
What should ivermectin not be given with
Other drugs that enhance GABA (barbiturates, benzodiazepines, valproic acid)
341
Pyrantel pamoate MOA
Neuromuscular blocking agent causes release of acetylcholine and inhibito cholinesterase resulting in paralysis and expulsion fo the nematode
342
N americanus and A duodenal
Albendazole
343
A lumbricoides
Albendazole | Mebendazole
344
S stercoralis
Ivermectin
345
T trichuria
Mebendazole
346
E vermicularis
Albendazole Mebendazole Pyrantel pamoate
347
Schistosoma
Eggs in fresh water hatch larva infect and mature in snail Get into skin Mature in intrahepatic portion of portal venous migrate to veins surrounding intestine of bladder to lay effs Dermatitis, katakana fever, chronic fibrosis
348
Drug for schistomiasis
Praziquantel
349
Praziquantel MOA
Increase permeability of nematode and cestodes cell membranes to calcium resulting in paralysis , dislodgement and death
350
Adverse effects praziquantel
Headache, dizzy, drowsylow grade fever, itchy, rash
351
Tania solium (pork) and Tania saginata (beef)
Weight loss malnutrition Pigs and cows ingest from field contaminated with human feces larva disseminate through he intestine into the muscle of the animal Human ingest undercooked meat, tape worm matures in intestine Proglottids in stool or eggs
352
Diphyllobothrium datum
Acquired by intestine fresh water larva Proglttids and eggs in feces
353
Echinococcus granulosis
Extra intestinal tapeworm infection humans ingest eggs from dog feces Eggs hatch in intestine and larva form hydration cysts
354
Treat cestodes
Praziquantel Niclosamide Albendazole
355
Nicolsamide
Alternative drug for treatment of most tape worms | Not effective against hydration cysts
356
MOA niclosamide
Inhibitoin of oxidative phosphorylation or stimulation of ATPase
357
INTERFERON A
Host cytokines that exert antiviral , immunomodulatory and antiprolifeative actions Interferon a-2B PEGylated interferon a-2B PEGylated interferon a-2a Treat with well compensated liver disease, not wanting long term treatment, pregnant within next 2-3 years
358
Pros of interferons in chronic HBV infection
``` Shorter course Efficacious Decreased HBV DNA Decreased HBeAg Resistance rare ```
359
Cons interferons chronic HBV infection
Parenteral administation Expensive Side effects DANGEROUS IN DECOMPENSATED CIRRHOSIS
360
Pharmacokinetics interferon a-2B vs PEGylated interferon a-2a/2B
1. Short | 2. Long
361
MOA endogenous interferons
Infected cells release interferons to protect nearby healthy cells by allowing them to mount a defense Signal nearby macrophages and NK cells to clear infected cell Interferons act in an autocrine fashion to stimulate lysosomes lysis which leads to the lysis of the infected cell
362
Interferon a MOA
Bind to type 1 interferon receptor and activates JAK1 and TYK2 which phosphorylation the intracellular domains of the type 1 interferon receptos Phosphorylation of type 1 interferon leads to recruitment , phosphorylation and dimerization of signal transducer and activator of transcription 1 and 2 STAT1 and 2 Which translocate to the nucleus and activate the transcription of interon stimulated genes
363
Antiviral mechanism of ISG
Inhibit multiple steps of viral replication Viral protein synthesis and translocation Zap, IFIT family, OAS RNAseL path PKR
364
Immunomodulatory molecular mechanisms of interferon a
Inhibits HBV replciation and depends on immune clearance of HBV infected cells increased inflammation and fibrosis
365
PEGylated interferon a treatment induced an increase in ALT during seroconversion
Hepatitis flare can be a sign that seroconversion is in progress ALT up!
366
Contraindication PEGylated interferon a
Decompensated cirrhosis
367
Adverse effects interferon a and PEGylated interferon a
Flu like Headache, fever, chills, myalgia, malaise, fatigue and mental depression Bone marrow suppression, neurotoxicity
368
Nucleosides for HBV treatment
HBV DNA reverse transcriptase DNA polymerase inhibitors Oral agents that are used to suppress HBV Better tolerated than interferon a Higher response rate than interferon a Can be used in decompensated cirrhosis
369
NRTI
Nucleotide reverse treansciptase inhibitors stops synthesis Require conversion into their corresponding nucleotide triphosphates -cellular kinases convert both synthetic and endogenous nucleosides into nucleotides, the synthetic nucleotide triphosphate is the active antiviral aren’t
370
NRTA
Terminated HBV replication via viral DNA polymerase reverse transcriptase
371
HBV resistance to nucleosides/nucleotides
Impaired purine/pyramiding kinase activity - patient resistant to nucleoside analogs (lamivudine, entecavir, telbivudine) - patient responsive to nucleoside analogs (tenofovir) - resistance due to slow or low conversion of nucleosides into a nucleotide monophosphate form Mutation DNA polymerase
372
Why get HBV viral breakthrough
Resistance or non compliance
373
Nucleosides for treat HBV
Lamivudine Telbivudine Entecavir
374
Nucleotides for HBV infection
Tenofovir | Adefovir
375
Factors affecting the selection of antiviral nucleosides/nucleotides
Resistance Efficacy Usefulness with HIV co infection Pregnancy
376
Tenofovir
First line treatment for wild type HBV Used in patients with lamivudine, telbivudine or entecavir resistance Resistance rare Nephrotoxicity-proximal renal tubule
377
Entecavir-guanosine nucleoside analog
First line HBC Potent antiviral and low resistance -resistance in patients resistant to lamivudine Better choice than adefovir or tenofovir in patients with renal insuffiency Well tolerated
378
Long term efficacy of lamivudine limited by frequent emergence of drug resistance
YMDD to YVDD mutant in catalytic domain of HBV polymerase Leads to subsequent virological breakthrough
379
Lamivudine resistance increases over __
Time
380
Important to remember about HBV therapies
Therapies fail to eradicate the virus Relapse of hepatitis induced by HBV is always possible
381
Key drugs for HBV
Interferons-interferon a-2b, PEGylated interferon a-2B, PEGylated interferon a-2a Nucleosides-lamivudine, telbivudine, entecavir Nucleotides-tenofovir, adefovir
382
Can HCV be cured
Yup its an RNA virus not incorporated into DNA PEGylated interferon a plus ribavirin 24-48 week wegimen Less than 50% cure rate
383
Ribavirin
Interferes with the synthesis of GTP Inhibits capping of viral messenger RNA Inhibits the viral RNA dependent polymerase of certain viruses Potentiation the action of PEGylated interferon a-2a and a-2B -upregulated interferon stimulated genes (ISGs) Broad spectrum r
384
Contraindications ribavirin
Anemia | Pregnant
385
Protease inhibitors for HCV
Simeprevir Telaprevir Boceprevic
386
MOA protease inhibitors
Block NS3 catalytic site or the NS3/NS4 interaction
387
Simeprevir
Second generation Administered in combination with PEGylated interferon a-2a or a-2B Or sofosbuvir and ribavirin for chronic genotype 1 infection
388
Telaprevir and boceprevir
First generation protease inhibitors Administered in combination with PEGYlated interferons a-2a or a-2B and ribavirin Simeprevir better tolerated
389
NS5B
RNA dependent RNA polymerase needed for HCV
390
Sofosbuvir
Nucleotide analog First NS5B inhibitor available in US Disrupts all genotypes of HCV
391
NS5A proteins
Important for viral replciation and assembly of HCV | Exact MOA unknown
392
Ledipasvir, elbasvir, velpatasvir
Inhibit NS5a Effective across all genotypes Low barrier to resistsance, not given as a monotherapy Ledipasvir traditionally given in combination with ribavirin and PEGylated interferon a-2a or a-2B -significant reduction HCV RNA
393
Genotype 1 HCV no ribavirin
Ledipasvir+sofosbuvir
394
Genotype 1,2,3 HCV no ribavirin
Velpatasvir+sofosbuvir Elbasvir+grazoprevir
395
How manage coinfection HBV HCV
Treat predominant circus PEGylated interferon a-2a or a-2B and ribavirin for 48 weeks
396
Interferons for HCV
PEGylated interferon a-2B | PEGylated interferon a-2a
397
Nucleoside HCV
Ribavirin
398
Nucleotide HCV
Sofosbuvir
399
Protease inhibtiors for HCV
Simeprevire Telaprevir Boceprevir Grazoprevir
400
NA5A inhibitors for HCV
Ledipasvir Elbasvir Velpatasvir
401
Enterotoxin Enteroadherent Cytotoxin
Watery diarrhea Cramp fever High fever abdominal pain
402
Day care
Shigella, giardia, cryptosporidium, rotavirus
403
Infectious diarrhea treatment
Usually self limited , Do work up if blood, high fever, pain, immunocomp
404
What order for work up diarrhea
CBC, electrolytes, BUN Cr, stool cultures
405
hemolytic uremic syndrome
Anemia, thrombocytopenia, renal fail
406
Salmonella typhimurium
Gram neg rod No antibiotics Septic arthritis osteomyelitis
407
Vaccination
Hep, roar, shigella, salmonella typhi, CHOLERA
408
Vibrio parahemolyticus (cytotoxin) vs vulnificus
Bloody diarrhea seafood Gram neg bacillus Seafood Bulbous skin leasion coasatal salt water gram negative bacillus Cirrhosis hemochromatosis
409
Aeromonas hydrophilia
Gram negative, nonspore forming, rod shaped facultatively anaerobic bacteria, motile with flagellum Fresh water Necrotizing fasciitis, flesh eating bacteria Cholera like or blood stool Scuba divers with enteritis
410
Traveler diarrhea most common
Enterotoxigenic from ETEC Clinical diagnosis
411
EHEC and fever (cytotoxin)
No
412
Shiva toxin
Cytotoxin
413
Yersinia enterocolitica
``` Gram negative coccobacilli Iron metabolism (hemochromatosis) ``` Bloody Appendicitis, crohns Clinically indistinguishable from salmonella or shigella Dairy
414
Listeria monocytogenes
Gram positive rod Water diarrhea Dairy Need select media to grow
415
What antibiotics cause c diff
Clindamycin, cephalosporin, fluoroquinolones PO or IV metronidazole PO vancomycin
416
Cmv
Double stranded linear DNA immunosuppressed Endoscopy ulcerations
417
Giardia lamblia
Watery Steatorrhea Flatulence
418
Cryptosporidium
Watery diarrhea Direct microscopy acid fast Self limited imuunook Continuous and biliary disease-acalculous cholecystitis if not RUQ pain, fever
419
Cyclospora cayentanesis
Produce travel subtropical and tropical Watery 21 days in immunocompetent Indefinetely in immunosuppressed Cl resistant
420
Cystosporia belli
Tropical subtropical ``` Malabsorption weight loss Acid fast Non bloody Eosinophilia Need repeat stool exam ```
421
Schistomiasis
Bloody fresh water snails varices
422
Enteric fever
Samonalle yersinia
423
Reactive arthritis
Salmonella, camp, shigella, yersinia

Pharmacology (52 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions