G.I. Drugs Flashcards
1
Q
Two major classes of drugs affecting the GI system
A
Drugs affecting secretion
Drugs affecting GI motility
2
Q
Classes of drugs affecting secretion
A
Antacids
H2 histamine receptor antagonists
Proton pump inhibitors
3
Q
Class of drugs affecting GI motility
A
Prokinetic
Anti-diarrheal/emetics
4
Q
Drugs affecting GI secretions are used in the treatment of
A
- Peptic ulcers (gastric or guodenal)
- Gastroesophageal reflux (GERD/Barrett’s Esophagus)
- Hypersecretory states such as Zollinger-Ellison syndrome
5
Q
Ulcers are a failure of
A
mucosal protection
6
Q
What do proton pump inhibitors inhibit
A
H+/K+ ATPase in the parietal cells
7
Q
Name the 4 antacids
A
- NaHCO3
- CaCO3
- AL(OH)3
- Mg(OH)2
8
Q
Adverse effects of NaHCO3
A
systemic alkalosis, fluid retention
9
Q
Adverse effects of CaCO3
A
Milk-alkali syndrome: hypercalcemia and nephrolithiasis
10
Q
Adverse effects of Al(OH)3
A
Constipation and hypophosphatemia
11
Q
Adverse effects of Mg(OH)2
A
Diarrhea and hypermagesemia
12
Q
What is Alternagel?
A
Al(OH)3
13
Q
What is Mallox and Mylanta?
A
Al(OH)3 and Mg(OH)2
14
Q
What is Tums?
A
CaCO3
15
Q
What is Gaviscon and what does it do?
A
Sodium alginate + antacids: viscous, weak base; prevents reflex and effective in GERD
16
Q
What is Mylicon/Phazyme and what do they do?
A
Simethicone: mild surfactant; enhances the release of gas
17
Q
First generation H2-histamine receptor antagonists
A
Diphenhydramine and Cimetidine
18
Q
Mechanism of Cimetidine
A
competitive antagonist of H2 histamine receptor
19
Q
Cimetidine reduces gastric acid secretion in response to what?
A
in response to histamine, gastrin, and acetylcholine
20
Q
Cimetidine inhibits which metabolic enzymes? Which drugs does this effect?
A
Inhibits CYP 2C6 and 2D9: warfarin, phenytoin, theophylline, benzodiazepines and sulfonylureas
21
Q
Side effects of Cimetidine?
A
- CNS effects (confusion, delirium headaches) seen with IV admin to elderly patients
- Antiandrogen (gynecomastia, impotence)
- Inhibition of estradiol metabolism (galactorrhea)
- Thrombocytopenia
22
Q
Second generation H2 blockers
A
Ranitidine (Zantac); Nizatidine (Axid); Famotidine (Pepcid)
23
Q
How are second generation H2 blockers different from 1st generation H2 blockers?
A
longer half life; increase ethanol bioavailability by reducing first-pass metabolism (except Famotidine); fewer effects of CYP450 system; greater potency
24
Q
Proton pump inhibitors (PPIs)
A
Omeprezole; lansoprazole; raberprazole, pantoprazole
25
Action of proton pump inhibitors
Irreversible inhibitor of H+/K+ ATPase
26
What are PPIs activated by?
Prodrugs: activated by acidic pH
27
Describe the pharmacokinetics of PPIs
Short plasma half-life (~1hr) but long duration of action (>24 hrs)
28
PPIs can cause hypergastrinemia, which can result in?
can result in rebound hypersecretion of gastric acids
29
Increase in gastric pH with PPIs can affect what?
drug absorption and potentially increase risk of infections
30
Adverse effects of PPIs
few side effects; nausea most common; Vitamin B12 deficiency; osteoporotic fracture
31
Drugs interactions of PPIs
Omeprazole inhibits CYP2C19: diazepam, warfarin, phenytoin levels increase; clopidogrel activity may be reduced
All PPIs: decreased absorption of digoxin and ketoconazole
32
What is acid rebound?
increased gastric acid secretion upon withdrawal of acid-suppressing medications (more common with H2 antagonists)
33
Reduced gastric acid removes what inhibition?
removes somatostatin inhibition of gastrin secretion (hypergastrinemia)
34
What can occur with H2 antagonists
tolerance
35
Mucosal protective agents
Sucralfate (Carafate) and Misoprostol (Cytotec)
36
Sucralfate
Aluminum hydroxide complex of sucrose; polymerizes and forms protective barrier at ulder site
37
What activates sucralfate?
acidic pH activates complex
38
Sucralfate may decrease the absorption of what?
tetracycline, digoxin, and phenytoin
39
Misoprostol (Cytotec)
semi-synthetic prostaglandin E1 derivative; reduces acid secretion (parietal cell)
40
Cytoprotectant effects of Misoprostol
enhanced mucus and bicarbonate secretion
41
What is Misoprostol used in combination with
chronic NSAIDs
42
Adverse effects of Misoprostol?
diarrhea, abortifacient (abortion inducing)
43
Many peptic ulcers are associated with infection of the gastric mucosa by?
the gram-negative bacilli, Helicobacter pylori
44
Mechanism of peptic ulcer formation by H. pylori infection
reduction in D-cell production of somatostatin; increased secretion of gastrin
45
Combination therapy of peptic ulcers associated with H pylori infection
1. Bismuth salt (PeptoBismol)
2. Antibiotic (Metronidazole, tetracycline, amoxicillin, clarithromycin
3. H2 blocker of PPI
4. Ranitidine bismuth citrate (Tritec)
46
Bismuth subsalicylate (PeptoBismol) coverted to what in the GI tract
converted to bismuth salts and salicylic acid
47
Activity of Bismuth subsalicylate
antibacterial, antiviral and antisecretory activity
48
Uses of Bismuth subsalicylate
treatment of mild diarrhea; part of multi-drug therapy for H. pylori eradication
49
Classes of drugs that increase GI motility
1. Prokinetic drugs
| 2. Laxatives
50
Classes of drugs that reduce GI motility
1. Antidiarrheals
| 2. Anti-emetics
51
Prokinetic drugs
Metoclopramide (Reglan); Cisapride (Propulsid); Erythromycin (motilin agonist); Linaclotide (Linzess)
52
Metoclopramide is a
D2 dopamine receptor antagonist
53
Blockade of D2 receptors in the myenteric plexus leads to
increased acetylcholine release; also produces anti-emetic effects
54
Clinical uses of Metoclopramide
facilitate small bowel intubation, post-op and diabetic gastroparesis, gastro-esophageal reflex disease (GERD) and anti-emetic
55
Side effects of Metoclopramide
sedation, Parkinson's-like syndrome, hyperprolactinemia (gynecomastia, galactorrhea, and breast tenderness)
56
What limits the usefulness of Erythromycin as a motilin agonist
rapid tolerance
57
What is Linaclotide used for treatment of?
a peptide activator of guanylate cyclase 2 used for the treatment of IBS + constipation and idiopathic constipation
58
How do you take Linaclotide?
taken orally 30 minutes before first meal; not absorpted systemically
59
Main adverse effect of Linaclotide?
diarrhea
60
Secretory or stimulant laxatives
Castor oil, Bisacodyl (Dulcolax), Cascara, senna, aloes; Lubiprostone (Amatiza)
61
Castor oil hydrolyzed in the upper small intestine to
ricinoleic acid
62
How do secretory/stimulant laxatives work?
open Cl- channels in the intestinal mucosa to facilitate movement of Cl-, Na+ and H20 in the intestinal lumen
63
What for and how does Lubiprostone work?
specific ClC2 activatory for chronic idiopathic constipation; used in IBS with chronic constipation
64
Bulk and saline laxatives
Psyllium, Methylcellulose, Bran, Milk of Magnesia, Lactulose
65
Lactulose is also used in
hepatic encephalopathy
66
How do bulk and saline laxatives work?
non-absorbable and form hydrophilic mass in the presence of water; increase water in the intestinal lumen by osmotic force, leading to distention and an increase in peristalsis
67
What produces similar effects to bulk and saline laxatives
isoosmotic electrolyte solutions with polyethylene glycol
68
Stool softeners
docusate sodium (Colace), mineral oil, glycerin, surfactants and lubricants
69
How do stool softeners work?
incorporate into stool to make passage easier; lubricate lower bowel to reduce fecal impaction
70
Stool softeners can decrease absorption of what?
fat-soluble vitamins
71
Two mechanisms that anti-diarrheals work by
1. Slow peristalsis to increase water and electrolyte absorption
2. Adsorb potential intestinal toxins and water
72
Anti-diarrheals that work by slowing peristalsis
Anticholinerics and opiates
73
Opiate anti-diarrheals
Diphenoxylate (with atropine; Lomotil) and Loperamide (Imodium)
74
Where do opiate anti-diarrheals act?
act locally to delay gastric emptying; poorly transverse the BBB
75
Opiate anti-diarrheals are contraindicated in patients with
severe ulcerative colitis and bacterially-induced diarrhea
76
Anti-diarrheals that work by adsorbing potential intestinal toxins and water
Kaolin (or attapulgite) and pectin, and low-dose fiber
77
Symptoms of IBS
abdominal pain and distension + altered bowel habits
78
Alosetron (Lotronex) MOA/Use
5HT3 receptor antagonist; blocks visceral afferent pain sensation and decreases colon motility; for women with IBS + diarrhea
79
GI side effects of Alosetron
constipation, ischemic colitis
80
Anti-emetics target which receptors
Chemoreceptors, D2 receptors, NK1 receptors?, 5-HT receptor
81
Anti-emetic D2 dopamine receptor antagonists
Promethazine (Phenergan) and Prochlorperazine (Compazine)
82
Anti-emetic Anticholinergics/Antihistamines
Meclizine (Antivert) and Scopolamine
83
5-HT3 receptor antagonists used as anti-emetics
Odansetron (Zofran), Aprepitant, Granisetron (Kytril)
84
5-HT3 receptor antagonists block activity in
CTZ and vagal afferents from stomach and small intestine which activate CNS emetic centers
85
Clinical use of 5-HT3 receptor antagonists
nausea and vomiting associated with chemotherapy
86
Cannabinoids used as anti-emetics
dronabinol (marinol) and nabilone (cesamet), synthetic tetrahydrocannabinol (THC)
87
Cannabinoids used for
nausea and vomiting associated with chemotherapy; limited to patients who are refractory to other agents
88
What may you experience with cannabinoids?
may experience psychoactive side effects
