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Pharmacology Test #5 > G.I. Drugs > Flashcards

G.I. Drugs Flashcards

1
Q

Two major classes of drugs affecting the GI system

A

Drugs affecting secretion

Drugs affecting GI motility

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2
Q

Classes of drugs affecting secretion

A

Antacids
H2 histamine receptor antagonists
Proton pump inhibitors

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3
Q

Class of drugs affecting GI motility

A

Prokinetic

Anti-diarrheal/emetics

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4
Q

Drugs affecting GI secretions are used in the treatment of

A
  1. Peptic ulcers (gastric or guodenal)
  2. Gastroesophageal reflux (GERD/Barrett’s Esophagus)
  3. Hypersecretory states such as Zollinger-Ellison syndrome
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5
Q

Ulcers are a failure of

A

mucosal protection

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6
Q

What do proton pump inhibitors inhibit

A

H+/K+ ATPase in the parietal cells

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7
Q

Name the 4 antacids

A
  1. NaHCO3
  2. CaCO3
  3. AL(OH)3
  4. Mg(OH)2
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8
Q

Adverse effects of NaHCO3

A

systemic alkalosis, fluid retention

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9
Q

Adverse effects of CaCO3

A

Milk-alkali syndrome: hypercalcemia and nephrolithiasis

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10
Q

Adverse effects of Al(OH)3

A

Constipation and hypophosphatemia

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11
Q

Adverse effects of Mg(OH)2

A

Diarrhea and hypermagesemia

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12
Q

What is Alternagel?

A

Al(OH)3

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13
Q

What is Mallox and Mylanta?

A

Al(OH)3 and Mg(OH)2

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14
Q

What is Tums?

A

CaCO3

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15
Q

What is Gaviscon and what does it do?

A

Sodium alginate + antacids: viscous, weak base; prevents reflex and effective in GERD

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16
Q

What is Mylicon/Phazyme and what do they do?

A

Simethicone: mild surfactant; enhances the release of gas

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17
Q

First generation H2-histamine receptor antagonists

A

Diphenhydramine and Cimetidine

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18
Q

Mechanism of Cimetidine

A

competitive antagonist of H2 histamine receptor

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19
Q

Cimetidine reduces gastric acid secretion in response to what?

A

in response to histamine, gastrin, and acetylcholine

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20
Q

Cimetidine inhibits which metabolic enzymes? Which drugs does this effect?

A

Inhibits CYP 2C6 and 2D9: warfarin, phenytoin, theophylline, benzodiazepines and sulfonylureas

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21
Q

Side effects of Cimetidine?

A
  1. CNS effects (confusion, delirium headaches) seen with IV admin to elderly patients
  2. Antiandrogen (gynecomastia, impotence)
  3. Inhibition of estradiol metabolism (galactorrhea)
  4. Thrombocytopenia
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22
Q

Second generation H2 blockers

A

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

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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

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24
Q

Proton pump inhibitors (PPIs)

A

Omeprezole; lansoprazole; raberprazole, pantoprazole

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25
Q

Action of proton pump inhibitors

A

Irreversible inhibitor of H+/K+ ATPase

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26
Q

What are PPIs activated by?

A

Prodrugs: activated by acidic pH

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27
Q

Describe the pharmacokinetics of PPIs

A

Short plasma half-life (~1hr) but long duration of action (>24 hrs)

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28
Q

PPIs can cause hypergastrinemia, which can result in?

A

can result in rebound hypersecretion of gastric acids

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29
Q

Increase in gastric pH with PPIs can affect what?

A

drug absorption and potentially increase risk of infections

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30
Q

Adverse effects of PPIs

A

few side effects; nausea most common; Vitamin B12 deficiency; osteoporotic fracture

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31
Q

Drugs interactions of PPIs

A

Omeprazole inhibits CYP2C19: diazepam, warfarin, phenytoin levels increase; clopidogrel activity may be reduced
All PPIs: decreased absorption of digoxin and ketoconazole

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32
Q

What is acid rebound?

A

increased gastric acid secretion upon withdrawal of acid-suppressing medications (more common with H2 antagonists)

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33
Q

Reduced gastric acid removes what inhibition?

A

removes somatostatin inhibition of gastrin secretion (hypergastrinemia)

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34
Q

What can occur with H2 antagonists

A

tolerance

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35
Q

Mucosal protective agents

A

Sucralfate (Carafate) and Misoprostol (Cytotec)

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36
Q

Sucralfate

A

Aluminum hydroxide complex of sucrose; polymerizes and forms protective barrier at ulder site

37
Q

What activates sucralfate?

A

acidic pH activates complex

38
Q

Sucralfate may decrease the absorption of what?

A

tetracycline, digoxin, and phenytoin

39
Q

Misoprostol (Cytotec)

A

semi-synthetic prostaglandin E1 derivative; reduces acid secretion (parietal cell)

40
Q

Cytoprotectant effects of Misoprostol

A

enhanced mucus and bicarbonate secretion

41
Q

What is Misoprostol used in combination with

A

chronic NSAIDs

42
Q

Adverse effects of Misoprostol?

A

diarrhea, abortifacient (abortion inducing)

43
Q

Many peptic ulcers are associated with infection of the gastric mucosa by?

A

the gram-negative bacilli, Helicobacter pylori

44
Q

Mechanism of peptic ulcer formation by H. pylori infection

A

reduction in D-cell production of somatostatin; increased secretion of gastrin

45
Q

Combination therapy of peptic ulcers associated with H pylori infection

A
  1. Bismuth salt (PeptoBismol)
  2. Antibiotic (Metronidazole, tetracycline, amoxicillin, clarithromycin
  3. H2 blocker of PPI
  4. Ranitidine bismuth citrate (Tritec)
46
Q

Bismuth subsalicylate (PeptoBismol) coverted to what in the GI tract

A

converted to bismuth salts and salicylic acid

47
Q

Activity of Bismuth subsalicylate

A

antibacterial, antiviral and antisecretory activity

48
Q

Uses of Bismuth subsalicylate

A

treatment of mild diarrhea; part of multi-drug therapy for H. pylori eradication

49
Q

Classes of drugs that increase GI motility

A
  1. Prokinetic drugs

2. Laxatives

50
Q

Classes of drugs that reduce GI motility

A
  1. Antidiarrheals

2. Anti-emetics

51
Q

Prokinetic drugs

A

Metoclopramide (Reglan); Cisapride (Propulsid); Erythromycin (motilin agonist); Linaclotide (Linzess)

52
Q

Metoclopramide is a

A

D2 dopamine receptor antagonist

53
Q

Blockade of D2 receptors in the myenteric plexus leads to

A

increased acetylcholine release; also produces anti-emetic effects

54
Q

Clinical uses of Metoclopramide

A

facilitate small bowel intubation, post-op and diabetic gastroparesis, gastro-esophageal reflex disease (GERD) and anti-emetic

55
Q

Side effects of Metoclopramide

A

sedation, Parkinson’s-like syndrome, hyperprolactinemia (gynecomastia, galactorrhea, and breast tenderness)

56
Q

What limits the usefulness of Erythromycin as a motilin agonist

A

rapid tolerance

57
Q

What is Linaclotide used for treatment of?

A

a peptide activator of guanylate cyclase 2 used for the treatment of IBS + constipation and idiopathic constipation

58
Q

How do you take Linaclotide?

A

taken orally 30 minutes before first meal; not absorpted systemically

59
Q

Main adverse effect of Linaclotide?

A

diarrhea

60
Q

Secretory or stimulant laxatives

A

Castor oil, Bisacodyl (Dulcolax), Cascara, senna, aloes; Lubiprostone (Amatiza)

61
Q

Castor oil hydrolyzed in the upper small intestine to

A

ricinoleic acid

62
Q

How do secretory/stimulant laxatives work?

A

open Cl- channels in the intestinal mucosa to facilitate movement of Cl-, Na+ and H20 in the intestinal lumen

63
Q

What for and how does Lubiprostone work?

A

specific ClC2 activatory for chronic idiopathic constipation; used in IBS with chronic constipation

64
Q

Bulk and saline laxatives

A

Psyllium, Methylcellulose, Bran, Milk of Magnesia, Lactulose

65
Q

Lactulose is also used in

A

hepatic encephalopathy

66
Q

How do bulk and saline laxatives work?

A

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
Q

What produces similar effects to bulk and saline laxatives

A

isoosmotic electrolyte solutions with polyethylene glycol

68
Q

Stool softeners

A

docusate sodium (Colace), mineral oil, glycerin, surfactants and lubricants

69
Q

How do stool softeners work?

A

incorporate into stool to make passage easier; lubricate lower bowel to reduce fecal impaction

70
Q

Stool softeners can decrease absorption of what?

A

fat-soluble vitamins

71
Q

Two mechanisms that anti-diarrheals work by

A
  1. Slow peristalsis to increase water and electrolyte absorption
  2. Adsorb potential intestinal toxins and water
72
Q

Anti-diarrheals that work by slowing peristalsis

A

Anticholinerics and opiates

73
Q

Opiate anti-diarrheals

A

Diphenoxylate (with atropine; Lomotil) and Loperamide (Imodium)

74
Q

Where do opiate anti-diarrheals act?

A

act locally to delay gastric emptying; poorly transverse the BBB

75
Q

Opiate anti-diarrheals are contraindicated in patients with

A

severe ulcerative colitis and bacterially-induced diarrhea

76
Q

Anti-diarrheals that work by adsorbing potential intestinal toxins and water

A

Kaolin (or attapulgite) and pectin, and low-dose fiber

77
Q

Symptoms of IBS

A

abdominal pain and distension + altered bowel habits

78
Q

Alosetron (Lotronex) MOA/Use

A

5HT3 receptor antagonist; blocks visceral afferent pain sensation and decreases colon motility; for women with IBS + diarrhea

79
Q

GI side effects of Alosetron

A

constipation, ischemic colitis

80
Q

Anti-emetics target which receptors

A

Chemoreceptors, D2 receptors, NK1 receptors?, 5-HT receptor

81
Q

Anti-emetic D2 dopamine receptor antagonists

A

Promethazine (Phenergan) and Prochlorperazine (Compazine)

82
Q

Anti-emetic Anticholinergics/Antihistamines

A

Meclizine (Antivert) and Scopolamine

83
Q

5-HT3 receptor antagonists used as anti-emetics

A

Odansetron (Zofran), Aprepitant, Granisetron (Kytril)

84
Q

5-HT3 receptor antagonists block activity in

A

CTZ and vagal afferents from stomach and small intestine which activate CNS emetic centers

85
Q

Clinical use of 5-HT3 receptor antagonists

A

nausea and vomiting associated with chemotherapy

86
Q

Cannabinoids used as anti-emetics

A

dronabinol (marinol) and nabilone (cesamet), synthetic tetrahydrocannabinol (THC)

87
Q

Cannabinoids used for

A

nausea and vomiting associated with chemotherapy; limited to patients who are refractory to other agents

88
Q

What may you experience with cannabinoids?

A

may experience psychoactive side effects

Pharmacology Test #5 (11 decks)

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