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DERS Pharm > GI Drugs > Flashcards

GI Drugs Flashcards

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1
Q

What is the treatment of gastroesophageal reflux and peptic ulcer disease?

A
  • antacids
  • H2 receptor antagonists
  • Proton pump inhibitors
  • mucosal protective agents
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2
Q

What are corroding factors?

A

Gastric acid
pepsin
bile
H. pylori

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3
Q

What are protective factors?

A

Secretion of mucus and bicarbonate
Blood flow
Mucosal cellular regeneration
Prostaglandins

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4
Q

How do antacids work?

A

antacids + HCl –> salt and H20

neutralizes gastric pH and protects esophageal mucosa from reflex corrosion

onset: 5 min
duration of action: 30 min–>1 hr

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5
Q

Types of antacids

A

Aluminum hydroxide: constipation
Magnesium hydroxide: diarrhea
Calcium carbonate: causes CO2 belching (can cause metabolic alkalosis)

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6
Q

Antacids drug interactions

A
  • binding of other drugs

- tetracyclines, fluoroquiniolones, iron, etc

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7
Q

How does H2 receptor antagonists work?

A

suppress histamine induced gastric acid secretion

  • reduce signal transduction for Ach and Gastrin induced acid production
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8
Q

H2 antagonists act by ___

A

competitively inhibiting the parietal cell H2 Gs receptor

onset: 2.5 hr
duration of action: 4-10 hr
Tacyphylaxis develops in 2-4 weeks

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9
Q

H2 antagonist drugs

A

Cimetidine: lots of AE
Famotidine
Nizatidine

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10
Q

H2RAs suppress___

A

basal gastric acid secretion*

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11
Q

H2RA inidications

A
  • GERD
  • PUD
  • non ulcer dyspepsia
  • prophylaxis
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12
Q

H2RA AE

A
  • myelosuppression
  • increased gastric pH
  • b12 deficiency
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13
Q

Cimetidine AE

A
  • galactorrhea, male impotence due to anti-androgen and prolactin stimulant
  • CNS effects
  • inhibits CYP450 increasing conc of warfarin, diazepam, phenytoin
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14
Q

Proton Pump inhibitors MOA

A

suppress final common pathway of gastric acid secretion

irreversibly bind and inhibit the H-K ATPase pump of gastric parietal cells

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15
Q

PPI suppress

A

BOTH basal and meal stimulated gastric acid production

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16
Q

PPI

A

most potent inhibitors

inhibit 90-98% of 24 hr acid secretion

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17
Q

PPI drugs

A 
Omeprazole
Esomeprazole
Reabeprazole
Pantoprazole
Lansoprazole
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18
Q

PPI indications

A
  • Gastrinoma
  • non ulcer dyspepsia
  • prophylaxis
  • GERD
  • PUD
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19
Q

PPI AE

A
  • pretty safe but can give you diarrhea, AB pain, headache
  • b12 deficiency
  • increased risk of pneumonia and C.difficile
  • hypomagnesemia
  • osteopenia

** fractures

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20
Q

Omeprazole may inhibit ___ of ___

A

CYP450, warfarin diazepam and phenytoin

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21
Q

What prodrug requires activation by hepatic P450 CYPC19 isoenzyme?

A

Clopidogrel

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22
Q

Omeprazole, Esomeprazole, and Lansoprazole inhibit

A

CYP2C19 –> reduce clopidogrel activation

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23
Q

H.Pylori treatment

A
  • triple therapy
  • quadruple therapy
  • both
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24
Q

Triple therapy

A

2 antibiotics and PPI:

  1. clarithromycin + amoxicillin + PPI
  2. clarithromycin + metronidazole + PPI
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25
Quadruple therapy
2 antibiotics with PPI and bismuth subsalicylate 1. Bisthmus subsalicylate + metronidazole + tetracycline + PPI
26
Both therapy
antibiotics given for 10-13 days and the PPI for 1 month
27
Mucosal protective agents:
Misoprostol Sucralfate Bismuth Subsalicylate
28
Misoprostol
analog of PGE binds to EP3 receptor to decrease GA secretion stimulates mucus and bicarb enhances blood flow
29
Misoprostol uses and contraindications
- prevention of NSAID induced ulcers in high risk pt | - CI in pregnant ppl
30
Sucralfate
forms a paste that binds to ulcers stimulates mucosal prostaglandin and bicarb secretion initial management of GERD in pregnancy
31
Bismuth subsalicylate and AE
suppresses H.pylori no neutralizing action PEPTO BISMOL AE: - blackening of stool - cause toxicity - CI in pt with renal failure
32
Prokinetic drugs are ___
- Motilin agonist | - Serotonin receptor agonist
33
Prokinetic drugs:
Erythromycin Cisapride Metoclopramide
34
Erythromycin
- antibiotic - agonist at motilin receptor indication: diabetic gastroparesis
35
Cisapride
5HT4 receptor agonist 5HT3 receptor antagonist - direct smooth muscle stimulant - used for GERD, gastroparesis
36
Metoclopramide
5HT4 agonist 5HT3 receptor antagonist D2 receptor antagonist Upper digestive tract effects: - increases LES tone - Stimulates antral and small intestine contractions
37
Metoclopramide indications and AE
indications: - gasteroparesis - antiemetic - GERD AE: - extrapyramidal effects due to DA antagonism - galactorrhea
38
Anti- emetic drugs
* Anti-Histamines * Cholinergic Antagonists * D2 Antagonists * 5-HT3 Receptor Antagonists * Corticosteroids * Neurokinin-1 receptor Blockers * Benzodiazepines * Cannabinoids
39
Cholinergic Antagonists
Scopolamine | motion sickness
40
Anti-Histamines
Diphenhydramine Meclizine Cyclizine motion sickness
41
D2 Antagonists
Promethazine | Droperidol
42
Promethazine
motion sickness | Chemo nausea
43
Droperidol
adverse extrapyramidal effects | - prolonged QT interval
44
5-HT3 Receptor Antagonists
Ondansetron Granisetron - DOC for acute chemo nausea - DOC for hyperemesis gravidarum (pregnancy)
45
Corticosteroids
Dexamethasone Methylprednisolone - used for nausea in pt with metastatic cancer
46
NK1 Antagonists
Aprepitant Fosaprepitant - used for delayed Chemo nausea - given with dexamethasone and 5HT R antagonist - affects metabolism of warfarin and oral contraceptives
47
Benzodiazepines
Lorazepam Alprazolam Diazepam - reduce anticipatory component - GABAa action - AE: CNS depression and dependence
48
Cannabinoids
Dronabinol (Δ- 9 - tetrahydrocannabinol) Cannabis sativa CB1 receptors in brainstem used for cancer chemo AE: - tachycardia - hypotension - paranoid
49
Laxatives
``` Bulk forming laxatives Cathartics Stool softeners Lubricant laxatives Osmotic laxatives Selective Mu opioid receptor antagonists ```
50
Bulk forming laxatives
Methyl cellulose Psyllium Bran non digestible colloids that absorb water to form bulky jelly Contraindicated in pt that are immobile or using opioid therapy
51
Cathartics
directly stimulate enteric nervous system to increase motility Bisacodyl Senna Castor oil
52
Bisacodyl
acts on nerve fibers of mucosa of colon
53
Senna
natural in plants water and electrolyte secretion chronic use can lead to melanosis coli: brown colonic mucosa
54
Castor oil
broken into ricinoleic acid in small intestine | CI in pregnant pt
55
Stool softeners
surfactant which allow water and lipids to penetrate Docusate Glycerin
56
Lubricant laxatives
Mineral oil: coals feces to prevent water reabsorption DO not give with docusate
57
Osmotic laxatives
Lactulose Mg Salts Polyethylene glycol (PEG) non absorbable sugars or salts which exert an osmotic pull to retain water in lumen
58
Lactulose
metabolized by colonic bacteria --> AB cramping
59
Mg salts
dont use for long time in pt with renal problems
60
Polyethylene glycol (PEG)
creates high osmotic pressure in gut used for bowel preparations before GI endoscopy management for chronic constipation
61
Lubiprostone
stimulates type 2 Cl channels of SI --> increased motility indicated for chronic constipation and IBS AE: - diarrhea - CI in children
62
Selective Mu opioid receptor antagonists
Alvinmopan Methylnaltrexone normal motility do not cross BBB
63
Antidiarrheal drugs
Opioid agonists Somatostatin analogs Bismuth compounds
64
Opioid agonists
Loperamide | Diphenoxylate
65
Loperamide
does not cross BBB no analgesia or addiction CI in kids and pt with colitis
66
Diphenoxylate
high dose have CNS effects --> dependence CI in kids and pt with colitis
67
Somatostatin analogs
Octreotide indicated in diarrhea due to neuroendocrine tumors, vagotomy, dumping syndrome, short bowel syndrome, and AIDS
68
Octreotide AE
decreased pancreatic exocrine function (steatorrhea) inhibition of gallbladder contractility --> gallstones
69
Bismuth subsalicylate
travellers diarrhea
70
IBS treatment first line
``` no meds food diary: - exclude gas producing foods - low diet in fermentable FODMAPs - lactose of gluten free ```
71
Constipation type IBS treatment
Psyllium Lubiprostone Polyethylene Glycol Docusate
72
Diarrhea type IBS
Opioid agonist like loperamide | 5HT antagonist alosetron
73
IBS anticholinergics
Hyoscyamine Dicyclomine Glycopyrrolate Methscopolamine
74
Mild IBD
no systemic disease no bowl obstruction < 10% weight loss
75
Moderate to severe IBD
Nausea or vomiting fever AB pain anemia
76
Severe fulminant disease
high fever persistant vomiting obstruction cachexia
77
IBD drug groups
``` Triple A GI: Aminosalicylates Glucocorticoids Immunosuppressants Anti TNFa drugs Anti-integrins ```
78
Aminosalicylates
Sulfasalazine Balsalazide Mesalamine long term maintenance IBD remission active group is 5-ASA
79
Aminosalicylates MOA
modulate COX and LOG pathway inhibition of NF-KB inhibition of cellular immunity
80
Sulfasalazine
passes into colon is reduced by azoreductase
81
Aminosalicylates AE
unable to tolerate due to nausea, headache, GI upset, etc
82
Balsalazide
5 ASA linked to carrier molecule well tolerated
83
Mesalamine
packaged 5 ASA that release drug to the desired place well tolerated
84
Glucocorticoids
Prednisone Prednisolone Budesonide
85
Glucocorticoids use
• remission of acute exacerbations of IBD • Not indicated for maintaining remission • Immunosuppressive and anti-inflammatory effects via: - Interaction with intracellular glucocorticoid response elements - Inhibition of phospholipase A2 and COX - Inhibition of NF-κB
86
Prednisone & Prednisolone
choice for oral therapy hydrocortisone is in enema for sigmoid and rectal IBD flares AE: adrenal suppression, hyperglycemia, immunosuppression
87
Budesonide
topical effects less AEs undergoes rapid first pass metabolism --> low bioavailability
88
Immunosuppressants
Mercaptopurine (6-MP) Azathioprine Methotrexate Cyclosporine * maintenance of IBD remission * Steroid-sparing effect AE: - Nausea - Bone marrow depression - Vomiting - Hepatotoxicity
89
Mercaptopurine (6-MP) & Azathioprine drug interactions
Allopurinol: | - reduces xanthine oxidase activity --> increase serum concentration 6-thioguanine
90
Methotrexate
- Inhibits dihydrofolate reductase, an - Reduces the inflammatory actions of IL1 - Stimulates increase release of adenosine AE: - bone marrow depression - megaloblastic anemia - mucositis AE reduced by folate
91
Cyclosporine
calcinurin is needed to activate NFAT--> cytokine genes Cyclosporine inhibits calcineurin ``` AE: • Nephrotoxicity • Neurotoxicity • Hypertension • Hyperkalemia • GI complaints • Hyperglycemia ```
92
Anti TNF a drugs
Infliximab- moderate to severe colitis Adalimumab Indicated in acute and chronic treatment of IBD** • inactivate TNF • TNF is a key mediator of: - Release of proinflammatory cytokines - Stimulation of hepatic acute phase reactants - Upregulation of endothelial adhesion molecules promoting leukocyte migration
93
Anti TNF a drugs AE
• Suppression of Th1 activity: - Severe infections including invasive fungal disease - Reactivation of latent tuberculosis • Antibodies may develop against these biologics: - Elimination of clinical response to therapy - Acute or delayed infusion reactions • Increased risks of lymphoma, acute hepatic failure and congestive heart failure have also been reported
94
Anti-integrins
Natalizumab
95
Natalizumab
monoclonal antibody targeting several integrins on circulating inflammatory cells - moderate to severe, unresponsive Crohn’s disease AE: - infusion rx - opportunistic infections - reactivation of HPV
96
How to treat mild IBD
5 ASA antibiotics Budesonide corticosteroids
97
How to treat severe IBD
``` IV corticosteroids TNF antagonists Cyclosporine Natalizumab Surgery ```
98
Pancrelipase
Pancreatic Enzyme Supplements • Combination of amylase, lipase and proteases which are rapidly degraded by gastric acids • Enteric-coated formulations should be used or non-coated forms given with acid suppression therapy • Given by mouth with each meal AE: - diarrhea - AB pain

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