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DERS Pharm > GI Drugs > Flashcards

GI Drugs Flashcards

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
Q

Quadruple therapy

A

2 antibiotics with PPI and bismuth subsalicylate

  1. Bisthmus subsalicylate + metronidazole + tetracycline + PPI
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26
Q

Both therapy

A

antibiotics given for 10-13 days and the PPI for 1 month

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27
Q

Mucosal protective agents:

A

Misoprostol
Sucralfate
Bismuth Subsalicylate

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28
Q

Misoprostol

A

analog of PGE
binds to EP3 receptor to decrease GA secretion
stimulates mucus and bicarb
enhances blood flow

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29
Q

Misoprostol uses and contraindications

A
  • prevention of NSAID induced ulcers in high risk pt

- CI in pregnant ppl

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30
Q

Sucralfate

A

forms a paste that binds to ulcers
stimulates mucosal prostaglandin and bicarb secretion

initial management of GERD in pregnancy

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31
Q

Bismuth subsalicylate and AE

A

suppresses H.pylori
no neutralizing action
PEPTO BISMOL

AE:

  • blackening of stool
  • cause toxicity
  • CI in pt with renal failure
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32
Q

Prokinetic drugs are ___

A
  • Motilin agonist

- Serotonin receptor agonist

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33
Q

Prokinetic drugs:

A

Erythromycin
Cisapride
Metoclopramide

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34
Q

Erythromycin

A
  • antibiotic
  • agonist at motilin receptor
    indication: diabetic gastroparesis
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35
Q

Cisapride

A

5HT4 receptor agonist
5HT3 receptor antagonist
- direct smooth muscle stimulant
- used for GERD, gastroparesis

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36
Q

Metoclopramide

A

5HT4 agonist
5HT3 receptor antagonist
D2 receptor antagonist

Upper digestive tract effects:

  • increases LES tone
  • Stimulates antral and small intestine contractions
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37
Q

Metoclopramide indications and AE

A

indications:

  • gasteroparesis
  • antiemetic
  • GERD

AE:

  • extrapyramidal effects due to DA antagonism
  • galactorrhea
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38
Q

Anti- emetic drugs

A
  • Anti-Histamines
  • Cholinergic Antagonists
  • D2 Antagonists
  • 5-HT3 Receptor Antagonists
  • Corticosteroids
  • Neurokinin-1 receptor Blockers
  • Benzodiazepines
  • Cannabinoids
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39
Q

Cholinergic Antagonists

A

Scopolamine

motion sickness

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40
Q

Anti-Histamines

A

Diphenhydramine
Meclizine
Cyclizine

motion sickness

41
Q

D2 Antagonists

A

Promethazine

Droperidol

42
Q

Promethazine

A

motion sickness

Chemo nausea

43
Q

Droperidol

A

adverse extrapyramidal effects

- prolonged QT interval

44
Q

5-HT3 Receptor Antagonists

A

Ondansetron
Granisetron

  • DOC for acute chemo nausea
  • DOC for hyperemesis gravidarum (pregnancy)
45
Q

Corticosteroids

A

Dexamethasone
Methylprednisolone

  • used for nausea in pt with metastatic cancer
46
Q

NK1 Antagonists

A

Aprepitant
Fosaprepitant

  • used for delayed Chemo nausea
  • given with dexamethasone and 5HT R antagonist
  • affects metabolism of warfarin and oral contraceptives
47
Q

Benzodiazepines

A

Lorazepam
Alprazolam
Diazepam

  • reduce anticipatory component
  • GABAa action
  • AE: CNS depression and dependence
48
Q

Cannabinoids

A

Dronabinol (Δ- 9 - tetrahydrocannabinol)

Cannabis sativa
CB1 receptors in brainstem
used for cancer chemo

AE:

  • tachycardia
  • hypotension
  • paranoid
49
Q

Laxatives

A 
Bulk forming laxatives
Cathartics
Stool softeners
Lubricant laxatives
Osmotic laxatives
Selective Mu opioid receptor antagonists
50
Q

Bulk forming laxatives

A

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
Q

Cathartics

A

directly stimulate enteric nervous system to increase motility

Bisacodyl
Senna
Castor oil

52
Q

Bisacodyl

A

acts on nerve fibers of mucosa of colon

53
Q

Senna

A

natural in plants
water and electrolyte secretion

chronic use can lead to melanosis coli: brown colonic mucosa

54
Q

Castor oil

A

broken into ricinoleic acid in small intestine

CI in pregnant pt

55
Q

Stool softeners

A

surfactant which allow water and lipids to penetrate

Docusate
Glycerin

56
Q

Lubricant laxatives

A

Mineral oil: coals feces to prevent water reabsorption

DO not give with docusate

57
Q

Osmotic laxatives

A

Lactulose
Mg Salts
Polyethylene glycol (PEG)

non absorbable sugars or salts which exert an osmotic pull to retain water in lumen

58
Q

Lactulose

A

metabolized by colonic bacteria –> AB cramping

59
Q

Mg salts

A

dont use for long time in pt with renal problems

60
Q

Polyethylene glycol (PEG)

A

creates high osmotic pressure in gut

used for bowel preparations before GI endoscopy

management for chronic constipation

61
Q

Lubiprostone

A

stimulates type 2 Cl channels of SI –> increased motility

indicated for chronic constipation and IBS

AE:

  • diarrhea
  • CI in children
62
Q

Selective Mu opioid receptor antagonists

A

Alvinmopan
Methylnaltrexone

normal motility
do not cross BBB

63
Q

Antidiarrheal drugs

A

Opioid agonists
Somatostatin analogs
Bismuth compounds

64
Q

Opioid agonists

A

Loperamide

Diphenoxylate

65
Q

Loperamide

A

does not cross BBB
no analgesia or addiction

CI in kids and pt with colitis

66
Q

Diphenoxylate

A

high dose have CNS effects –> dependence

CI in kids and pt with colitis

67
Q

Somatostatin analogs

A

Octreotide

indicated in diarrhea due to neuroendocrine tumors, vagotomy, dumping syndrome, short bowel syndrome, and AIDS

68
Q

Octreotide AE

A

decreased pancreatic exocrine function (steatorrhea)

inhibition of gallbladder contractility –> gallstones

69
Q

Bismuth subsalicylate

A

travellers diarrhea

70
Q

IBS treatment first line

A 
no meds
food diary:
- exclude gas producing foods
- low diet in fermentable FODMAPs
- lactose of gluten free
71
Q

Constipation type IBS treatment

A

Psyllium
Lubiprostone
Polyethylene Glycol
Docusate

72
Q

Diarrhea type IBS

A

Opioid agonist like loperamide

5HT antagonist alosetron

73
Q

IBS anticholinergics

A

Hyoscyamine
Dicyclomine
Glycopyrrolate
Methscopolamine

74
Q

Mild IBD

A

no systemic disease
no bowl obstruction
< 10% weight loss

75
Q

Moderate to severe IBD

A

Nausea or vomiting
fever
AB pain
anemia

76
Q

Severe fulminant disease

A

high fever
persistant vomiting
obstruction
cachexia

77
Q

IBD drug groups

A 
Triple A GI:
Aminosalicylates
Glucocorticoids
Immunosuppressants
Anti TNFa drugs
Anti-integrins
78
Q

Aminosalicylates

A

Sulfasalazine
Balsalazide
Mesalamine

long term maintenance IBD remission
active group is 5-ASA

79
Q

Aminosalicylates MOA

A

modulate COX and LOG pathway
inhibition of NF-KB
inhibition of cellular immunity

80
Q

Sulfasalazine

A

passes into colon is reduced by azoreductase

81
Q

Aminosalicylates AE

A

unable to tolerate due to nausea, headache, GI upset, etc

82
Q

Balsalazide

A

5 ASA linked to carrier molecule

well tolerated

83
Q

Mesalamine

A

packaged 5 ASA that release drug to the desired place

well tolerated

84
Q

Glucocorticoids

A

Prednisone
Prednisolone
Budesonide

85
Q

Glucocorticoids use

A

• 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
Q

Prednisone & Prednisolone

A

choice for oral therapy

hydrocortisone is in enema for sigmoid and rectal IBD flares

AE: adrenal suppression, hyperglycemia, immunosuppression

87
Q

Budesonide

A

topical effects
less AEs
undergoes rapid first pass metabolism –> low bioavailability

88
Q

Immunosuppressants

A

Mercaptopurine (6-MP)
Azathioprine
Methotrexate
Cyclosporine

  • maintenance of IBD remission
  • Steroid-sparing effect

AE:

  • Nausea
  • Bone marrow depression
  • Vomiting
  • Hepatotoxicity
89
Q

Mercaptopurine (6-MP) & Azathioprine drug interactions

A

Allopurinol:

- reduces xanthine oxidase activity –> increase serum concentration 6-thioguanine

90
Q

Methotrexate

A
  • 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
Q

Cyclosporine

A

calcinurin is needed to activate NFAT–> cytokine genes

Cyclosporine inhibits calcineurin

AE:
• Nephrotoxicity
• Neurotoxicity
• Hypertension
• Hyperkalemia
• GI complaints
• Hyperglycemia
92
Q

Anti TNF a drugs

A

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
Q

Anti TNF a drugs AE

A

• 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
Q

Anti-integrins

A

Natalizumab

95
Q

Natalizumab

A

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
Q

How to treat mild IBD

A

5 ASA
antibiotics
Budesonide
corticosteroids

97
Q

How to treat severe IBD

A 
IV corticosteroids 
TNF antagonists
Cyclosporine
Natalizumab
Surgery
98
Q

Pancrelipase

A

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

DERS Pharm (2 decks)

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