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GI Drugs 2 Flashcards

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1
Q

Examples of laxatives

A
  • Bulk Forming Laxatives
  • Cathartics (Stimulant Laxatives)
  • Stool Softeners
  • Lubricant Laxatives
  • Osmotic Laxatives
  • Selective Mu-Opioid Receptor Antagonists
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2
Q

These drugs are Non-digestible colloids which absorb water to form a bulky, soft jelly that distends the colon to promote peristalsis

A

Bulk-Forming Laxatives:

Methylcellulose
Psyllium
Bran

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3
Q

When are Methylcellulose, Psyllium and Bran contraindicated?

A

in patients who are immobile or in long-term opioid therapy as intestinal obstruction may result

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4
Q

Examples of Cathartics (Stimulant laxatives)

A

Bisacodyl
Senna
Caster oil

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5
Q

This laxative acts on nerve fibers in the mucosa of the colon and causes minimal systemic absorption

A

Bisacodyl

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6
Q

This laxative causes water and electrolyte secretion into the bowel; chronic use may lead to melanosis coli

A

Senna

melanosis coli: a harmless brown pigmentation of the colonic mucosa unrelated to colon cancer risk

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7
Q

This laxative is broken down into ricinoleic acid in the small intestine and is contraindicated in pregnancy as this may cause uterine contractions

A

Castor oil

  • Required on a long-term basis for patients who are neurologically impaired and in bed bound patients
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8
Q

Who are the stool softeners

A

Docusate and Glycerin

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9
Q

Function of lubricant laxatives such as mineral oil

A

coats fecal material preventing water reabsorption

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10
Q

What should not be given with mineral oil

A

Docusate

- the mineral oil will be absorbed into the stool thereby negating its laxative effects

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11
Q

Non-absorbable sugars or salts which exert an osmotic pull to retain water in the intestinal lumen

A

Osmotic laxatives

- lactulose, magnesium salts, polyethylene glycol

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12
Q

This drug is metabolized by colonic bacteria and can lead to severe flatus with abdominal cramping

A

Lactulose

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13
Q

This drug should not be used for prolonged periods in persons with renal insufficiency as they may cause hypermagnesemia

A

Magnesium salts

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14
Q

This drug is commonly used for complete bowel preparation before gastrointestinal endoscopic procedures and does not produce significant flats or cramping

A

Polyethylene glycol (PEG)

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15
Q

This drug stimulates the type 2 chloride channels of the small intestine and increases secretion of chloride-rich fluid which stimulates intestinal motility

A

Lubiprostone

- Indicated for chronic constipation and IBS with predominant constipation

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16
Q

Adverse effects of lubiprostone

A
  • Diarrhea (most common)

* Contraindicated in children

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17
Q

Who are the Selective Mu-Opioid Receptor Antagonists?

A

Alvimopan
Methylnaltrexone

  • Act at the level of the gut to maintain normal motility
  • Do not cross the blood-brain barrier and thus do not negate the analgesic effect of opiods
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18
Q

Analogs of the opioid meperidine which activates presynaptic mu- opioid receptors in the enteric nervous system to inhibit ACh release and decrease gut peristalsis

A

Opioid agonists
- loperamide and diphenoxylate

Both drugs are contraindicated in children and patients with severe colitis

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19
Q

This opioid agonist does not cross blood brain barrier and has no analgesic properties or potential for addiction

A

Loperamide

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20
Q

This opioid agonist at higher doses can have CNS effects and with prolonged use that leads to opioid dependence

A

Diphenoxylate

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21
Q

synthetic octapeptide with 30x the serum half-life of somatostatin

A

Octreotide

Somatostatin analog

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22
Q

When do you use octreotide ?

A
  • Secretory diarrhea due to neuroendocrine tumors such as carcinoid and VIPoma
  • Diarrhea caused by vagotomy, dumping syndrome, short bowel syndrome and AIDS
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23
Q

Adverse effects of octreotide

A

• Decrease pancreatic exocrine function
- resultant steatorrhea —> deficiency of fat-soluble vitamins
• Inhibition of gallbladder contractility leads to formation of biliary sludge which may precipitate gallstones

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24
Q

Which drug controls traveller’s diarrhea by decreasing fluid secretion in the enteric tract

A

Bismuth subsalicylate (Pepto-Bismol)

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25
First line strategy to treat irritable bowel syndrome
1) Exclusion of gas-producing foods 2) Diet low in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) 3) Lactose and/or gluten omission Moderate to severe symptoms that impair quality of life qualify for pharmacologic intervention
26
Drugs to treat constipation predominant IBS
* Psyllium * Lubiprostone * Polyethylene Glycol * Docusate
27
Drugs used to treat diarrhea predominant IBS
- Loperamide (opioid agonist) - Alosetron ( 5-HT3 antagonist )- reduce nausea and vomiting - Anticholinergics (Hyoscyamine, Dicyclomine, Glycopyrrolate, Methscopolamine)
28
Mild IBD is characterized by
* Ambulatory * Tolerating orally * < 10% weightloss * No symptoms of systemic disease or bowel obstruction
29
Moderate to severe IBD IS CHARACTERIZED By
* Failed treatment for mild to moderate disease * Intermittent nausea or vomiting * > 10% weightloss * Fever * Abdominal pain * Anemia
30
Severe to fulminant IBD is characterized by
* High fevers * Persistant vomiting * Intestinal obstruction * Peritoneal signs * Cachexia
31
Treatment for mild IBD
Tropical corticosteroids Budesonide Antibiotics 5-ASA
32
Treatment for moderate IBD
Oral corticosteroids TNF Antagonists Methotrexate Azathioprine
33
Treatment for severe IBD
``` IV Corticosteroids TNF Antagonists Cyclosporine Natalizumab Surgery ```
34
Drugs used for long term maintenance of IBD remission
Aminosalicylates: Active group is 5-aminosalicylic acid (5-ASA) Sulfasalazine Balsalazide Mesalamine
35
MOA of Aminosalicylates
* Inhibition of the activity of nuclear factor-κB (NF- κB): an important transcription factor for proinflammatory cytokines * Inhibition of cellular immunity mechanisms * Modulation of both cyclooxygenase and lipoxygenase pathways
36
Clinical efficacy of 5ASA
Needs to achieve high concentrations at the target sites • given orally- completely absorbed by the jejunum • No therapeutic effect in the more distal ileum, colon and rectum would be obtained • Suppository or enema if isolated sigmoid colon or rectal disease
37
Composition of sulfasalazine
5ASA linked to sulfapyridine by an Azo bond
38
sulfasalazine is reduced by coli form bacterial enzyme called_______ to sulfapyridine and 5ASA
Azoreductase 5 ASA may backwash into the terminal ileum to act there
39
Adverse effects of Aminosalicylates
- Nausea - GI upset - Headaches - Arthralgias - Myalgias - Bone marrow suppression - Hypersensitivity reactions
40
This drug involves 5-ASA linked to an inert, unabsorbed carrier molecule that allows maximal amounts of 5-ASA to be delivered to the colon
Balsalazide
41
This drug involves Physically packaged 5-ASA in extended release or pH sensitive microgranules that release the active drug into the desired specific portion of the gut actively affected by IBD
Mesalamine
42
List the glucocorticoids used in IBD
Prednisone Prednisolone Budesonide
43
How do glucocorticoids work
- Inhibition of phospholipase A2 and cyclooxygenase | - Inhibition of nuclear factor-κB
44
Glucocorticoids of choice for oral therapy
Prednisone and prednisolone
45
_________is administered via enema for sigmoid and rectal IBD flares
Hydrocortisone
46
Adverse effects of glucocorticoids
- Adrenal suppression - Immunosuppression - Hyperglycemia - Osteoporosis
47
This drug treats * Topical effects on the luminal surface of the inflamed bowel * Following enteric absorption, undergoes rapid first-pass metabolism thus has low systemic bioavailability * Significantly decreased rate of systemic adverse effects a compared to prednisone
Budesonide
48
* Immunosuppressive purine analogs * Indicated for induction and maintenance of IBD remission * Steroid-sparing effect
``` Immunosuppressants: Mercaptopurine (6-MP) Azathioprine Methotrexate Cyclosporine ```
49
Adverse effects of immunosuppressants
- Nausea - Vomiting - Bone marrow depression - Hepatotoxicity
50
Allopurinol reduces _______ activity which can increase serum concentration of 6-thioguanine nucleotides to precipitate life-threatening leucopenia
Xanthine oxidase • Use allopurinol with caution in patients taking 6-MP or azathioprine
51
* Inhibits dihydrofolate reductase, an enzyme important in the production of thymidine and purines * Reduces the inflammatory actions of Interleukin-1 * Stimulates increase release of adenosine
Methotrexate
52
Adverse effects of methotrexate
* Bone marrow depression • Megaloblastic anemia | * Mucositis
53
Explain the relationship between cyclosporine and calcineurin
Calcineurin activates NFAT which is required for induction of cytokine genes Cyclosporine forms a complex with cyclophilin—> immunophilin This complex inhibits calcineurin
54
Adverse facets of cyclosporine
* Nephrotoxicity * Neurotoxicity * Hypertension * Hyperkalemia * GI complaints * Hyperglycemia
55
Anti – TNF - α Drugs for IBD
Infliximab: for moderate to severe colitis which is not responsive to mesalamine or corticosteroids Adalimumab
56
Function of Anti – TNF - α Drugs
Bind and inactivate human Tumor Necrosis Factor (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
57
Adverse effects of Anti – TNF - α Drugs
• Suppression of Th1 activity: - 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
58
* Humanized monoclonal antibody targeting several integrins on circulating inflammatory cells * Disruption of leukocyte vascular wall adhesion and subsequent tissue migration * Indicated in moderate to severe, unresponsive Crohn’s disease
Anti- Integrins | - natalizumab
59
Adverse effects of natalizumab
* Infusion reactions * Opportunistic infections * Reactivation of the human polyomavirus (JC virus) resulting in progressive multifocal leukoencephalopathy
60
Causes of exocrine pancreatic insufficiency ( when secretion of pancreatic enzymes fall below 10% of normal)
Cystic fibrosis Chronic pancreatitis Pancreatic resection Presents with stentorian, ADEK vitamin malabsorption, weight loss
61
Pancrelipase
* 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
62
Adverse effects of pancrelipase
• Diarrhea • Abdominal pain Rare: hyperuricosuria, renal stones, colonic strictures

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