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3. Clin Pharm > GI drugs 2 > Flashcards

GI drugs 2 Flashcards

1
Q

categories of prokinetics

A
  1. Dopamine Antagonists
    - Metoclopramide
    - Domperidone
  2. Serotonin Receptor Modulators
    - Cisapride
  3. Miscellaneous agents
    - H2-receptor antagonists
    - Cholinergics
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2
Q

types of dopamine antagonists used as prokinetics?

A
  • Metoclopramide (Maxeran®)
  • Domperidone (Motilium®)
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3
Q

how does metoclopramide work as a prokinetic? mechanism of action? where does it act?

A
  • Acts peripherally as a prokinetic to increase ACh
    > activates prejunctional 5-HT4 (serotonin) receptors on enteric cholinergic nerves
    > blocks inhibitory dopamine (D2) receptors on enteric cholinergic nerves
  • Effects are limited to upper GI tract; however, not well-established
    > Increase lower esophageal sphincter and promote gastric emptying; less effect on the distal bowel
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4
Q

what animals is metoclopramide used in? what animal should we exhibit caution with and why?

A
  • Used in horses; dogs and cats
  • Caution: horses–behavioural (excitement) changes
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5
Q

what forms does metoclopramide come in?

A

Tablets, oral solution, injectable

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6
Q

difference between domperidone and metoclopramide?

A

Domperidone is similar to metoclopramide; does not cross BBB as readily;

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7
Q

Serotonin Receptor Modulator used as a prokinetic

A

Cisapride

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8
Q

how does Cisapride work? availability and adverse effects? what applications and species is it used for?

A
  • Acts peripherally to stimulate 5-HT4 receptors on presynaptic enteric neurons promoting the release of ACh
  • Withdrawn from market due to adverse cardiac effects in humans
    > Can be obtained as a compounded product from pharmacies
  • Broadest spectrum prokinetic
    > Gastric reflux, gastroparesis (delayed emptying)
    > Ileus; dog, cat, horse
    > Constipation and megacolon in cats
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9
Q

How do H2-receptor antagonists work as prokinetics?

A

Nizatidine (Axid®) and Ranitidine (Zantac®)
- Appear to inhibit acetylcholinesterase which increases ACh levels promoting GI motility throughout the stomach, SI and colon
- Reduction in HCl production also stimulates stomach motility promoting emptying

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10
Q

what are two H2-receptor antagonists that are used as prokinetics

A

Nizatidine (Axid®) and Ranitidine (Zantac®)

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11
Q

what cholinergic is used as a prokinetic? is it commonly used and why?

A
  • Bethanechol (Urecholine®, generic, compounded)
  • Use is limited by adverse effects
    > Salivation, abd cramps, diarrhea, bradycardia
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12
Q

adverse effects of bethanechol

A

Salivation, abd cramps, diarrhea, bradycardia

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13
Q

how does bethanechol work as a prokinetic?

A

Promotes contractility throughout GI tract

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14
Q

species and possible application for bethanechol use as a prokinetic?

A
  • Cats, dogs, cattle? horses?
  • May be of benefit in canine idiopathic megaesophagus
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15
Q

Diarrhea can result from an imbalance with:

A
  • motility (hyper or hypo)
  • water and electrolyte secretion
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16
Q

most treatments for diarreah use what strategy?

A

Most treatment is symptomatic and does not address the underlying problem
- replace fluids
- replace electrolytes and maintain acid/base balance
- provide relief

17
Q

how can diarreah be a defence mechanism?

A
  • eliminate pathogens
  • eliminate toxins
18
Q

categories of antidiarrheals

A
  • Adsorbents
  • Antimotility
  • Antisecretory
19
Q

how do adsorbents work?

A

Adsorbents bind chemicals, toxins preventing their absorption
- bound agents are eliminated in feces
- adsorbents can bind other drugs interactions
- many adsorbents also have protectant effects
> bind and coat mucosal surface

20
Q

adsorbents used as antidiarrheals

A
  • Bismuth Subsalicylate (Pepto-Bismol®)
  • Kaolin/Pectin (Kaopectate®)
21
Q

when is Bismuth Subsalicylate (Pepto-Bismol®) used? how does it work? adverse effects?

A
  • used in acute diarrheas; may darken stool !
  • chronic use can yield constipation
  • bismuth, like sucralfate, acts as a protectant and coats the mucosa
  • salicylate component inhibits PG’s yielding an anti-inflammatory effect
    > caution due to salicylate component, which is absorbed in dogs and cats; unlikely in standard dosages to produce toxicity
    > however, use in cats probably should be cautious or avoided
22
Q

how do Kaolin/Pectin (Kaopectate®) work as antidiarrheals? efficacy? should be careful with what formulations? what product versions are available?

A
  • adsorbents
  • Kaolin (attapulgite or aluminum silicate) and pectin (carbohydrate)
  • Supposedly binds toxins, bacteria….and other drugs

> Efficacy is questionable for binding toxins
Does not appear to reduce electrolyte and fluid loss
- Careful with salicylate containing formulations
- Veterinary products can be kaolin and pectin only, or contain other anti-
diarrhea drugs and compounds

23
Q

Antimotility & Antisecretory drug categories for antidiarrheals

A
  1. Opioids
  2. Anticholinergics
24
Q

types of opioids that are used as antidiarrheals

A
  • Loperamide (Imodium®)
  • Diphenoxylate (Lomotil®)
25
Q

increased gut motility is usually accompanied by what in diarrheic animals?

A

Increased motility is usually accompanied by increased fluid and electrolyte secretion in diarrheic animals

26
Q

opioids mechanism of action as an antidiarrheal? issue with prolonged use?

A
  • Inhibit release of ACh by cholinergic nerves
  • decreased propulsive activity but increase non-propulsive activity (segmentation)
    > Allows for more time for reabsorption of fecal fluid
  • decrease intestinal secretion and increase tone in sphincters
  • increase fluid, electrolyte, glucose uptake
  • Causes constipation and ileus with prolonged use
27
Q

loperamide vs diphenoxylate; which opiate has less side effects and why? which is used more commonly?

A

Loperamide
> Does not cross the BBB—less side effects
> Used more commonly than diphenoxylate

28
Q

Diphenoxylate; what is it derived from? combined with what?

A

Meperidine derivative; formulated combined with atropine to reduce abuse
potential; atropine may help with diarrhea

29
Q

how do anticholinergics work as antidiarrheals? when are they useful and what are their effects? what are their limitations?

A

Diminish motility/secretions in hypermotile hypersecretory
intestinal tract
- “antispasmodics” or “spasmolytics”
- main benefit in diarrhea may be reduced intestinal secretions
- may decrease urgency associated with some forms of diarrhea
- may decrease abdominal discomfort
- use in infectious diarrhea should be avoided as should impactions or ileus
- adverse effects limits their use

30
Q

adverse effects of anticholinergics

A

constipation, urinary retention, blurred vision, CNS stimulation and tachycardia and dry mouth (xerostomia)

31
Q

types of anticholinergics used as antidiarrheals

A
  • Belladonna alkaloids (atropine, hyoscine butylbromide)
  • Synthetic anticholinergics (propantheline)
32
Q

what are the uses of belladonna alkaloids for diarrhea? what are some examples?

A

-Antimotility & Antisecretory

Belladonna alkaloids (atropine, hyoscine butylbromide)
- hyoscine butylbromide (Buscopan®)
- approved in horses for colic relief; injectable (slow IV)
- can be used to relax the large bowel and facilitate rectal examination and
colonoscopy
- atropine is present in many calf scour preparations along with kaolin, pectin and neomycin
- these alkaloids can cross BBB—more side effects

33
Q

benefits and uses of synthetic anticholinergics for diarrhea treatment

A

-Antimotility & Antisecretory

v less likely to cross BBB
v used in dogs and cats as antidiarrheic; tablets
v has been used in horses: facilitate rectal exam & colonic spasms

34
Q

Normal gastrointestinal transit is a function of

A

motility and mucosal absorption/secretion

35
Q

Laxatives and cathartics promote defecation of a stool by:

A

v increasing frequency of defecation
v increasing fecal volume and consistency
v laxatives promote elimination of a soft-formed stool, while cathartics produce a more fluid evacuation

36
Q

Excessive or continuous use of cathartics
may result in

A

diarrhea, colic, dehydration and shock

37
Q

General uses for laxatives/cathartics include:

A

v chronic constipation and reduce impactions
v empty bowel for radiography, surgery, proctoscopy
v ease straining

3. Clin Pharm (11 decks)

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