AHHHHH S*** (antidiarrheals and laxatives)

What are the TWO drugs that fall under the category of Motility Modifiers?

loperamide (51)

n-butylscopolammonium bromide (53)

T/F loperamide is an opioid and it decreases segmental contractions

False, it increases it

What does n-butylscopolammonium bromide do?

Decreased peristalsis and increased segmental contractions

T/F The motility modifiers have little use in the management of diarrhea in small animals

True

Opioids also can be used as antidiarrheal compounds by virtue of what?

their inhibition of GI tract smooth muscle

What are the effects of opioids mediated by what receptor? What receptor is inibitory?

mu receptor

kappa receptors are inhibitory

Why are opioids generally preferred as antidiarrheals?

enhance segmentation, thus providing resistance to outflow, and inhibit peristalsis

Why would you want to inhibit peristalsis? (2)

This allows the body to absorb excessive secretions.

They also probably facilitate absorption of electrolytes, while inhibiting

their secretions.

What is the opioid that is used for its effects on secretory diarrhea? Can you get it OTC?

Loperamide (Imodium®) (51)

Yes

T/F Loperamide cannot penetrate the BBB

TRUE

Why can the Loperamide NOT cross the BBB?

P-glycoprotein substrate

T/F The use of antidiarrheal opiates in cats is controversial because of the risk of CNS excitation.

True

What is the MOA for Loperamide? (3)

Increase segmentation and decrease propulsive contractions

Increase the tone of the GI sphincters

Stimulate absorption of fluid, electrolytes, and glucose

Loperamide has antisecretory MOA. What is it?

inhibition of Ca2+ influx and decreased calmodulin activity

How does inhibition of Ca2+ influx and decreased calmodulin activity effect secretory diarrhea?

Decreases chloride secretion and reduces diarrhea

N-Butylscopolammonium bromide is what drug class?

Anticholinergics

N-Butylscopolammonium bromide is an FDA drug approved to treat what?

colic in horses

What is the MOA of N-Butylscopolammonium bromide? (2)

Decrease GI motility: antispasmodic or spasmolytic

Reduce intestinal secretions

What are the THREE indications of N-Butylscopolammonium bromide?

Severe forms of diarrhea: absence of segmentation movement

Rectal examination or imaging

Recurrent airway obstruction*

What are the Contraindication for N-Butylscopolammonium bromide? (6)

Severe ulcerative colitis

GI obstruction

Ileus

Gastritis

vomiting

infectious diarrhea

What are some of the other Anticholinergics drugs?

Atropine, Scopolamine, Isopropamide

What are the TWO things that GI Mucosal protectants do?

- Coating the GI epithelium

- Preventing irritation or erosion

What do GI Mucosal Absorbents do?

Physically bind to chemical compounds

What do Prebiotics do?

What do Probiotics do?

Stimulate the growth

Establish the beneficial bacterial population

What do Synbiotics?

they do what pre and probiotics do

What is an example of a fermented by colonic bacteria to usable materials that encourage bacterial proliferation?

Psyllium

What is the MOA for Psyllium?

Fermentable in colon ->Bacteria proliferation >Produces short chain fatty acids

What are some of the bacteria that probiotics typically have in them?

Lactobacillus

Gram positives (Streptococcus thermophilus* and enterococcus faecium)

Yeast

What is the class and MOA of Kaolin-pectin formulation?

Protectants and Adsorbents

Reduction of inflammation

T/F Kaolin-pectin does not reduce fluid or electrolyte loss, so it is not effective for severe diarrhea.

True

T/F Kaolin-pectin shortens the duration of the disease

False, does not

What electrolyte will Kaolin-pectin formulation increase the loss of?

sodium

T/F Kaolin-pectin formulation is can be gotten OTC

True

Which of the Mucosal Protectants and Adsorbents is used as a systemic treatment for acute diarrhea?

Bismuth subsalicylate

What does the bismuth and subsalicylate do in Bismuth subsalicylate?

bismuth: an antisecretory and protective effect

subsalicylate: produces an inhibitor effect on inflammatory prostaglandins, which may be modulating GI tract motility and stimulating GI secretions.

What are the TWO main things that Bismuth subsalicylate does for the GI tract?

protectant

antisecretory effects

Bismuth subsalicylate has some ability to absorb ____ ____ and some ___ or ____ effect

bacterial enterotoxins

gastric or intestinal protective effect

T/F Bismuth subsalicylate has some Anti-inflammatory action

True

What animal should you be careful in with Bismuth subsalicylate? Why is this?

Cats (of course)

Deficient in glucuronyl transferase which lead to toxic metabolite formation

What is the Protectants and Adsorbents that isnt a model drug but good to know?

Activated charcoal

Activated charcoal adsorbs ____ such that they are removed from the GI tract

toxins

In equine practice, the product "_____" - or ___-____ - is basically a clay based product given via an NGT with the intent of binding toxins in the colon

Biosponge

di-trioctahedral

Inflammatory bowel disease (IBD) is a clinical condition that involves chronic inflammation of GI tract, what part of the GIT is it mostly?

lower GI

What are the TWO Aminosalicylates that help with IBD?

Sulfasalazine (Azulfidine®) Mesalamine (5-aminosalicylic acid)

What TWO other things can be used to trea IBD?

Glucocorticoid

N-3 fatty acids

Sulfasalazine (Azulfidine) is a combination of what?

sulfapyrimidine and 5-aminosalicylic acid (mesalamine)

Where is it broken down at and by what?

Broken by bacteria in the colon

Sulfasalazine is a combination of ____ and ____ agents (5- aminosalicyclic acid or aspirin

antimicrobial

antiinflammatory

Sulfasalazine has ____ effect since it is required the bacteria at colon to break this drug combination

local

T/F Salfapyrimidince will be absorbed to the system but 5-aminosalicyclic acid remains in the GI tract

True

Due to the MOA of Sulfasalazine, what types of effects does it have and where are they?

a local antiinflammatory effect at the colon

What is the passive form of drug that promotes elimination of soft-formed stool?

Laxatives

What is the active drugs that promote more fluid evacuation?

Cathartics

What are Laxatives and Cathartics used to treat? What do they treat in horses?

constipation

impaction (increase the passage of intestinal contents to relieve an

impaction)

What is something else that Laxatives and Cathartics can be used for clinically?

Cleanse the bowel prior to lower GI examination or procedures

What are the TWO categories that laxatives can be?

Emollient

Simple Bulk

What is the MOA for Emollient?

Coating surface of stool with a film so that it lubricates to ease passage of stool

What is an example of a Emollient?

Mineral oil (56)

Docusate Sodium (Dioctynate)

Mineral oil is used in ____ via ___ ___ to treat impactions which is presumably resolved one mineral oil is present on the feces

horses via a NGT

Docusate sodium (Dioctynate) is a non-absorbed anionic surfactant which reduces ____ ____

surface tension

___ ____ laxatives absorb ____, causing swelling and formation of an

emollient gel form which causes colonic distention, reflex contraction and peristaltic activity

Simple bulk

water

What is the MOA for Simple bulk laxatives?

Absorb water

Emollient gel forms

Colonic distention

Reflex peristaltic activity

What are some examples of Simple bulk laxatives?

Psyllium Seed (57)

(PUMPkin)

T/F Simple bulk laxatives often result in soft stool

False fluid stool

What are the TWO types of Cathartics used?

Hyperosmotic

Irritant

____ (__) attract water into the intestine by osmotic forces

Osmotics (hyperosmotics)

____ appear to cause electrolyte loss by inhibiting the Na+/K+ ATPase

pumps in the intestine, thus leaving fluid in the lumen/fecal content

Irritants

How would you administer a Cathartics?

by enemas

What are some examples of Hyperosmotic Cathartics? (4)

Mg(OH)2 (58, milk of magnesia),

Magnesium citrate Sodium sulfate (Glauber’s salt)

Magnesium salt: MgSO4 (Epsom salt),

Nonabsorbed sugar: Mannitol, lactulose (59, Cephulac)

What is the MOA generally for Hyperosmotic Cathartics?

Attract water into the intestinal lumen by osmotic forces

What are the Contraindications for Hyperosmotic Cathartics?

dehydration

How does the Mg ions work for Hyperosmotic Cathartics?

causes the release of CCK which leads to the increase in peristaltic activity

How does magnesium hydroxide (Milk of Magnesia; Epsom salts) worl?

The magnesium salts in magnesium hydroxide are also use as a saline purgative because magnesium attracts water into the intestine.

What is lactulose (Cephulac)?

Lactulose is a synthetic disaccharide (galactose + fructose) that colonic bacteria break down into organic acids (acetic, lactic, etc.).

How does lactulose (Cephulac) work?

Breaks down organic acids:

↑ Osmotic pressure → draw water into intestine → cathartic effect.

Acidify colon → trap ammonia as NH₄⁺ → ↓ ammonia absorption.

Helps lower blood ammonia in patients with hepatic encephalopathy

T/F Mg ions increase osmotic pressure ,draw water into intestine causing a cathartic effect

False, Lactulose does this

What is the generic name for MiraLAX and what is it commonly used for?

polyethylene glycol (PEG) is a commonly used

human osmotic laxative used for a variety of indications

T/F MiraLAX is has been proven safe in dogs and cats

TRUE

What are some examples of Irritant Cathartics? (2)

Diphenylmethane derivatives (Bisacodyl), Olive oil

What is the MOA for Irritant Cathartics?

initiate a local myenteric impulse and increase secretion into the colonic lumen which appears to cause electrolyte loss by inhibiting the Na+/K+ ATPase in the intestine

What is a Contraindication with Irritant Cathartics?

intestinal obstruction

What occurs if you use Irritant Cathartics chronically?

potential injury to myenteric neurons

What is introduction of solution or suppositories into the rectum to initiate defecation reflex?

Enemas

T/F Compounds administered as enemas include soaps, sodium chloride solution, sorbitol, glycerol and mineral or castor oil.

True

Phosphate enemas (marketed often simply as saline enemas) are administered as a ____ ____

saline laxative

What can phosphate cause in animals that are particularly ill? (3)

hyperphosphatemia, hypernatremia and hyopcalcemia