GI drugs 2

list 3 centrally acting emetic drugs

1. apomorphine

2. ropinirole

3. xylazine

why can xylazine be used to induce emesis in cats?

because it’s an alpha 2 agonist so it is a stimulator of alpha 2 receptors on the CTZ and emetic center which produces vomiting since cats have more alpha 2 receptors

how do locally acting emetic drugs work?

by locally irritating/distending the GI tract which then causes the vagus nerve to signal the emetic center to release acetylcholine which causes vomiting to occur

list 1 locally acting emetic drug

hydrogen peroxide

what’s the caveat with using hydrogen peroxide?

it needs to be active/fizzy to distend/irritate

what is the limit at which hydrogen peroxide can be given?

45lbs - ~0.5-1mL/lb

why should you not administer more than 45mL, even in large dogs?

because it can cause severe gastritis

what is another, less common and controversial, locally acting emetic drug?

table salt/salt water

why is using salt to produce emesis controversial?

toxicologists have warned about hypernatremia if salt is swallowed

what are the 5 types of antiemetic drugs?

1. phenothiazines tranquilizers

2. antihistamines

3. prokinetic agents

4. serotonin antagonists

5. NK-1 antagonists

how do phenothiazine tranquilizers work as antiemetic drugs?

block dopamine, histamine, acetylcholine, and alpha 2 receptors in the CTZ/emetic center.

what’s an example of an antiemetic phenothiazine drug?

acepromazine

what’s the caveat with using phenothiazine tranquilizers as antiemetic drugs?

causes hypotension so patients must be given IV fluids either during phenothiazine administration or before.

how do antihistamines work as antiemetic drugs?

by blocking H1 receptors which blocks histamine mediated signals from inner ear (motion sickness)

what are examples of an antiemetic antihistamine drug?

benadryl ® (diphenhydramine) and dramamine ® (dimenhydrinate)

what are side effects of antohistamine drugs?

• can cause sedation side effects which may affect performance of working dogs

• decrease “wheal and flare” reaction from skin testing for allergies so cannot be used 4 days before allergy test

why are anticholinergic drugs generally not used in vet med?

because they affect the entire parasympathetic nervous system (PNS) so pts have too many side effects

which antiemetic drug is both centrally- and locally-acting?

prokinetic agents

what are examples of an antiemetic prokinetic agents?

metoclopramide (reglan ®) and cisapride

how do prokinetic agents work to produce emesis?

• locally:

  • an antidopaminergic and at higher doses blocks serotonin receptors

• centrally:

  • prokinetic = increases “motion”

    • increases muscle tone of lower esophagus

    • increases gastric motility in the “right” direction

    • relaxes pylorus

    • increase motility of duodenum and jejunum

how do serotonin antagonists work as antiemetic drugs?

stimulation of serotonin (5-HT) receptors on CTZ or in GI tract results in vomiting so it block serotonin receptors

what are examples of an antiemetic serotonin antagonist drugs?

ondansetron (zofran ®) and granisetron (kytril ®)

serotonin antagonists are a popular choice of antiemetic drugs in patients with:

• cancer chemotherapy in dogs

• parvo viral enteritis in dogs

• pancreatitis in cats

how do neurokinin-1 (NK-1) antagonists work as antiemetic drugs?

blocks substance P effect by blocking the NK-1 receptor in the nucelus tractus solitarus (NTS)

what’s an example of an antiemetic neurokinin-1 (NK-1) antagonist drug?

cerenia ® (maropitant)

why is maropitant (Cerenia ®) a popular choice for antiemetic purposes?

because the NK-1 receptors in the emetic center are the last receptors in the emetic pathway before vomiting, so blocking these receptors prevents vomiting due to various reasons like motion sickness, GI tract stimulation, CTZ, etc.

why does diarrhea occur?

results from imbalances between fluid absorbed from the GI tract and fluid extended into the GI tract

what are the 4 types of diarrhea?

1. secretory

2. exudative

3. motility

4. osmotic or malabsorption

how is secretory diarrhea caused?

increased secretion of fluid by GI tract glands that exceeds capacity to reabsorb the fluid from GI tract. caused by bacterial enterotoxins which in turn causes inflammation and causes pt to be in danger of dehydration

should patients with secretory bacteria be treated with antidiarrheic drugs? why or why not?

NO! because if bacteria is not excreted it could stay trapped in stomach and cause more problems

how is exudative diarrhea caused?

damage to GI tract wall sufficient to allow large proteins, electrolytes, and blood to lean into the GI tract which causes blood loss and fluids, but also allows dangerous bacteria to enter body

how is motility diarrhea caused?

contents of GI tract rapidly move along before adequate digestion and absorption can occur usually in the form of small bowel diarrhea

what’s the difference between small and large bowel diarrhea?

• small bowel: usually large volumes and not frequently

• large bowel: small amounts and frequently, pt will strain to pass stool

how is osmotic/malabsorption diarrhea caused?

osmotic particles hold water in bowl and reduce ability of fluid to be absorbed from GI tract and this osmotic effect can result in a large amount volume of of fluid to be lost

• osmotic particles can be digested food, fober, laxative agents, unabsorbed salts, or large sugar molecules

in which dogs is osmotic/malabsorption diarrhea most common?

german shepherds with exocrine pancreatic insufficiency

what is exocrine pancreatic insufficiency?

a lack of pancreatic digestive enzymes that cause food to not be absorbed (osmotic effect) and thus causes gray, voluminous, rancid BMs (undigested fat)

how do antidiarrheal drugs work?

• decreasing secretions from GI tract wall

• modifying the intestinal motility (not just slowing it down)

• decreasing the underlying problem that caused diarrhea in the first place, like:

  • reduce inflammation

  • kill bacteria

  • add enzymes to digest and absorb food

what are two types of contractions?

1. peristaltic contractions

2. segmental contractions

what are peristaltic contractions?

moves food along GI tract in waves and relaxes bowels in front of food bolus then constricts behind it to push the bolus forwards

how does an increased peristalsis affect digestion?

increases the speed at which food (ingesta) moves along the GI tract

what is hypermotility?

increased peristaltic movement where food is unable to be digested and passes out as incompletely absorbed (diarrhea)

what are segmental contractions?

circular contractions of a segment of bowel that mixes the contents of the bowel and also slows the movement of ingesta along the bowel (creates resistance flow)

how does small bowel diarrhea occur?

starts with short period of hypermotility (rapid peristalsis and audible gut sounds) followed by longer period of hypomotility or atony and few or no audible gut sounds - loss of segmental contractions during hypomotility removes resistance of flow

how does large bowel diarrhea occur?

associated with increased contractions or spasms - inflammation stimulates defecation reflex without there being any stool to pass so animal strains to defecate (tenesmus)

which types of antidiarrheal drugs should be used?

ones that increase segmental contractions

what’s special about Imodium A-D ® (loperamide HCl) when giving it to patients?

is not absorbed from GI tract due to P-glycoprotein pump in GI tract wall that keeps drug from entering body and pump in blood brain barrier prevents it from becoming an abused drug - so doses must take the pump into effect

why should you exercise caution when giving collies and other herding breeds Imodium A-D ® (loperamide HCl)?

they tend to have MDR1 gene defect which doesn’t code for a fully functional P-gp pump so these animals tend to show opioid toxicity if normal, unadjusted doses are used

if anticholinergics block the effect of acetylcholine and the PNS, why are they not good drugs to use as antidiarrhetics?

because they reduce ALL contractions, including segmental contractions (think - “rest and digest)p bacterial

what are increased intestinal secretions caused by?

• bacterial endotoxins

• inflammatory mediators (prostaglandins or leukotrienes)

why are prostaglandins or leukotrienes problematic in the GI tract?

causes exudative diarrhea by damaging tight junctions between GI tract cells, allowing fluid, proteins, and blood to enter lumen

how can prostaglandins or leukotrienes be blocked to reduce secretion and exudation?

using NSAIDs

which NSAIDs are typically used to reduce secretions in the GI tract?

bismuth subsalicylate (pepto-bismol ®, kaopectate ®)

what does bismuth subsalicylate break down into in the gut?

• bismuth carbonate: coats GI tract

• salicylate: produces anti-inflammatory effect (blocks prostaglandins + leukotrienes formation)

with which species should you be careful giving salicylates to and why?

cats - because they can’t metabolize them very fast/well