TUTOR - GI Drugs

What are the protective functions of the GI tract?

-vomiting

-diarrhea

-constipation

-colic

-bloat

gastric =

stomach

enteric =

small intestine

colonic =

colon

monogastric uses what type of digestion to break down food?

enzymatic

ruminants use what type of digestion to break down food?

fermentative

Which nervous system is the "rest and digest" system?

Parasympathetic NS

What neurotransmitter controls the parasympathetic nervous system?

acetylcholine

How does the parasympathetic nervous system affect the GI tract (physiologically)?

-stimulates GI motility, secretions and blood flow

-increases digestion and absorption of food

What neurotransmitter controls the sympathetic nervous system?

epinephrine and norepinephrine

Which nervous system is the "fight or flight" system

sympathetic nervous system

How does the sympathetic nervous system affect the GI tract (physiologically)?

-reduces GI blood flow, motility and secretions

What is the term for drugs that stimulate vomting?

emetic drugs

What is the term for drugs that block vomiting?

antiemetics

What area of the brainstem controls the act of vomiting?

emetic center

What is the Nucleus tractus solitarius (NTS)?

part of emetic center that has receptors to drugs that stimulate emetic center which = vomiting

What are the 5 receptors found on emetic center that can stimulate vomiting?

-acetylcholine

-norepinephrine/epinephrine

-histamine

-dopamine

-serotonin

What is the receptor found in the NTS that can also stimulate vomiting?

Substance P

what are the 5 mechanisms to stimulate emesis?

1. emetic center receptor stimulation

2. CRTZ receptor stimulation

3. signals from viscera

4. signals from inner ear

5. signals from higher centers or emotional centers

What is the CRTZ or CTZ stand for?

Chemoreceptor Trigger Zone

What is the CRTZ?

Area near the emetic center than can be stimulated by drugs or chemicals in CSF fluid or blood. This can send receptors to emetic center which = vomiting

What are another anatomical locations have mechanism that can send signals to the emetic center via the vagus nerve?

distension/irritation of the pharynx, GI tract, kidney, gall bladder, peritoneum, uterus

What mechanism will stimulate "motion sickness" and will send signals to the emetic center via histamine

vestibular apparatus- this is the balance center of the inner ear

What vomiting mechanism is histamine involved with?

vestibular apparatus

What is the final way to stimulate vomiting, which is more of a human mechanism that is more sudden and unpredictable?

higher centers/emotional centers

Is the emetic center protected by the blood brain barrier?

yes, so most of its input comes from nerves that release neurotransmitters on the emetic center

is the CRTZ protected by the blood brain barrier?

no, it directly detects emesis producing compounds in the blood and CSF

What type of receptors does the CRTZ have and what do those receptors respond to

opioid receptors that respond to certain drugs (like morphine) and metabolic toxins (renal failure, bacterial infections)

What are 2 receptors that dogs are more senstive to, causing them to vomit from them?

dopamine and histamine (motion sickness)

What receptors do cats have a greater # of?

alpha receptors to epinephrine and norepinephrine

(think of ALPHA-2 sedatives such as xylazine)

What type of receptors are found in the CRTZ and GI tract, and its used for vomiting associated with chemotherapy patients?

Serotonin (5-HT)

Reason we should NOT induce vomiting?

-there is risk of aspiration

-ingested substance is corrosive or a light petroleum product

-patient is unconscious

-patient is about to have a seizure

-obstruction or bloat

-they are unable to vomit

-injury to esophagus

-if already vomiting

When is it too late to induce vomiting after a liquid ingestion?

>2 hours

When is it too late to induce vomiting aftere solids ingestion?

>4 hours

How do centrally-acting emetics work?

stimulating receptors on the CRTZ or emetic center

How do locally-acting emetics work?

irritating GI tract, distending stomach, sending parasympathetic nervous sysstem signals (via vagus nerve) to emetic center

Is apomorphine a centrally or locally acting emetic drug?

centrally acting emetic drug

Which species does apomorphine work better in? why?

dogs because they have more dopamine receptors

Which route of administration is less consistent for apomorphine? why?

PO because it has a significant first pass effect (liver), which means that not a lot of the active drug will make it to systemic circulation

Which drug has dopamine in it that stimulates the CRTZ, but opioid part depresses the CNS?

apomorphine

True or False: apomorphine can be crushed and mixed with saline and adminstered in the eye

True

Why is the injectable form of apomorphine more effective?

There is a higher concentration of the drug in the blood faster, this means it stimulates CRTZ before it becomes depressed

True or false: apomorphine is reversed using opioid antagonists

False: dopamine antagonists

What emetic dopamine agonist is an FDA approved ophthalmic formulation?

Ropinirole (Clevor)

What is the injectable drug of choice for inducing emesis in cats? why?

Xylazine, cats have more alpha receptors

What is the locally acting emetic drug of choice that works by irritating/distending GI tract?

hydrogen peroxide

How do locally acting emetic drugs irritate/distend GI tract?

Vagus nerve signals to emetic center release acetylcholine = emesis

What is the dose for hydrogen peroxide?

0.5-1 mL/lb with max 45 mL

What is a risk of giving hydrogen peroxide?

Can produce severe gastritis, especially in cats

How do you administer table salt or salt water to stimulate vomiting?

place in the back of the throat

Why do we need to be cautious with giving table salt/salt water?

If they swallow it and don't vomit, it can produce hypernatremia

What are the 4 emetic drugs?

1. Apomorphine

2. Ropinorole

3. Xylazine

4. Hydrogen peroxide

Vomiting is what type of reflex?

Protective reflex- removes potentially dangerous substances from the GI tract

Vomiting only removes contents from what parts of the GI tract?

stomach and proximal duodenum

What drug class that is widely used in anesthestic protocols acts as a "broad spectrum" anti emetic?

phenothiazine tranquilizers (acepromazine)

Which receptor(s) does acepromazine block?

-dopamine (dogs esp)

-histamine

-a little bit of acetylcholine

-alpha receptors

What happens when alpha receptors are blocked?

vasodilation --> hypotension

What antihistamines are used as anti emetic drugs? How do they work?

-dimenhydrinate (Dramamine)

-diphenhydramine (Benadryl)

blocks H1 receptor which blocks signals from inner ear (motion sickness)

What drug class should be an antiemetic but has too many side effects due to affecting the entire PNS?

anticholinergics

What are the side effects of anticholinergics?

cant pee, can't spit, can't sit, can't shit

What are 2 examples of prokinetic agents?

-Metoclopramide (Reglan)

-Cisapride

Metoclopramide, when acting centrally, it acts as an antidopaminergic agent, so do you think it is more effective in dogs or cats?

dogs

What other receptor besides dopamine does metoclopramide block? And what patients would it be good for?

serotonin receptors, good for chemo patients

What does metoclopramides prokinetic effect mean?

drug increases motion = prevents GI stasis that precedes vomiting

What antiemetic drug blocks serotonin receptors associated with chemo in dogs, parvo in dogs, and pancreatitis in cats

serotonin antagonists (ondansetron)

What receptors in the emetic center are last step in the emetic pathway before vomiting?

NK-1 receptors

what antiemetic drug is is a neurokinin-1 (NK-1) antagonists, and blocks the Substance P effect by blocking the NK-1 receptors in the (NTS), which prevents vomiting from motion sickness, GI tract stimulation, or the CRTZ

*it is bad of the patient vomits through this drug

maropitant (Cerenia)

What are the 5 antiemetic drugs?

1. Phenothiazines (acepromazine)

2. Antihistamines (diphenhydramine, dimenhydrinate)

3. Prokinetic agents (metoclopramide)

4. Serotonin antagonists (Ondansetron)

5. NK-1 antagonists (maropitant)

What are the 4 types of diarrhea?

1. secretory

2. exudative

3. motility

4. osmotic or malabsorption

Which type of diarrhea has increased secretions of fluids by GI tract glands, which exceeds capacity to reabsorb fluid from GI tract?

-caused by bacterial enterotoxins that cause inflammation

secretory diarrhea

What do we need to watch out for with secretory diarrhea?

dehydration due to the amount of fluids that the body is unable to absorb - pumping out of body

What type of diarrhea has damage to GI tract wall that will allow proteins, electrolytes and blood to leak into the GI tract?

exudative diarrhea

What do we usually see with exudative diarrhea?

with the destruction of Gi tract the patient could have loss of blood or fluids, but bacteria can also enter the body

ex. parvo virus, transmissible gastroenteritis in pigs

Which type of diarrhea means the contents of Gi tract rapidly move along before the patient is actually able to digest and absorb?

Motility diarrhea

What is tenesmus?

straining to defecate

What type of diarrhea means that there are osmotic particles that hold water in bowel leading to reduced ability to absorb fluid from GI tract

osmotic or malabsorption diarrhea

What breed of dog does osmotic diarrhea occur in, and with what disease?

German Shepherds with exocrine pancreatic insufficiency (EPI)

Is it large or small bowel diarrhea: small amounts and frequently

large bowel

How do anti-diarrheal drugs work?

-decreasing sections from GI tract wall

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

-decreasing the underlying problem that caused diarrhea in the first place (NSAIDS, antibiotics, enzymes)

What are the 2 types of contractions?

peristaltic and segmental

What do peristaltic contractions do?

moves food along GI tract in waves, relaxed bowel in front of food then constricts behind it to push the food forward

What is hypermotility and what can it cause?

increased peristaltic movement which means food is unable to be digested = diarrhea

What do segmental contractions do?

circular contractions of a segment of bowel, mizes the contents of the bowel

Drugs that decrease peristalsis and increase segmental contractions should do what?

slow flow of ingesta and reduce diarrhea

How does narcotic (opioid) antidiarrheals work?

-all opioids can produce "opioid-induced constipation)

-they combine with the mu receptors in the gut to increase segmental contractions and decrease peristalsis

Dogs with this gene defect do not code for a fully function P-glycoprotein pump in the GI tract wall (prevents narcotic antidiarrheal absorption) and these animals will show opioid toxicity from administering these drugs

MDR1 gene

What are the drugs that block the effect of acetylcholine and parasympathetic NS

anticholinergics

Why are anticholinergics ineffective for reducing diarrhea?

because they reduce ALL contractions including segmental

What are things that increase intestinal secretions? What do we use to reduce this?

-bacterial endotoxins (making cells pump)- inflammatory mediators: prostaglandins or leukotrienes (from inflammation)

-use NSAIDs

what are NSAID antidiarrheal drugs that are used to reduce secretions (aspirin like compound)?

salicylate compound-bismuth subsalicylate

Why do we need to be cautious when giving salicylate compounds to cats?

cats don't metabolize them well so can cause salicylate toxicity

What are some concerning but normal side effects of salicylate compounds?

-bismuth turns dark --> melena

-radiopaque so will act like GI contrast

What antiemetic drug can also be used as an adjunct (or additional) drug for antidiarrheal treatment because it blocks receptors on the CRTZ and within the GI tract?

5-HT serotonin antagonist drugs (Ondansetron)

What antidiarrheal drug is used for colonic inflammatory conditions like ulcerative colitis? Also has risk for dry eye or KCS

Sulfasalazine (Azulfidine)

what it is called when this kind of antidiarrheal causes other molecules to stick to the surface?

ADsorbent

what is it called when this kind of antidiarrheal drug forms a physical BARRIER between lumen contents and lining of the GI tract (is a bandaid for the stomach)?

protectants

what is an antidiarrheal ADsorbent that isn't an antidiarrheal agent, but it absorbs the poison and prevents them from getting to and being absorbed in the GI wall?

activated charcoal

what are the 5 kinds of antidiarrheal drugs?

- narcotic opioids (loperamide, diphenoxylate)

- busmuth subsalicylate

- 5-HT seratonin antagonists (ondansetron)

- sulfasalzine

- adsorbents (bismuth subsalicylate, activated charcoal)

How do laxatives, cathargics and purgatives work?

-increase fluid content of feces making them softer, eases or promotes defecation

What is the most gentle: laxatives, cathartics or purgatives?

laxatives