GI drugs

Pharmacology

Emetic - (dopamine) tablets or intra eye

apomorphine

Emetic

locally acting

vagus nerve in pharynx to emetic center (acetylcholine)

drug of choice

hydrogen peroxide

Emetic

(Dopamine Agonist)

Clevor ^R

Ropinirole

Emetic, centrally acting

(alpha 2 receptor stimulation)

drug of choice for cats

Xylazine

Emetic, locally acting NOT to use

(hypernatremia)

Table salt/salt water, Syrup of ipecac

antiemetic -phenothiazine tranquilizers

Blocks: dopamine, histamine receptors, lesser amount of acetylcholine, and a receptors

acepromazine

antiemetic - antihistamines

Dramamine

Blocks H1receptor; vestibular apparatus

dimenhydrinate

antiemetic- antihistamine

Benadryl

Blocks H1 receptor; vestibular apparatus

Diphenhydramine

antiemetic- anticholinergics

block acetylcholine receptors on CRTZ or emetic center

Muscarinic (M1), Scopolamine (patch)

antiemetic - prokinetic agents

Reglan

Central: antidopaminergic, higher doses block serotonin (good for chemo)

Local: increases motion

Metoclopramide

antiemetic- serotonin antagonists

Zofran

Ondansetron

antiemetic-serotonin antagonists

Kytril

Granisetron

NK-1 antagonists

Cerenia

Blocks Substance P effect by blocking the NK-1 receptor in the NTS

blocks vom. from motion sickness, GI tract stim, CRTZ

Maropitant

Antidiarrheal- modify motility

Narcotic (opioid) antidiarrheal (usually atropine is added)

Imodium A-D (combines with mu receptors in gut)

Loperamide

Antidiarrheal- modify motility

Narcotic (opioid) antidiarrheal (usually atropine is added)

Lomotil (combines with mu receptors in the gut)

Diphenoxylate

Antidiarrheal- reduce secretions

NSAIDs - salicylate

Pepto-Bismol, Kaopectate

Bismuth subsalicylate

Antidiarrheal- reduce secretions

5-HT serotonin antagonists

Blocks 5-HT receptors in GI tract; reduces secretions

Zofran

ondansetron

Antidiarrheal- reduce secretions

Azulfidine

sulfonamide antibiotic→ risk for side effect “dry eye“

Sulfasalazine

Antidiarrheal- Adsorbents

Bismuth in bismuth subsalicylate is adsorbent

adsorbs some E. coli enterotoxins

Bismuth subsalicylate, Kaolin (old Kaopectate)

Antidiarrheal- Adsorbents

ToxiBan

‘universal antidote” - adsorbes poison molecules

Activated charcoal

Laxative

liquid petrolatum- emollient laxative

stomach stube for colic, doesnt trigger swallowing reflex, can aspirate

Mineral Oil

Laxative -emollient laxative

dog laxative, cat hairball prevention

White petrolatum

Laxative - emollient laxative “natural“

found in hairball remedies

Cod liver oil

Laxative

used as a suppository

used for severe pelvic fractures

Glycerin

Laxative

Colace

acts as a wetting agent

may stimulate colonic secretions to add fluid

DSS, Docusate sodium, or dioctyl sulfosuccinate

Laxatives

Hydrophilic colloids or indigestible plant fiber

creates osmotic forces that pulls water into lumen and retains it

Bulk Laxatives

bran, psyllium, methylcellulose

Osmotic (saline) cathartics - hypertonic salts

magnesium hydroxide

magnesium sulfate

(Na+, Cl-, K+) - can be absorbed

*do not use PHOSPHATE laxatives or enemas in cats*

Milk of magnesia, Epsom salts

Cathartics

Poorly absorbed SUGAR osmotic cathartic -chronic constipation-

used to control CNS signs from liver disease and nigh blood ammonia called Hepatic Encephalopathy

-changes pH of colon causing ammonia to become more ionized and hence NOT absorbed as much from colon

Lactulose

Cathartic - irritant laxative

Dulcolax

irritating the bowel→ get increased peristalsis and aggressive movements

castor oil, bisacodyl

Non systemic antacid- Ca++,Mg++, Al-

-directly neutralize the acid by chemically combining with it and turning it into a less acidic molecule

Tums, Rolaids, Mylants, Maalox, Di-Gel, Amphojel

Non systemic antacid

Mylanta, Maalox, Di-Gel

allow some Mg to be absorbed - Mg++ is excreted by kidneys, dont’ use in renal failure pts

Magnesium products

Ca/Al → constipation

Mg → diarrhea

get acid rebound with Ca++ antacids - Ca++ triggers gastrin release → increase HCL production

balancing two effects Ca/Mg or Al/Mg

Creates a more alkaline pH in stomach liquid

Ca++, Mg++ or Al-- may combine with drugs and chelate
them (they precipitate out of solution, not absorbed)
• Older tetracyclines (tetracycline, oxytetracycline)
• Enrofloxacin (Baytril®)
In this case, give antacid 2 hrs before or 3 hrs after drug

Antacid

Systemic Antacid- H2 blockers

work by blocking histamine’s access to the H2 receptor on the parietal cell

(if using decrease doses on beta-blocker cardiac drugs, theophylline bronchodilator, diazepam)

Tagamet

Cimetidine

Systemic Antacid- H2 blockers

work by blocking histamine’s access to the H2 receptor on parietal cell

Zantac

Ranitidine

Systemic Antacid- H2 blockers

work by blocking histamine’s access to the H2 receptor on parietal cell

Pepcid

Famotidine

Systemic Antacid- H2 blockers

work by blocking histamine’s access to the H2 receptor on parietal cell

Axid

Nizatidine

Systemic Antacid- Proton Pump Inhibitors

work by blocking histamine’s access to the H2 receptor on parietal cell

Prilosec PO

works by binding to the lumen side of the PP and inhibit H+ pumping into the lumen

Omeprazole

Systemic Antacid- Proton Pump Inhibitors

work by blocking histamine’s access to the H2 receptor on parietal cell

Nexium PO

works by binding to the lumen side of the PP and inhibit H+ pumping into the lumen

Esomeprazole

Systemic Antacid- Proton Pump Inhibitors

work by blocking histamine’s access to the H2 receptor on parietal cell

Protonix IV

works by binding to the lumen side of the PP and inhibit H+ pumping into the lumen

Pantoprazole

Antiulcer - Synthetic Prostaglandin

Cytotec -synthestic PG-E1

-increases mucus production, decreases acid production, increases rate of cell turnover so ulcers/injurgy heal quicker

Misoprostol

Antiulcer: “gastric band-aid”

Carafate

forms a sticky paste that binds to the ulcer site when exposed to acid

Sucralfate

Emetic drugs

Apomorphine, ropinirole, xylazine, hydrogen peroxide

antiemetic drugs

Phenothiazine tranq.(acepromazine), antihistamines (diphenhydramine, dimenhydrinate), anticholinergics (Muscarinic), Prokinetic agents (Metoclopramide), Serotonin antagonists (ondansetron, granisetron), Neurokinin-1 antagonists (maropitant)

Antidiarrheals

Narcotic opioids (loperamide, diphenoxylate), Bismuth subsalicylate, 5-HT serotonin antagonists (ondansetron), Sulfasalazine, Adsorbents (bismuth subsalicylate, activated charcoal)

Laxatives, Cathartics, and Purgatives

Emollient Laxatives (Mineral oil, White petrolatum, cod liver oil, Glycerin, DSS) Bulk laxatives (bran, psyllium, methylcellulose), Osmotic cathartics (milk of magnesia, Epsom salts), Lactulose, Irritant cathartics (castor oil, bisacodyl)

Nonsystemic antacids – Ca++, Mg++, Al–

Tums, Rolaids, Mylanta, Maalox, Di-Gel, Amphojel

Systemic antacids- H2 blockers

cimetidine, ranitidine, famotidine

Systemic antacids - Proton Pump inhibitors

omeprazole, esomeprazole, pantoprazole

Synthetic Prostaglandin

Misoprostol

Sucralfate

gastric Band-Aid

is the CRTZ protected by the blood brain barrier?

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

what area of the brainstem controls the act of vomiting

emetic center

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

when is it too late to induce vomiting

greater than 4hours

What are the 4 types of diarrhea

1. secretory

2. exudative

3. motility

4. osmotic or malabsorption

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 are some of the protectants within the layer of mucus of the stomach lining to protect it from the acidic stomach contents?

- mucus is made of mucin (slimy)
-bicarbonate ions neutralizes the acid
- prostaglandins stimulate mucus production and reduce acid production

What are the protective functions of the GI tract?

vomiting
-diarrhea
-constipation
-colic
-bloat

ruminants use what type of digestion to break down food?

fermentative

gastric

stomach

enteric

small intestine

colonic

colon

monogastric uses what type of digestion to break down food?

enzymatic

What neurotransmitter controls the parasympathetic nervous system?

acetylcholine

What neurotransmitter controls the sympathetic nervous system?

epinephrine and norepinephrine

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

high centers/emotional centers

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)

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

>2hours

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 system signals (via vagus nerve) to emetic center

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

German Shepherds with exocrine pancreatic insufficiency (EPI)

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 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

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

-when ruminants get sick, one of the side effects may be rumen stasis (rumen stops)

-Altered function/motility of rumen means that complex biochemical reactions of fermentative digestion are disrupted

-excessive gas may be produced → bloat

-Excessive acid may be produced → acidosis and killing off of rumen microbes needed for fermentative digestion

-necessary to keep rumen microbes “happy“ → happy rumen happy cow

challenges with rumen health

____ are pro-kinetic drugs that stimulate drugs that stimulate an atonic (w/o tone) rumen to start contracting again

-were a “historical“ tx involving a wide variety of home remedies that directly irritated rumen or mimicked acetylcholine

• tartar emetic, strychnine, caffeine

• plants that had acetylcholine-like compounds in them

Side effects: from old remedies are considered unacceptable in modern livestock production

Ruminatorics

Ruminatorics - Prokinetic drugs

-modern ruminatoric - ____ - binds to acetylcholinesterase enzyme (AChE)

-AChE normally breaks down acetylcholine (Ach) - terminates action

-This interference with AChE increases acetylcholine’s effect

-Increases PSNS effect: increased GI motility and secretions, decreased heart rate, pupil constriction, bronchoconstriction

neostigmine

a group of drugs discovered in the 1950’s that killed coccidia protozoa

• this refers toability of these drugs to facilitate transport of ions (Na +, K+, etc) across cell membranes

-Ions disrupts electrolyte balance → death

Ionophores

Ionophores - (Rumensin)

-one of the most commonly used to control coccidial in livestock and poultry; improve conversion of feed to weight; reduces risk of bloat

-IS FATAL if given to horses!

(Feed mix-up story: 6 dead from contaminated feed mixer)

Monensin

-Normally rumen contents are regurgitated (eructation), chewed again (chewing cud), and swallowed → allows excess carbon dioxide or methane gas t obe expelled

-eating lush grass or excessive clover/alfalfa → alters rumen flora → changes surface tension of rumen fluid → can’t eructate foam or froth → get bloat (rumen tympany)

antibloat medications

Antibloat Medication

-reduces viscosity and froth

Mineral oil, Vegetable oil

Antibloat Medication

-reduces the viscosity of the rumen contents and dissipates the foam

-given oral tube or injected directly into rumen with large needle

Dioctyl Sodium Sulfosuccinate (DSS)

-Many GI disease are viral (Abx don’t work)

-Oral Abx kill gram positive bacteria allowing more pathogenic gram negative bacteria to proliferate → gram negative bacterial disease

-Salmonella - Abx used only if bacteria invade GI tract wall and produce systemic disease

-Use of Abx in mild Salmonella cases can actually prolong time that Salmonella bacteria are shed

Antibiotics NOT recommended by most gastroenterologists for most vomiting and diarrhea

-calf diarrhea

-chronic long-term diarrhea

-diarrhea related to bacterial overgrowth

-bacteria that have invaded or are likely to invade the blood (bacteremia or septicemia)

Antibiotics ARE used to treat

Antibiotics in GI Disease - (Tylan)

-macrolide antibiotic

-used in BO and PO to treat GI and respiratory infections

-oral form has been used in dogs to treat bacterial overgrowth, irritable bowel disease, and colitis associated with Clostridium

-Oral form also used to treat “tylosin-responsive chronic diarrhea“ syndrome

-can produce severe diarrhea in horses

Tylosin

Antibiotics in GI Disease - Flagyl

-used to treat Giardia - a protozoa

-trade name reflects the flagella

-giardia produce chronic diarrhea

-other chronic diarrhea NOT caused by Giardia also respond to metronidazole

Side effects: neurological - head tilt, weakness, staggering, seizures - temporary, stops after stop drug - COMMON with high dose or long term use

-Prohibited from all use in food animals because possible carcinogenesis reported in lab rats and mice

Metronidazole

Antibiotics in GI Disease

-macrolide antibiotics (like tylosin - very similar)

-most often used to treat baterial pneumonia and bronchitis

-at lower than bacteriicidal doses, it mimics the action of natural intestinal motility molecule called motilin

• Side effect of E. : GI cramping, increased GI motility

• has been used to stimulate gastric emptying in K9/FE

• Used to decrease esophageal refluc by increasing lower esophagus muscle tone in K9 (acts like prokinetic agent metoclopramide)

Erythromycin and Azithromycin