Induction of Emesis (Emetics)

Indication(s) - ingestion of toxicants, clean the stomach prior to emergency surgery

Contraindications do not induce vomiting if the patient has ingested caustics or petroleum products or if the patient has had recent abdominal surgery, if hernias are present, or if the patient is in severe abdominal pain.

NEW since 2008 Printed notes:
In human medicine, inducing vomiting is no longer recommended in cases of accidental or intentional posoining. Reasons for this include:

1. Limited efficacy of the practice
2. Vomiting may continue after the initial episode, making treatment of the poisoning difficult
3. Recognition of hazards associated with typical emetics (ipecac)
4. Abuse of ipecac (eating disorders, idiots on YouTube). It is actually unlikely that pet owners will have effective emetics available to them.

Peripheral-acting emetics

Mechanism(s) - irritation of pharynx, esophagus, stomach, duodenum; or stretch of the muscular layer of the stomach or duodenum. Either mechanism evokes normal reflex arc to produce vomiting. These vary in reliability, safety, availability (do you have them).

Saturated sodium chloride solutions

• good efficacy in dogs
• must be given by stomach tube

1% copper sulfate

• efficacious in dogs and swine
• stomach tube only

1% zinc sulfate

• swine and dogs only
  
• less reliable than copper sulfate

Neutral salts (sodium chloride, sodium bicarbonate)

• placed or thrown into the pharynx
  
• useful in "home" setting

Syrup of ipecac

• available in many homes
• recommended for parents by poison control centers
• emetine irritates the lining of the stomach to invoke reflex
• toxic to heart, liver, kidney
• recover by gastric lavage if emesis does not occur

Freshly ground mustard

• available in some homes
• client must have mustard SEED and grind it prior to use

Hydrogen peroxide

• squirt into oro-pharynx
• rather difficult to accomplish

Central-acting emetics

Mechanism(s) - stimulation of chemoreceptor trigger zone (CRTZ) and/or direct stimulation of emetic center

Apomorphine

• stimulates CRTZ, then depression of emetic center
  • reflex can only be triggered once
  • no emesis ® recover by lavage
  • depression of CNS in most species
  • excitement in cats
• most effective (reliable) emetic in the dog
• absolutely ineffective in swine
• Routes CHANGED SINCE PRINTING OF 2008 NOTES.
  • Solution for subcutaneous injection is the only form I can find available.
  • tablets for injection (old timey, actually very slick)
  • subconjunctival placement of tablet

Morphine

• mechanism as for apomorphine
• choose this as pre-med when emesis is desired pre-operatively
• otherwise, apomorphine is preferred

Xylazine

• stimulation of CRTZ
• effective in cats (0.44 mg/kg)
• less effective in dogs

Syrup of Ipecac

• emetine stimulates CRTZ

Control of Emesis

Rationale

1. once vomiting is no longer serving in a protective capacity
2. radiation therapy, cancer chemotherapy
3. uremia, other "disease related toxins"
4. severe abdominal pain (pancreatitis)

Peripheral-Acting Antiemetics

Demulcents - Kaolin, Pectin, Bismuth salts

Indication(s): control of vomiting associated with pharyngitis, gastritis. poor efficacy (may even stimulate vomiting)

Antacids - aluminum hydroxide, aluminum phosphate, magnesium hydroxide, etc.

Specific indication: vomiting associated with excess gastric acidity. Efficacy is questionable except to prevent recurrence (may stimulate vomiting in acute cases)

H-2 receptor antagonists - cimetidine, ranitidine, etc.

Specific Indication: vomiting associated with excess gastric acidity. Injectable dose forms will not stimulate vomiting so probably preferred over oral antacids

Local Anesthetics (e.g., Lidocaine viscous)

Specific Indication: vomiting associated with pharyngitis. Poor efficacy, may stimulate vomiting

Anticholinergics - aminopentamide, atropine, scopolamine

Indications are non-specific. Peripheral action alleged - block sensory input to CNS. Effective drugs in this class also have central action

Metoclopramide

Indications for regurgitation, pylorospasm. Improves coordination of motility and gastric emptying. Also possesses central action (CRTZ) described below

Central-acting antiemetics

Potential Sites of Action for the Central-acting antiemetics include the, vestibular apparatus, the chemoreceptor trigger zone (CRTZ), and the emetic center. Central-acting Anti-emetic drugs may be limited spectrum (one, maybe two sites) or broad spectrum (multiple or all sites).

Limited Spectrum Anti-emetics

Anticholinergic - aminopentamide (Centrine^® ), scopolamine

• only scopolamine penetrates CNS
• vestibular vomiting only
• aminopentamide is very questionable for vomiting
• duration of action of scopolamine short (requires continuous application - patch used in people - for efficacy)

Anti-histamines (H-1 receptor)

Short duration (4-8 hours) - diphenhydramine, dimenhydrinate

• motion sickness

Long duration (12 -24 hours) - meclizine, promethazine

• motion sickness
• vestibular disease (usually inflammation)

Trimethobenzamide

• block of CRTZ is the only known pharmacologic action
  
  • uremia
  • radiation sickness
  • chemotherapy, other drug-induced

Metoclopramide

• block of CRTZ in addition to peripheral actions
  
• radiation sickness
  
• chemotherapy
  
• motility disorders associated with:
  
  • pylorospasm
    
  • peritonitis
    
  • pancreatitis

ondansetron, ganesetron (5-HT3 receptor blockers)

• Central and peripheral receptors, location of primary mechanism unclear
• Effective for Cancer chemotherapy-induced and radiation-induced vomiting (acute vomiting, not as good for delayed vomiting).
• Effective for post-operative vomiting
• Ineffective for motion sickness
• Fairly expensive

Maropitant (Cerenia^TM Dog); aprepitant (Emend Human) (NK-1 receptor blocker)

• Central receptors
• Effective for Cancer chemotherapy-induced and radiation-induced vomiting. (Better than 5-HT3 for delayed vomiting)
• Effective for post-operative vomiting
• Maropitant approved for motion sickness prevention - dogs
• Emend - Extremely expensive
  Cerenia?

Broad-spectrum anti-emetics

block more than one site

Phenothiazines - chlorpromazine, acepromazine, prochlorperazine

1. block CRTZ at low doses
2. block emetic center at high doses

• excessive CNS depression
• hypotension
• lower seizure threshold
• avoid with recent OP exposure

Increase Gastrointestinal Motility

Gastrointestinal motility is influenced by hormonal activity, myogenic activity (contractile response to stretch), and neurogenic factors. It is divided into rhythmic segmentation (mixing activity and "average GI tone") and peristaltic activity (mainly propulsive).

Cholinergic Drugs

Rationale Cholinergic drugs are used for symptomatic treatment for diminished gastrointestinal motility (ruminal atony, abomasal displacement, ileus). Unfortunately they produce an uncoordinated increase in motility (coordinated would be preferred - see metoclopramide) You may see evidence of activity (abdominal pain, cramping) without improving patient condition

Pilocarpine

• marked effects on all muscarinic sites
• readily antagonized by atropine

Bethanechol - (Urecholine^®)

• selective for smooth muscle stimulation
• readily antagonized by atropine
• terminated by elimination (not by cholinesterases)

Carbachol

• relatively selective for smooth muscle
• may stimulate nicotinic receptors at therapeutic doses
  • muscle fasciculations
  • sympathetic stimulation - antagonizes smooth muscle actions
• poorly antagonized by atropine

Pantethol

• converted to pantothenic acid, a precursor of Coenzyme A
• ultimate action related to increase in acetylcholine production
• QUACK, QUACK, QUACK

Cholinesterase inhibitors

These agents increase concentrations of acetycholine at the nerve terminal. The net effect is the same as if a direct-acting cholinergic agent were administered though the ultimate effect may be less predictable.

Physostigmine (tertiary amine)

• oral absorption possible but variable
• dose vs response is unreliable

Neostigmine (quarternary amine)

• no oral absorption
• may stimulate cholinergic receptors directly
• most reliable of the two cholinesterase inhibitors

Cathartics, Surfactants, Lubricants

Indications these drugs are indicated for bowel cleansing (pre-surgical, pre-radiography, pre-proctoscopy), to promote elimination of toxicants, to facilitate defecation (hernias, surgeries) and to alleviate simple constipation

Irritant Cathartics

Mechanism stimulate smooth muscle directly

Contraindications

Colitis, enteritis, obstruction.
• They may induce parturition in late pregnancy
• most are secreted in milk may purge suckling offspring

Arthroquinone derivatives - aloe, senna, cascara sagrada and danthron (synthetic)

• hydrolized in colon
• variable onset (6 - 12 hour delay)
• unreliable
• produce considerable discomfort

Phenylphthalein

• swine and primates only
• 6 - 8 hour delay
• pink urine (if alkaline)

Bisacodyl

• hydrolyzed in small intestine to produce irritating sodium and potassium salts
• more predictable and reliable than arthroquinone

"Saline" Cathartics

1. unabsorbed electrolytes which exert an osmotic effect (and)
2. water moves from circulation ® fecal mass (which causes)
3. stretch of mucosa and activation of "mechanoreceptors" (which)
4. increases peristalsis

Sodium sulfate

• most effective on a molar basis
• must be administered by stomach tube

Magnesium salts (oxide, hydroxide, sulfate)

• most are also used as antacids
  • generally balanced with aluminum salts (aluminum constipates) when used for antacid action only
• magnesium toxicity only with increased GI transit times or renal dysfunction
• suitable for dogs, cats, foals, calves, piglets

Hydrophilic colloids (bran mash, linseed mash, psyllium)

• the "natural" way

Polyethylene Glycol Electrolyte (Go-LYTELY^®)

• very effective bowel cleansing
  
• use reserved for diagnostic or surgical preparation

Lubricants

• enough said

Liquid petrolatum (mineral oil), petrolatum (vasoline, Cat-a-lax^®)

• used in feline (petrolatum), equine, and bovine (liquid petrolatum) patients
• not for household pet animals (loss of defecatory control)
• foreign body reactions in intestinal wall
• avoid following rectal-anal surgery (oil foreign-body in wound)

Raw linseed oil

• mechanism as for liquid petrolatum
• no foreign body reactions

Surfactants

Mechanism non-irritating soaps that facilitate movement of water into fecal mass. These are classically referred to as "stool-softeners". Can be given as enemas or by mouth.

Caution. These may facilitate absorption of mineral oil when the two are given together

Dioctyl sodium sulfosuccinate and Dioctyl calcium sulfosuccinate

Prokinetic Agents

Metoclopramide

Mechanism Effect is probably mediated through both cholinergic systems enhanced and dopaminergic systems blocked.

Indications Pylorospasm and associated gastric reflux, presurgical emptying of the stomach, to facilitate passage of endoscope (maybe not in veterinary patients - per M.Leib), prevention of gastric dilatation and volvulus, displaced abomasum (investigational)

Cisapride

Mechanism Increase release of acetylcholine from postganglionic nerve endings of myenteric plexis. Both large and small bowel motility are enhanced

Indications Gastroesophageal reflux disease, Gastric atony uses in ileus, large bowel hypomotility speculative (clinical trials are sparse) but are probably appropriate given the limited number of alternatives.

"Investigational Prokinetics" - Erythromycin, Lidocaine

Alter gastrointestinal motility to control small bowel diarrhea.

Opiates

Mechanism(s)Increase tone in intestinal smooth muscle, increase rhythmic segmentation as compared to peristalsis, enhances fluid absorption, decreases average "lumen diameter". Decrease intestinal secretion (second action discussed later)

Indications Controlling signs of small bowel diarrhea

Loperamide (Imodium)

• mixed agonist/antagonist with "no" abuse potential
• available over the counter
  
• liquid forms available

Diphenoxylate (Lomotil)

• mixed agonist/antagonist with relatively low abuse potential
• alter motility with few systemic effects

Paregoric (tincture of opium)

• occasionally preferred for small dogs, though loperamide is probably the drug of choice.

Decreased gastrointestinal motility

Management of drug induced "increased motility" or know these side effects when drugs are used for other purposes

Anticholinergic Drugs

Mechansim(s) Decrease parasympathetic tone in the gastrointestinal tract. Administration of these drugs is VERY questionable for the treatment of small bowel diarrhea, simply because gastrointestinal motility and associated disorders are controlled by a VERY complex set of neurogenic inputs that include a variety of other mediators. Further, many small bowel diarrheal diseases actually include low motility as a significant feature.

Indications Overzealous administration of cholinergic drugs and cholinesterase inhibiters, organophosphate and carbamate intoxication. Use in diarrhea may prolong clinical signs and may produce ileus (signs of which may include diarrhea)

atropine, scopolamine

• cross into central nervous system
  
• depression (most species), excitement (cats)

methscopolamine, propanthaline, isopropamide (Darbazine^®)

• quarternary nitrogen (do not reach CNS)
• may also inhibit nicotinic receptors (ganglia)

Adrenergic Drugs

Reduced GI motility is a side effect of administration for other purposes

a-1 agonists

• reduce intestinal and gastric blood flow
• suppress acetylcholine release from nerve terminals

• directly inhibit activity of GI smooth muscle

Management of Severe Visceral Pain

Caution: although is is part of the veterinarian's oath to alleviate pain and suffering, pain may be the most (or only) useful clinical sign to the veterinary therapist as a guide to the animals response to other therapy. Relief of visceral pain should never be the ONLY therapy employed and may, in fact, be contraindicated early in the management of certain conditions.

Central Acting Analgesics

Mechanism(s) Raise the threshold for pain, decrease the reaction to pain, and promote drowsiness

Opiates / Opioids

Morphine

• most versatile, least expensive
  
• Duration = 6 hours in dogs and cats, 2 + in horses (depends on severity of pain)
• Progressive depression in dogs, rabbits
• Progressive excitement in horses, cats, swine
• Little or no action in ruminants

Methadone

• equal potency to morphine
• preferred by some to produce analgesia without excitement in horses

Meperidine

• 1/10 the potency of morphine
  
• short duration (Horses - 20 minutes; Cats - 2 hours; Dogs - 45 minutes)
• excessive doses may produce seizures

Oxymorphone

• potency 10x that of morphine
• little real advantage over morphine

Pentazocine

• potency 1/4 of morphine
• agonist/antagonist (lower abuse potential)
• short duration (Horse - 2 hours; Dogs and Cats - 1 hour or less)

Butorphanol

• potency 4x - 7x morphine
• agonist/antagonist (very low abuse potential)

Non-narcotic Analgesics

a 2 Agonists (Xylazine, Detomadine, Metdetomidine)

• ONLY effective central acting drugs in ruminants
• duration of action is short (Horses - 30 to 40 minutes; Dogs and Cats - 15 to 30 minutes; Ruminants - 1 to 2 hours

"Peripheral Acting Analgesics" - NSAIDS

Useful for the relief of visceral pain associated with intestinal spasm triggered by inflammatory mediators. Only flunixin meglumine and ketoprofen (of available agents) reduce gastrointestinal pain by other means. Mechanism of action of these compounds is discussed under anti-inflammatory drugs (http://cpharm.vetmed.vt.edu/VM8784/nsaids/nsaids.htm). Agents mentioned here enjoy special action or reputation for GI therapeutics.

Flunixin meglumine

• potent analgesic in the horse and ruminants
• duration of action may be too long (see colic)

Ketoprofen

• clinically, this seems to be very similar to flunixin meglumine
• head-to-head comparisons are just beginning in the literature

Gastrointestinal secretion

Decrease flow of Saliva

see anesthesia notes

Decrease Gastric Acid Secretion

Anticholinergics
although these agents may decrease the secretion of gastric acid, there efficacy is very poor because acetylcholine is not a primary mediator for acid secretion

Anti-histamines (H-2 receptor blockers)

Cimetidine (Tagamet^® )

• prototype of this class
• effective and safe in a number of veterinary species
  • not ruminants (no GI H-2 receptors)
  • maybe not Llamas etc (ruminant-like?)
• very effective for treatment of gastric and duodenal ulcers
• possibly effective for prevention of ulcers
  
  • depends on cause of ulcers
  • not effective against NSAID induced ulcers in dogs (1 study)
• moderately effective for gastro-esophageal reflux

• short duration of action (must be given BID,TID)
• refractoriness may appear (increasing doses to produce same effect)

• reduced metabolism of other drugs (Cytochrome P-450, Hepatic blood flow)
• reduced absorption of drugs which depend on acidity for absorption ketoconazole
• anti-androgen effects

Ranitidine (Zantac^® )

• increased potency vs cimetidine
• longer duration of action (12 - 24 hours depending on condition and dose)
• virtually NO side effects, this drug should definitely be preferred in critically ill patients and those receiving multiple drugs.
• increased cost vs cimetidine

Famotidine (Pepsid^® )

• increased potency and cost
• reduced side effects vs cimetidine

Hydrogen ion-pump blockers

Omeprazole - (GastroGard^® , Prilosec^®, Nexium^® AcipHex^® , etc., etc.)

Mechanism block hydrogen ion secretion by direct inhibition of an ATPase

Indications Conditions related to hyperacidity refractory to other H-2 blockers. Approved indication in horses for treatment of gastric ulcers and prevention of recurrance.

Protect mucous membranes

• protect the mucous membrane linings of the GI tract
  
• acute and chronic gastroenteritis
  
• esophageal, peptic, duodenal ulcers

Barium sulfate

• obvious action (just look at the radiographs)
• legendary "barium cures"
• doses similar to radiologic doses seem reasonable

Bismuth subsalicylate

• OTC coating agent
• dosing in horses and ruminants is questionable (seems low based on "size" of the total GI tract)

Sucralfate

• novel coating agent
  
• forms an ulcer-adherent complex with exudate at ulcer site
  
• inhibits pepsin activity in gastric juice by 1/3
  
• sucralfate-albumin film provides barrier to diffusion of hydrogen ions ("artificial mucus")
• true role in veterinary patients remains to be defined
• probably indicated in combination with H-2 blockers for ulcer treatment and prevention

Misoprostol

• analogue of prostaglandin E2
• PGE2 is a stimulant of mucus secretion and an inhibitor of acid secretion
• indicated for prevention of gastritis and gastric ulcer disease associated with administration of NSAID drugs.

Modify Intestinal Secretion

A number of different drug classes, including non-steroidal anti-inflammatories and opiates alter intestinal secretion. In fact, this may be a major mechanism of their activity in the treatment of small and large bowel diarrheas. In addition, oral electrolyte solutions serve as a valuable adjunct to therapy in neonatal diarrheas. Their primary activity is to maintain circulating blood volume, but they do so by fostering intestinal absorption of electrolytes and fluids in opposition to disease-induced secretion.

Topic Summary (Gastrointestinal Tract)

1. Many acute gastrointestinal diseases (especially small animal) are self-limiting. In part, this explains why so many of us have faith in therapies that are not rational (anticholinergics for diarrhea).
2. A wide variety of substances can be used to induce emesis by either peripheral or central actions. None of the emetics are absolutely reliable. The most reliable (and convenient) are apomorphine for dogs and xylazine in cats.
3. The mechanism of action of anti-emetic drugs should be matched carefully to the cause of vomiting:
   
   

   	Antihistamines	vestibular	motion sickness
   	Phenothiazines	CRTZ	drug/toxin induced
   	Phenothiazines	Emetic Center	all causes
   	Metoclopramide	CRTZ	drug/toxin induced
   	Metoclopramide	Peripheral	abn. GI function
   	Butyrophenones	Vestibular	Labyrinthitis
   	Butyrophenones	Emetic Center	All causes

4. Few genuine indications for increasing gastrointestinal motility exist. Only metoclopramide produces a coordinated increase in motility of the upper gastrointestinal tract.
5. Diarrhea is usually associated with hypomotility rather than hypermotility. For this reason anticholinergics are specifically contraindicated for the treatment of diarrhea. Opiates reduce symptoms by increasing rhythmic segmentation (and possibly by antisecretory mechanisms). This slows the rate of passage of ingesta.
6. Visceral pain is best managed with central acting analgesics (opiates). Opiates do not relieve visceral pain in ruminants but xylazine does. A limited subset of NSAIDs (specifically banamine) may be potent enough to reduce visceral pain.
7. Gastric acid secretion is reduced by the administration of H-2 blocking antihistamines (eg. cimetidine), H-pump blockers (omeprazole), and PGE2 analogues. PGE2 analogues have the additional benefit of stimulating the secretion of mucus.
8. Oral electrolyte solutions are either isotonic or hypertonic. Relative benefits of either approach have not been studied systematically.