antinauseadrugs

Canine Anti-Nausea Drugs

Anti-emetics.
Different chemotherapy drugs cause nausea/vomiting or diarrhea in different ways. In order to prescribe an effective anti-emetic, we must first understand the mechanism of toxicity. For example, cisplatin activates the chemoreceptor trigger zone as it is being administerd, so drugs designed to block that pathway of nausea (IV butorphanol, ondansetron, dolasetron) are the most effective and are given prior to the cisplatin administration. In contrast, those few dogs who develop nausea/vomiting or diarrhea after doxorubicin treatment most commonly do so 2-4 days after the chemotherapy is given. The mechanism of the vomiting/diarrhea is that the chemotherapy kills the gut crypt enterocytes, so several days later, the villus tips in the small intestine are denuded (similar to viral enteritis). Carafate and pepcid will not help as the problem is rarely gastric. Peptobismol is often very helpful, as is metoclopramide. If this side effect of doxorubicin occurs in one patient, that same patient will develop the problem with subsequent doses of doxorubicin. Prevention by using glutamine (an essential amino acid for gut enterocytes) and peptobismol beginning prior to the next chemo and continuing for 4 days after that chemo is usually successful.

Butorphanol
Metoclopramide

Butorphanol Tartrate (Stadol, Torbutrol, Torbugesic)

Brand Name: Stadol, Torbutrol, Torbugesic
Available in 1 mg, 5 mg and 10 mg tablets

Background
The opiate class of medication is complicated to describe. There are several types of receptors in the nervous system that respond to opiates. These receptors are designated by different Greek letters (“mu,” “kappa,” and “sigma”). Opiates work by binding and stimulating some receptors (such opiates are said to be “agonists” of the receptors they stimulate) or they may bind and block receptors (in which case they are “antagonizing” the receptor). What the effects of a given opiate are (euphoria, cough suppression, pain relief, hallucination, addiction etc.) depend on which receptors are stimulated and which are blocked. Some opiates only stimulate receptors. These are called “pure agonists.” Some opiates, like butorphanol, stimulate some receptors and block others. This makes butorphanol what is called an “agonist/antagonist.” It seems to stimulate the kappa and sigma receptors and antagonize mu receptors.

Butorphanol is a controlled substance, which means there are special legal requirements for prescribing and stocking it.

How this Medication Is Used
Regardless of which receptors are stimulated and which antagonized, butorphanol ultimately is a cough suppressant as well as a short-acting analgesic. It also has some sedating properties. Many people are familiar with codeine, which has nearly identical uses and is also in the opiate family (though it is not an agonist/antagonist like butorphanol). It may be helpful to think of butorphanol as being similar to codeine: lower doses can be used to suppress cough, higher doses for pain relief.

Most opiates can be used to suppress cough but, unlike other opiates, butorphanol does not suppress the respiratory center in the brain (and does not slow respiration nor make breathing more shallow).

Butorphanol is also sometimes used as a pre-anesthetic tranquilizer though it is very mild in this regard. It may also be used for pain relief following a surgical procedure (it acts rapidly but only for a short time so usually a longer acting pain reliever is used in combination).

Butorphanol has some anti-nausea properties and is commonly used in this way prior to the administration of cisplatin in cancer chemotherapy.

Side Effects
The chief side effect is sedation. Occasionally, it can cause diarrhea or appetite loss. Butorphanol is able to slow the heart rate though this is rarely of meaningful significance to normal patients.

Interactions with Other Drugs
Because butorphanol antagonizes the mu receptor, it will fight against opiates that are mu agonists: morphine, oxymorphone, meperidine, etc.

If butorphanol is used with any other drugs that have sedating properties, these sedating properties will be more blatant.

While butorphanol does not normally cause respiratory suppression, it might if used in conjunction with antihistamines or tranquilizers.

Concerns and Cautions
There are several circumstances where butorphanol is considered inappropriate. Butorphanol should be used cautiously or not at all in patients with: liver disease, kidney failure, hypothyroidism, hypoadrenocorticism (Addison's disease), head trauma, hydrocephalus, or in very debilitated patients.

Butorphanol will cross the placenta and will be secreted in milk. It should not be used in pregnancy and lactation.

Butorphanol is removed from the body by the liver. If the liver is diseased, one may see abnormal clearance of the drug.

Butorphanol should not be used in respiratory conditions where cough suppression is not desired (such as pneumonia).

It is our policy not to give dosing information over the Internet.

Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com

This work was originally published by Veterinary Information
Network, Inc. (VIN) and is republished with VIN's permission

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Metoclopramide (Reglan)

Brand Name: Reglan
Available in 5 mg & 10 mg tablets (oral suspension exists but is famous for unpalatable taste to pets)

How This Medication Works
One of the stomach's most important functions is to grind the food we eat into a fine slurry that passes freely through the intestines. A strong rhythm of contraction is necessary to affect this and this rhythm creates the stomach's motility.

Motility disorders are common and may be chronic (of long duration) or of sudden onset. When motility is reduced in the stomach, food pools there and creates a sensation of nausea and bloating. In some cases, bile refluxes from the intestine back into the stomach, causing irritation and more nausea. Metoclopramide normalizes stomach contractions so that food and bile can pass in the correct direction.

An additional effect of metoclopramide is helpful in the control of nausea. There is a biochemical barrier separating the brain and central nervous system from the blood stream so that only certain biochemicals can cross over. This partition is called the blood-brain barrier. Metoclopramide is able to cross the blood-brain barrier and act on the brain directly to control the sensation of nausea.

Metoclopramide thus helps the vomiting patient by normalizing stomach motility and acting directly on the brain to reduce the sensation of nausea.

How This Medication Is Used
Signs of nausea in pets include:

Loss of appetite
Vomiting
Drooling
Loud stomach or intestinal sounds
Chewing motions

Metoclopramide can be used to control nausea in any situation except in the event of stomach or intestinal obstruction. If a motility problem is suspected (a classical history would include vomiting food many hours after eating), metoclopramide should also be helpful. If a motility disorder extends beyond the stomach (for example, a colon motility disorder might lead to constipation), metoclopramide would not expected to be helpful.

METOCLOPRAMIDE IS BEST GIVEN 20 MINUTES BEFORE A MEAL.

Side Effects
Side effects are rare with metoclopramide but generally stem from the ability to penetrate the blood-brain barrier. Animals predisposed to seizures (i.e., epileptics) may experience seizures, although this should not be a problem for normal animals.

Some animals experience drowsiness and others will experience marked hyperactivity. Hyperactivity can be reversed with a dose of Benedryl (diphenhydramine).

Constipation has been reported as a side effect in some individuals. This is not a common side effect.

If you suspect your pet is having an adverse reaction to metoclopramide, discontinue the medication and inform your veterinarian. There is another motility modifier called cisapride (Propulsid) that may be a good alternative. This medication does not cross the blood-brain barrier and hence does not have the behavioral side effects that metoclopramide can, but it also does not reduce the sensation of nausea by this additional mechanism either.

Interactions With Other Medications
Metoclopramide should not be used with phenothiazine tranquilizers such as acepromazine if there is any potential for seizures in the patient. Both medications serve to lower the threshold to seizures.

Propantheline bromide (Pro-Banthine), which is used to treat some cardiac arrhythmias, will inactivate metoclopramide.

Narcotic analgesics may negate the effects of metoclopramide.

Cautions and Contraindications
In patients with pheochromocytoma (a rare adrenal tumor) the use of metoclopramide can induce dangerously high blood pressure.

If stomach obstruction is suspected in a patient, it is best not to encourage motility and some other anti-nausea drug is preferred.

Metoclopramide crosses the placenta and into milk and is probably best avoided in pregnant or nursing mothers

It is our policy not to give dosing information over the Internet.

By Wendy C. Brooks, DVM, DipABVP Educational Director, VeterinaryPartner.com
Copyright 2007 - 2008 by the Veterinary Information Network, Inc. All rights reserved.

This work was originally published by Veterinary Information
Network, Inc. (VIN) and is republished with VIN's permission

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Cerenia

The above information is simply informational. It's intent is not to replace the advice of a veterinarian nor to assist you in making a diagnosis of your pet. Please consult with your own veterinarian for confirmation of any diagnosis. Your pets life may depend on it.