Veterinary Medicine - February 2008 - (Page MV9) readily available. I know some drugs used in humans are also available as suppositories, which can have bene ts for outpatient administration. Twedt: My other fear is that because the e ective antiemetic dose is low and below the tranquilization dose, there may be a tendency for people to overdose these patients, tranqulizing them. Leib: When we use them, we try to stay just below the dose that causes tranquilization. Often, that is di cult to do because it is a very low dose. The next important class is serotonin antagonists. A classic example would be ondansetron. Twedt: One of the major indications for ondansetron in human medicine is chemotherapy. Simpson: If metoclopramide fails, ondansetron is the next drug that our residents usually reach for. I haven’t seen good studies on ondansetron in nonchemotherapeutic patients, but clinicians seem to be happy with it in terms of puppies with parvovirus and some pancreatitis cases. Jergens: I agree that when animals fail to respond adequately to metoclopramide, they get ondansetron. I don’t use it that often outside the realm of the chemotherapeutic patients. But the doctors in the residency training programs seem to make that a rst or second choice in many nonchemotherapeutic vomiting patients. Simpson: I understand that it is the 5-hydroxytryptamine (5-HT3) receptors in the peripheral vagal a erent nerves that are the main ones where it exerts its antiemetic e ect, but there are some central 5-HT3 receptors as well. I think there is also a dog-cat di erence in the distribution of 5-HT3 receptors with dogs having con rmed peripheral receptors. Leib: So we’re getting some peripheral e ects by blocking a erent transmission as well as central e ects through the chemoreceptor trigger zone? Simpson: Yes, likely through the peripheral vagal 5-HT3 receptors that are being blocked. Twedt: Yes, there are 5-HT3 receptors on peripheral a erent nerves as well as the chemoreceptor trigger zone. So this class of antiemetics has an e ect centrally and peripherally. It has become less expensive because there are generic forms now, but the oral product is still price prohibitive. Leib: In our clinic, the practical limitation has been expense. We use ondansetron when everything else fails. Our decision to utilize ondansetron is somewhat related to the size of the animal. If we are treating a cocker spaniel, an owner can usually a ord to use the drug. If it is a German shepherd or Great Dane, the answer is usually no. Williams: Granisetron is used more widely now in veterinary medicine than ondansetron for that reason. Granisetron is used as a second-choice agent when metoclopramide isn’t working. Simpson: Granisetron might work better peripherally, especially with some of our puppies with parvovirus. It has become standard for parvoviral-related vomiting. Some studies indicate that granisetron may bind irreversibly to peripheral 5-HT3 receptors, and this may account for its e cacy. Take note • Metoclopramide works at the chemoreceptor trigger zone, blocking dopamine receptors. • If given subcutaneously or intramuscularly, metoclopramide is rapidly absorbed and removed, so it doesn’t have a prolonged effect. • Hydration is important when using phenothiazines because they may cause vasodilation and hypotension. • Phenothiazines may cause tranquilization, which can make it difficult to monitor a patient’s mental status and identify signs of discomfort. Leib: There are four approved serotonin antagonists available for use in humans. Is anybody aware of the di erent e cacies or mechanisms of the other drugs in this class? Williams: I believe they are equally e ective. Leib: How about contraindications for ondansetron? Jergens: I am unaware of major contraindications. Leib: So it really would be a nancial decision more than anything. Are there any other commonly used antiemetics that we haven’t commented on? Simpson: Opioids, such as buprenorphine, are supposed to o er some antiemetic e ects. Leib: Working through opioid receptors in the vomiting center? Simpson: Yes, I think so. They were used to ameliorate chemo9
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