Which of the following drugs would be appropriate for this patient?
Based on the information provided, how would you grade the following drugs and why?
The following represents the best responses based on drug metabolism, pharmacokinetics, species, diagnostic differentials, clinical and laboratory data, and other pertinent findings.
Correct ResponseProceed with CautionGemfibrozil reduces circulating triglyceride levels by reducing production and enhancing clearance. It is used in conjunction with dietary modification to treat some patients with primary hyperlipidemia. The adverse effect profile of gemfibrozil mimics pancreatitis (ie, abdominal pain, vomiting, diarrhea, hepatopathy); thus, this drug may complicate monitoring of pancreatitis. In this patient, abdominal ultrasonographic findings played a more important role than potential adverse drug effects in identifying pancreatitis as the cause of illness. Gemfibrozil must be administered orally, so administration should be suspended in this dog. Because hypertriglyceridemia appears to contribute to the pathogenesis of pancreatitis, reinstituting therapy with gemfibrozil as soon as vomiting and abdominal pain are controlled is recommended.
Correct ResponseProceed with CautionHydrochlorothiazide, when used chronically, reduces urinary calcium excretion and thus is often used for prevention of calcium oxalate urolithiasis, to which miniature schnauzers are predisposed. The drug may cause hypercalcemia, hypotension, or volume depletion, all of which predispose to pancreatitis. Thiazides also induce insulin resistance and may contribute to the acute development of overt diabetes mellitus in this dog.1,2 Hydrochlorothiazide administration should be discontinued during management of this dog’s pancreatitis, then cautiously reintroduced. Reinstitution of hydrochlorothiazide therapy may increase the dog’s insulin dosage requirements.
Correct ResponseSafePain management is essential in the treatment of patients with pancreatitis, with opioids as the mainstay of therapy. Fentanyl administered by injection followed by a constant rate infusion or a transdermal patch for continued analgesia is recommended. Patients should be monitored for bradycardia, which may occur as a result of increased vagal tone related to abdominal inflammatory disease; constipation; and hypothermia, which may arise secondary to shock in critically ill patients with pancreatitis. Buprenorphine or hydromorphone are acceptable alternatives for analgesia and have similar adverse effect profiles. Opioids may increase bile duct pressure and—like pancreatitis and dehydration—may cause increases in serum amylase and lipase concentrations.
Correct ResponseSafeVomiting is a common and often persistent problem in dogs with pancreatitis, and both central (eg, circulating compounds, fluid/electrolyte/acid-base disturbances) and peripheral (eg, pancreatic swelling, intestinal distension, abdominal inflammation) emetic pathways are likely triggered. Control of emesis is important for patient comfort, prevention of aspiration pneumonia, and maintenance of fluid and electrolytes. Even in patients that are not actively vomiting, antiemetic use may help control nausea that could otherwise prevent return of voluntary nutritional intake. Maropitant is a good choice as an antiemetic for dogs with pancreatitis because of its peripheral and central antiemetic effects and excellent safety profile. In addition, maropitant has anti-inflammatory properties that may be beneficial in animals with acute pancreatitis.3
Ondansetron or dolasetron
Correct ResponseSafeIf maropitant administration does not adequately control vomiting in patients with acute pancreatitis or if apparent nausea without vomiting is evident, a serotonergic antagonist (eg, ondansetron, dolasetron), which acts at the level of the chemoreceptor trigger zone to block the emetic reflex and has antinausea properties, may be added to the treatment regimen.
Correct ResponseProceed with CautionMetoclopramide is frequently used in dogs with acute pancreatitis because of its antiemetic and prokinetic effects. However, metoclopramide has relatively weak antiemetic properties, and side effects associated with its prokinetic action include nausea and abdominal pain, which may overlap with signs of persisting or worsening pancreatitis. In addition, metoclopramide may enhance pancreatic enzyme secretion and has general hypotensive effects in rats and humans and may therefore negatively impact pancreatic perfusion.4-9 Consideration of and monitoring for these potential adverse effects and maintenance of normovolemia in pancreatic patients receiving metoclopramide are advised.
Correct ResponseProceed with CautionThere is insufficient evidence to support routine use of corticosteroids in dogs with acute pancreatitis. Although pancreatitis is an inflammatory disease, use of glucocorticoids has not been shown to benefit patients, and there has been concern that they may promote pancreatic inflammation via their lipolytic effect, resulting in increased circulating fatty acids. However, there is also no evidence that corticosteroids are harmful in patients with pancreatitis, and corticosteroids have many potentially beneficial effects in countering inflammation, increasing levels of the protective compound pancreatitis-associated peptide, and addressing critical illness-related corticosteroid insufficiency. Although routine use of dexamethasone is still discouraged pending further studies, use of short-acting, low-dose corticosteroids may be warranted in patients with acute pancreatitis with secondary cardiovascular shock (ie, with poor systolic blood pressure with poor response to IV fluid and vasopressor administration).10
Correct ResponseDo Not UseAcute pancreatitis is typically a sterile inflammatory process, and bacterial translocation has not been documented in naturally-occurring pancreatitis in dogs; therefore, routine use of antimicrobial agents in dogs with pancreatitis is not indicated. In addition, amoxicillin may contribute to GI upset, as vomiting and diarrhea are potential side effects of use. Administration of oral medications should be avoided in vomiting patients, as oral administration may trigger vomiting and retention of an orally-administered drug for absorption and desired action cannot be assured. In patients with overt evidence of disruption of the intestinal mucosal barrier (eg, melena, hematochezia), concurrent bacterial translocation may be more likely, and parenteral antibiotics that are effective against potential pathogens originating in the small intestine may be considered.
Correct ResponseDo Not UseThere is no evidence that suppression of gastric acid secretion is beneficial in the treatment of canine acute pancreatitis, and use of H2 antagonists is not indicated. However, proton-pump inhibitors, independent of their acid suppression activity, may offer some benefit in reducing secretion of pancreatic enzymes11 and reducing pancreatic inflammation,12 though these effects have not been demonstrated in dogs.
Correct ResponseSafeThis patient has a fasting hyperglycemia and glucosuria and therefore is releasing inadequate amounts of endogenous insulin. Whether this is associated with her acute pancreatitis or she had pre-existing diabetes mellitus (that was not identified because she was already polyuric due to hydrochlorothiazide administration) is not clear; regardless, she requires exogenous insulin. Regular insulin administered via intermittent injection or as a constant rate infusion is advised in this patient until vomiting is controlled and she is eating reliably on her own, at which time she can be transitioned to an intermediate- or long-acting insulin for maintenance. Diabetes mellitus precipitated by pancreatitis (ie, reduced pancreatic insulin production and increased insulin resistance as a result of pancreatic inflammation) may resolve with the resolution of the pancreatitis; thus, this patient should be monitored for decreasing requirements for exogenous insulin with clinical improvement. However, the diabetes mellitus may not resolve because the patient may remain overtly diabetic subsequent to pancreatic injury from this episode of pancreatitis or she may have been diabetic prior to the onset of this bout of pancreatic illness. Reinstitution of hydrochlorothiazide therapy after the patient’s recovery from pancreatitis may cause an increase in her insulin requirements because of drug-induced insulin resistance.