Historically, the role of zinc in health and disease has been studied through patients with toxicity or severe deficiency with obvious clinical signs. As the ubiquitous contribution of zinc to structure and function in biological systems was discovered, clinically significant but subtle deficiency states have been revealed. In human medicine, mild zinc deficiencies are currently thought to cause chronic metabolic derangement leading to or exacerbating immune deficiency, gastrointestinal problems, endocrine disorders, neurologic dysfunction, cancer, accelerated aging, degenerative disease, and more. Determining the causal relationships between mild zinc deficiency and concurrent disease is complicated by the lack of sensitive or specific tests for zinc deficiency. The prevalence of zinc deficiency and its contribution to disease in veterinary patients is not well known. Continued research is warranted to develop more sensitive and specific tests to assess zinc status, to determine which patients are at risk for deficiency, and to optimize supplementation in health and disease.

Objectives -To review the role of thrombin in physiology and clinical disease and to discuss the pharmacology of antithrombosis. Data Sources -Original research articles, scientific reviews, textbooks. Human Data Synthesis -Thrombin and thrombin receptors are involved in a variety of physiologic and pathologic processes resulting in a great deal of interest in thrombin-related pharmacologic intervention. Veterinary Data Synthesis -Although there is little clinical research data available on thrombin specifically in veterinary patients, some of the original research on protease activated receptors was performed at veterinary institutions and many of the human molecular biology studies have been done on animals including dogs. Conclusion -Thrombin plays a significant role in coagulation, anticoagulation, and fibrinolysis. Antithrombotic treatment is focused on preventing thrombosis while maintaining hemostasis. Pharmaceutical agents are selected for the specific component of the coagulation pathway associated with a specific disease process, for a proven prophylactic benefit with procedures that carry a risk of thromboembolism, for rapidity of onset and ease of reversibility, for limited monitoring requirements, and for oral formulation and bioavailablity. Recent insight into other aspects of thrombin physiology presents an opportunity for pharmacologic intervention in a variety of other processes such as inflammation and sepsis, peripheral blood cell activation and chemotaxis, vascular endothelial and smooth muscle activity, cellular development and tissue repair, mitogenesis, neoplasia, and the function of nervous tissue following injury.

Objective: To review phosphorus and phosphate metabolism and the importance of phosphate abnormalities in veterinary patients. Data sources: A review of recent human and veterinary medical literature. Human data synthesis: There is a significant amount of original research on human patients with phosphate abnormalities. Hypophosphatemia has been studied in patients with diabetic ketoacidosis (DKA), head trauma, refeeding syndrome, hypothermia and in ventilator patients that fail to wean. Hyperphosphatemia has been studied in patients with renal failure and malignancy. Phosphate levels have also been evaluated for prognostic value in sepsis and acute liver failure. Veterinary data synthesis: Although animal models were used in early experimental research, fewer studies have been published on the effects of phosphate abnormalities in veterinary patients. Hypophosphatemia has been studied in animals with DKA, with refeeding syndrome and with hyperparathyroidism. Hyperphosphatemia has been studied in animals with renal failure and with secondary hypoparathyroidism. Conclusion: Phosphorus and phosphate are important in many biological functions. This paper is a review of their role in normal metabolism and the clinical importance of phosphate imbalances for our emergency and critical care patients.

Histamine plays a key role in the morbidity and mortality associated with allergy, asthma, gastric ulcers, anaphylaxis, sepsis, hemorrhagic shock, anesthesia, surgery, cardiovascular disease, cancer, CNS disorders, and immune-mediated disease. Histamine antagonism has been in common use to block its adverse effects. With recent advances in the understanding of histamine receptor physiology, pharmaceutical agents targeting these receptors have increased the therapeutic options.

Objective: To review the clinical spectrum and mechanisms of action of furosemide in human and small animal veterinary patients.Data sources: Review of human and veterinary literature.Data synthesis: Furosemide is used primarily for its properties as a loop diuretic; however, it has many other actions that may be clinically applicable. Furosemide has a vasodilatory effect that precedes diuresis that may confer its immediate benefit in patients with volume overload. Furosemide can be inhaled to relieve dyspnea in patients with bronchospasm. Furosemide also shows promise as an adjunct to antiseizure therapy to help control epilepsy, status epilepticus, and acute ischemic damage related to seizures. It has activity as an antioxidant, iodine depletive, and may increase thoracic lymph duct flow. Reported furosemide side effects include altered drug metabolism, electrolyte depletion, ototoxicity, mucociliary impairment, endocrine and exocrine pancreatic effects, delayed wound healing, sulfonamide toxicity, and thyroid binding interference. It is worthwhile to consider the implications of these effects when using furosemide either alone or in combination with other drugs.Conclusions: Despite the research in animal models that demonstrates a wide spectrum of pharmacologic activity, furosemide has not been widely recognized or used clinically in veterinary medicine except as a loop diuretic.