Nonsteroidal anti-inflammatory drugs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are substances other than steroids that inhibit a component of the inflammatory cascade. This article is dedicated to those substances which specifically inhibit cyclooxygenase. NSAIDs are used extensively in the veterinary field. This article discusses their pharmacologic mechanism of action, indications, and toxicity. The two isoforms of cyclooxygenase (COX-1 and COX-2) are reviewed along with the newer NSAID which are more effective and less toxic due to more specific COX-2 inhibition. Specific effects on soft tissue, bone, cartilage, and synovium are summarized. Pain modulation is extensively reviewed as well as the antiendotoxic and antithrombotic uses.     

Nonsteroidal anti-inflammatory drugs in cats: a review

OBJECTIVE: To review the evidence regarding the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in cats. DATABASES USED: PubMed, CAB abstracts. CONCLUSIONS: Nonsteroidal anti-inflammatory drugs should be used with caution in cats because of their low capacity for hepatic glucuronidation, which is the major mechanism of metabolism and excretion for this category of drugs. However, the evidence presented supports the short-term use of carprofen, flunixin, ketoprofen, meloxicam and tolfenamic acid as analgesics in cats. There were no data to support the safe chronic use of NSAIDs in cats.     

Compounding in veterinary ophthalmology.

Compounded medications provide treatment options that can improve the clinical outcome for patients, improve compliance, and increase the potential for cure. This article provides an overview of the types and uses of compounded ophthalmic products in veterinary practice as well as criteria for selecting a pharmacist skilled in sterile compounding.     

Nonhypotensive autonomic agents in veterinary ophthalmology.

The parasympathetic and sympathetic divisions of the autonomic nervous system are involved in homeostatic control of a wide variety of ocular functions, including accommodation, pupillomotor control, lacrimation, eyelid position, and aqueous humor production. Familiarity with the functional anatomy of the autonomic nervous system is paramount to the understanding and application of the large number of autonomic drugs used in veterinary ophthalmology. The cholinergic and adrenergic agents discussed in this article are commonly employed to facilitate routine ophthalmic examination, in the diagnosis of autonomic dysfunction, and in the treatment of a variety of ocular diseases.     

Nonsteroidal anti-inflammatory drugs: a review. New applications in hypersensitivity reactions of cattle and horses.

Nonsteroidal anti-inflammatory drugs inhibit the biosynthesis of kinins and prostaglandins and stabilize leukocyte lysosomal membranes. Nonsteroidal anti-inflammatory drugs also weakly block the biosynthesis of histamine and serotonin, and pharmacologically antagonize kinins, prostaglandins and slow-reacting substance of anaphylaxis. Nonsteroidal anti-inflammatory drugs effectively control both cardiovascular and respiratory manifestations of hypersensitivity in cattle and horses. This, coupled with the contrasting lack of effectiveness of "antiamine" drugs, suggests that bio-amines such as histamine and serotonin (5-hydroxytryptamine) may be less important than kinins, postaglandins and slow-reacting substance in the mediation of the hypersensitivity/inflammatory reaction, at least in cardiopulmonary systems of these species. Nonsteroidal anti-inflammatory drugs justify more prominence in the clinical control of acute respiratory disease in domestic herbivores.     

Antifungals and their use in veterinary ophthalmology.

Many variables affect the outcome of keratomycosis and systemic fungal infections in animals. These include pathogenicity of the fungal organism(toxins, trophisms, and evasion of host response); previous treatment with topical or systemic corticosteroids, which can have a dramatic negative impact on host defense mechanisms: concurrent systemic illness or immunocompromise: severity/extent of infection; and degree of pain (ie,increased reflex tearing dilutes topical medication) [14]. Experimental work suggests that antibiotics may occasionally exacerbate fungal infections [142],and some researchers advocate that concurrent antibiotic therapy is contraindicated in horses with yeast infections and septate fungal infections unless bacterial infection is also suspected [14]. Nevertheless, given that normal conjunctival flora often include bacteria and fungi and because care of keratomycoses often includes mixed bacterial and fungal infections, the possible dynamics (natural influences and local competition) between ocular surface microorganisms merit further investigation. There are many unanswered questions regarding the accuracy of in vitro susceptibilities and corneal concentration capabilities for antifungal topical medications [14].Inherent host resistance or other immune interactions between the patient and fungus are perhaps the most important determinants of the outcome but are currently difficult to measure or assess except by subjective clinical observation [14].     

Viscoelastic materials in veterinary ophthalmology

Viscoelastic materials have applications in both human and veterinary ophthalmology and orthopedics and for humans in otorhinolaryngology, urinary incontinence, cosmetic surgery and cosmetics. In ophthalmology, viscoelasties are most commonly used in facilitating cataract and other anterior segment surgeries, but also have applications in posterior segment surgery and in the topical management of keratoconjunctivitis sicca. Viscoelastics are routinely used during anterior segment surgery in filling and maintaining the anterior chamber, repositioning the iris, and to coat and protect the corneal endothelium, and expand the capsular bag prior to intraocular lens implantation. Viscoelastics can also be essential in the management of intraoperative complications such as miosis, hemorrhage, posterior capsular tears, and vitreous presentation. The most common products available for ophthalmic use include various concentrations of sodium hyaluronate, chondroitin sulfate, and hydroxypropylmethylcellulose. The physical properties of each viscoelastic material are dependent on chain length, and intra-and interchain interactions. The rheologic properties of viscosity, pseudoplasticity, viscoelasticity, and surface tension dictate the usefulness of each material for a specific purpose.     

Nonsteroidal anti-inflammatory drugs induce hypermotilinemia and disturbance of interdigestive migrating contractions in instrumented dogs

Nonsteroidal anti-inflammatory drugs (NSAIDs) induce gastric ulcers due to inhibition of prostaglandin production. Prostaglandins have an influence on physiological gastrointestinal motility, but the relationships between NSAID-induced gastric ulcer, gastrointestinal motility and motilin are unknown. Fifteen dogs were allocated randomly to three groups in which either gelatin, meloxicam or indomethacin was administered. Fecal occult blood and gastrointestinal motility were monitored continuously for 6 days. In addition, analyses of the plasma motilin concentration, gastrointestinal endoscopy and gastric emptying, and detection of motilin cells were performed. Gastrointestinal motility was disturbed in the indomethacin group, presenting as disappearance of interdigestive migrating contractions (IMCs) 3 days before gastric ulcers were detected. Delayed gastric emptying and hypermotilinemia were observed significantly more often in the indomethacin group compared with the other groups. Motilin cell-crypt/villi ratio in the indomethacin group significantly decreased in the duodenum and jejunum, compared with the other groups. No significant changes in any tests were observed in the meloxicam group, when compared with the gelatin group. These findings suggest that the disturbance of IMCs caused by hypermotilinemia, with changes in motilin cell distribution, and delayed gastric emptying induced by indomethacin may contribute to the development of gastric ulcers.     

Pharmacodynamics and pharmacokinetics of nonsteroidal anti-inflammatory drugs in species of veterinary interest

This review summarises selected aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of nonsteroidal anti-inflammatory drugs (NSAIDs). It is not intended to be comprehensive, in that it covers neither minor species nor several important aspects of NSAID PD. The limited objective of the review is to summarise those aspects of NSAID PK and PD, which are important to an understanding of PK-PD integration and PK-PD modelling (the subject of the next review in this issue). The general features of NSAID PK are: usually good bioavailability from oral, intramuscular and subcutaneous administration routes (but with delayed absorption in horses and ruminants after oral dosing), a high degree of binding to plasma protein, low volumes of distribution, limited excretion of administered dose as parent drug in urine, marked inter-species differences in clearance and elimination half-life and ready penetration into and slow clearance from acute inflammatory exudate. The therapeutic effects of NSAIDs are exerted both locally (at peripheral inflammatory sites) and centrally. There is widespread acceptance that the principal mechanism of action (both PD and toxicodynamics) of NSAIDs at the molecular level comprises inhibition of cyclooxygenase (COX), an enzyme in the arachidonic acid cascade, which generates inflammatory mediators of the prostaglandin group. However, NSAIDs possess also many other actions at the molecular level. Two isoforms of COX have been identified. Inhibition of COX-1 is likely to account for most of the side-effects of NSAIDs (gastrointestinal irritation, renotoxicity and inhibition of blood clotting) but a minor contribution also to some of the therapeutic effects (analgesic and anti-inflammatory actions) cannot be excluded. Inhibition of COX-2 accounts for most and possibly all of the therapeutic effects of NSAIDs. Consequently, there has been an intensive search to identify and develop drugs with selectivity for inhibition of COX-2. Whole blood in vitro assays are used to investigate quantitatively the three key PD parameters (efficacy, potency and sensitivity) for NSAID inhibition of COX isoforms, providing data on COX-1:COX-2 inhibition ratios. Limited published data point to species differences in NSAID-induced COX inhibition, for both potency and potency ratios. Members of the 2-arylpropionate sub-groups of NSAIDs exist in two enantiomeric forms [R-(-) and S-(+)] and are licensed as racemic mixtures. For these drugs there are marked enantiomeric differences in PK and PD properties of individual drugs in a given species, as well as important species differences in both PK and PD properties.     

Cross-sectional imaging techniques in veterinary ophthalmology

Ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI) are useful, complementary cross-sectional imaging modalities of the eye and orbit. High-resolution US provides excellent morphological information of ocular structures but offers limited information on the periocular tissues. CT and MRI provide valuable morphologic and topographic images of both ocular and periocular structures, thereby giving a more complete picture of the pathological process. US can be performed on awake patients, whereas CT and MRI require general anesthesia. In addition, US equipment is readily available and less costly than CT or MRI units. Fine-needle aspirations and biopsies under US or CT guidance can also be performed. This article reviews the technique and normal findings of ocular and orbital structures as displayed in each of these imaging modalities. Representative clinical cases are presented to illustrate the interpretation principles as well as to provide an illustrative reference for common ocular and orbital changes.     

New drugs in veterinary dermatology.

This article discusses several different new drugs currently being used in dermatology. Most of the drugs discussed showed some promise as being a useful therapy in veterinary medicine, but a few have questionable efficacy (nonsedating antihistamines). The majority of these drugs have not had any pharmacokinetic or clinical trials conducted on them in small animals. Hopefully, in the future, more studies are funded so that we can determine the clinical therapeutical efficacy and appropriate doses for these drugs.     

Nonsteroidal anti-inflammatory agents: Species differences in pharmacodynamics

The disposition kinetics and systemic availability of nonsteroidal anti-inflammatory (NSAI) agents as well as their antipyretic and anti-nociceptive properties are reviewed in different species. The anti-inflammatory versus bradykinin, serotonin and kaolin oedema activities of aspirin (ASA), phenylbutazone (PBZ) and indomethacin (IDM) explain their large use in veterinary medicine. The low analgesic effect versus NO₃Ag arthritis, radiant heat and tail pressure of indomethacin and oxyphenbutazone contrasts with the widespread activity of phenazone. The comparative inhibitory effect of NSAI agents on the rat fundus contraction due to arachidonic acid is an indication of their relative inhibition of prostaglandin biosynthesis. Among the side-effects of NSAI agents, the long-lasting hyperactivity and hypomotility induced by a parenteral injection of phenylbutazone in the dog is of importance despite the fact that in this species, as in the horse, the average half life is only 6 h due to side-chain hydroxylation (versus 42 h in man for whom conjugation is a major pathway). Initiation of therapy with a loading dose followed by maintenance doses (each half the size of the loading dose) at constant intervals equal to the half-life of the drug has been shown to be suitable for most drugs with long half-life values. According to this a tentative harmless dosage regimen can be calculated for NSAI therapy in different species.