Edetate Calcium Disodium

ed′eh-tate kal′see-um dye-soe-dee-um

Trade and Other Names: Calcium disodium versenate and calcium disodium ethylenediaminetetra-acetate (EDTA)

Pharmacology and Mechanism of Action

Chelating agent. Readily chelates with lead, zinc, cadmium, copper, iron, and manganese.

Indications and Clinical Uses

Edetate calcium disodium is indicated for treatment of acute and chronic lead poisoning. It is sometimes used in combination with dimercaprol.

Precautionary Information

Adverse Reactions and Side Effects

No adverse effects reported in animals. In people, allergic reactions (release of histamine) have occured after intravenous administration.

Contraindications and Precautions

Do not use edetate disodium to substitute for edetate calcium disodium because it will chelate calcium in the patient.

Drug Interactions

No specific drug interactions are reported. However, it has the potential to chelate other drugs if mixed together.

Instructions for Use

Edetate calcium disodium may be used with dimercaprol. It is equally effective when administered IV or IM, but intramuscular injection may be painful. Ensure adequate urine flow before the first dose is administered.

Patient Monitoring and Laboratory Tests

Monitor lead concentrations to assess treatment.

Formulations

Edetate calcium disodium is available in a 20-mg/mL injection.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated.

Small Animal Dosage

• 25 mg/kg q6h for 2-5 days SQ, IM, or IV.

Large Animal Dosage

• 25 mg/kg q6h for 2-5 days SQ, IM, or IV.

Regulatory Information

Withdrawal time: 2 days for meat; 2 days for milk (extralabel).

Edrophonium Chloride

ed-roe-foe′nee-um klor′ide

Trade and Other Names: Tensilon and generic brands

Functional Classification: Antimyasthenic, anticholinesterase

Pharmacology and Mechanism of Action

Cholinesterase inhibitor. Edrophonium causes cholinergic effects by inhibiting metabolism of acetylcholine. Its effects do not last long and is used for short-term use only.

Indications and Clinical Uses

Because edrophonium is short acting, it ordinarily is only used for diagnostic purposes (e.g., myasthenia gravis). It also has been used to reverse neuromuscular blockade of nondepolarizing agents (pancuronium).

Precautionary Information

Adverse Reactions and Side Effects

Edrophonium is short acting and side effects are minimal. Overdose in nonmyasthenia animals may cause salivation, retching, vomiting, and diarrhea. If this is observed, administer atropine at 0.02-0.04 mg/kg. Excessive muscarinic/cholinergic effects may occur with high doses; these may also be counteracted with atropine.

Contraindications and Precautions

Edrophonium will potentiate effects of other cholinergic drugs. Cats are especially sensitive to edrophonium (see dose differences in Small Animal Dosage section).

Drug Interactions

Use cautiously with other cholinergic drugs.

Instructions for Use

Edrophonium is used only for determination of diagnosis of myasthenia gravis. An alternative drug for this purpose is neostigmine methylsulfate (Prostigmin) at 40 mcg/kg IM or 20 mcg/kg IV.

Patient Monitoring and Laboratory Tests

No specific monitoring is necessary.

Formulations

Edrophonium is available in a 10-mg/mL injection.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated.

Small Animal Dosage

Dogs

• 0.11-0.22 mg/kg IV (maximum dose is 5 mg per dog).

Cats

• 0.25-0.5 mg/cat IV.

Large Animal Dose

No large animal doses have been reported.

Regulatory Information

No regulatory information is available. Because of a short half-life, no risk of residue is anticipated in food animals.

RCI Classification: 3

Enalapril Maleate

eh-nal′ah-prill mal′ee-ate

Trade and Other Names: Enacard (veterinary preparation) and Vasotec (human preparation)

Functional Classification: Vasodilator, angiotensin-converting enzyme (ACE) inhibitor

Pharmacology and Mechanism of Action

ACE inhibitor. Like other ACE inhibitors, it inhibits conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor and will also stimulate sympathetic stimulation, renal hypertension, and synthesis of aldosterone. The ability of aldosterone to cause sodium and water retention contributes to congestion.

Enalapril, like other ACE inhibitors, will cause vasodilation and decrease aldosterone-induced congestion, but ACE inhibitors also contribute to vasodilation by increasing concentrations of some vasodilating kinins and prostaglandins.

Indications and Clinical Uses

Enalapril, like other ACE inhibitors, is used to treat hypertension and CHF. Efficacy for CHF is good and can be used with other drugs such as pimobendan, furosemide, digoxin, and spironolactone. It is primarily used in dogs. In addition to its use for treatment of congestive heart failure, enalapril has been used to delay onset of CHF in dogs with mitral regurgitation. The benefit of enalapril and other ACE inhibitors for occult heart disease is controversial; some studies have shown a benefit and others have not. Enalapril has been used in some cats in heart failure or with systemic hypertension. Unfortunately, approximately 50% of cats with hypertension do not respond to enalapril, and ACE inhibitors are not considered a primary treatment for hypertension in cats.

ACE inhibitors also have been shown to be beneficial in the management of certain types of kidney disorders (nephropathy) and for renal hypertension. Renal benefits result from limiting systemic and glomerular capillary hypertension, the antiproteinuric effect to decrease in urine protein-to-creatinine ratio, and retarding the development of glomerular sclerosis and tubulointerstitial lesions. ACE inhibitors have decreased proteinurina in patients, but long-term benefits on survival have not been established. The benefits of ACE inhibitor treatment in cats with chronic renal disease are somewhat modest and have little effect on survival time or long-term prognosis.

Large animal uses have not been established, but in horses the metabolite enalaprilat at 0.5 mg/kg IV completely inhibited ACE activity but did not change blood pressure or other hemodynamic variables in response to exercise.

Precautionary Information

Adverse Reactions and Side Effects

Enalapril may cause azotemia in some patients; carefully monitor patients receiving high doses of diuretics.

Contraindications and Precautions

Discontinue ACE inhibitors in pregnant animals; they cross the placenta and have caused fetal malformations and death of the fetus.

Drug Interactions

Use cautiously with other hypotensive drugs and diuretics. Nonsteroidal anti-inflammatory drugs (NSAIDs) may decrease vasodilating effects.

Instructions for Use

Doses are based on clinical trials conducted in dogs. For dogs, start with once-daily administration and increase to q12h if needed. Other drugs used for treatment of heart failure may be used concurrently.

Patient Monitoring and Laboratory Tests

Monitor patients carefully to avoid hypotension. With all ACE inhibitors, monitor electrolytes and renal function 3-7 days after initiating therapy and periodically thereafter.

Formulations

Enalapril is available as Vasotec (human preparation) in 2.5-, 5-, 10-, and 20-mg tablets and as Enacard (veterinary preparation) in 1-, 2.5-, 5-, 10-, and 20-mg tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Enalapril, compounded in a variety of oral suspensions and flavorings, was stable for 60 days. Above pH of 5, degradation occurs more quickly.

Large Animal Dosage

• There are no clinical studies available to establish doses for horses.

Regulatory Information

No regulatory information is available. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

RCI Classification: 3

Enflurane

en-floor′ane

Trade and Other Names: Ethrane

Functional Classification: Inhalant anesthetic

Pharmacology and Mechanism of Action

Inhalant anesthetic. Like other inhalant anesthetics, the mechanism of action is uncertain. Enflurane produces a generalized, reversible, depression of the CNS. The inhalant anesthetics vary in their solubility in blood, their potency, and the rate of induction and recovery. Those with low blood/gas partition coefficients are associated with the most rapid rates of induction and recovery. Enflurane has a vapor pressure of 175 mm Hg (at 20°C), a blood/gas partition coefficient of 1.8, and a fat/blood coefficient of 36.

Indications and Clinical Uses

Enflurane, like other inhalant anesthetics, is used for general anesthesia in animals. It has a minimum alveolar concentration (MAC) value of 2.37%, 2.06%, and 2.12% in cats, dogs, and horses, respectively.

Precautionary Information

Adverse Reactions and Side Effects

Like other inhalant anesthetics, enflurane produces vasodilation and increased blood flow to cerebral blood vessels. This may increase intracranial pressure. Like other inhalant anesthetics, it produces a dose-dependent myocardial depression with accompanying decrease in cardiac output. It also depresses respiratory rate and alveolar ventilation. Like other inhalant anesthetics it increases the risk of ventricular arrhythmias, especially in response to catecholamines.

Contraindications and Precautions

No specific contraindications are reported for animals.

Drug Interactions

Other sedatives and anesthetics (e.g., opiates, benzodiazepines, phenothiazines, alpha-2 agonists) will lower the requirement for inhalent gas anesthesia.

Instructions for Use

Titrate dose for each individual with anesthetic monitoring.

Patient Monitoring and Laboratory Tests

Monitor anesthesia parameters. During anesthesia, monitor heart rate and rhythm and respiratory rate.

Formulations

Enflurane is available as a solution for inhalation.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature.

Small Animal Dosage

• Induction: 2%-3% Maintenance: 1.5%-3%

Large Animal Dosage

• MAC value: 1.66%.

Regulatory Information

No withdrawal times are established for food animals. Clearance is rapid and short withdrawal times are suggested. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

Enilconazole

en-il-kah′nah-zole

Trade and Other Names: Imaverol and ClinaFarm-EC

Functional Classification: Antifungal

Pharmacology and Mechanism of Action

Azole antifungal agent for topical use only. Like other azoles, enilconazole inhibits membrane synthesis (ergosterol) in fungus and weakens the cell wall. It is highly active against dermatophytes.

Indications and Clinical Uses

Enilconazole is used only topically. It is used as a topical agent to apply on the skin for treatment of dermatophytes; as a spray, it is used to treat the environment. It may be applied to animal bedding, stalls, and cages. In addition to dermatologic use, enilconazole has been instilled into the nasal sinus of dogs for treatment of nasal aspergillosis.

Precautionary Information

Adverse Reactions and Side Effects

Adverse effects have not been reported. However, it is reported that if used on cats, they should be prevented from licking fur after application until the drug has dried.

Contraindications and Precautions

No specific contraindications are reported.

Drug Interactions

No specific interactions are reported. However, like other azoles, systemic treatment may result in cytochrome P450 enzyme inhibition.

Instructions for Use

It is used only topically. Imaverol is available only in Canada as 10% emulsion. In the US, Clinafarm EC is available for use in poultry units as 13.8% solution. Dilute solution to at least 50 : 1 and apply topically every 3-4 days for 2-3 weeks. Enilconazole also has been instilled as 1 : 1 dilution into nasal sinus for nasal aspergillosis. Enilconazole also has been used—in a diluted form—as a spray to kill fungi on bedding, equine tack, and cages.

Patient Monitoring and Laboratory Tests

No specific monitoring is necessary.

Formulations Available

Enilconazole is available as 10% or 13.8% emulsion.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Stability of compounded formulations has not been evaluated. When the emulsion is mixed, it should be used immediately and not stored.

Small Animal Dosage

• Nasal aspergillosis: 10 mg/kg q12h instilled into nasal sinus for 14 days (10% solution diluted 50/50 with water).

• Dermatophytes: dilute 10% solution to 0.2% and wash lesion with solution four times at 3 to 4-day intervals. Solution may be sponged directly on animal. Allow solution to air dry.

Regulatory Information

No regulatory information is available. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

Enoxaparin sodium

en-oks′ah-pare-in

Trade and Other Names: Lovenox and low-molecular-weight heparin (LMWH)

Functional Classification: Anticoagulant

Pharmacology and Mechanism of Action

Low-molecular-weight heparin (LMWH), also known as fragmented heparin. LMWH is characterized by a molecular weight composed of approximately 5000, compared to conventional heparin (unfractionated) with a molecular weight of approximately 15,000. Subsequently, the absorption, clearance, and activity of LMWH differ from unfractionated heparin (UFH). LMWHs produce their effect by binding to antithrombin (AT) and increasing antithrombin III–mediated inhibition of synthesis and activity of coagulation factor Xa. However, LMWH, unlike conventional heparin, produces less inhibition of thrombin (factor IIa). LMWH’s activity is described by the Anti-factor Xa/Anti-factor IIa ratio. Enoxaparin has a ratio of 3.8 : 1 (conventional unfractionated heparin ratio is 1 : 1). In people, LMWHs have several advantages compared to UFH and include greater anti-Xa/IIa activity, more complete and predictable absorption from injection, longer duration, less frequent administration, reduced risk of bleeding, and a more predictable anticoagulant response. However, in dogs and cats, the half-life of LMWH is much shorter than in humans, reducing some of this advantage. In dogs the half-life of enoxaparin is approximately 5 hours; in cats it is estimated to be 1.9 hours, which requires much more frequent administration in either species to maintain anti-Xa activity compared to humans. LMWHs used in veterinary medicine include tinzaparin (Innohep), enoxaparin (Lovenox), and dalteparin (Fragmin).

Indications and Clinical Uses

Enoxaparin, like other LMWHs, is used to treat hypercoagulability disorders and prevent coagulation disorders such as thromboembolism, venous thrombosis, disseminated intravascular coagulopathy (DIC), and pulmonary thromboembolism. Clinical indications are derived from uses of conventional heparin or extrapolated from human medicine. There have been few clinical studies to examine efficacy of LMWH in animals. Previously published doses extrapolated from humans have been shown not to produce adequate and consistent anti-Xa activity in dogs and cats, and the doses listed in this entry are needed for therapy.

Precautionary Information

Adverse Reactions and Side Effects

Although better tolerated than regular heparin, bleeding is a risk. However, LMWHs produce less bleeding problems than administration of conventional heparin. LMWHs are associated with a lower incidence of heparin-induced thrombocytopenia in people, but heparin-induced thrombocytopenia from any form of heparin has not been a clinical problem in animals. If excessive anticoagulation and bleeding occur as a result of an overdose, protamine sulfate should be administered to reverse heparin therapy. Protamine dose is 1.0 mg protamine for every 1.0 mg enoxaparin administered by slow IV infusion. Protamine complexes with heparin to form a stable, inactive compound.

Contraindications and Precautions

Do not administer IM to prevent hematoma; administer SQ only. LMWH is excreted by renal clearance in animals; therefore, if renal disease is present, the elimination will be prolonged. Rebound hypercoagulability may occur after discontinuation of heparin treatment; therefore, it may be advised to taper the dose slowly when discontinuing treatment.

Drug Interactions

Do not mix with other injectable drugs. Use cautiously in animals that are already receiving other drugs that can interfere with coagulation, such as aspirin and warfarin. Although a specific interaction has not been identified, use cautiously in animals that may be receiving certain chondroprotective compounds such as glycosaminoglycans for treatment of arthritis. Some antibiotics, such as cephalosporins, may inhibit coagulation.

Instructions for Use

Dosing recommendations extrapolated from human medicine are not appropriate for animals. Animal owners should be warned that LMWHs are expensive compared to conventional heparin. When dosing, do not interchange doses on a unit-for-unit basis with heparin or other low-molecular-weight heparins because they differ in manufacturing process, molecular weight distribution, anti-Xa and anti-IIa activities, units, and dosage.

Patient Monitoring and Laboratory Tests

Monitor patients for clinical signs of bleeding problems. When administering LMWH, aPTT and PT clotting times are not reliable indicators of therapy, although prolonged aPTT is a sign of overdosing. Anti-Xa activity is considered the preferred laboratory measure of LMWH activity in people, but the use of this parameter is controversial in animals. Peak anti-Xa activity occurs 3-4 hours after dosing and the target range for anti-Xa activity should be 0.5-1.0 U/mL for cats and 0.5-2.0 U/mL for dogs.

Formulations

Enoxaparin is available in 30 mg in 0.3 mL, 40 mg in 0.4 mL, 60 mg in 0.6 mL, 80 mg in 0.8 mL, 100 mg in 1 mL injection, 100 mg/mL injection, 120 mg per 0.8 mL, 150-mg/mL injection, and 300 mg per 3 mL

Stability and Storage

Store in a tightly sealed container protected from light. The pH of the injection is 5.5 to 7.5.

Small Animal Dosage

Dogs

• 0.8 mg/kg SQ, q6h (see monitoring section for dose adjustment).

Cats

• 1 mg/kg SQ, q12h, up to 1.25 mg/kg SQ, q6h (see monitoring section for dose adjustment).

Large Animal Dosage

Horses

• Prophylaxis: 0.5 mg/kg q24h SQ and 1 mg/kg q24h SQ for high-risk patients.

Regulatory Information

Extralabel withdrawal times are not established. However, 24-hour withdrawal times are suggested because this drug has little risk from residues.

Enrofloxacin

en-roe-floks′ah-sin

Trade and Other Names: Baytril

Functional Classification: Antibacterial

Pharmacology and Mechanism of Action

Fluoroquinolone antibacterial drug. Enrofloxacin acts via inhibition of DNA gyrase in bacteria to inhibit DNA and RNA synthesis. Enrofloxacin is a bactericidal with a broad spectrum of activity. In most animal species, enrofloxacin is metabolized to ciprofloxacin. Ciprofloxacin is an active desmethyl metabolite of enrofloxacin and may contribute in an additive fashion to the antibacterial effects. At the peak concentration, ciprofloxacin may account for approximately 10% and 20% of the total concentration in cats and dogs, respectively. Susceptible bacteria include Staphylococcus, Escherichia coli, Proteus, Klebsiella, and Pasteurella. Pseudomonas aeruginosa is moderately sensitive but requires higher concentrations. Enrofloxacin has poor activity against Streptococcus and anaerobic bacteria.

Indications and Clinical Uses

Enrofloxacin, like other fluoroquinolones, is used to treat susceptible bacteria in a variety of species. Treatment has included infections of skin and soft tissue, UTIs in dogs and cats, Chlamydophila felis infections in cats, and and ulcerrative colitis caused by Escherichia coli in dogs. In horses it has been used for a variety of soft tissue infections and respiratory infections, although this use is based primarily on anecdotal experience. Enrofloxacin is approved for the treatment and control of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis. It is also approved for treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, P. multocida, and Haemophilus somni (previously Haemophilus somnus). Enrofloxacin has been shown effective for treating Rickettsia infections in dogs. However, it is not effective for treating Ehrlichia (see Doxycycline). Enrofloxacin is also used in most exotic animal species because of its safety and activity against a wide variety of pathogens.

Precautionary Information

Adverse Reactions and Side Effects

High concentrations may cause CNS toxicity, especially in animals with renal failure. It may cause occasional vomiting and, at high doses, may cause some nausea and diarrhea. All of the fluoroquinolones may cause arthropathy in young animals. Dogs are most sensitive at 4 weeks to 28 weeks of age. Large, rapidly growing dogs are the most susceptible. Cats are relatively resistant to cartilage injury, but foals are susceptible. Blindness in cats that is caused by retinal degeneration has been reported. Affected cats have had permanent blindness. This may be a dose-related effect. Cats administered doses of 20 mg/kg developed retinal degeneration but did not at 5 mg/kg. Therefore, dose restrictions in cats have been used. Administration of concentrated solution (100 mg/mL) given orally to horses has caused oral mucosal lesions. When injected, this solution (pH 10.5) may be irritating to some tissues.

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