Ibuprofen

eye-byoo-proe′fen

Trade and Other Names: Motrin, Advil, and Nuprin

Functional Classification: Nonsteroidal anti-inflammatory drug (NSAID)

Pharmacology and Mechanism of Action

Like other NSAIDs in this class, ibuprofen produces analgesic and anti-inflammatory effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAIDs is the cyclo-oxygenase enzyme (COX). The COX enzyme exists in two isoforms: COX-1 and COX-2. COX-1 is primarily responsible for synthesis of prostaglandins important for maintaining a healthy GI tract, renal function, platelet function, and other normal functions. COX-2 is induced and responsible for synthesizing prostaglandins that are important mediators of pain, inflammation, and fever. However, it is known that there is some crossover of COX-1 and COX-2 effects in some situations and COX-2 activity is important for some biological effects. Ibuprofen is not selective for either COX-1 or COX-2. Ibuprofen is registered for human use, and experience with this drug in veterinary medicine is limited.

Pharmacokinetics have been studied in a variety of animals. In horses, the half-life is approximately 60-90 minutes. Oral absorption is high in horses (80%-90%) regardless of the dose form used, including a compounded paste. Ibuprofen was 90%-100% absorbed when administered orally to dairy goats.

Indications and Clinical Uses

Ibuprofen is not registered for any animals in veterinary medicine. There are drugs in small animals that have been safer for the GI tract and are preferred. Use of ibuprofen in dogs is discouraged because of high risk of GI ulceration. It has been used for musculoskeletal inflammation in horses and ruminants. Administration of 25 mg/kg IV to cows reduced some systemic variables in endotoxin-induced mastitis.

In horses, doses of 10-25 mg/kg have been used, but clinical trials of efficacy have not been reported.

Instructions for Use

Avoid use in dogs. Safe dosages for other species have not been established, although there has been some off-label use in ruminants and horses.

Patient Monitoring and Laboratory Tests

Monitor for signs of GI ulcers. Monitor renal function during therapy.

Formulations

Ibuprofen is available in 200-, 400-, 600-, and 800-mg tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. It has been compounded in alcohol (ethanol) and propylene glycol solutions without loss of stability. It is poorly soluble in water. It has been compounded as an oral paste for horses without compromising the oral absorption.

Small Animal Dosage

Dogs and Cats

Safe dose not established.

Large Animal Dosage

Horses

• 25 mg/kg q8h PO, up to 6 days.

Ruminants

• 14-25 mg/kg/day.

Regulatory Information

No withdrawal times are established for animals intended for food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

RCI Classification: 4

Imidocarb Hydrochloride

im-id′oh-carb hye-droe-klor′ide

Trade and Other Names: Imizol

Functional Classification: Antiprotozoal

Pharmacology and Mechanism of Action

Imidocarb is an aromatic diamidine. It inhibits nucleic acid metabolism in susceptible organisms and produces anticholinergic effects. Antimicrobial activity against protozoal organisms accounts for its clinical use.

Indications and Clinical Uses

Imidocarb has been used in animals to treat intracellular tickborne pathogens. It has been used to treat Babesia infections. In addition, it has been used to treat haemobartonellosis in cats caused by the organisms Mycoplasma haemofelis and Mycoplasma haemominutum. It also has been used to treat Cytauxzoon felis infections in cats and ehrlichial infections in dogs and cats.

Instructions for Use

Use of imidocarb has been limited in animals. Most protocols are established from small clinical trials or extrapolation from human use.

Patient Monitoring and Laboratory Tests

No specific monitoring is necessary.

Formulations

Imidocarb compounded formulations are available from some pharmacies.

Stability and Storage

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

Small Animal Dosage

Cats

• 5 mg/kg IM twice, q14d.

Dogs

• (Ehrlichia canis): 6.6 mg/kg IM, twice, q14d.

Large Animal Dosage

No large animal doses are available.

Regulatory Information

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

Imipenem + Cilastatin

ih-mih-pen′em + sye-lah-stat′in

Trade and Other Names: Primaxin

Functional Classification: Antibacterial

Pharmacology and Mechanism of Action

Imipenem + cilastatin is a beta-lactam antibiotic of the carbapenems class with a broad spectrum of activity. Action on the cell wall is similar to other beta-lactams, which is to bind penicillin-binding proteins (PBP) that weaken or interfere with cell wall formation. The carbapenems are capable of binding to a specific PBP (PBP-1) that results in more rapid lysis compared to other beta-lactams. This results in greater bactericidal activity and a longer postantibiotic effect. Carbapenems have a broad spectrum of activity and are among the most active of all antibiotics. Spectrum includes gram-negative bacilli, including Enterobacteriaceae and Pseudomonas aeruginosa. It also is active against most gram-positive bacteria, except methicillin-resistant strains of Staphylococcus and Enterococcus. Compared to imipenem, meropenem and doripenem are slightly more active. Cilastatin has no antibacterial activity, but it is a specific inhibitor of renal dipeptidase, dehydropeptidase (DHP-I). Therefore, cilastatin blocks renal tubular metabolism of imipenem and improves urinary recovery of imipenem.

Indications and Clinical Uses

Imipenem is used primarily for infections caused by bacteria resistant to other drugs. Imipenem is especially valuable for treating resistant infections caused by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. Although active against gram-positive bacteria such as staphylococci (but not methicillin-resistant strains), other less expensive drugs should be used for gram-positive infections. Meropenem and doripenem are newer drugs in the class of carbapenems and have some advantages with respect to activity and convenience of administration.

Instructions for Use

Doses and efficacy studies have not been determined in animals. Recommendations are based on extrapolation of studies performed in humans. Reserve the use of this drug for resistant, refractory infections. Observe manufacturer’s instructions carefully for proper administration. When the vial is initially reconstituted, it should not be given IV. It first must be diluted in a suitable intravenous fluid solution (at least 100 mL). For intravenous administration, add to intravenous fluids. After reconstitution in vial, 250 or 500 mg should be added to not less than 100 mL of fluids and given IV over 30-60 minutes. Intravenous fluid solutions are stable for 48 hours if refrigerated or 8 hours at room temperature. For intramuscular administration, add 2 mL lidocaine (1%). The suspension is stable for only 1 hour. In some hospitals, the intravenous solution has been diluted in fluids and administered SQ without any sign of injection-site reactions (usually 8-14 mL per injection in dogs).

Patient Monitoring and Laboratory Tests

Susceptibility testing: CLSI break points for sensitive organisms are ≤1 mcg/mL. Most veterinary pathogens have minimum inhibitory concentration (MIC) values less than 1.0 mcg/mL.

Formulations

Imipenem + cilastatin is available in 250- and 500-mg vials for injection. Intramuscular suspension is available in 500- and 750-mg vials.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. After reconstitution it is stable for 4 hours at room temperature and 24 hours refrigerated. Do not freeze intravenous fluid solutions. Slight yellow discoloration is acceptable, but discard if color turns brown.

Small Animal Dosage

Dogs and Cats

• 3-10 mg/kg q6-8h IV or IM. Generally, 5 mg/kg q6-8h IV, IM, or SQ.

Large Animal Dosage

Horses

• 10-20 mg/kg q6h by slow IV infusion.

Regulatory Information

Withdrawal times are not established for animals that produce food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

Imipramine Hydrochloride

im-ip′rah-meen hye-droe-klor′ide

Trade and Other Names: Tofranil and generic brand

Functional Classification: Behavior modification

Pharmacology and Mechanism of Action

Tricyclic antidepressant drug (TCA). Imipramine, like others in this class, is used in people to treat anxiety and depression. Action is via inhibition of uptake of serotonin and norepinephrine at presynaptic nerve terminals. Other TCA drugs used in animals include clomipramine and amitriptyline.

Indications and Clinical Uses

Like other TCAs, imipramine is used in animals to treat a variety of behavioral disorders, including obsessive-compulsive disorders, separation anxiety, and inappropriate urination. There have been fewer studies of efficacy with imipramine than with clomipramine or amitriptyline. Generally, other behavior-modifying drugs such as SSRIs (eg, fluoxetine) or other TCAs (clomipramine) are preferred by behavior experts for treating small animals.

Instructions for Use

Doses are primarily based on empiricism. There are few controlled efficacy trials available for animals to compare with other drugs in this class. There may be a 2- to 4-week delay after initiation of therapy before beneficial effects are seen.

Patient Monitoring and Laboratory Tests

Monitor heart rate and rhythm in treated animals. Like other TCAs, imipramine may decrease total T4 and free-T4 concentrations in dogs.

Formulations

Imipramine is available in 10-, 25-, and 50-mg tablets.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Although imipramine has been compounded for veterinary use, the potency and stability has not been evaluated for compounded products.

Small Animal Dosage

Dogs

• 2-4 mg/kg q12-24h PO.

Cats

• 0.5-1 mg/kg q12-24h PO.

Large Animal Dosage

No large animal doses have been reported.

Regulatory Information

Do not administer to animals intended for food.

RCI Classification: 2

Indomethacin

in-doe-meth′ah-sin

Trade and Other Names: Indocin

Functional Classification: Nonsteroidal anti-inflammatory drug (NSAID)

Pharmacology and Mechanism of Action

NSAID and analgesic. Like other NSAIDs, indomethacin produces potent analgesic and anti-inflammatory effects by inhibiting the synthesis of prostaglandins. The enzyme inhibited by NSAID is the cyclo-oxygenase enzyme (COX). The COX enzyme exists in two isoforms: COX-1 and COX-2. COX-1 is primarily responsible for synthesis of prostaglandins important for maintaining a healthy GI tract, renal function, platelet function, and other normal functions. COX-2 is induced and responsible for synthesizing prostaglandins that are important mediators of pain, inflammation, and fever. However, it is known that there is some crossover of COX-1 and COX-2 effects in some situations and COX-2 activity is important for some biological effects. Indomethacin is considered a prototype for a nonselective drug because it inhibits equally both COX-1 and COX-2. Indomethacin is registered for human use and experience with this drug in veterinary medicine is limited. Indomethacin acts to inhibit COX that synthesizes prostaglandins. Other anti-inflammatory effects may occur (such as effects on leukocytes) but have not been well characterized. It is used primarily for short-term treatment of moderate pain and inflammation.

Indications and Clinical Uses

Indomethacin, like other NSAIDs, has been used to treat pain and inflammation in people. However, indomethacin has not been used often in clinical veterinary medicine because other safer, registered drugs are available. Indomethacin is used as a prototypical nonselective COX-1 and COX-2 blocker in research. In dogs, the high risk of GI ulceration prohibits its routine use.

Instructions for Use

Use cautiously, if at all, because safe doses have not been determined for clinical use in animals.

Patient Monitoring and Laboratory Tests

Monitor for signs of GI toxicity (hemorrhage, ulcers, and perforation).

Formulations

Indomethacin is available in 25- and 50-mg capsules and 5-mg/mL oral suspension.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Indomethacin is practically insoluble in water but is soluble in ethanol. It decomposes in alkaline conditions and is maximally stable at pH 3.75.

Small Animal Dosage

Dogs and Cats

Safe dose has not been established.

Large Animal Dosage

No large animal doses have been reported.

Regulatory Information

Withdrawal times are not established for animals that produce food. For extralabel use withdrawal interval estimates, contact FARAD at 1-888-USFARAD (1-888-873-2723).

RCI Classification: 4

Insulin

in′syoo-lin

Trade and Other Names: ProZinc, Lente insulin, Ultralente insulin, Regular insulin, Glargine insulin, NPH insulin, Caninsulin, Protamine zinc insulin (PZI), Humulin (human insulin; discontinued), Vetsulin is porcine insulin zinc suspension (veterinary), and PZI Vet (veterinary protamine zinc insulin)

Functional Classification: Hormone

Pharmacology and Mechanism of Action

Insulin has multiple effects associated with utilization of glucose. Dog insulin is identical to pork insulin, and cat insulin is similar to beef insulin with only one amino acid difference. Most beef–pork insulin combinations for humans have been discontinued and are not usually available for veterinary use. Human-recombinant insulins can be used in dogs and cats with the same effects as natural insulin. Insulin is available in several preparations:

1 Regular insulin: Short acting. Peak is 1-5 hours and duration is 4-10 hours.

2 Neutral Protamine Hagedorn (isophane, also called NPH, and Humulin or Novolin): A human-recombinant insulin of crystalline suspension with protamine zinc that is intermediate acting. Peak is 2-10 hours in dogs and 2-8 hours in cats with a duration of action of 4-24 hours in dogs and 4-12 hours in cats (but usually 2-3 hours in cats).

3 Lente insulin. Peak is 2-10 hours in dogs and 2-8 hours in cats with a duration of action of 4-24 hours in dogs and 4-12 hours in cats. Addition of protamine or zinc to insulin will produce a crystallized insulin in suspension that has a longer absorption rate than dissolved insulin. The lente forms of insulin control their duration by the size of the crystal. For example, semilente is practically amorphous, whereas ultralente has large crystals, and lente is a combination of ultralente and semilente.

4 Ultralente insulin: Peak is 4-16 hours in dogs and 2-14 hours in cats and has a duration of 8-28 hours in dogs and 12-24 hours in cats. It is poorly absorbed in cats and usually not recommended.

5 Vetsulin: Also known as Caninsulin. Vetsulin is a U-40 porcine insulin, identical to canine insulin in amino acid content, and is a lente insulin of aqueous zinc suspension of crystaline and noncrystalline insulins. It produces a shorter peak of activity (4 hours) and duration than PZI insulin. This product has been temporarily suspended by some sources.

6 Protamine-zinc insulin (PZI): Developed from recombinant human insulin and long acting. Veterinary form is called ProZinc in a 40 unit/mL form for cats. The forms used in animals are identical to the forms marketed for people. Peak is 4-14 hours in dogs and 5-7 hours in cats, with a duration of 6-28 hours in dogs and cats. PZI insulin of animal origin (90% bovine and 10% porcine) has been unavailable.

7 Glargine insulin: A human insulin analogue made from recombinant technology. It has a slow onset of 4-18 hours and a duration of 24 hours or greater. This analogue is produced by the substitution of glycine for asparagine and addition of two arginine molecules. These changes shift the isoelectric point toward neutral, which reduces solubility at the pH of SQ tissue and causes it to be released slowly from the injection site, without a peak. It produces consistent concentrations without large fluctuation in peak and trough. It has four amino acid differences from feline insulin. The glucose-lowering properties are shorter in cats than in people, with a peak at 16 hours and duration of 24 hours. However, it produces greater glycemic control in cats than other insulins. Remission rates are highest with glargine insulin in cats. Despite the long-lasting effect, optimum control is achieved with twice-daily dosing in cats with Glargine insulin.

8 Insulin detemir (Levemir): Long-acting insulin. Insulin detemir has a 14 carbon fatty acid chain, which decreases absorption, and is highly bound to albumin. Duration is 6-24 hours in people, with peak at 6-8 hours, but has not been established for animals.

9 Insulin glulisine (Apidra), insulin lispro (Humalog), and insulin aspart (NovoLog): Rapidly acting insulins used in people. They are used for their rapid onset and short duration of action. In people, they are typically used with a meal and combined with a longer-acting form. These rapid-acting insulin analogues have not been evaluated for animals.

Indications and Clinical Uses

Insulin, in the various forms, is used to treat diabetes mellitus in dogs and cats. It is used to replace insulin that is deficient. In some cats (approximately 50%) some oral hypoglycemic drugs have been used to reduce use of insulin. However, diabetic dogs are more insulin dependent. Regular insulin is short acting and more useful for emergencies such as diabetic ketoacidosis or acute nonketotic syndromes.

Intermediate or long-acting insulin preparations are used for maintenance and are available in a variety of forms (see previous). Most of the animal sources of insulin (beef and pork) have been discontinued and human recombinant insulin formulations have been substituted without differences in efficacy. In cats, glargine insulin has shown better efficacy than other forms and has been associated with a better remission rate. In addition to diabetes mellitus, insulin is occasionally used to treat severe cases of hyperkalemia.

Instructions for Use

Dietary management is essential for optimal glucose control. Feed cats a high-protein, low-carbohydrate diet. Feed dogs a high-fiber, low-fat diet.Doses should be carefully adjusted in each patient depending on response.

For cats with ketoacidosis, alternative dosing regimen has used 0.2 units/kg IM initially, then 0.1 units/kg IM every hour until the glucose level is less than 300, then 0.25-0.4 units/kg q6h SQ. With most forms of insulin (including protamine zinc insulin and Glargine insulin) in cats, twice-daily dosing usually is required. However, consider once-daily dosing in cats if blood glucose nadir develops 10 hours or longer after administration. Pet owners are instructed to use appropriate syringe types for administration (e.g., U-40 vs. U-100). Many cats, if properly managed, may go into remission and not require lifelong insulin treatment.

Patient Monitoring and Laboratory Tests

Monitor blood glucose, glycosylated hemoglobin, and/or fructosamine concentrations. When treating diabetes, it is desirable to maintain glucose concentrations between 100 and 300 mg/dL, with the nadir (lowest point) being 80-150 mg/dL. Serum fructosamine concentrations also can be monitored with the following guidance: ≤450 µmol/L good control; 450-500 µmol/L moderate control; >500 µmol/L poor control.

Formulations

Insulin is usually available in 100 units/mL injection (U-100), with some products available in smaller concentration of 40 units/mL (U-40, e.g., ProZinc or Vetsulin). Protamine zinc beef–pork (PZI VET) insulin also may be available as 40 units/mL injection (U-40). Some previously available insulin products have been discontinued, such as Iletin II Pork Insulin (Regular and NPH formulations), Humulin U Ultralente, and Humulin L Lente (Humulin U and Humulin L).

Stability and Storage

Proper storage is critical for proper action of insulin: Keep refrigerated. Warm gently and roll vial prior to injection to ensure proper mixing of vial contents. Do not freeze vials of insulin. Do not allow vials of insulin exposure to heat. Do not mix types of insulin in the same vial or syringe. Veterinarians should not use formulations of insulin that are compounded in unreliable conditions. Dilution of insulin should only be done by a pharmacist because specific diluents must be used.

Small Animal Dosage

Regulatory Information

No regulatory information is available for animals intended for food. Because of low risk of residues, no withdrawal times are suggested.

Interferon

in-ter-feer′on

Trade and Other Names: Virbagen omega

Functional Classification: Immunostimulant

Pharmacology and Mechanism of Action

Recombinant omega interferon contained in Virbagen omega is produced by silkworms previously inoculated with interferon-recombinant baculovirus. It allows the production of pure interferon. Omega interferon of feline origin, produced by genetic engineering, is a Type 1 interferon closely related to alpha interferon. The exact mechanism of action of interferon omega is not understood, but it may enhance nonspecific defenses in dogs and cats. Interferon does not act directly and specifically on the pathogenic virus but exerts its effect by inhibition of the internal synthesis mechanisms of the infected cells. After injection it has a half-life of 1.4 hours in dogs and 1.7 hours in cats. It is bound to receptors in cells infected by virus.

There are multiple interferons available for human use (e.g., treatment of AIDS-related diseases and cancer-associated diseases). These interferons may be alpha-2a, alpha 2b, n-1, and n-3. These types of interferons are not interchangeable.

Indications and Clinical Uses

Interferon is used to stimulate the immune system in patients. It has been used to stimulate immune cells in dogs with parvovirus and in cats with feline retrovirus (feline leukemia virus [FeLV] and feline immunodeficiency virus [FIV]). It has not been effective for FIP in cats. Human interferon alpha, orally, has improved clinical signs in cats with FIV.

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Tags: Saunders Handbook of Veterinary Drugs Small and Large Animal

Jul 18, 2016 | Posted by admin in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off

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