Gabapentin

gab′ah-pen-tin

Trade and other names: Gabapetin, Neurontin, and generic brands

Functional classification: Anticonvulsant, analgesic

Pharmacology and Mechanism of Action

Anticonvulsant and analgesic. Gabapentin is an analogue of the inhibitory neurotransmitter GABA; however, it is not an agonist or antagonist for the GABA receptor. The mechanism of anticonvulsant action and analgesic effects is not clear, but there is evidence that the mechanism of action appears to be via blocking calcium-dependent channels. Gabapentin inhibits the alpha-2-delta (α₂ δ) subunit of the N-type voltage-dependent calcium channel on neurons. Via inhibition, it reduces calcium influx that is needed for release of neurotransmitters—specifically, excitatory amino acids—from presynaptic neurons. Blocking the channels has little effect on normal neurons, but it may suppress simulated neurons involved in seizure activity and pain. Half-life in dogs and cats is only 3-4 hours, which may necessitate frequent administration. In horses the half-life is 8 hours (range 6.7-12 hrs), but the oral absorption is only 16%. Another related drug is pregabalin (Lyrica), which is used in people for neuropathic pain and has also been used in dogs. Gabapentin is eliminated for neuropathic pain and has also been used in dogs. Gabapentin is eliminated entirely by renal clearance in people, but there is 30-40% hepatic metabolism in dogs. Therefore, some interactions are possible with drugs that affect hepatic clearance, or with hepatic disease may compromise hepatic function.

Indications and Clinical Uses

Gabapentin is used as an anticonvulsant and to treat chronic pain syndromes, including neuropathic pain. It is used to treat neuropathic pain that does not respond to nonsteroidal anti-inflammatory drugs (NSAIDs) or opiates. However, studies demonstrating efficacy for pain treatment in dogs and cats are currently lacking. When used to treat epilepsy, it (or pregabalin) is usually considered when the seizures have become refractory to other drugs. Clinical efficacy studies in veterinary medicine are lacking for either use, and treatment regimens have been mostly derived from anecdotal evidence or extrapolation from human medicine.

Instructions for Use

Gabapentin has been used in some animals as an anticonvulsant when they are refractory to other drugs. It can be used with other drugs such as phenobarbital and bromide. It also has been used to treat neuropathic pain syndromes and can be used with NSAIDs and opioids. Efficacy for each of these indications is anecdotal; there are no controlled studies published.

Patient Monitoring and Laboratory Tests

No specific monitoring is necessary.

Formulations

Gabapentin is available in 100-, 300-, and 400-mg capsules; 100-, 300-, 400-, 600-, and 800-mg scored tablets; and 50-mg/mL oral solution.

Stability and Storage

If stored at high temperatures and high humidity, there may be degradation within 9 weeks. Split tablets and intact tablets are stable after storage at room temperature for 9 weeks. Stability of compounded formulations has not been evaluated.

Large Animal Dosage

Horses

• Neuropathic pain: 2.5 mg/kg, q12h, PO.

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: 4

Gemfibrozil

jem-fih′broe-zil

Trade and other names: Lopid

Functional classification: Antihyperlipidemic agent

Pharmacology and Mechanism of Action

Gemfibrozil is an agent that lowers cholesterol, reduces plasma triglyceride and very-low-density-lipoprotein (VLDL), and increases high-density lipoproteins (HDL). Mechanism results from inhibition of peripheral lipolysis and reduced hepatic extraction of free fatty acids.

Indications and Clinical Uses

It is used for treatment of hyperlipidemia. It has been used in dogs for treatment of some hyperlipidemia syndromes, but the efficacy has not been reported.

Instructions for Use

Used primarily in people to treat hyperlipidemia, but it is used occasionally in dogs. Clinical studies have not been performed in animals.

Patient Monitoring and Laboratory Tests

Monitor cholesterol concentrations.

Formulations

Gemfibrozil is available in 600-mg tablets and 300-mg capsules (Canada only).

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 and Cats

• 7.5 mg/kg q12h PO.

Large Animal Dosage

No large animal doses have been reported.

Regulatory Information

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

Gentamicin Sulfate

jen-tah-mye′sin sul′fate

Trade and other names: Gentocin, Garasol, Garacin, and generic

Functional classification: Antibacterial

Pharmacology and Mechanism of Action

Aminoglycoside antibiotic. Action is to inhibit bacteria protein synthesis via binding to 30S ribosome. Bactericidal. Gentamicin has a broad spectrum of activity that includes most bacterial isolates in animals, including staphylococci and gram-negative bacilli of the Enterobacteriaceae. It is not very active against streptococci and anaerobic bacteria. The pharmacokinetics have been studied in many domestic and exotic animal species. The half-life is typically 1-2 hours in mammals, and the volume of distribution is approximately 0.2-0.3 L/kg. Clearance is via glomerular filtration.

Indications and Clinical Uses

Gentamicin has a rapid, bactericidal action and is indicated for acute serious infections, such as those caused by gram-negative bacilli. Gentamicin has been administered IM, SQ, and IV. It is not absorbed after oral administration, and this use is restricted to labeled use in pigs. Gentamicin, like other aminoglycosides, can be used with beta-lactam antibiotics because it broadens the spectrum when used with drugs such as penicillins, ampicillin, or cephalosporins. Although gentamicin is generally active against most gram-negative bacilli, amikacin is more consistently active against resistant strains. The only approved use in food animals is oral treatment in pigs for swine dysentery.

Precautionary Information

Instructions for Use

Dosing regimens are based on sensitivity of organisms. Some studies have suggested that once-daily therapy (combining multiple doses into a single daily dose) is as efficacious as multiple treatments. Activity against some bacteria (e.g., Pseudomonas aeruginosa) is enhanced when combined with a beta-lactam antibiotic, such as ceftazidime. Nephrotoxicity is increased with persistently high trough concentrations.

Patient Monitoring and Laboratory Tests

Susceptibility testing: The CLSI minimum inhibitory concentration (MIC) break point for susceptibility is ≤2 mcg/mL. Monitor BUN, creatinine, and urine for evidence of renal toxicity. Blood levels can be monitored to measure for problems with systemic clearance. When monitoring trough levels in patient doses once daily, the trough levels should be below the limit of detection. Alternatively, measure half-life from samples taken at 1 hour and 2 to 4 hours postdosing. Clearance should be approximately equal to the glomerular filtration rate (GFR) (>1.0 mL/kg/min), and half-life should be less than 2 hours.

Formulations

Gentamicin is available in a 50- and 100-mg/mL solution for injection and a 50-mg/mL oral solution for pigs.

Stability and Storage

Store in a tightly sealed container, protected from light, and at room temperature. Gentamicin is soluble in water. Do not mix with other drugs, especially in a vial, syringe, or fluid administration set. Inactivation may occur. Avoid long-term storage in plastic containers.

Regulatory Information

With the exception of licensed products for pigs, aminoglycosides should not be administered to food animals because of residue concerns.

Withdrawal time for pigs: 3 days meat at 1.1 mg/kg PO and 40 days meat at 5 mg/kg IM; 14 days meat at 5 mg/kg PO.

If gentamicin is administered systemically to cattle, an extended withdrawal time is necessary because of persistence of residues in kidney. FARAD recommends 18 months. After systemic administration of 5 mg/kg, milk withdrawal time should be 5 days. If gentamicin is administered intramammary (500 mg per quarter), a milk withdrawal time of at least 10 days and a meat withdrawal time of 180 days should be used.

Contact FARAD for additional information at 1-888-USFARAD (1-888-873-2723).

Glipizide

glip-ih′zide

Trade and other names: Glucotrol

Functional classification: Antidiabetic agent, hypoglycemic agent

Pharmacology and Mechanism of Action

Sulfonylurea oral hypoglycemic agent. This drug acts to increase secretion of insulin from beta cells of the pancreas, probably by interacting with sulfonylurea receptors on beta cells or by inhibiting adenosine triphosphate (ATP)–sensitive potassium channels on the pancreatic beta cells, which increases insulin secretion. These drugs also may increase sensitivity of existing insulin receptors. Studies in cats showed that glipizide had a half-life of 17 hours and effective plasma concentration for 50% efficacy (EC₅₀) of 70 mcg/mL.

Indications and Clinical Uses

Glipizide is used as oral treatment in the management of diabetes mellitus, particularly in cats. Response rate in cats is approximately 44%-65% (some reports are 30% or lower). The response rate in dogs is poor. It has been more common to administer the sulfonylurea class of drugs in animals than other oral hypoglycemic drugs because they have had better efficacy. Glipizide is the most common of this class. Other oral hypoglycemic drugs include acetohexamide, chlorpropamide, glyburide (DiaBeta, Micronase), gliclazide, and tolazamide. Metformin is of the biguanide class of oral drugs for diabetes and has not had efficacy as high as glipizide in cats.

Glipizide transdermal absorption from a pluronic transdermal gel (pluronic organogel [PLO]) vehicle is poor in cats (<20%) and inconsistent. This route is not recommended.

Precautionary Information

Adverse Reactions and Side Effects

It may cause dose-related vomiting, anorexia, increased bilirubin, and elevated liver enzymes in some cats (15%). It may exacerbate deposits of amyloid in feline pancrease and increase the loss of pancreatic beta cells. Glipizide may cause hypoglycemia, but less so than insulin. In people, increased cardiac mortality is possible, but this has not been reported in cats.

Contraindications and Precautions

Many cats do not respond and will require insulin therapy. Do not rely on glipizide in cats that are not stable or if they are dehydrated or debilitated.

Drug Interactions

Many drug interactions have been reported in people. It is not known if these occur in animals. Use cautiously with beta blockers, antifungal drugs, anticoagulants, fluoroquinolones, sulfonamides, and others.

Instructions for Use

Oral hypoglycemic agents are successful in people only for noninsulin-dependent diabetes. There has been only limited use in animals. Because response to oral hypoglycemic agents in cats is unpredictable, it is recommended to use a trial first of at least 4 weeks. If the cat responds, the drug can be continued; otherwise, insulin may be indicated. Feed cats a high-fiber diet when using oral hypoglycemic agents. Transdermal glipizide (5-mg dose) in a PLO gel was evaluated in cats. Although the transdermal formulation produced a modest change in glucose concentrations, systemic absorption was only 20%.

Patient Monitoring and Laboratory Tests

Monitor blood glucose levels to determine if the drug is effective. Monitor liver enzymes. It may increase alanine transaminase (ALT) and alkaline phosphatase.

Formulations

Glipizide is available in 5- and 10-mg tablets.

Stability and Storage

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

Small Animal Dosage

Dogs

No effective dose available.

Cats

• 2.5-7.5 mg/cat q12h PO. Usual dose is 2.5 mg/cat initially, then increase to 5 mg/cat, q12h.

Large Animal Dosage

No large animal doses have been reported.

Regulatory Information

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

Glucosamine + Chondroitin Sulfate

gloo-koe′seh-meen + kahn-droy′ten sul′fate

Trade and other names: Cosequin, Glycoflex, and generic brands

Functional classification: Nutritional supplement

Pharmacology and Mechanism of Action

Glucosamine is an amino sugar synthesized from glucose and glutamine. It is a source of glucosamine-6-phosphate and n-acetylglucosamine. It is an intermediate compound, converted to an ester that is incorporated into articular cartilage. Therefore, it is a direct precursor in the formation of glycosaminoglycans in cartilage. Glucosamine is usually administered as a combination of glucosamine HCl and chondroitin sulfate. Other forms include glucosamine sodium sulfate and glucosamine potassium sulfate. Glucosamine has been promoted to stimulate synthesis of synovial fluid, inhibit degradation, and improve healing of articular cartilage. Additional information is available in the section on chondroitin sulfate. Bioavailability studies have produced varying results depending on formulation, assay technique, and species. Oral absorption of glucosamine has varied, ranging from 12% in dogs to only 2.5% (125 mg/kg) or 6% (20 mg/kg) in horses. Although in vitro studies have demonstrated benefits to articular cartilage, some studies have questioned whether oral glucosamine is absorbed systemically intact to a high enough extent to provide these benefits. Oral absorption may be affected by the form administered because glucosamine sulfate may be better absorbed than glucosamine hydrochloride.

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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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