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Valproic Acid, Valproate Sodium



val-proe′ik ass′id, val′proe-ate soe′dee-um


Trade and Other Names: Depakene (Valproic acid), Depakote (Divalproex), and Epival (in Canada)


Functional Classification: Anticonvulsant



Pharmacology and Mechanism of Action


Anticonvulsant. Action is not known, but valproate may increase GABA concentrations in the CNS. Both valproic acid and valproate sodium are used. Divalproex is composed of both valproic acid and sodium valproate. Equivalent oral doses of divalproex sodium and valproic acid deliver equivalent quantities of valproate ion.



Indications and Clinical Uses


Valproate is used, usually in combination with phenobarbital, to treat refractory epilepsy in animals. Most use has been in dogs, but limited efficacy studies have been reported. The use of valproate in animals has declined because other anticonvulsants for treating refractory epilepsy have been identified such as gabapentin, pregabalin, zonisamide, and levetiracetam.



Precautionary Information



Adverse Reactions and Side Effects


Adverse effects have not been reported in animals, but hepatic failure has been reported in people. Sedation may be seen in some animals.



Contraindications and Precautions


Do not use in pregnant animals. Birth defects have been reported in people.



Drug Interactions


Valproate may cause bleeding if used with drugs that inhibit platelets.



Instructions for Use


This drug is usually used as an add-on with phenobarbital. Controlled-release forms designed for people do not show the same oral absorption profile in dogs as in people.



Patient Monitoring and Laboratory Tests


Therapeutic drug monitoring can be performed; however, therapeutic concentrations have not been established for dogs and cats, and ranges cited for people, 50-100 mcg/mL (desired trough concentration), should be used. Concentrations greater than 100 mcg/mL are associated with adverse effects.



Formulations


Valproic acid immediate release formulations are available in 250-mg capsules and 50-mg/mL syrup. Delayed-release formulations of valproic acid and divalproex are available in 125, 250, and 500 mg tablets or capsules. Divalproex is also available in 125 mg capsules and 250, and 500 mg extended release tablets. Valproate sodium (Depacon) is available in 100-mg/mL injection.



Stability and Storage


Store in a tightly sealed container, protected from light, and at room temperature. Valproic acid is slightly soluble in water, but valproate sodium is soluble in water. Extemporaneous emulsions have been prepared and were comparable to absorption of syrup.



Small Animal Dosage



Dogs



• 50-250 mg per dog, (depending on size) q8h PO.

• Delayed-release formulations: Start with 250 mg per dog q12h PO, and increase to 500 mg per dog q12h, as needed.

Higher doses should be used if dogs are also receiving phenobarbital.



Cats


Dose not established.



Large Animal Dosage


No dose has been reported for large animals.



Regulatory Information


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



Vancomycin



van-koe-mye′sin


Trade and Other Names: Vancocin and Vancoled


Functional Classification: Antibacterial



Pharmacology and Mechanism of Action


Antibacterial drug. Vancomycin is bactericidal for most organisms and bacteriostatic for enterococci. It inhibits the cell wall by binding to the D-alanyl-D-allanine portion of cell wall precursors and interfering with the bacterial cell wall. The bactericidal action occurs by activating bacterial cell wall autolysins. Spectrum includes Streptococcus, Enterococcus, and Staphylococcus. Strains of Staphylococcus treated often are called methicillin-resistant Staphylococcus (e.g., methicillin-resistant Staphylococcus aureus [MRSA] or Staphylococcus pseudintermedius [MRSP]).



Indications and Clinical Uses


Vancomycin is used for resistant strains of Staphylococcus or Enterococcus in animals. It is the most common injectable drug to treat methicillin-resistant Staphylococcus species and drug-resistant Enterococcus spp. It is not effective against gram-negative bacteria. Vancomycin use is not common in animals because it is inconvenient to administer. However, it can be valuable for treatment of enterococci or staphylococci that are resistant to other antibiotics. It also has been administered orally to people for diarrhea caused by Clostridium spp. Occasionally it has been used in horses for local infiltration, such as with regional limb perfusion. It is not allowed in food animals.



Precautionary Information



Adverse Reactions and Side Effects


Adverse effects have not been reported in animals, but the use has been limited to a small number of animals and a full range of possible adverse effects have not been recognized. Adverse effects in people include neutropenia, renal injury (more common with older products that contained impurities), and histamine release. Reactions, especially those associated with histamine release, are more likely with a rapid injection.



Contraindications and Precautions


Do not administer rapidly IV. It will cause pain if injected by other routes (IM, SQ). Administer by slow infusion to avoid acute adverse reactions.



Drug Interactions


Do not mix with other drugs in infusion solution; there are incompatibilities identified for many drugs. It is incompatible with alkaline solutions.



Instructions for Use


Vancomycin must be administered via IV infusion, although in rare instances intraperitoneal administration has been used in people. (Oral administration is limited to intestinal infections.) Vancomycin systemic use in horses is rare. Local administration in horses via regional limb perfusion has been used for localized joint or bone infections.


Doses are derived from pharmacokinetic studies in each species. In dogs, to maintain the plasma concentration between a suggested window of 10 to 30 µg/mL, the dose rate of 15 mg/kg q8h, IV, is recommended. (This dose actually produces peaks and troughs of approximately 40 and 5 µg/mL, respectively, but it is the most convenient dose that can be used because of the short half-life in dogs.) This dose should be infused slowly over 30 to 60 minutes, or at a rate of approximately 10 mg/min. The total dose to be administered can be diluted in 0.9% saline or 5% dextrose solution but not alkalinizing solutions. Vancomycin is available in vials of 500 mg to 5 g (Vancocin, other brands, and generic).



Patient Monitoring and Laboratory Tests


Monitoring of trough plasma concentrations is recommended to ensure proper dose. Maintain trough concentration above 10 mcg/mL. CLSI guidelines for susceptibility testing list a breakpoint of ≤4 mcg/mL for Enterococcus, ≤1 mcg/mL for Streptococcus, and ≤4 mcg/mL for Staphylococcus.



Formulations


Vancomycin is available in 500-mg and 1-, 5-, and 10-g vials for injection.



Stability and Storage


Stability may be compromised if mixed with other drugs in infusion solutions. Store in a tightly sealed container, protected from light, and at room temperature. It is soluble in water and ethanol. After reconstitution with sterile water, it may be further diluted in 5% dextrose or saline. Solutions may have a dark color. After reconstitution it is stable for 14 days either at room temperature or in the refrigerator. Some ophthalmic compounded formulations are not stable and have a low pH that can be irritating to the eyes.



Small Animal Dosage



Dogs



• 15 mg/kg q6-8h IV infusion.

• Constant rate infusion (CRI): Loading dose of 3.5 mg/kg, followed by CRI of 1.5 mg/kg/hr mixed in 5% dextrose in water.


Cats



• 12-15 mg/kg q8h IV infusion


Large Animal Dosage



Horses



• 4.3-7.5 mg/kg q8h IV given as an infusion over 1 hour.

• Regional limb perfusion: Infuse 300 mg diluted in a 0.5% solution.


Regulatory Information


Do not administer to animals intended for food. The Food and Drug Administration has prohibited the extralabel use of glycopeptides in food-producing animals because of risk of producing glycopeptide-resistant bacteria.



Vasopressin



vay-zoe-press′in


Trade and Other Names: Arginine Vasopressin (AVP), Antidiuretic hormone (ADH), Pitressin


Functional Classification: Hormone



Pharmacology and Mechanism of Action


Antidiuretic hormone. Vasopressin mimics the effect of antidiuretic hormone (ADH) on the tubule of the renal tubule. ADH permits reabsorption of water in the renal tubule. Without ADH, more diluted urine is excreted. (See Desmopressin manuscript for additional formulations and use.) Vasopressin also has potent vasopressive activity via activation of the V1 vascular receptor. The V1 vascular receptors are in high density on vascular smooth muscle. V2 receptors occur on the renal-collecting duct, and stimulation increases water reabsorption. Because of the vasopressive action, it has been used to treat vasodilatory shock. During infusion it rapidly increases mean arterial pressure. A related drug, terlipressin, is more specific for the vascular V1 receptor.



Indications and Clinical Uses


Vasopressin is used for treatment of polyuria caused by central diabetes insipidus. It is not effective for polyuria caused by renal disease. Desmopressin is the preferred formulation used more frequently in animals for treating diabetes insipidus. Vasopressin is used to treat vasodilatory shock via constant rate infusion (CRI) in addition to fluid therapy.



Precautionary Information



Adverse Reactions and Side Effects


Adverse effects have not been reported. Allergic reactions and increase in blood pressure have been reported in people.



Contraindications and Precautions


No contraindications are reported for animals.



Drug Interactions


No drug interactions have been reported in animals.



Instructions for Use


For IV use, dilute in 0.9% saline and titrate dose to effect. For antidiuretic use, doses are adjusted on the basis of monitoring of water intake and urine output.



Patient Monitoring and Laboratory Tests


Monitor blood pressure during infusion to maintain systolic blood pressure of 100-120 mm Hg and urine output of 0.5-1.5 mL/kg/hr. Titrate infusion rate to achieve desired pressure response. When used for antidiuretic effects, monitor water intake, urine output, and urine-specific gravity.



Formulations


Vasopressin is available in 20-units/mL (aqueous) solution.



Stability and Storage


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



Small Animal Dosage



Dogs and Cats



• Antidiuretic: 10 units IV or IM.

• Vasopressor (shock): 0.01-0.04 units/min. Do not exceed 0.04 Units/min.

• CPR: 0.2-0.8 Units/kg IV.


Large Animal Dosage


No dose has been reported for large animals.



Regulatory Information


Because of low risk of harmful residues in animals intended for food, no withdrawal time is suggested.



Verapamil Hydrochloride



ver-ap′ah-mill hye-droe-klor′ide


Trade and Other Names: Calan and Isoptin


Functional Classification: Calcium antagonist



Pharmacology and Mechanism of Action


Calcium-channel blocking drug of the nondihydropyridine group. Verapamil blocks calcium entry into cells via blockade of voltage-dependent slow channel. Verapamil produces vasodilation, negative chronotropic, and negative inotropic effects.



Indications and Clinical Uses


Verapamil has been used to control supraventricular arrhythmias. The use of verapamil has diminished because of adverse effects; it has practically become an outdated drug. The preferred drug from this class to use in animals is usually diltiazem.



Precautionary Information



Adverse Reactions and Side Effects


Adverse effects include hypotension, cardiac depression, bradycardia, and AV block. It may cause anorexia in some patients. Verapamil has caused sudden cardiac arrest in some patients with intravenous administration.

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

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