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Veterinary Prescribing Review and Update

Veterinary Prescribing Review and Update. Cory Theberge University of New England College of Pharmacy MPA Spring Conference April, 2014. Outline. Veterinary Pharmacy Review Essential Facts Effective veterinary pharmacists are… Information Resources Maine Statute

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Veterinary Prescribing Review and Update

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  1. Veterinary Prescribing Review and Update Cory Theberge University of New England College of Pharmacy MPA Spring Conference April, 2014

  2. Outline • Veterinary Pharmacy Review • Essential Facts • Effective veterinary pharmacists are… • Information Resources • Maine Statute • UNE Pharmacy Animal Health Network • Diabetes and Insulin Therapy • Epilepsy • Summary

  3. Veterinary Pharmacy • Companion Animals • Food Animals • Veterinarian-Client-Patient Relationship (VCPR) • Extra-Label Drug Use (ELDU) • “Cultural Sensitivity”

  4. An effective veterinary pharmacist: • Is integrated into the world of veterinary pharmacy information • Understands legal and regulatory guidelines • Understands basic animal health and pharmacological considerations • Has compounding skills • Appreciates the culture of animal health and animal clinical practice

  5. Veterinary Information Resources • Gold Standard: Plumb’s Veterinary Drug Handbook • Monographs • Dosing • Mobile/online versions

  6. Veterinary Information Resources • Compounding formularies • Databases for purchase • Internal databases • Stability Studies of Compounded Preparations: Look for “Stability Indicating Methods” (not just Potency) • International Journal of Pharmaceutical Compounding • Journal of Pharmaceutical and Biomedical Science • Journal of Applied Pharmaceutical Science • PK data • Journal of Veterinary Pharmacology and Therapeutics • FARAD database

  7. VCPR and Prescriptions – Maine Statute

  8. UNE Pharmacy Student Animal Health Experience Network • 19 students in veterinary pharmacy elective course • 13 Sites (two outside map) + State Veterinarian: Pilot Study • Each student required to obtain >2 hours clinical experience • Survey of vet, student experience • Outcomes: • Enhanced communication skills • Exposure to routine in small animal clinics • Improved learning objectives • Case study examples

  9. Diabetes and Insulin Therapy: Companion Animals

  10. Background • What is it? • Disorder where the body is unable to regulate blood sugar levels • The animal is either deficient in or insensitive to insulin • Diagnosis • Hyperglycemia • Glucosuria • Ketonuria (sometimes) • Prevalence • 1 in 400-500 cats and dogs • Neutered male cats and unspayed female dogs are more prone to diabetes • No breed susceptibilities in cats • Genetic predisposition: Keeshond, puli, miniature pinscher, and cairn terriers • Abnormally high rates: poodle, dachshund, miniature schnauzer, and beagle breeds http://www.caninediabetes.org/pdorg/diabetes_concepts.htm http://www.caninediabetes.org/caninediabetespg.html

  11. Types of Diabetes http://www.caninediabetes.org/pdorg/diabetes_concepts.htm http://www.caninediabetes.org/caninediabetespg.html

  12. The Classic Signs • Polyuria: excessive urination • Polydipsia: excessive thirst • Polyphagia: excessive hunger or increased appetite • Weight loss • Lethargy • Hyperglycemia • Cats are highly susceptible to stress-induced hyperglycemia (ex: trip to the vet), so diabetes cannot be diagnosed based on one abnormal blood glucose reading http://www.caninediabetes.org/pdorg/diabetes_concepts.htm

  13. Signs of Disease Progression • Retinopathy/cataracts: Some dogs aren’t diagnosed until they become blind • Diabetic neuropathy: Some cats aren’t diagnosed until the cat has weak rear legs or it walks on its hocks, which is called plantigrade posture. http://pets.purina.com.au/purinaone/article/articledetails.aspx?id=750 http://www.caninediabetes.org/pdorg/diabetes_concepts.htm

  14. Where to Test Blood Glucose • Cat  ear prick http://www.sugarcats.net/sites/harry/earprick.html#anchor144779 • Dog  lip prick http://www.sugarcats.net/sites/harry/lipprick.html

  15. Use a Human Blood Glucose Meter? • Portable meters test whole blood • Blood glucose standards are based on glucose in plasma Red Blood Cells Plasma Source: Abbott Labs AlphaTrak2 Veterinarian brochure http://www.alphatrakmeter.com/static/cms_workspace/pdfs/AlphaTRAK_2_Veterinarians_Brochure.pdf

  16. Treatment • AAHA (American Animal Hospital Assoc.) Diabetes Management Guidelines for Dogs and Cats http://www.aahanet.org/PublicDocuments/AAHADiabetesGuidelines.pdf • Insulin • Mainstay treatment for dogs • Human NPH can be used twice daily in dogs and cats • Novolin N™ • Humulin N™ • Vetsulin™ (porcine insulin zinc suspension) • Prozinc™(protamine zinc recombinant human insulin) Plumb, DC. Plumb’s Veterinary Drug Handbook. Sixth Edition. Pages 479-484. http://www.vetsulin.com/PDF/Vetsulin-Package-Insert.pdf Davidson, G. Providing Care for Diabetic Veterinary Patients. Int J of Pharm Compounding. 2000; 4(5):386-389.

  17. VetsulinTM • Indication: reduction of hyperglycemia and hyperglycemia-associated clinical signs in dogs and cats with diabetes mellitus • Intermediate-acting insulin • Composition (40 units/ml) • 35% amorphous  rapid onset • 65% crystalline  slowly absorbed • Must administer with a U-40 syringe • Can’t use if animal has a systemic allergy to pork or pork products • It is a suspension… requires shaking! • Allow froth to settle prior to drawing up in syringe http://www.vetsulin.com/PDF/Vetsulin-Package-Insert.pdf

  18. VetsulinTM • In dogs, Vetsulin™ has two peaks of activity • First peak occurs at 2 to 6 hours • Second peak at 8 to 14 hours • Duration of activity varies between 14 and 24 hours • In cats, Vetsulin™ has a single peak of activity • Peak ranges from 2 to 6 hours • Duration of activity varies between 8 to 24 hours Graham P., Nash A., and McKellar Q. “Pharmacokinetics of porcine insulin zinc suspension in diabetic dogs” Journal of Small Animal Practice. 1997. Vol 38, October: 434-438. Martin G.J. and Rand J.S. “Pharmacokinetic and Pharmacodynamic Study of Caninsulin in Cats with Diabetes Mellitus” (2000), Internal Study Report.

  19. Cat Treatment • Most cats require insulin • Metabolize insulin more rapidly than dogs • Less predictable response than dogs • May use Lantus™ (insulin glargine) twice daily due to cat’s unique metabolism • Prozinc™ (protamine zinc recombinant human insulin) • Approved only for cats • Long-acting insulin • Can use oral hypoglycemics (glipizide, glyburide, etc) but <30% response rate • Metformin use is controversial • Very limited success when the drug is used alone • In a study evaluating metformin, 1 of 5 diabetic cats studied died 11 days after receiving metformin. The cause of death was undetermined, but metformin could not be ruled out. Plumb, DC. Plumb’s Veterinary Drug Handbook. Sixth Edition. Pages 423-425, 432-433, 479-484. http://www.bi-vetmedica.com/content/dam/internet/ah/vetmedica/com_EN/product_files/ProZinc/prozinc_reference%20page.pdf Nelson, R., D. Spann, et al. (2004). “Evaluation of the oral antihyperglycemic drug metformin in normal and diabetic cats.” J Vet Intern Med 18(1): 18 -24.

  20. Dog Treatment • Mainstay treatment: insulin • Canine insulin receptors are more sensitive to detemir than human and feline receptors • The starting detemir dose for dogs is less than other insulin products • Hypoglycemia is more likely • Why aren’t oral hypoglycemics used in dogs? • Most dogs with IDDM lose the ability to produce insulin • Metformin, glyburide, glipizide, etc would not be effective Fleeman LM, Rand JS. Management of Canine Diabetes. Vet Clin of North Am: Small Animal Practice. 2001; 31(5): 855-880.

  21. Insulin Counseling Point - Storage • Insulin usually has a beyond-use date of 28 or 42 days. • Due to high costs, pet owners usually extend this period. • Counsel on storage and handling techniques • No sun, fridge • Contamination by needle re-use (!) CLEAR Regular Glargine Detemir Lispro Aspart Glulisine Degludec CLOUDY NPH PZI (clear w/white sediment)

  22. Insulin Counseling Point: IM Injections • Long hair cats – injecting into fur or in/out skin • Feel for wet fur • Repeated injections/site – scarring can reduce local absorption

  23. Converting a U-40 dose to a U-100 Dose STEP 1 4 x = 40 100 4 10 STEP 2 = 40 100

  24. U-40 1 ml U-100 1 ml 4 10 10 20 50 30 40 100

  25. EPILEPSY: Companion Animals

  26. Background • Seizure: clinical manifestation of abnormal neuronal hyperactivity • Seizures are partial or generalized • Seizure characteristics depend on the brain area involved • Seizures may occur with or without the presence of brain lesions • With lesions  symptoms based on brain area • Without lesions  primary idiopathic epilepsy http://michaelpodelldvm.com/EPILEPSY.html

  27. Seizure Types • Primary idiopathic epilepsy • Recurrent seizures in the absence of morphologic brain lesions • No pathologic cause • Secondary epileptic seizures – result of brain injury • Reactive epileptic seizures – metabolic or toxic problem • Status epilepticus • Life-threatening condition • One continuous seizure lasting longer than 5 minutes OR • Recurrent seizures without regaining consciousness between seizures for greater than 5 minutes http://michaelpodelldvm.com/EPILEPSY.html Nair, PP; Kalita, J, Misra, UK (2011 Jul-Sep). "Status epilepticus: why, what, and how.". Journal of postgraduate medicine 57 (3): 242–52. PMID 21941070.

  28. Causes • Seizures can be caused by brain damage, such as lesions http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/overview_of_the_nervous_system.html

  29. Other Causes • Thiamine deficiency  ataxia, stupor, seizures, coma • Vitamin B6 deficiency • Inherited epilepsy – manifests around 2-3 years of age • Idiopathic epilepsy – often normal EEGs http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/overview_of_the_nervous_system.html

  30. Majority of cases are: • Brain tumor • Ideo • Tox-related • Liver Disease • Seizures related to food ingestion – liver shunt

  31. Diagnosis • History, history, history • No test to diagnose epilepsy; current tests just rule out other causes of seizures. • Electroencephalogram (EEG) • May determine whether seizures are focal or diffuse. • EEG is usually normal in idiopathic epilepsy, unless the seizures are uncontrolled or interictal spikes are present. http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/electrodiagnosis_in_neurologic_disease.html http://www.peteducation.com/article.cfm?c=2+2105&aid=433

  32. Common Treatments: Phenobarbitol • Maintenance drug of choice in dogs and cats • More effective and works faster than KBr • Clinically effective in 72 hours • Increases liver enzymes and cholesterol, but decreases thyroid levels. Usually don’t require treatment. • Watch for drug interactions! Why? http://michaelpodelldvm.com/EPILEPSY.html http://www.peteducation.com/article.cfm?c=2+2105&aid=433 http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/principles_of_therapy_of_neurologic_disease.html http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

  33. Common Treatments: Phenobarbitol • Levels are usually checked every 6-12 months to determine if dose is therapeutic • Therapeutic serum concentrations • Cat and Dog: 15 – 45 μg/mL • Human: 15 – 40 μg/mL • 20-30% of seizures cannot be controlled by phenobarbital alone http://michaelpodelldvm.com/EPILEPSY.html http://www.peteducation.com/article.cfm?c=2+2105&aid=433 http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/principles_of_therapy_of_neurologic_disease.html http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

  34. Common Treatments: Potassium Bromide (KBr) • MOA: • Stabilizes neuronal cell membranes by interfering with chloride transport across cell membranes • Potentiate the effect of GABA via hyperpolarizing membranes • Less liver toxicity than phenobarbital • Don’t use in cats  respiratory problems • Give with food • Long half-life (24 days)  takes 3-4 months to reach steady state http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/principles_of_therapy_of_neurologic_disease.html http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

  35. Common Treatments: Potassium Bromide (KBr) • Serum levels are affected by the diet’s salt content • Maintain a consistent diet • The higher the dietary salt content, the faster the excretion via the kidneys. • Biggest side effects = sedation & GI upset • NOT given IV due to the potassium content • Linked to megaesophagus and pancreatitis in dogs • Not commercially available, must be compounded http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/principles_of_therapy_of_neurologic_disease.html http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

  36. Other Treatments • Sodium bromide • Biggest side effect = sedation • Dosing is not interchangeable with KBr • Felbamate – No sedation • Zonisamide • Metabolized by hepatic microsomal enzymes • A double dose is required if a hepatic enzyme inducer (phenobarbital) is also used • Levels must be tested • Can cause drowsiness http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

  37. Other Treatments • Valproic Acid • Adjunct to phenobarbital for refractory seizures in dogs • Can cause sedation and tremor • Clonazepam (dogs) • Gabapentin – Higher doses can cause sedation and ataxia • Levetiracetam • Disadvantage = TID dosing • Diazepam http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

  38. Diazepam • Used for status epilepticus • Midazolam can be substituted for diazepam • Usually given IV • If IV access is not possible, administer rectally • If a dog has cluster seizures, rectal diazepam is recommended as an at-home emergency treatment. • Diazepam (especially repeated doses) can cause hepatic necrosis in cats http://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/anticonvulsants_used_to_stop_ongoing_seizure_activity.html

  39. Summary • Encourage familiarity with veterinary information sources • Explore veterinary pharmacology literature • Focus on companion animals…and then branch out. • Essential dog/cat diabetes facts • Essential dog/cat epilepsy facts

  40. Assessment Questions

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