Veterinary Prescribing Review and Update

Cory ThebergeUniversity 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– UNE Pharmacy Animal Health Network

• Diabetes and Insulin Therapy• Epilepsy• Summary

Veterinary Pharmacy

• Companion Animals• Food Animals• Veterinarian-Client-Patient Relationship

(VCPR)• Extra-Label Drug Use (ELDU)• “Cultural Sensitivity”

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

Veterinary Information Resources

• Gold Standard: Plumb’s Veterinary Drug Handbook– Monographs– Dosing– Mobile/online versions

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

VCPR and Prescriptions – Maine Statute

State Citation VCPR Definition

VCPR- Prescription Rule

Maine None None A licensed veterinarian may sell and dispense the written prescription of another licensed veterinarian with respect to any prescription or administration of a drug, medicine or nutritional substance on, for or to any animal.

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 experienceOutcomes: Enhanced communication skills Exposure to routine in small animal

clinics Improved learning objectives

Case study examples

DIABETES AND INSULIN THERAPY: COMPANION ANIMALS

• 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.htmhttp://www.caninediabetes.org/caninediabetespg.html

Background

Type DescriptionType I Decreased or no insulin production by the pancreatic

beta cells Always insulin dependent (IDDM) Affects cats and dogs If a dog is diabetic, it is most likely IDDM.

Type II Decreased sensitivity of the body’s cells to insulin OR dysfunctional beta cells

May be IDDM or non-insulin dependent (NIDDM) Affects cats and rarely dogs

Transient DM Insulin requirements are on and off These periods may range from weeks to months ~20% of diabetic cats experience periods where they no

longer require insulin

http://www.caninediabetes.org/pdorg/diabetes_concepts.htmhttp://www.caninediabetes.org/caninediabetespg.html

Types of Diabetes

• 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

The Classic Signs

• 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=750http://www.caninediabetes.org/pdorg/diabetes_concepts.htm

Signs of Disease Progression

• Cat ear prickhttp://www.sugarcats.net/sites/harry/earprick.html#anchor144779

• Dog lip prickhttp://www.sugarcats.net/sites/harry/lipprick.html

Where to Test Blood Glucose

Use a Human Blood Glucose Meter?

Source: Abbott Labs AlphaTrak2 Veterinarian brochure http://www.alphatrakmeter.com/static/cms_workspace/pdfs/AlphaTRAK_2_Veterinarians_Brochure.pdf

Red Blood Cells Plasma

Patient % of Glucose in Red Blood Cells

% of Glucose in Plasma

Human Glucose Meter

Human 42 58 Accurate Glucose ReadingDog 12.5 87.5 May Underestimate Glucose LevelCat 7 93 May Underestimate Glucose Level

• Portable meters test whole blood• Blood glucose standards are based

on glucose in plasma

• AAHA (American Animal Hospital Assoc.) Diabetes Management Guidelines for Dogs and Catshttp://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.pdfDavidson, G. Providing Care for Diabetic Veterinary Patients. Int J of Pharm Compounding. 2000; 4(5):386-389.

Treatment

• 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

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.

VetsulinTM

• 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.pdfNelson, 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.

Cat 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.

Dog Treatment

• 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 (!)

CLEARRegularGlargineDetemirLisproAspart

GlulisineDegludec

CLOUDYNPH

PZI (clear w/white

sediment)

Insulin Counseling Point - Storage

• Long hair cats – injecting into fur or in/out skin

• Feel for wet fur

• Repeated injections/site – scarring can reduce local absorption

Insulin Counseling Point: IM Injections

4

40

10

100=

4

40

x

100=

STEP 1

STEP 2

Converting a U-40 dose to a U-100 Dose

U-401 ml

U-1001 ml

10

20

30

40

4

50

10

100

EPILEPSY: COMPANION ANIMALS

• 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

Background

• 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.htmlNair, PP; Kalita, J, Misra, UK (2011 Jul-Sep). "Status epilepticus: why, what, and how.". Journal of postgraduate medicine 57 (3): 242–52. PMID 21941070.

Seizure Types

• Seizures can be caused by brain damage, such as lesions

Lesion Location Symptoms

Frontal cortex Contralateral involuntary muscle twitchingContralateral hoppingPlacing deficits

Temporal lobe Hysterical running

Temporal-occipital region Fly-biting hallucinationsStar-gazing hallucinations

Pyriform area (paleocortex) of the temporal lobe

Aggression

http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/overview_of_the_nervous_system.html

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

Other Causes

Brain tumor Ideo Tox-related Liver Disease

Seizures related to food ingestion – liver shunt

Majority of cases are:

• 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.htmlhttp://www.peteducation.com/article.cfm?c=2+2105&aid=433

Diagnosis

• 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.htmlhttp://www.peteducation.com/article.cfm?c=2+2105&aid=433http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/principles_of_therapy_of_neurologic_disease.htmlhttp://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

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.htmlhttp://www.peteducation.com/article.cfm?c=2+2105&aid=433http://www.merckmanuals.com/vet/nervous_system/nervous_system_introduction/principles_of_therapy_of_neurologic_disease.htmlhttp://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

Common Treatments: Phenobarbitol

• 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.htmlhttp://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

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.htmlhttp://www.merckmanuals.com/vet/pharmacology/systemic_pharmacotherapeutics_of_the_nervous_system/maintenance_anticonvulsant_therapy.html

Common Treatments: Potassium Bromide (KBr)

• 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

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

Other Treatments

• 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

Diazepam

• 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

Summary

Assessment Questions