veterinary prescribing review and update
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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 - PowerPoint PPT PresentationTRANSCRIPT
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