Transcript Veterinary Pharmacy

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
– 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
Maine None
VCPR
VCPR- Prescription Rule
Definition
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 experience
Outcomes:
 Enhanced communication skills
 Exposure to routine in small animal
clinics
 Improved learning objectives
 Case study examples
DIABETES AND INSULIN THERAPY:
COMPANION ANIMALS
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)
http://www.caninediabetes.org/pdorg/diabetes_concepts.htm
http://www.caninediabetes.org/caninediabetespg.html
• 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
Types of Diabetes
Type
Description
Type 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.htm
http://www.caninediabetes.org/caninediabetespg.html
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
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
Where to Test Blood Glucose
• Cat  ear prick
http://www.sugarcats.net/sites/harry/earprick.ht
ml#anchor144779
• Dog  lip prick
http://www.sugarcats.net/sites/harry/lipprick.html
Use a Human Blood Glucose Meter?
• Portable meters test whole blood
• Blood glucose standards are based
on glucose in plasma
Red Blood Cells
Plasma
Patient
% of Glucose
in Red Blood
Cells
% of
Human Glucose Meter
Glucose in
Plasma
Human
42
58
Accurate Glucose Reading
Dog
12.5
87.5
May Underestimate Glucose Level
Cat
7
93
May Underestimate Glucose Level
Source: Abbott Labs AlphaTrak2 Veterinarian brochure http://www.alphatrakmeter.com/static/cms_workspace/pdfs/AlphaTRAK_2_Veterinarians_Brochure.pdf
Treatment
• AAHA (American Animal Hospital Assoc.) Diabetes
Management Guidelines for Dogs and Cats
http://www.aahanet.org/PublicDocuments/AAHADiabetes
Guidelines.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.
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
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.
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.
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.
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)
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
Converting a U-40 dose to a U100 Dose
STEP 1
4
40
STEP 2
4
40
=
=
x
100
10
100
U-40
1 ml
4
U-100
1 ml
10
10
20
50
30
40
100
EPILEPSY: COMPANION ANIMALS
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
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.
Causes
• Seizures can be caused by brain damage, such
as lesions
Lesion Location
Symptoms
Frontal cortex
Contralateral involuntary muscle twitching
Contralateral hopping
Placing deficits
Temporal lobe
Hysterical running
Temporal-occipital region
Fly-biting hallucinations
Star-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
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
Majority of cases are:
 Brain tumor
 Ideo
 Tox-related
 Liver Disease
 Seizures related to food ingestion – liver
shunt
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
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_the
rapy.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.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_the
rapy.html
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
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
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_the
rapy.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_the
rapy.html
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_o
ngoing_seizure_activity.html
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
Assessment Questions