Pharm test 2

Phenobarbital

-anticonvulsant
-long-term seizure medication
-inexpensive
-long 1/2 life so may only be needed 1-2 times a day
-concentrations must remain in therapeutic ranges to stay effective
-Side effects: sedation, ataxia, PU, PD, PP, increases ALP/ALT

Diazepam

-benzodiazepine tranquilizer
-used for emergency treatment of status epilepticus
-controls seizures by rapidly penetrating blood-brain barrier
-comes in oral and IV (if cant give IV can give Diastat rectally)
-side effects: ataxia, weakness, aggression

Potassium Bromide

-one of the most common adjunct therapies for animals whose seizures are not well controlled by phenobarbital alone
-long 1/2 life
-takes 3-5 months to reach study concentration in dogs
-large doses used to estimate concentrations within therapeutic range

Primidone

-has some anticonvulsant activity
-efficacy is highly dependent on the metabolism of primidone to phenobarbital

Phenytoin (Dilantin)

-human meds that was once popular for epilepsy in animals
-disadvantage: maintenance therapeutic concentration

Clonazepam (Klonopin), Lorazepam, Clorazepate

-most animals develop a significant tolerance to these in a short time (limiting long term use)

Levetiracetam (keppra)

-rapidly metabolized with elimination
1/2 life b/w 4-8 hours
-side effects: sedation, ataxia
- limiting factors: given up to 3 times a day, expensive
-useful for canine epilepsy as an add on treatment
-cases that can't tolerate phenobarbital or potassium bromide

T/F: An imbalance of neurotransmitters can result in clinical depression, behavioral changes, self-destructing activities, or anxiety/fear

true

What is GABA?

gamma-aminobutyric acid
-a chemical messenger widely distributed in the brain

What can increase brain activity?

-use of Methylxanthines compounds
(caffeine, coffee, theobromine, chocolate)

What do behavior modifying drugs do?

change the concentrations of selected neurotransmitters in the brain
-the goal is to decrease or enhance specific mental activity

How do behavior modifying drugs work?

-enhancing the release of neurotransmitters
-enhancing the binding affinity of neurotransmitters to their receptors
-imitating the natural neurotransmitter and combining with the neurotransmitter's receptor to stimulate the receptor (agonist effect)
-imitating the natural and combining with the neurotransmitter receptor, but produces little or no stimulation of the receptor (antagonist)
-Prolonging the action of the neurotransmitter by decreasing the breakdown or slowing the rate of termination of the neurotransmitter
-Shortening the action of the neurotransmitter by enhancing or termination of it

Antipsychotics

major tranquilizers (acepromazine)

Antidepressants

mood elevating drugs (clomicalm)

Anxiolytics

drugs that lyse anxiety, or decrease fear responses (diazepam)

Phenothiazine tranquilizers (acepromazine)

-used to decrease inappropriate behavioral responses to stimuli
-disadvantage - reduces response to both normal and abnormal stimuli in the environment
-animals will have less interest in their environment, fewer emotional responses to stimuli
-used to control learned fear responses to thunder, fireworks

T/F: antipsychotic medications do not suppress instinctual responses

true

Trazodone (antipsychotic)

- a better option
-SARI - induce sedation and anxiolysis
-good for separation, noise phobia, veterinary visits, hospitalization

What are the three classes of antidepressants?

-Tricyclic antidepressants (TCA)
-Selective serotonin reuptake inhibitors (SSRI)
-Monoamine oxidase inhibitors (MAOI)

Tricyclic antidepressants (TCAs)

amitriptyline, clomipramine (Clomicalm)

How do Tricyclic antidepressants work?

-by decreasing the reuptake of serotonin which allows neurotransmitters to accumulate and prolongs the activity
-Amitriptyline blocks the reuptake of norepinephrine

What are Tricyclic antidepressants used for?

-to treat generalized anxiety and separation anxiety behaviors in dogs

Selective Serotonin Reuptake Inhibitors (SSRIs)

-fluoxetine, Fluvoxamine, paroxetine, sertraline

What do selective serotonin reuptake inhibitors do?

-enhance the effect of serotonin neurotransmitter by blocking the removal from the synaptic cleft
-this causes the serotonin to remain for a longer period in its site of action --\> accumulation --\> extends effects

What are selective serotonin reuptake inhibitors used for?

-types of behaviors that are similar to that of the TCAs (OCD anxiety, and aggression)

T/F: selective serotonin reuptake inhibitors are more selective for blocking serotonin without blocking the other neurotransmitters

true

Monoamine oxidase inhibitors (MAOIs)

Selegiline (deprenil, veterinary marketed name --\> Anipryl)

What is Monoamine oxidase inhibitors used for?

-treatment of cognitive dysfunction (old-dog senility)

What do Monoamine oxidase inhibitors do?

-they are going to increase the amount of dopamine found in selected cells of the CNS and enhance the effects of dopamine

T?F MAOI can be used to improve cognitive function

true

Anxiolytics

-not frequently used for behavior modification b/c ability to interfere with animals ability to learn
-can be used to reduce general anxiety, but are not the best drug for the reduction of aggression

Other behavior modifying drugs

beta blockers, antihistamines, anticonvulsants, progestin

What is induction therapy?

-a phase of chemotherapy that involves more intensified therapy than the maintenance phase
-The goal is to reduce the \# of cancer cells, and ideally induce remission

What is maintenance therapy?

-a continuation of chemotherapy protocol that maintains remission and prevent relapse

What is rescue (salvage) therapy?

-re-induction chemotherapy for patients who fail one standard protocol
-drugs used in this protocol are not the 1st line treatments for the particular tumor

General side effects of chemotherapy drugs

-inappetence, nauseam vomiting, +/- diarrhea, dehydration, myelosuppression, alopecia

How can accidental exposure to chemo drugs occur?

-absorption through the skin
-indigestion of food contaminated with drug by aerosolization or direct contact
-absorption or inhalation during opening of glass impulses containing antineoplastic agents

Who is at risk for accidental exposure of chemo drugs?

pharmacy staff, animal caretakers, stocking personnel, technicians, veterinarian, clients

Guidelines for safe preparation, administration, and disposal of toxic drugs

- prepare and administer in low-traffic, well-ventilated area with a ventilated hood
-wear PPE
-use syringes and IV lines with screw-on attachments
-recheck the calculated dose
-confirm that the catheter is in place within the vein and patent
-discard syringes and needles in sealable plastic bag after use

Storage of chemo drugs

-always wear gloves
-read the storage requirements on container
-store hazardous drugs separately from other drugs in a zip-lock bag

Safe handling instruction for clients

-if drug is excreted in urine encourage pet to urinate on soil, treat urine as chemo drug, discard soil bedding, contaminated surfaces should be washed gently/never pressure washed, follow these during treatment, and following therapy for a minimum of 48-72 hours
-same instructions for feces

T/F: pregnant women should not handle antineoplastic drugs, clean cages, or handle wast from animals at any time during their cancer treatment

true

Dosing of Antineoplastic drugs

-based on body surface area
-read package insert and other published resources for stability information for reconstituted vials
-pay close attention to the route you're administrating, how well the drug is diluted, the rat of administration

Most commonly used chemotherapy drugs

Carboplatin
Chlorambucil
Cisplatin
Doxorubicin
Lomustine
Mitoxantron
Vinca Alkaloids

Carboplatin

-Trade name: Paraplatin
-Clinical use: used to treat osteosarcoma, melanoma, and a variety of carcinomas, and sarcomas in cats and dogs
-less renal toxicity than cisplatin, myelosuppression is greater than cisplatin, will not cause vomiting

Common adverse effects of Carboplatin

anorexia 2-4 days after dose, dose-related bone marrow suppression exhibited primarily as thrombocytopenia and/or neutropenia

Major drug interactions of Carboplatin

ahminoglycosides can increase risk of nephrotoxicity and vaccines may not be as effective

Contridictions of Carboplatin

Hypersensitivity to carboplatin or severe bone marrow suppression already present in patient

Chlorambucil

-trade name: Leukeran
-Clinical use: immunosuppressant and antieoplastic
-generally is less effective for maintenance therapy of high-grade lymphomas than cyclophosphamide but is used in place of cyclophosphamide when patients are intolerant of it

Adverse affects of Chlorambucil

Myelosuppression and GI toxicity
-bone marrow suppression is commonly seen 1 month after therapy but treatable if caught early

Major drug interactions of Chlorambucil

myelosuppressive drug can cause additive bone marrow suppression

Contraindications of Chlorambucil

hypersensitivity
-do not give with food
tablets should be stored in fridge

Cisplatin

Trade name: Platinol-AQ
Clinical use: used for a variety of carcinomas and sarcomas, intracavity lesions of equine sarcoids, and cutaneous neoplasia

Adverse effects of Cisplatin

vomiting, Nephrotoxicity, myelosuppression

Drug interactions of Cisplatin

Aminoglycerides and amphotericin B can increase risk of nephrotoxicity, Furosemide increases risk of ototoxicity

Contraindications of Cisplatin

Cannot be used in cats!! It causes total pulmonary edema and pleural effusion if administered systemically
-also contraindicated in patients with siginificant renal impairment or myelosuppression

Doxorubicin

Trade name: Adriamycin, Doxil
-Clinical use: lymphoma, leukemias, certain sarcomas, and carcinomas in dogs
-it is the broadest spectrum antineoplastic drug in vet med

Adverse effects of Doxorubicin

bone marrow suppression, cardiac toxicity, nephrotoxicity, alopecia, gastroenteritis and stomatitis, and severe consequences of extravasation occurs resulting in local phlebitis and pain

Drug interactions of Doxorubicin

alciuother antineoplastic agents may potentiate effects, calcium-channel blockers may increase risk for cardiotoxicity; phenobarbital may increase elimination

Contraindications of Doxorubicin

Myelosuppression, impaired cardiac function, or patients who have reached the total cumulative dose of doxorubicin

Lomustine

Trade name: CeeNu
Clinical use: useful in adjunctive treatment of CNS neoplasms, lymphomas, mast cell tumors in dogs and cats, and as a rescue agent for lymphosarcoma

Adverse effects of Lomustine

Hepatic toxicity in dogs, may cause vomiting immediately following administration, major bone marrow suppression can occur, neutropenia can occur after one week and persist for up to six weeks and may require IV antibiotics

Drug interactions of Lomustine

immunosuppressive drugs may increase risk of infection; myelosuppressive drugs may cause additive bone marrow suppression

Mitoxantrone

Trade name: Novantrone
Clinical use: its main use is for lymphomas resistant to other drugs
-it has a 25% higher response rate than doxorubicin but does not cause mast cell degranulation lock doxorubicin

Adverse effects of Mitoxantrone

mile to moderate GI toxicity, can cause severe colitis, bone marrow suppression, lethargy, local severe reactions following extravasation, turns the sclera of the eye and urine a blue-green color after therapy (warn clients)
-is less cardio toxic than doxorubicin

Drug interactions of Miloxantrone

vaccines should be used with caution during therapy

Contraindications of Miloxantrone

hypersensitivity

Vinblastin Sulfate

Trade name: Velban
Class: Vinca Alkaloid
Clinical use: used primarily for mast cell tumors in dogs and cats as rescue therapy in lymphosarcoma

Adverse effects of Vinblastin Sulfate

highly myleosuppressive and severe consequences of extravasation occurs resulting in local phlebitis and pain, nausea and vomiting are common but usually subside within 24 hours, neurotoxicity is less frequently seen than in vincristine

Drug interactions of Vinblastin sulfate

ototoxic drugs may increase risk of ototoxicity

Contraindications of Vinblastin sulfate

Preexisting leukopenia, if neutrophil count is less than 5,000. Also if the patient is suffering from a sever bacterial infection

Vincristine Sulfate

Trade name: Oncovin
Class: Vinca Alkaloid
Clinical use: commonly used in combination with other drugs to treat lymphoma, leukemia, mast cell tumors, and soft tissue sarcomas
-Successful single agent for treatment of transmissible venereal tumors
Also used to treat immune-mediated thrombocytopenia

Adverse effects of Vincristine Sulfate

Much less myelosuppressive than vinblastine but may cause more peripheral neurotoxic effects. Severe consequences if extravasation occurs, resulting in local phlebitis and severe pain. Anorexia and nausea may occur, especially in high doses

Drug interactions of Viscristine Sulfate

Asparingase may cause additive neurotoxicity; mitomycin may cause severe bronchospasm

Hypothyroidism

-Levothyroxine (T4) supplement
-oral and IV injectable
-Generally safe unless grossly overdosed

Hyperthyroidism in cats

-radioactive iodine (I-131)
-in cats the diseased tissue if preferentially destroyed while preserving normal thyroid tissue
-requires special facilities as cats must be quarantined until radioactive is minimal (Varies by state law - often 3-4 weeks)

Hyperthyroidism

-Methimazole (Tapazole)- primary treatment used either as maintenance therapy or prior to surgery or I-131 treatment
-Beta antagonist (blocker) - Atenolol, a beta-1 selective antagonist, sometimes used initially to control tachycardia

Diabetes mellitus (Glipizide)

-oral human tablet that increases insulin in type II diabetes
-never used in dogs - they only have type I
-Occasionally used in cats (25% are type II)
0High incidence of side effects (GI, liver damage)
-Insulin is always a better choice

Diabetes mellitus (insulin)

-necessary in dogs and preferred in cats
-cab be categorized based on
1.) species source: bovine; antigenic all similar to cats, porcine similar to dogs, human recombinant
2.) Duration of action

Insulin duration of action (Short acting)

(1-4 hr)
-Regular \= crystalline insulin
-used primarily in DKA
-Given SQ or as a CRI IV

Insulin duration of action (Intermediate)

(6-20 hr)
-Lente (Vetsulin), NPH
Give SQ only

Insulin duration of action (Long-acting

(8-24 hr)
-PZI (protamine zinc insulin)
-Glargine
-Give SQ only

Use of insulin

-first dose or dose change - primary monitor for hypoglycemia
-After steady-state (3-7 days) --\> glucose curve
-Roll vial to mix; dong shake
-Use correct syringe type!! (Veterinarian insulins U40; humanU100)
-to dilute, use only company supplied diluent
-essential that patient maintains consistent diet and exercise

Use of insulin (patient does not eat)

-first time give half dose of insulin and watch for hypocgycemia
-stop insulin if anorexia continues

Use of insulin (insulin shock \= hypoglycemia)

-due to overdose, deceased food intake, increased exercise
-50% dextrose IV at about 1cc/10 lbs,; dilute to 10-20% if using peripheral vein
-corn syrup or honey on gums
-monosaccharide absorbed across gums
-table sugar is disaccharide that has to be digested before absorption occurs in intestine

Insulinoma treatment

-insulin secreting tumor causes hypoglycemia
--give IV dextrose if in seizures and until medical management started
-Diazoxide
--decreases insulin secretion, mild diuretic
-Glucocorticoids
--decrease glucose use by tissues and promotes glucose production

Hypoadrenocorticism (Cushing's disease)

-mainly a disease of dogs (ferret adrenal tumors produce sex hormones rather than cortisol)
--production of excess cortisol
--2 types: adrenal turmor vs. pituitary-dependent
-Rarely, an adrenal tumor can be removed surgically - most managed medically instead

Hypoadrenocorticism (Cushing's disease) treatment

-oral only
-Selegilene-seldom used
-Ketoconazole - anti fungal that inhibits steroidgenesis (replaced by trilostane - more effective with fewer side-effects)
-mitotane
-trilostane

Hypoadrenocorticism (Cushing's disease)\---- milotane

-Lysodren
-selectively destroys the adrenal cortex
-not approved in animals but historically the main treatment used in dog
-Adjust based on ACTH stimulation test
-Major toxicity is iatrogenic Addison's disease
-Monitor appetite closely during induction dosing and perform ACTH stimulation at first sign of decreased appetite

Hypoadrenocorticism (Cushing's disease) \--- Trilostane

- inhibits enzyme necessary for cortisol production
-approved in dogs
-adjust dose based on ACTH stimulation test
-can cause iatrogenic Addison's disease
--as it does not destroy tissue, it is more reversible than mitotane induced Addison's

Hypoadrenocorticism (Addison's Disease)

-lack of glucocorticoids causes GI signs and decreased vascular tone, lack of mineralocorticoids causes high potassium, low sodium, and hypovolemia
Acute form: treat for hypovolemic shock and high potassium
Treatment provides supplemental glucocorticoids and mineralocorticoids

Hypoadrenocorticism (Addison's Disease) \---- Glucocorticoid supplement

- do not use prednisolone or prednisone until after ACTH stimulation test is done to make DX
--pred cross-reacts with cortisol on assay
--use low-dose dexamethasone instead
-maintenace: low dose prednisolone
--adjust based on clinical signs
--PU/PD\=dose too high
--Anorexia, vomiting \= dose too low

Hypoadrenocorticism (Addison's Disease) \---Fludocortisone (Florinel)

-One drug having both glucocorticoid and mineralocorticoid activity

Hypoadrenocorticism (Addison's Disease) \----DOCP (Percorten)

-pure mineralocorticoid
-give IM ever 21 to 30 days
-Adjust based on potassium and sodium serum concentrations

Hypoadrenocorticism (Addison's Disease)

-excess secretion of parathyroid hormone leads to high blood calcium
-surgically treated disease to remove the parathyroid tumor
-Prior to surgery the hypercalcemia must be managed
-Post-op hypocalcemia must be managed

Management of Hypoadrenocorticism (Addison's Disease)

-Promote removal of calcium from the kidney
--saline diuresis
--furosemide
-glucocorticoids
-Drive calcium back into the cell
--calcitonin IM/SQ
--pamidronate IV

Management of Hypoadrenocorticism (Addison's Disease)

-Supplemental calcium gluconate
--given IV slowly and monitor heart rate
-Vitamin D supplementation
--Vitamin D is activated by renal mechanisms, parathyroid hormone
--Vitamin D forms used Calcitrol
Dihydrotachysterol

Oxytocin

-used to cause milk "let down" (small doses) in nursing dams
-causes uterine contraction during birth and for next 2 days
-give IM or IV short half-life

Estrogen

-toxicity - bone marrow suppression in the dog, ovarian follicular cysts in cows
--Estradio cypionate injection \= "mismate shot" in bitch
-Only legitimate in small animal use is compounded diethylstilbestrol to control hormone-responsive urinary incontinence in the spayed bitch
-Used in some beef cattle implants as growth promoting; sometimes in combination with progesterone

Progesterone

-Use to keep animals out of estrus
-megaetrol acetate
--feed additive for feedlot heifers
-ovaban for the bitch
--can be given to either prevent estrus or shorten estrus
-do not use back-to-back due to high risk of pyometria
-has glucocorticoid activity, may cause diabetes
-alternogest (ReguMate
--oral liquid given daily to suppress estrus in mares
-Use in some beef cattle implants as growth promoting; usually in combination with estrogen