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76 Cards in this Set

  • Front
  • Back
6 thyroid functions
1. Maintains metabolic homeostasis
2. Normal development
3. Regulates myocardial gene expression
4. Stimulates metabolism of cholesterol to bile acids
5. Stimulates synthesis of proteins
6. Stimulates increased cellular demand for oxygen
Hypothyroidism Signs
* Lethargy
* Weight gain
* Alopecia
* Cold intolerance
* Bradycardia
* Hypercholesterolemia
Hyperthyroidism Signs
* Weight loss
* Polyphagia
* Hyperactivity
* Tachycardia
* Vomiting
What is the enzyme responsible for catalyzing iodine/globulin into T4 & T3
Thyroid peroxidase
What is the enzyme responsible for catalyzing T4 to T3 in cells?
5’ Deiodinase
What drug types cause inhibition of 5'-deiodinase?
* Glucocorticoids
* Quinidine
What drug types cause displacement of thyroid function?
* Salicylates
* Furosemide
* Oleic acid
* NSAIDs
What drug types intefere with thyroid hormone secretion?
* Glucocorticoids
What drug types cause increased clearance of thyroid function?
* Phenobarbital
What drugs involve iodine and affect thyroid function?
* Potassium bromide
* Radiocontrast agents
* TMPS
How do glucocorticoids in dogs effect thyroid function?
* Lowers serum T3 (antiinflammtory dosage)

* T4 affected with chronic, high dose, daily therapy or immunosuppressive therapy.

* May be due to inhibition of 5’-deiodinase, reduced availability of plasma T4, or interference w/ thyroid hormone secretion
How do glucocorticoids in cats and horses effect thyroid function?
Has little effect on T4 in cat/horse
How does use of anticonvulsants effect thyroid function?
Decrease serum T4 concentrations
How does use of Quinidine effect thyroid function?
inhibit 5’-deiodinase
How does use of Salicylates, furosemide, or oleic acid effect thyroid function?
directly displace thyroid hormone from plasma binding sites
How does use of NSAIDs effect thyroid function?
because thyroid hormones are highly protein bound and NSAIDS can displace them
How does use of Phenylbutazone (NSAID) effect thyroid function?
Direct antithyroid (goitrogenic) effect, decreases total/free T4 in the horse
How does use of Carprofen (NSAID) effect thyroid function?
can cause a transient decrease in T4
How does use of Radiocontrast agents effect thyroid function?
Directly binds 5’-deiodinase or releases iodine to exert an antithyroid effect on the thyroid gland
How does use of Trimethoprim/ Sulfamethoxazole effect thyroid function?
T4 falls with long-term treatment due to interference with iodine metabolism
Thyroid Hormone Synthesis
What are the 2 thyroid hormone drugs?
1. L-thyroxine (T4)
2. L-triiodothyronine (T3)
Why would an animal be given L-thyroxine (T4) instead of L-triiodothyronine (T3)?
*Given to hypothyroid animals

* More physiological (in the body, T4 is released by the thyroid and then converted to T3)

* Gives better serum balance of T3/T4

* less expensive

* More consistent in bioavalability
Why would an animal be given L-triiodothyronine (T3) instead of L-thyroxine (T4)?
* Given to hypothyroid animals

* Non-responsive to T4

* Less desirable b/c less physiologic
Three Anti-Thyroid drugs discussed in class
1.Methimazole (MMI)
2.Propylthiouracil (PTU)
3.Radioactive Iodine
MOA of Methimazole (MMI)
and Propylthiouracil (PTU)

(anti-thyroid drugs)
* Blocks incorporation of iodine into thyroglobulin

* Prevents coupling of iodotyrosil groups

* Inhibits thyroid peroxidase
Adverse Effects of Methimazole (MMI)
and Propylthiouracil (PTU)
vomiting, GI signs, excoriations, liver toxicity
Why is Propylthiouracil (PTU)
not used as much anymore?
not used much anymore b/c autoimmune prob in cats; also inhibits 5’ diodinase
MOA of Radioactive Iodine
* Selectively destroys thyroid tissue after take up by thyroid gland

* Emits gamma rays and beta particles; most local tissue destroyed by beta particles
How is radioactive iodine given?
orally
Three Anti-Thyroid drugs discussed in class
1.Methimazole (MMI)
2.Propylthiouracil (PTU)
3.Radioactive Iodine
MOA of Methimazole (MMI)
and Propylthiouracil (PTU)

(anti-thyroid drugs)
* Blocks incorporation of iodine into thyroglobulin

* Prevents coupling of iodotyrosil groups

* Inhibits thyroid peroxidase
Adverse Effects of Methimazole (MMI)
and Propylthiouracil (PTU)
vomiting, GI signs, excoriations, liver toxicity
Why is Propylthiouracil (PTU)
not used as much anymore?
not used much anymore b/c autoimmune prob in cats; also inhibits 5’ diodinase
MOA of Radioactive Iodine
* Selectively destroys thyroid tissue after take up by thyroid gland

* Emits gamma rays and beta particles; most local tissue destroyed by beta particles
How is radioactive iodine given?
orally
Hypoadrenocorticism Signs
* Nausea
* Vomiting
* Hyponatremia
* Hyperkalemia
* Lethargy
* Dehydration
Hyperadrenocorticism Signs
 PU/PD
 Polyphagia
 Lethargy
 Pot belly
 Thin skin
 Alopecia
 Muscle wasting
3 zones of the adrenal cortex? What is each zone responisble for?
1. Zona Glomerulosa-Mineralocorticoids

2. Zona Fasiculata-Glucocorticoids

3. Zona Reticularis-Sex
Hormones
Treatment of adrenal insufficiency involves physiologic replacement of glucocorticoids and mineralocorticoids
Treatment of adrenal insufficiency involves physiologic replacement of glucocorticoids and mineralocorticoids
What are the 2 mineralocorticoid drugs used to for treatment of adrenal insufficiency?
1. Desoxycorticosterone
pivalate (DOCP)
2. Fludrocortisone acetate
MOA of Desoxycorticosterone
pivalate (DOCP)
Acts like aldosterone to retain Na+ and secrete K+
How often is Desoxycorticosterone
pivalate (DOCP) given?
Given every 25 days
In what species Desoxycorticosterone
pivalate (DOCP) is approved for?
Approved for use in dogs
MOA of Fludrocortisone acetate
Acts like aldosterone to retain Na+ and secrete K+
How often is Fludrocortisone acetate given?
Given every day

* Can see GCC side effects
What 3 drugs are used to treat Pituitary and Adrenal dependant hyperadrenocorticism?
1.Mitotane
2.Trilostane
3. Ketoconazole
MOA of Mitotane
Selectively destroys zona fasciculata/reticularis
(less effect on glomerulosa – aldosterone)
Adverse effects of Mitotane
GI signs, hypoglycemia, CNS depression, liver damage,electrolyte imbalances
In what animals should Mitotane not be used in?
Do not use in pregnant animals
MOA of Trilostane
Inhibits 3-Beta, hydroxysteroid dehydrogenase which
blocks synthesis of adrenal steroids


(pregnenolone to progesterone doesn’t happen)
In what species is Trilostane FDA approved?
FDA Approved in dogs
What contraindications are associated with Trilostane?
Pregnant animals - affects sex hormones
Adverse effects of Trilostane
vomiting, diarrhea, lethargy
MOA of Ketoconazole
Prevents conversion of lanosterol to cholesterol by
inhibiting CYP450 enzymes
Under what conditions is Ketoconazole used
Used in animals that don’t respond well to trilostane/mitotane
Why is Ketoconazole given in combination with other drugs?
Used in combination with other drugs to decrease dose because
inhibits CYP450 enzymes, preventing metabolism of drug in liver
Adverse effects of Ketoconazole
vomiting, diarrhea
What 2 drugs are used for only Pituitary dependant hyperadrenocorticism?
1.Selegiline (L-deprenyl)
2. Pergolide
MOA of Selegiline (L-deprenyl)
Monoamine oxidase B inhibitor
B – dopamine breakdown is inhibited so increases dopamine
What does Selegiline (L-deprenyl) do to dopamine, ACTH, and cortisol?
-Increases dopamine, decreases ACTH, decreases cortisol
How does Selegiline (L-deprenyl) affect the disease process?
Alters clinical signs, not disease process
Adverse effects of Selegiline (L-deprenyl)
generally safe, vomiting/diarrhea
MOA of Pergolide
Dopamine agonist @ D1 & D2 receptors
Why is Pergolide no longer formulated
-No longer formulated because of human cardiovascular effects
so must be compounded
What species is Pergolide used in?
Used in horses
Adverse effects of Pergolide
Dopamine suppresses prolactin which inhibits lactation in
pregnant or nursing
How/where is insulin produced?
Produced in Beta cells of islets of langerhans as preproinsulin then becomes proinsulin and finally becomes insulin
Diabetes Mellitus Symptoms
 PU/PD
 Polyphagia
 Weight loss
 Lethargy
 Hyperglycemia
 Glycosuria
Goal of treatment when using insulin
want to get blood glucose close to normal, but avoid hypoglycemia
MOA of all insulin replacers
binds to insulin receptor and autophosphorylation occurs, other proteins are phosphorylated/dephosphorylated
What are the actions of insulin drugs?
* Facilitate cellular uptake & metabolism of glucose

* Promote glycogen/protein/fat synthesis

* Uptake of ions into cells
What are the 3 fast acting insulin drugs? When do you use them?
1. Regular human insulin
2. Lispro – synthetic human recombinant
3. Aspart – synthetic human recombinant


* Use for complicated diabetes (not eating, emergency, diabetic ketoacidosis); act quickly but don’t last long
What are the 4 intermediate to long acting insulin drugs?
1. NPH (isophane) – human insulin recombinant

2. Protamine zinc (pork insulin) t

3. Glargine – synthetic, used in cats

4. Detemir – synthetic, used in cats
What is the one insulin drug that is a sulfonylurea?
Glipizide
MOA of Glipizide
inhibit ATP dep K+ channels, resulting in depolarization of beta cells and release of insulin


*** Glipizide is an oral hypoglycemic agent so must be capable of secreting insulin from beta cells
Adverse effect of Glipizide
amyloid deposition in cats