Pharm Exam 2: Endocrine P1 & 2

Exocrine, endocrine

2 Portions of the Pancreas:

-____ pancreas = hormones for digestion (lipase, amylase)

- ____ pancreas = hormones for blood glucose regulation (insulin, glucagon)

Exocrine (endocrine = 2-3% of pan. mass)

Does the exocrine or endocrine pancreas compose the bulk of the organ?

Glucagon, insulin

Endocrine pancreas Cells:

-Alpha cells (25%) produce ____

-Beta cells (60%) produce ____

GLUTs (Facilitated diffusion), SGLTs (Sodium-glucose linked)

Glucose can't pass through the cell membrane by simple diffusion. What are the 2 types of glucose transporters?

GLUT4

What glucose transporter is insulin-regulated/

Insulin, glucose

____ stimulates the translocation/deposition of GLUT-4 into the cell membrane & allows ____ to move into cell

True

True or False: GLUT-4 channels separate from the cell membrane & move back inside the cell when insulin is not available.

False (most cells require insulin but not neurons, RBC, liver, WBC, beta cells, renal tubular epithelium, & intestinal epithelium)

True or False: Insulin is needed for glucose transport in all

cells in the body.

Potassium, phosphorus

Insulin binding increases cell membrane permeability & decreases blood concentration to ____ & ____.

*Increases perm to amino acids (not clinically helpful)

Potassium

In blocked cats, what electrolyte can cause heart problems?

-Treatment: Insulin can be given to decrease blood concentrations & increase cellular concentration of this electrolyte

In starved animals, what electrolyte can enter the cells too quick in Refeeding Syndrome?

-Treatment: Insulin can be given to decrease blood concentrations & increase cellular concentration of this electrolyte

Type 1

Diabetes mellitus that's an absolute deficiency seen in children & almost all dogs

-Beta cells don't make insulin = Insulin dependent for life

-Causes: immune-mediated, genetic, pancreatitis, idiopathic

Type 2

Diabetes mellitus that's a relative deficiency seen in adults & cats

-Due to Dysfunctional B cells (can't produce enough insulin) or insulin resistance (insulin not creating proper response)

Type 2

Do 10-20% of cats go into remission from Type 1 or Type 2 diabetes mellitus once the underlying cause is treated?

Obesity

What condition can predispose dogs & cats to diabetes mellitus?

Amino acids, chains, C peptide (connecting peptide)

What is the general structure of insulin?

-Similar structure across species

Bovine

What insulin source is antigenically similar to cats?

*No immune response/attack should be mounted when given

Porcine

What insulin source is antigenically similar to dogs?

*No immune response/attack should be mounted when given

Short Acting (1-4 hours)

What are the duration of these types of insulin:

-Humulin R & Novolin R

-Usually used for DKA

-Subcutaneous or CRI

Intermediate Acting (6-20 hours)

What are the duration of these types of insulin:

-Humulin N & Novolin N

-Lente (Vetsulin®)

-Subcutaneous

Long Acting (8-24 hours)

What are the duration of these types of insulin:

-PZI (ProZinc®)

-Glargine (cats), Detemir

-Subcutaneous

Hypoglycemia

After the first dose or dose change of insulin, monitor for???

3-10 days

How long does it take to reach a steady state after beginning insulin or changing doses?

*Can assess by observing with clinical signs, glucose curve, or continuos glucose monitor

Blood, subcutaneous

Glucose Curves measure _____ glucose, while Continuous Glucose Monitors measure _____ glucose.

U-40, U-100

Insulin Syringes:

-ProZinc & Vetsulin = ____ syringes

-Glargine, NPH, & Regular = ____ syringes

*Refrigerate insulin & roll gently to mix (shaking = bubbles)

Dogs

Are these insulins for dogs or cats:

-Porcine Lente (Vetsulin) =Start BID

-NPH (Novolin) =Start BID

-PZI (ProZinc)

Cats

Are these insulins for dogs or cats:

-Glargine (Lantus)

-Porcine Lente (Vetsulin)

-PZI (ProZinc)

After

Should insulin be given before or after a meal?

Half dosage (Stop insulin if anorexia continues)

How much insulin should be given to a patient if they don't eat/skip their scheduled meal?

Hypoglycemic

Should the insulin dose be changed if the patient is hypoglycemic or hyperglycemic?

Insulin overdose

In relation to diabetes, what do these actions treat?

-Give animal food

-Rub Karyo/corn syrup/honey on gums

-IV 50% dextrose

Control clinical signs

When monitoring insulin therapy, is it more important to control clinical signs (PU/PD, polyphagia, weight loss, etc) or ensure the glucose levels are WNL?

True

True or False: Diabetics are more prone to infection.

Acarbose

Oral α-glucosidase inhibitor (maltase, sucrase) that prevents the breakdown of starch to glucose

-Not very effective in Dogs or cats

*Side effects: Diarrhea, weight loss in 35%

-Expensive, can be used as a supplemental therapy possibly

Glipizide

Oral medication that stimulates β-cell secretion of insulin in cats with some residual B-cell function (Non-Insulin Dependent Diabetes Mellitus)

-Don't use for treatment of DKA, side effects= GI signs, hepatotoxicity

-Not very effective in general

SGLTs

Glucose transporters that are ATP & sodium dependent

-Don't need insulin

SGLT1, SGLT2

Glucose Transporters:

-____ causes glucose absorption in Intestinal epithelium (lumen) from any glucose in the diet, while ____ causes glucose retention in the proximal tubules (kidney).

SGLT2 Inhibitors (Flozins)

Drugs that prevent the reabsorption of glucose in proximal tubules

-Cats may urinate out more glucose & initially drink more water to alleviate dysfunction of beta cells

*Reduces risk of hypoglycemia

Cats (Drug requires functional β cells/circulating insulin - dogs don't have this)

Are Flozins (SGLT2 Inhibitors) for cats or dogs only?

SGLT2 Inhibitors (Flozins)

What type of drug are these (Hint: in cats only):

-Velagliflozin

-Bexagliflozin (BexaCat®)

Insulinoma

Neoplastic disorder that causes an excessive excretion of insulin

*Therapy of choice is surgical excision but sometimes medical management must be selected instead

Hypoglycemia

What is a major complication of insulinomas?

Prednisone

Steroid used to manage insulinomas & prevent hypoglycemia by:

-Increasing gluconeogenesis

-Decreasing blood glucose uptake

-Stimulating glucagon secretion

Diazoxide

Drug that helps manage insulinomas & decrease hypoglycemia by decreasing insulin secretion

Glucagon

Hormone that can help manage insulinomas & prevent hypoglycemia by stimulating:

-Hepatic glycogenolysis

-Hepatic gluconeogenesis (amino acid mobilization)

-Lipolysis

Hyperthyroidism

Most common endocrine disorder in cats

-Excessive production & secretion of thyroid hormone (T4 & T3) by the thyroid gland

*One of the most common geriatric diseases in cats

Metabolic rate

Thyroid hormone increases ___ ____ by increasing catabolic effects, cardiovascular (increase HR & CO), & GFR.

*Reason why hyperthyroid cats get so skinny & can have high BP

Adenoma (or adenomatous hyperplasia)

What benign lesion in the thyroid is the main cause of hyperthyroidism in cats?

No (cats would then require supplemental thyroid hormone for the rest of their lives)

Is surgery to remove the thyroid recommended in hyperthyroid cats?

Hypothyroidism

Endocrine disorder seen in dogs due to either:

1) Lymphocytic destruction ("thyroiditis") with inflammatory infiltration & replacement with fibrous connective tissue or

2) Atrophy of thyroid; Replaced by adipose & connective tissue

Hypercalcemia

Excessive calcium in the blood that can cause Azotemia/dehydration, weakness, & Decreased appetite

Hypercalcemia

What condition has the following treatment options:

-Symptomatic treatment

-Saline diuresis (0.9% NaCl)

-Bisphosphonates

-Glucocorticoids

Hyperadrenocorticism (Cushing's disease)

Excessive cortical secretion due to a functional tumor in the pituitary gland or adrenal gland

ACTH

Functional pituitary tumors produce too much ____, which causes Cushing's disease.

-Treatments: Surgical, radiation, or Medical management

Cortisol

Functional adrenal gland tumors produce too much ____, which leads to Cushing's disease.

*Treatments: Adrenalectomy or Medical management

Radioactive Iodine (I-131)

Ideal therapy for Hyperthyroidism in cats

-Subcutaneous injection that preferentially destroys diseased tissue (concentrates in hyper functional Thyroid cells) while preserving normal thyroid tissue

-Cats must be Quarantined for ~1 week post treatment

Methimazole

Hyperthyroidism drug that inhibits thyroid peroxidase to block thyroid hormone synthesis

*Prevents Iodide oxidation & "Coupling" of tyrosine residues

Radioactive Iodine (I-131)

Is Radioactive Iodine (I-131) or Methimazole the ideal treatment for hyperthyroidism in cats?

Levothyroxine

Oral or intravenous thyroid (T4) supplement used to treat Canine Hypothyroidism

-Human products = Poor absorption

-Improvement in 1-6 weeks; Requires T4 concentration monitoring after 4-8 weeks

1/2 dose

How much levothyroxine should dogs with cardiac disease receive compared to non-diseased dogs?

Hyperthyroidism

Levothyroxine is generally a safe treatment for canine hypothyroidism but overdoses can cause ....

Saline diuresis (0.9% NaCl)

What is used to correct the dehydration due to hypercalcemia in addition to increasing renal Ca2+ excretion?

Bisphosphonates

Hypercalcemia drug that decreases osteoclastic activity to prevent Ca being extracted from bones & released into the blood

*Zoledronate (lasts wks), Pamidronate (last wks), & Alendronate (Fosamax, oral med in cats mostly)

-Not a 1st line for hypercalcemia

Glucocorticoids

Hypercalcemia drug used to decrease bone resorption and decrease GI & renal absorption (which increases Ca excretion)

-Could potentially make obtaining a definitive diagnosis difficult

Furosemide

Diuretic that's rarely used to treat Hypercalcemia in a rehydrated animal

-Inhibits renal Ca2++ reabsorption in ascending Loop of Henle

***Avoid if dehydrated

Gluconate, carbonate

Supplemental Calcium To treat Hypocalcemia:

- Calcium _____ = Given IV slowly & monitor HR

- Calcium ____ = Give orally, Ex: tums

Calcitriol

Active form of vitamin D used to treat hypocalcemia by targeting the SI to increase Ca absorption & bone to increase Ca resorption

-Other uses: Treat active form in renal disease & post parathyroidectomy (not PTH = low Ca)

Mitotane (Lysodren)

Drug used to treat Hyperadrenocorticism via selective adrenocorticolysis

-Destroys overactive cells in the adrenal gland's zona fasciculata & zona reticularis but spares the zona glomerula

*Must give with food

Zona glomerulosa

What layer of the adrenal gland is spared when using Mitotane (Lysodren)?

-Layer may be attacked in sensitive dogs or without proper monitoring

Adrenal

When using mitotane to treat Hyperadrenocorticism in dogs, are higher doses needed with pituitary or adrenal tumors?

Trilostane

Competitive inhibitor of 3β hydroxysteroid dehydrogenase (3βHSD) that decreases the synthesis of Cortisol, Aldosterone, & Androgens

Trilostane

Drug that can be used to control clinical signs of:

1) Dogs with pituitary dependent hyperadrenocorticism (PDH)

2) Dogs with adrenal dependent hyperadrenocorticism (ADH)

3) Feline PDH

Trilostane

Drug that doesn't directly treat Cushing's Disease but controls clinical signs & improves patient QOL

Ketoconazole

Anti-fungal agent that inhibits 11β-hydroxylase & other cP450 enzymes

*Can be used to treat Cushing's but should be cautious about it

*Side effects: Hepatotoxicity

Deprenyl (Selegiline)

Monoamine oxidase inhibitor that increases dopamine

-Rarely used to treat Cushing's (DON'T USE per Thomason)

Addison's (hypoadrenocorticism)

Trilostane should be given with food to avoid the development of _____'s disease in dogs.

*Reversible

Transdermal gel

Oral methimazole can cause the following side effects. What route can decrease the severity of these side effects?

-GI upset

-Bone marrow suppression (Neutropenia/Thrombocytopenia)

-Hepatotoxicity

-Facial excoriation

Renal decompensation

A side effect of any treatment for hyperthyroidism

-Occurs in 15-20% of pre-treatment non-azotemic cats

*Cats may have an underlying renal disease, hyperthyroidism increases GFR, treatment normalizes GFR, & renal disease is unmasked

Methimazole

To avoid significant renal decompensation, should a trial run be done with methimazole or Radioactive Iodine (I131) first?

Amlodipine, Propranolol, Atenolol

Treating Conditions In Hyperthyroid Cats

-Hypertension → _____

-Sympathetic Overdrive (Tachycardia, arrhythmias, hyperactivity, aggression) can be treated with ____ & _____ (Β-blockers)

Iatrogenic Addison's disease (hypoadrenocorticism)

Major toxicity associated with mitotane

-Monitor appetite closely during induction dosing & perform ACTH stim at first sign of decreased appetite

-Send home dexamethasone