Pharmacology Tutoring- Endocrine Drugs

What does the endocrine system rely on to control how much hromone is produced?

negative feedback mechanism

Describe the negative feedback mechanism related to endocrine hormones.

-Gland 1 detects low hormone levels

-Gland 1 sends a signal to Gland 2 which then produces enough of the hormone for the "end product"

-the hormone sends negative feedback to gland 1 to stop gland 2 from making too much of the hormone

What is gland 1?

hypothalamus in the brain

Hypothalamus produces what hormone, to do what?

produces hormone 1 to stimulate endocrine gland 2

What is gland 2?

the pituitary gland

The pituitary gland produces what hormone, to stimulate what?

produces hormone 2 to stimulate endocrine gland 3

What is endocrine gland 3? and what does it do?

-the target gland, it produces the hormone the body needs

-also produces the negative feedback

What is an exogenous compound?

originating outside of the body

ex. drug that is similar to natural endogenous hormone

What is an endogenous hormone?

originating from within the body

What are the 2 things an exogenous drug will do?

-the same beneficial effect as the natural endogenous hormone

-cause the same negative feedback mechanism that endogenous hormone does

Because exogenous drugs have the same effect as natural hormones AND causes same negative feedback loop, what do we need to remember when giving these drugs?

Have to be given carefully, or they can cause hormone imbalances

Describe the normal thyroid gland function?

1. Hypothalmus releases Thyrotropin-Releasing Hormone

2. TRH stimulates pituitary gland to release Thyroid Stimulating Hormone

3. Pituitary TSH stimulates thyroid gland to produce T3 and T4

What is T3?

Triiodothyronine- biologically active form of thyroid hormone

What is T4?

Thyroxin which is converted by enzymes in the body tissues to T3

Doing what converts T4 to T3?

Removing an iodine

What is TRH?

thyrotropin releasing hormone

What is TSH

thyroid stimulating hormone

What does T4 act as?

acts as a circulating precursor reservoir of hromone to be converted to T3 as needed

T3 and T4 are released into the blood and taken up by cell's in the body to do what?

increase the body's metabolic rate

What species more commonly get hypothyroidism (low T3, T4)?

dogs

What species more commonly get hyperthyroidism (high T3 T4)?

cats

What is primary thyroid disease?

problem with the thyroid gland itself

What is secondary thryoid disease?

thyroid normal; problem with the pituituary gland (TSH)

What is tertiary thyroid disease?

thyroid and pituituary normal; problem with hypothalamus (TRH)

What is different about secondary and tertiary thyroid disease?

the end result is the same, but the prognosis is much worse because it can affect other hormones as well

What is goiter?

Enlarged thyroid gland, BUT the problem is NOT with the thyroid gland itself

What species gets goiter and why?

cattle that are raised strictly on pasture without mineral supplementation -lacking iodine

Having a low T3 and T4 has what effect on TRH and TSH release?

Makes hypothalamus and pituitary send extra TRH and TSH, so the thyroid keeps trying to make hormones and enlarges

What is the treatment for goiter?

supplemental iodine

What are T3 and T4 the main regulators of?

metabolic rate and cellular metabolism

What are the clinical signs of hypothyroidism?

-lethargy

-weight gain (in spite of normal consumption of food)

-heat-seeking behavior

-bradycardia

-decreased growth of young animals,

-alopecia or dry scaly skin

What is the most common treatments of hypothyroidism?

-synthetic T4 (levothyroxine)

*this is preferred over synthetic T3 (liothyronine)

What is the advantage of T4 over synthetic T3?

-it allows each tissue to convert T4 to T3 based on metabolic need

-levothyroxine returns T4 and T3 to normal levels, but with T3, only T3 normalizes

Why does levothyroxine need to be dosed less frequently than T3?

it has a longer half life

Thyrotoxicosis

clinical signs resulting from excessive thyroid hormone

True or False: When giving a patient levothyroxine, you should always stick with the same brand and not constantly switch

True

What is the concern with hypothyroid animal that are also diabetic?

-If they have hypothyroidism, their insulin receptors become less responsive and can cause the patient to be hyperglycemic

-if the patient is taking meds and its thyroid levels become normal, then insulin will start working again and cause the patient to become hypoglycemic

What is better absorbed from GI tract, T3 or T4?

T3

What are the clinical signs of hyperthyroidism?

-weight loss, despite increased appetite

-tachycardia

-heat intolerant

-polydipsia, diarrhea, unkempt hair coat

-palpable enlargement of one side of thyroid gland

What are the 4 treatment options for hyperthyroidism?

-surgical excision of thyroid tumor

-injection of radioactive iodine

-inhibition of thyroid hormone production

-low iodine diet

What is the anti-thyroid drug used for treatment of hyperthyroidism?

methimazole (felimazole, tapazole)

-blocks thyroid tumor's ability to use iodine to produce T3 or T4

What can hyperthyroidism "hide" in cats and how can it be revealed?

it can hide reduced renal function and when you give methimazole, makes the thyroid levels normal and will reveal the reduced renal function

What is radioactive iodine also known as?

I131

What does radioactive iodine do to the tumor?

the tumor absorbs a lethal dose of the radiation and it destroys the tumor

How do iodine limited diets work?

prevent formation of T3/T4 by limiting iodine needed to create the hormones

True or False: the pancreas is both exocrine and endocrine function

True

What are 3 pancreatic hormones and which one is used for therapy?

-insulin, glucagon, somatostatin

-insulin is the only one used for therapy

What does insulin do?

causes cells to actively transport glucose from blood into cells

What happens without insulin?

glucose remains in blood --> hyperglycemia

What happens with lack of insulin?

diabetes mellitus

What produces insulin?

beta cells in the pancreas

What is the most common cause of diabetes mellitus?

destruction of beta cells

Type 1 diabetes

-AKA insulin dependent diabetes mellitus

-beta cell destruction and lack of enough insulin

-insulin must be given by injection

Type 2 diabetes

-AKA NON-insulin dependent diabetes mellitus

-results from a problem with the insulin receptor but the animal's beta cells are producing appropriate amounts of insulin

Porcine insulin zinc suspension (Vetsulin)

-pork insulin

-antigenically similar to do insulin

-insulin of choice for dogs and cats

What insulin is created by combining strands of DNA together that do not occur in nature

Recombinant human insulin (insulin glargine and insulin detemir)

What determines the duration of insulin?

How quickly/slowly the crystal dissolves and releases insulin

What type of insulin is short acting?

regular (crystalline) insulin

What is the only insulin that can be given IV?

regular (crystalline) insulin

What type of insulin is intermediate acting?

NPH (neutral protamine Hagedorn) and porcine insulin zinc suspension (Vetsulin)

What type of insulin is long acting?

protamine zinc insulins (PXI), insulin glargine, insulin detemir

How do we need to resuspend Vetsulin?

"should be shaken thoroughly"

*most other insulins need to be gently rolled

What drug is an oral hypoglycemic agent, combines with beta cels in pancreas and stimulate release of additional insulin?

*usually in dogs only

glipizide (sulfonylurea compounds)

What are the uses for reproductive drugs in food animals and equines?

-synchronize estrous cyle

-delay the onset of estrus

-terminate pregnancies

-induce ovulation (with persistant follicles)

What do we use reproductive drugs for in dogs and cats?

prevent pregnancy or alter the state of the uterus

How do female reproductive endocrine drugs work?

by blocking or enhancing the normal reproductive physiology

What are the two phases of the estrous cycle?

-follicular phase

-luteal phase

Phase that is controlled by corpus luteum and ends with lysis of CL and return to follicular phase

luteal phase

Phase that is controlled by ovarian follicular cells that contain the egg

follicular phase

How does the estrous cycle-follicular phase start?

starts with neural input, presence of estrogen or absence of progesterone

Describe the negative feedback mechanism for the estrous cycle-follicular phase.

-hypothalamus releases gonadotropin releasing hormone (GnRH)

-pituitary gland releases follicle stimulating hormone (FSH)

-FSH stimulates ovarian follicles development

-follicle produces estrogen

-follicle produces inhibin which creates negative feedback on pituitary to decrease FSH

What happens to the gonadotropin releasing hormone when the follicle matures?

-GnRH releases in a different way and now stimulates pituitary to release luteinizing hormone

-LH causes mature follicle to rupture and release the egg

-LH transforms the follicular cells into cells of the corpus luteum

*this ends follicular phase ans starts luteal phase

What does the corpus luteum produce?

progesterone

What is the function of progesterone?

shut down the hypothalamus, pituitary and follcile system and prepares uterus to receive implant and support of fertilized ovum

What happens when the corpus leteum degenerates?

-progesterone stops being produced

-negative feedback removed

-cycle starts over again to stimulate follicle formation

What is the hormone of pregnancy produced by the corpus luteum?

progesterone

What would terminate a pregnancy?

lack of progesterone

What does estrogen do during partuition?

-makes myometrium more "twitchy" in uterus

-causes more oxytocin receptors to appear on the myometrium

Gonadorelins tend to cause greater release of _______ than _______?

luteinzing hormone than follicle stimulating hormone

When are gonadotropin-releasing hormone drugs or gonadorelins used for cattle?

in timed-artificial insemination protocols which are used to bring all cattle in a herd into estrous at the same time

What are gonadotropins?

hormones or drugs that have an "affinity to" the gonads (ovaries, testis)

What do modern gonadorelins stimulate?

release of natural LH or FSH, so the gonadotropins are used far less in vet med than they used to be (gonadotropins are FSH or LH LIKE compounds, not natural)

Progestins

refers to group of progesterone-like hormones

Progestational hormones

progestins

Progestogen or progestagen

synthesized drug that mimics progesterone effects

synthetic progesterone like drug that is used in mares orally

Altrenogest (Regumate)

synthetic progesterone like drug-feed additive for heifers

Melengestrol acetate (MGA)

What are progestins, progestogens and progestational hormones used for?

they suppress GnRH, FSH, and LH which stops follicle developlemt and prevents estrus (heat)

-used in large animals to prevent them from coming into heat until they can be bred

How can progesterone like drugs lead to metritis or pyometra?

they cause uterus lining to thicken and secrete nutrient rich "uterine milk" to favor ova implantation which leads to bacterial growth

Why do we need to wear latex gloves with drugs like altrenogest or melengestrol?

progestogens are easily absorbed across skin and this can lead to prolonged pregnancy beyond expected due date

Why should people that have breast cancer not handle progesterone like drugs?

have estrogen effects

Name the 2 drugs that are estrogen compounds

estradiol and estrol (Incurin)

What are estrogens used for in dogs?

only for treatment of urinary incontinence in spayed female dogs (tightens baldder sphincter)

Why are all estrogens banned in food animals?

Diethyl stilbestrol has been shown to be a potential carcinogen in people

How can estrogen cause increased risk of pyometra?

estrogen increases # of progesterone receptors to uterus which means there can be greater changes in the uterus

What is estrogen toxic to?

bone marrow (can cause aplastic anemia)

Name the prostaglandin drugs?

-dinoprost tromethamine (Lutalyse, InSync)

-cloprostenol (Estrumate)

What is the only phase that prostaglandins work in?

luteal phase

What are prostaglandins used for?

to synchronize estrous cycles by lysing the CL and terminating progesterone, causing the cycle to start again

what species CL is more sensitive to PG F2 alpha?

horses and cattle are more sensitive than dogs and cats