endocrine drugs

describe the 3 hormone gland negative feedback control.

1. hypothalamus produces hormone #1 to stimulate pituitary gland

2. pituitary gland produces hormone #2 to stimulate the target gland

3. target gland produces the hormone the body needs and the negative feedback on the hypothalmus

what effect an increase or decrease of the target endocrine gland’s natural hormone production or the introduction of a drug that mimics the effects of the natural hormone would have on the pituitary, the hypothalamus, and the further production of the target gland’s natural hormone?

• exogenous drug will do the same beneficial effect as the natural endogenous hormone

• exogenous drug will cause the same negative feedback mechanism that the endogenous natural hormone does

what is the negative feedback system?

what the endocrine system uses to control how much hormone is produced

what is an exogenous compound?

a compound originating outside of the body

what is an endogenous compound?

a compound originating from within the body

what secretes TRH, TSH, T3, T4?

• TRH = hypothalamus

• TSH = pituitary gland

• T3 & T4 = thyroid

describe the thyroid gland control mechanism/system.

1. hypothalamus releases thyrotropin-releasing hormone (TRH)

2. TRH stimulates pituitary gland

3. pituitary releases thyroid-stimulating hormone (TSH)

4. TSH stimulates thyroid to produce T3 and T4

what produces the negative feedback on the thyroid system?

hormones T3 and T4

what is T3 (triiodothyronine)?

the biologically active form of thyroid hormone

what is T4 (tetraiodothyronine or thyroxin)?

gets converted to T3 in the body tissues

what is the biologically active thyroid hormone?

T3 (triiodothyronine)

what is the role of T4?

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

how is T4 converted to T3?

by removing iodine

what is the difference between primary, secondary, and tertiary thyroid disease?

• primary = problem with the thyroid gland itself

• secondary = thyroid normal - problem with pituitary gland

• tertiary = thyroid and pituitary normal - problem with hypothalamus

which type of thyroid disease (primary, secondary, or tertiary) has the worst prognosis and why?

prognosis is worse for secondary & tertiary because it often affects the hormones too

which species is most likely to develop hypothyroidism?

dogs & horses (not as common)

what is hypothyroidism?

decreased levels of T3 & T4

which species is most likely to develop hyperthyroidism?

cats

what is hyperthyroidism?

increased levels of T3 and T4

what is a goiter and how does a goiter occur?

• enlarged thyroid gland, but the issue isn’t due to the thyroid gland itself.

• caused by a lack of iodine. low levels of iodine cause low levels of T3 & T4 which increases the release of TSH which causes the thyroid gland to keep working to produce T3 & T4

what effect do T3 and T4 have on the body overall?

main regulators of metabolic rate and cellular metabolism

what are the clinical signs associated with hypothyroidism?

• lethargy

• weight gain despite normal food consumption

• heat-seeking behavior

• bradycardia

• decreased growth of young animals

• alopecia, decreased hair growth, dry scaly skin

• foals of affected horses have poor CNS development and contracted tendons

what is levothyroxine? what is liothyronine? which is the treatment of choice for
hypothyroidism and why?

• levothyroxine is synthetic T4

• liothyronine is synthetic T3

• levothyroxine is the treatment of choice for hypothyroidism because it allows each tissue to convert T4 to T3 based upon the metabolic need, and therefore normalizing both T4 & T3 levels. whereas liothyronine would only normalize T3 levels

what is thyrotoxicosis?

clinical signs resulting from excessive thyroid hormone

what is euthyroidism?

normal thyroid levels

what impact does hypothyroidism have on blood glucose? why?

hypothyroidism causes insulin receptors to become less responsive to insulin, which causes insulin resistance, leading to higher doses of insulin to be used

what is the concern when a patient with diabetes mellitus and hypothyroidism and the hypothyroidism is corrected?

when hypothyroidism is corrected, the insulin receptors will go back to working normally without the insulin resistance, so the increased dose of insulin that was being used during the animal’s hypothyroidism state will cause hypoglycemia.

under what conditions might synthetic T3 therapy be tried? why isn’t synthetic T3 therapy the first treatment of choice?

• T3 liothyronine will be used if synthetic T4 (levo) does not seem to be working

• T3 is usually not the treatment of choice because it bypasses the local tissue regulation of thyroid hormone using T4 to T3 conversion

what clinical signs are seen in patients with hyperthyroidism?

• weight loss despite increased appetite

• tachycardia

• heat intolerant

• polydipsia, diarrhea, unkempt hair coat

• more active, playful, aggressive

• palpable enlargement of one side of the thyroid gland

what are the 4 treatment options for hyperthyroidism? which are a control and which are a cure?

1. thyroidectomy - cure

2. radioactive iodine - cure

3. inhibition of thyroid hormone production - control

4. low iodine diet - control

why is methimazole sometimes used to determine if a hyperthyroid cat has an underlying renal insufficiency? why is renal disease sometimes hidden in a cat with hyperthyroidism? why does the kidney problem emerge when the cat is successfully treated for hyperthyroidism?

methimazole is an anti-thyroid drug that block’s the thyroid/tumor’s ability to use iodine to produce T3 & T4. so, it is used to decrease hyperthyroidism clinical signs, one of them being increased blood pressure. increased blood pressure causes increased perfusion of the kidneys, when an animal is euthyroid, signs of renal failure may appear since they no longer have increased blood pressure or increased perfusion of the kidneys.

how is radioactive iodine administered & how many times is it given?

given one time either SQ or IV

why does radioactive iodine only kill the thyroid producing tumor and not the normal thyroid tissue?

because iodine is only taken up by tissues that are actively secreting T3/T4, so since the thyroid isn’t producing any thyroid hormones because the tumor is doing all the work, only the tumor gets killed off

what determines how long a cat has to remain hospitalized in a special facility after ¹³¹I (radioactive iodine) treatment?

state regulations

how do prescription diets decrease the signs of hyperthyroidism? what are the special precautions that must be taken to prevent this treatment from failing?

• prescription diets decrease signs of hyperthyroidism by preventing the formation of T3/T4 by limiting iodine needed to create the hormones

• in order for this diet to work:

  • the diet must be strictly confined to prevent other sources of iodine from treats, snacks, other foods

  • patient cannot be on any other prescription diet

  • if multi-cat household, hyperthyroidism cat cannot have other cat’s food

what gland produces insulin and what cells within that gland produce insulin?

beta cells within the pancreas

what impact does insulin have on blood glucose? how does this occur?

insulin causes cells to actively transport glucose from blood into cells. without insulin, glucose remains in the blood which leads do hyperglycemia

why is there hyperglycemia in diabetes mellitus?

because in diabetes mellitus, there is a lack of insulin

what is the most common cause of diabetes mellitus in veterinary patients (especially dogs)?

destruction of beta cells

what causes type 1 diabetes/insulin dependent diabetes mellitus (IDDM)?

beta cell destruction and lack of enough insulin

what causes type 2 diabetes/non-insulin dependent diabetes mellitus (IDDM)?

a problem with the insulin receptors but the animal’s beta cells are producing appropriate amounts of insulin

which type of diabetes mellitus do dogs typically exhibit?

type 1

which type of diabetes mellitus do cats typically exhibit?

type 2

T/F - insulin must be given by injection only

true

why can’t insulin be given by mouth?

insulin is a protein and would be denatured by stomach acid and digested by intestinal enzymes, but it is a very big molecule so it would not be able to be absorbed

how is insulin classified?

1. species from which the insulin is derived

2. duration of action

what animal species of insulin can be safely used in dogs and cats? why can’t other species (e.g.,cattle) insulin be used in dogs or cats?

• porcine and human

• species differenced can generate antibodies against the insulin and reduce effectiveness

what does it mean if an insulin is a recombinant human insulin (what does recombinant refer to?)

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

what is insulin combined with to create crystals?

zinc or protamine (a fish protein)

what is the short acting insulin? intermediate acting? long acting?

• short acting = crystalline insulin

• intermediate acting = neutral protamine Hagedorn, porcine insulin zinc suspension

• long acting = protamine zin insulin, insulin glargine, insulin detemir

which form of insulin can be given IV?

crystalline insulin

what determines whether an insulin in short, intermediate, or long acting?

how quickly/slowly the crystal dissolves and releases insulin

which insulin is used to bring down high levels of glucose in the dog? what insulin is used to maintain control of diabetes in the dog? how is this different from the cat?

• bring down glucose in dog: crystalline insulin IV

• maintain control of diabetes in dog: neutral protamine Hagedorn or porcine insulin zinc suspension

• in cats: stabilize with crystalline insulin IV, then use protamine zinc to maintain

insulin is a suspension. how is it supposed to be re-suspended?

most insulin suspensions should be rolled gently back and forth between hands because shaking it can cause insulin molecule to break

• some manufacturer’s ask that you DO shake it (ex: vetsulin), in that case, follow the manufacturer’s instructions

where are insulin injections administered?

SQ ¾ to 2 inches on either side of the dorsal midline, any location between scapula and mid-lumbar

how do the oral hypoglycemic agents work? why don’t they work in the dog? are they still used in the cat?

• hypoglycemic agents lower (sulfonylurea compounds like glipizide) the blood glucose. they combine with beta cells in pancreas and stimulate release of additional insulin

• it does not work on dogs because the diabetes mellitus results primarily from a loss of beta cells. if not beta cells are present, they can’t be stimulated by glipizide or other hypoglycemic agents

• not used in cats

what cells or structure control the follicular phase? what indicates the end of the follicular phase?

• controlled by ovaria follicular cells

• ovulation ends follicular phase

what controls the luteal phase? what ends the luteal phase?

• controlled by corpus luteum

• ends with lysis of corpus luteum

describe the role of the hypothalamus, pituitary gland, and ovary in the follicular phase as far as what hormones they secrete, what those hormones do, and how they provide feedback on the cycle

• hypothalamus releases gonadotropin releasing hormone (GnRH)

• pituitary gland releases follicle stimulating hormone (FSH)

• FSH stimulates ovarian follicle development (oocytes). follicle also produces estrogen and inhibin

• inhibin creates negative feedback on pituitary to decrease FSH

what two hormones does GnRH release and from where are these hormones released?

follicle stimulating hormone and luteinizing hormone — both come from pituitary gland

what effect do FSH and LH have on the ovarian follicle?

• FSH = stimulates ovarian follicles development

• LH = causes the mature follicle to rupture and release the egg

what is the function of inhibin?

creates negative feedback on pituitary to decrease FSH which prevents litters

what hormone does the CL produce? what primary function does this hormone have on the uterus? what effect does it have on the estrous cycle?

• produces progesterone, whose job is to shut down the hypothalamus—pituitary—follicle system and prepare the uterus to receive, implant, and support a fertilized ovum

• the corpus luteum is on a “timer” and it degenerates if ovum is not fertilized. this causes progesterone production to stop, the negative feedback is removed from hypothalamus and pituitary gland and the cycle starts over

what is the hormone of pregnancy?

progesterone

what gland initiates the parturition process? what does it release? what does it cause to happen?

• fetus pituitary gland initiates parturition

• fetus pituitary gland releases adrenal corticotropic hormone (ACTH)

• the ACTH then causes the adrenal glands to produce cortisol

what does the uterus begin to secrete as a result of the cortisol release?

estrogen & prostaglandins

what impact does the prostaglandin release from the uterus have? what does that cause to happen?

• prostaglandins lyse the corpus luteum

• lysis of the corpus luteum terminates progesterone production, which maintained the pregnancy and kept the uterine myometrium “calm “

what impact does the estrogen released from the uterus have? what does it due relative to oxytocin?

• estrogen makes the myometrium “twitch”

• estrogen causes more oxytocin receptors to appear on the myometrium

what causes oxytocin release?

fetus pressure on cervix or stimulation of nipples

what does that oxytocin release do to the uterus?

causes uterine contractions

how are gonadorelins and gonadotropin releasing hormone (GnRH) related?

injections of gonadorelin drugs do not exactly mimic the pulse-pattern that natural GnRH uses to stimulate pituitary to release FSH or LH at appropriate times of the cycle

what do gonadorelins cause to be released, and from where are these hormones released?

cause a greater release of LH than FSH — pituitary gland

what are gonadorelins used for in cattle?

timed-artificial insemination

what is timed artificial insemination?

they’re protocols to bring the entire herd into estrous at the same time

how are gonadorelins different from gonadotropins? what are two examples of gonadotropins?

• gonadotropins are hormones or drugs that have an affinity for the gonads

  • ex: FSH and LH

what are two other sources for gonadotropins besides the anterior pituitary?

• human chorionic gonadotropin

• equine chorionic gonadotropin

what have gonadotropins been used for in the past? what is used more in place of gonadotropin drugs and why?

• were used to cause super-ovulation or stimulate testicular descent

• gonadorelins are used more now because they’re able to release natural LH or FSH

how is a progestin different from a progestational hormone and different from a progestogen?

• progestins = 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

synthetic progesterone-like drug used as a feed additive for heifers

melengestrol acetate

what effect do progestational hormones or progestogens have on the estrous cycle release of GnRH and FSH/LH?

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

why should you not handle progestogen drugs if you have breast cancer?

has an estrogen effect (estrogen can cause relapse of breast cancer)

what potential side effect in the uterus occurs with progestogen or progesterone use? why does it occur?

causes uterus lining to thicken and to secrete nutrient rich “uterine milk” to favor ova implantation → leads to bacterial growth that can predispose animal to metritis or pyometra

what precautions must pregnant women take when using progestogen drugs? why are progestogen drugs a potential threat?

should wear latex gloves because absorption of progestogen can prolong pregnancy beyond expected date

what effect do progesterones and progestogens have on insulin receptors? what does this do to the effectiveness of insulin? what happens to the blood sugar with progestational drug use?

• antagonizes ability of insulin to dock with insulin receptors

• glucose doesn’t move from blood into cells

• leads to hyperglycemia

for what purpose are estrogen drugs legitimately used for?

for treatment of urinary incontinence in spayed female dogs

what effect is possible on the uterus after estrogen administration? why is this?

increases risk of pyometra because estrogen increases the number of progesterone receptors on the uterus which makes it more sensitive to progesterone and thus causes greater changes in the uterus

what impact can estrogens have on the bone marrow production of cells? what is this condition called?

toxic to bone marrow, suppresses RBC and WBC production → anaplastic anemia

what are two prostaglandin drugs?

1. dinoprost tromethamine

2. cloprostenol

how do prostaglandins bring animals back into estrus when the animal is in the luteal phase? does this technique work in the follicular phase? why or why not?

they lyse the corpus luteum which terminates progesterone and causes the cycle to start again. does not work in the follicular phase because there is not a corpus luteum made in the follicular phase

how do prostaglandins terminate pregnancy?

terminating the corpus luteum source of progesterone

what other medical condition potentially puts people at risk if they accidentally come in contact with prostaglandins?

asthma

why is there concern about making sure prostaglandins are securely locked up?

people were stealing them to end unwanted pregnancies

how do prostaglandins control the estrous cycle?

lyse corpus luteum and terminates diestrus → animal returns to estrus within 2-5 days

how do progestins control the estrous cycle?

prolongs diestrus and prevents returning to heat until ready to do so (mimics corpus luteum lysis and return to heat)

for what are gonadorelins used for related to the estrous cycle control?

used in cows and mares to lyse persistent ovarian follicles or follicular cysts → takes them out of persistent estrus (nymphomania)

what is foal heat? how do progestins or progestogens prevent a mare from coming into foal heat?

• mares that come into heat shortly after foaling

• progestins inhibit FSH and LH release which stops follicular phase of cycle to prevent coming into heat

how do prostaglandins cause “short cycling”? How is this supposed to help a mare that has just foaled?

they’re given to mare as soon as she goes through estrus to shorten diestrus phase and bring back into estrus again soon

what is seasonal anestrus?

as days shorten, cycling stops

why are mares bred during the time of the year when they typically are not in heat?

so that they can foal as close to January as possible