Endocrine and Reproductive

Pharmacology

Dr. DHIREN B. BHOI

M.V.Sc., (Gynaecology)
E. Mail:[email protected]
 Learning Objectives
 Review the physiology of the endocrine
system, and know:
 The endocrine glands
 Control mechanisms of the system: + and -
feedback
 What hormones are: endogenous and
exogenous
 Be able to describe the neurohomonal reflex
 Be able to describe the location, function and
hormonal products of various endocrine
glands
 Learning Objectives
 Know the uses and classes of
gonadotropins, gonadal hormones,
progestins, and prostaglandins used in
Veterinary Medicine
 Know the uses and classes of drugs
affecting the uterus and uterine
contractility
 Be able to write a definition of pheromone
and give and example
 Learning Objectives
 Be able to describe the treatment for hypo and
hyperthyroidism
 Know the endogenous sources of insulin and
the metabolic effects of insulin
 Know the exogenous sources of insulin, and
their characteristics
 Know the mechanism of action of growth
promoters
 Know the clinical uses of anabolic steroids
 OUTLINE
 Introduction
 Anatomy and Physiology Review
 Hormones of reproduction
 Gonadotropins, gonadal hormones
 Prostaglandins
 Drugs affecting Uterine Contractility
 Pheromones
 OUTLINE
 Thyroid Hormones
 Hyperthyroidism
 Hypothyroidism
 Diabetes Mellitus treatment
 Insulin
 Hyperglycemic agents
 Growth promoters
 Anabolic Steroids
 Don’t forget to study definitions at the beginning
of the chapter!
 Introduction
 Endocrine System
 Glands
 Groups of cells that secrete regulatory
substances directly into blood stream
 Regulatory substances diffuse across cell
membranes
 One of two major control mechanisms for the
body (the other is the nervous system)
 Linked closely with the nervous system
through the hypothalamus to allow adaptation
of reproduction and survival to changes in the
environment.
 Introduction
 Glands:
 Pituitary, adrenals, thyroid, ovaries, testicles,
pancreas, kidneys
 Glands produce hormones: Be able to list
the hormones produced by each gland!
 Hormones act on target organs
 influence the physiologic activity
 Introduction
 2 reasons hormones are given to an
animal:
 Correct a deficiency
 Cause a desired effect

 Is supplementation of a hypothyroid dog done

through exogenous or endogenous hormone
supplementation?
 Anatomoy & Physiology
 Pituitary is the center
 Control of endocrine system
 Located in the base of the brain ventral to the
hypothalamus.
 Bi-lobed: anterior (adenohypophysis) and
posterior (neurohypophysis).
 Anatomoy & Physiology
 Hypothalamus controls the anterior
pituitary
 Releasing hormones
 Hypophyseal portal system
 Causes release of trophic hormones: TSH,
ACTH, LH, FSH, Prolactin (LTH) and
Growth hormone (GH)
 = indirect acting hormones
 Anatomoy & Physiology
 Hypothalamus PRODUCES vasopressin
and oxytocin
 Travel down the nerve fibers to the posterior
pituitary
 STORED IN THE POST. PIT.
 = direct acting hormones
 Anatomoy & Physiology
 CONTROL:
 Feedback mechanism:
 Plasma levels of a hormone affect its secretion by
affecting the gland that produces the hormone.
 Negative or Positive

 NEGATIVE feedback:
 High plasma levels
 POSITIVE feedback:
 Low plasma levels
 Anatomoy & Physiology
 Neurohormonal Reflex
 Release of oxytocin from the P.P.
 Stimulation of the udder by a nursing calf

 Stimulation of the uterus and vagina in

parturition
 Stimulation of the cerebral cortex by

sensory stimuli associated with nursing of

the calf
 Anatomoy & Physiology
 Reproductive control (estrus)
 Proestrus, estrus, diestrus and anestrus
 Or…
 Follicular (Estrogen) and luteal (Progesterone)
phases
 Hormones produced by the follicle vs the corpus
luteum on the ovaries
 Hypothalamus: GnRH which acts on the A.P.
 A.P. releases FSH and LH
 Anatomoy & Physiology
 FSH causes growth and maturation of the
follicle which produces estrogen and
inhibin (negative feedback to the
hypothalamus) (Follicular phase)
 LH causes ovulation and CL formation
(Luteal phase)
 CL produces progesterone which supports
pregnancy
 Progesterone acts as negative feedback on
the hypothalamus and GnRH release
 Anatomoy & Physiology
 Prostaglandin secreted by uterus
 Lysis of the CL
 End of diestrus if not pregnant
 Anatomoy & Physiology
 Parturition: hormones are also produced
by the baby!
 ACTH
 Increased cortisol from the adrenal glands
causes increased estrogen and prostaglandin
release from the uterus.
 This allows the uterus to be primed to
respond to oxytocin and contractions begin.
 Have to have a viable baby for this to occur
correctly – if not…dystocia often results.
Hormones of reproduction used
in practice
 Common in large animal practice
 Synchronize estrus
 Suppress estrus
 Induce estrus
 Treatment of cystic ovaries
 Termination of pregnancy
 Hormones of reproduction used
in practice
 Gonadotropins and Gonadal Hormones:
 Gonadotropins
 Estrogens
 Androgens
 Progestins
 Prostaglandins
 Dinoprost tromethamine
 Fenprostalene
 Fluprostanol
 Cloprostanol
Hormones of reproduction used
in practice
 Drugs affecting Uterine contractility
 Oxytocin
 Ergot
 Prostaglandins
 Corticosteroids
 Pheromones
 Misc…
 Bromocriptine, leuprolide, melatonin,
neutersol
Hormones of reproduction used
in practice
 Gonadotropins
 Act like GnRH, LH and FSH
 Cause RELEASE of LH and FSH or cause
activity like that of LH or FSH.
 LH: From pituitary extracts, pregnant woman
urine (hCG)
 FSH: pituitary extracts, PMS between days 40
and 140 of pregnancy
 GnRH: synthetic
Hormones of reproduction used
in practice
 Gonadotropins
 Examples:
 gonadorelin (GnRH) to treat cystic ovaries in cattle,
 chorionic gonadotropin (hCG), mimics LH in

females, and in males, stimulates production of

male hormones by the testicles. Used to treat
nymphomania and cryporchidism
 FSH-P: pituitary extract of FSH, follicle

stimulation, superovulation
Hormones of reproduction used
in practice
 Estrogens:
 Synthesized by ovaries, testes, adrenal
cortex, and placenta, or synthetic in origin
 Growth and development of female gonads
and female characteristics
 Inhibit ovulation, increase uterine tone,
proliferation of endometrium
 Uses: persistent CL, expulsion of retained
fetal membranes, weight gain, urinary
incontinence, induction of estrus during non-
breeding season
Hormones of reproduction used
in practice
 Estrogens:
 Examples: ECP, DES, implants
 Side effects/toxicity: Severe anemia,
prolonged estrus, follicular cysts, cervical
cancer and developmental anomalies in
female offspring of women who take DES
while pregnant (BANNED in food animals).
Should not be given during pregnancy.
Hormones of reproduction used
in practice
 Androgens:
 Male sex hormones produced in the ovaries,
testicles, adrenal cortex.
 Growth and development of male gonads,
characteristics and libido. Also promote
tissue anabolism, weight gain, RBC formation
 Examples:
 Testosterone: C-III controlled substances
 Milberone: prevent estrus by blocking release of

LH, no ovulation, weight gain

Hormones of reproduction used
in practice
 Progestins
 Similar to progesterone
 Produced by CL
 Increased secretions by the endometrium,
decreased contractility of uterus, increased
development of mammary tissue
 Inhibit release of gonadotropins from the
pituitary.
 Also have anti-insulin action, and suppress
the adrenal gland.
 Hormones of reproduction used
in practice
 Progestins
 Uses: treat false-pregnancy, behavioral disorders,

progestin-responsive dermatitis
 Examples:

 Megesterol acetate: synthetic progestin labeled

for use in dogs. Its side effects include:

hyperglycemia, adrenal suppression, endometrial
hyperplasia, increased appetite.
 Medroxyprogesterone acetate (MPA): human

drug
 Altrenogest (Regu-mate): for mares to suppress

estrus and maintain pregnancy. SHOULD NOT

BE HANDLED BY WOMEN
Hormones of reproduction used
in practice
 Progestins
 Examples cont…
 Norgestromet: synthetic progestin implant

in combination with estrogen for estrus

synchronization in beef cows and NON
LACTATING dairy cows.
Hormones of reproduction used
in practice
 PROSTAGLANDINS:
 Naturally occurring, LCFA
 Used for regulation of activity and treatment of
the female reproductive tract.
 Six classes: A, B, C, D, E & F – ONLY
PGF2α is used.
 Lysis of CL, contraction of uterine muscles,
relaxation of the cervix; uses: estrus
synchronization, expulsion of pyometra/fetal
tissues, abortion of feedlot cattle, induction of
parturition
 Hormones of reproduction used
in practice
 Prostaglandins
 Examples:
 Dinoprost: labeled for cattle, horses and swine

 Fenprostalene: synthetic analog for use in cattle

 Fluprostenol: synthetic analog for use in mares

 Cloprostenol sodium: synthetic analog for use in cattle

 Side effects: Sweating in horses, colic, urination/defacation,

dyspnea and panting, tachycardia, most effects are self-
limiting.
 Can cause bronchoconstriction, increased blood pressure,
and smooth muscle contraction in humans – PREGNANT
WOMEN and ASTHMATICS SHOULD AVOID HANDLING
THESE DRUGS!!!
 Drugs affecting uterine
contractility
 Induce abortion
 Induce labor
 Aid in delivery
 Involution of uterus

 CERVIX MUST BE DILATED BEFORE

THE USE OF THESE DRUGS!!!
 Drugs affecting uterine
contractility
 Oxytocin
 Made in the __________________ and
stored in the _________________________.
 Causes strong uterine myofibril contractions
 Uterus must be primed by progesterone and
estrogen to respond to oxytocin
 Also affects milk letdown through stimulation
of myoepithelial cells of the alveolar wall of
the mammary glands
 Drugs affecting uterine
contractility
 Ergot:
 Fungus in rye grass
 Causes smooth muscle contraction
 Large enough doses from pastures can cause
abortions in cattle
 Prostaglandins
 Also stimulate uterine smooth muscle
 Drugs affecting uterine
contractility
 Corticosteroids
 Can cause induction of labor in the last
trimester of some species – cattle…mimics
natural rise in the production of corticosteroids
by the fetus as the time for delivery draws
near
 Affects surfactant production in the fetus
 Pheromones
 Odors released by animals that influence
the behavior of other animals of the SAME
species
 Used by Pet Spas, etc…to help make
animals feel more comfortable…?
 Not FDA approved because…HOW DO
YOU TEST THEM?
 Individual responses vary widely.
 Misc…Reproductive Drugs
 Bromocriptine: dopamine agonist and prolactin
inhibitor used for mismating in dogs and
treatment of pseudopregnancy
 Leuprolide: synthetic analog of GnRH for
treatment of adrenal disease in ferrets and
inappropriate egg-laying in cockatiels
 Melatonin: Used for alopecia and sleep
disorders in dogs and cats, and to improve early
breeding and ovulation in sheep and goats
 Neuterosol: FDA APPROVED!!!  amino acid
and zinc salt that can cause sterility when
injected into the testicles of a puppy.
 Thyroid Hormones
 Thyroid gland:
 Bi-lobed near the trachea anywhere from the
larynx to the thorax – usually near the larynx.
 Follicles that when stimulated by the
hypothalamus produce two active products:
T3 and T4
 Has to trap iodide, oxidize it to iodine, and
combine with Tyrosine to form T3 and T4
 T3 is considered the active form
 T4 is Thyroxine, converted to T3 once
released.
 Thyroid Hormones
 Control  Hyper
 Metabolic  Hypo
 Growth  Diagnosis: measure
 Body temperature serum T3 and T4
 Heart rate before and after TSH
 Metabolism of administration
nutrients
 Goiter
 Skin condition
 Immunity
 …?
Thyroid Hormones
 Thyroid Hormones
 Hypothyroidism drugs:
 Thyroid hormone supplementation
 Levothyroxine Sodium (T4) (Soloxine)
 Liothyronine sodium (T3) (Cytobin)
 TSH (Dermathycin)
 Thyroid Hormones
 Hyperthyroidism drugs:
 Goal of treatment: decreased circulating
thyroid hormone levels (T3 and T4).
 Destroy or remove surgically the thyroid gland
 Block production
 Methimazole
 Carbimazole
 Ipodate
 Propylthiouracil
 Radioactive Iodine (I-131)
 Thyroid Hormones
 Hyperthyroidism drugs:
 Methimazole: interferes with incorporation of
iodine into the precursor molecules of T3 and
T4
 Doesn’t alter thyroid hormones released

into the bloodstream

 Tapazole

 Side effects: anorexia, vomiting, skin

eruptions
 Passed in milk from queen to kittens
 Thyroid Hormones
 Hyperthyroidism drugs:
 Carbimazole
 Canadian methimazole
 Ipodate:
 Organic iodine compound which inhibits the
conversion of T4 to T3
 For use in cats that don’t tolerate methimazole

 Propylthiouracil
 Antithyroid drug, dangerous in cats – potential
hematological complications
 Radioactive Iodine (I-131)
Scintigraphy of I-131 treated cat
with hyperactive thyroid
 Drugs for D. M.
 Insulin
 Source: Pancreas
 Cells: islets of Langerhans or Beta cells
 Always produced with GLUCAGON (alpha cells)
 Action: decreases blood glucose levels by what
mechanism?
 Also inhibits breakdown of fat, protein and glycogen
into forms that can be used as energy
 Promotes synthesis of protein, fatty acids, and
glycogen.
 Drugs for D. M.
 Diabetes Mellitus
 Complex disease: inability of the beta cells to produce
enough insulin, OR from altered insulin action on cells
(altered or faulty insulin receptors).
 Inadequate secretion of insulin = TYPE I or insulin dependent
 Resistance of tissue to the effects of insulin = TYPE II or

noninsulin-dependent Diabetes Mellitus (NIDDM)

 Both forms cause PU/PD, Polyphagia, and weight loss.

 Untreated progresses to Diabetic Ketoacidosis, metabolic

acidosis and death

 Drugs for D. M.
 Insulin
 Sources: beef or pork pancreas and purified
preparations or a combination of beef and pork
product.
 Pork insulin has closest structure to dogs and
humans, Beef is closest in structure to cats.
 Most human products are recombinant DNA or
synthetic in origin.
 Concentration measured in UNITS of Insulin /mL
 Human products are U-100
 Drugs for D. M.
 Insulin administration:
 Use U-40 syringes with U-40 insulin and U-100
syringes with U-100 insulin…there are few U-40
insulin syringes, so if using U-40 insulin, PAY
ATTENTION TO THE SYRINGE YOU ARE
USING!
 ALWAYS STOP AND DOUBLE CHECK!
 AN INSULIN OVERDOSE MAY BE FATAL
 Drugs for D. M.
 Handling insulin:
 DO NOT FREEZE, or heat
 Always check for precipitates and discoloration
before giving
 Resuspend by GENTLY ROLLING the vial
between the palms of your hands
 Always resuspend BEFORE drawing your dose
 Feed animal 30 minutes before giving insulin
 Rotate injection sites – have owners practice in
office using saline.
 Drugs for D. M.
 Insulin classifications:
 Duration of action: short acting, intermediate, and
long acting.
 Short: regular crystalline, Semilente
 Intermediate: NPH and Lente
 Long-acting: PZI and Ultralente
 Combination products available
 Be familiar with the onset of effect and route of
administration of different insulin preparations
 Drugs for D. M.
 Short-acting Insulin: regular crystalline or
semilente
 Made from zinc insulin crystals
 Clear solution – can be given IV, IM or SQ
 Used to treat diabetic ketoacidosis (DKA) until
blood glucose levels are reduced and animal is
stable. Then switch to long-acting formulation.
 Drugs for D. M.
 Intermediate-Acting Insulin:
NPH (isophane)/lente
 Cloudy suspension of zinc insulin crystals and protamine
zinc.
 Used for control of uncomplicated DM in dogs and cats.
 Lente doesn’t contain protamine
 Protamine is a protein derived from salmon testes that
helps slow down the onset and extend the duration of
action of NPH insulin.
 Once daily administration common.
 Drugs for D. M.
 Long-Acting Insulin
 Protamine Zinc Insulin (PZI), ultralente, and
glargine.
 Poor solubility and absorption from tissues = slow
absorption and maintains blood levels for long
time.
 Ultralente does not contain protamine
 Treatment of uncomplicated DM
 PZI is insulin of choice for cats…
 Drugs for D. M.
 YOUR ROLE!
 You will often be put in charge of teaching clients
how to give insulin injections, answering
questions, and taking histories in which it is
important to discern whether the owner is giving
the right amount, the correct way, to the right
animal!
 Counsel owners about diet and exercise of the
Diabetic patient
 What to look for that indicates their pet is getting
too much or too little insulin.
 Drugs for D. M.
 Type II diabetes can be treated with oral
hypoglycemic agents in HUMANS…no
veterinary approved products.
 Cats may respond to these products
 Includes glipizide and metformin
Drugs that cause Hyperglycemia
 Corticosteroids
 Epinephrine
 Progesterone

 Diazoxide (Proglycem)
 Octreotide (Sandostatin)

 Treat hypoglycemia associated with

insulinomas in dogs and ferrets
 Growth Promotants
 Sex steroids, synthetic steroid analogs and
Nonsteroidal analogs
 Strive to increase weight gain per pound of feed
fed.
 Primarily estrogen (estradiol)
 Promotes water retention, increases protein synthesis,
increases fat deposition, and increases release of
endogenous growth hormone (Bovine somatotropin)
 Growth Promotants
 Testosterone:
 Used in combination with estrogen for anabolic effects
 Progesterone can also be added:
 Slows the release of estradiol.
 Trenbolone:
 Synthetic anabolic agent
 Improves feed efficiency, weight gain in steers
 Zeranol:
 Analog of plant estrogen used to increase weight gain and
feed efficiency
 Growth Promotants
 Examples:
 Synovex C, H and S
 Compudose
 Implus-H and S
 Ralgro for calves and lambs
 Etc…
 Designed to last for a couple of months
 Residue????
 Growth Promotants
 Growth Hormone: Bovine Somatotropin
(BST) and Bovine Growth Hormone (BGH)
 Produced NORMALLY in the anterior pituitary
gland
 Stimulates growth of the animal before puberty,
and after puberty, stimulates anabolic activity.
 BST is a stimulator of milk production – as much
as 20% boost in milk production
 What does this do to the feed bill???
 Growth Promotants
 Recombinant BST (Posilac) is approved for use in
Dairy cows to improve feed efficiency, decrease
incidence of metabolic disease and increase milk
production.
 Anabolic Steroids
 Cause tissue building (anabolism)
 Testosterone, and many synthetic A.S.
 Causes positive nitrogen balance and reverses
the breakdown of tissue.
 Increased appetite, weight gain, improved overall
condition.
 Labeled for use in non-food animals for anorexia,
weight loss, and debilitation.
 C-III controlled substances
 Anabolic Steroids
 Examples:
 Stanozolol or Winstrol-V
 Do not use in pregnant animals, mares or stallions.
 BANNED IN FOOD ANIMALS

 Boldenone Undecylenate
 Horses – anabolic activity, little androgenic activity
 Equipose

 Caution: CAN CAUSE AGGRESSIVENESS

 Next Week
 Don’t forget the practice
exam on Black board
 It will be available until
Tuesday November 7th at 5
pm.
 Read Chapter 10 – Otic and
Ophthalmic Drugs

HAVE A GREAT
WEEKEND! 