Download Chapter 10 - Hormonal and Reproductive Drugs

Fundamentals of Pharmacology
for Veterinary Technicians
Chapter 10
Hormonal and Reproductive Drugs
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Basic Anatomy and Physiology
• The endocrine system is composed of
ductless glands that secrete chemical
messengers called hormones into the
blood
– Hormones are chemical substances produced
by cells in one part of the body and
transported to another part of the body where
they influence cellular activity
• The endocrine system is controlled by a
feedback mechanism that includes the
hypothalamus, pituitary gland, and the
other endocrine glands
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Basic Anatomy and Physiology
• Two types of feedback loops are involved
in regulating the endocrine system
• Feedback loops may be either negative or
positive
• Negative feedback loops are more
common and work in response to low or
high levels of hormone in the body
• Positive feedback loops occur when
hormone levels continue to rise in
response to stimuli
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Basic Anatomy and Physiology
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Pituitary Gland Hormones
• The pituitary gland is divided into two parts:
anterior (cranial) and posterior (caudal)
• Anterior pituitary hormones used in veterinary
practice include:
–
–
–
–
–
Thyroid stimulating hormone (TSH)
Adrenocorticotropic hormone (ACTH)
Follicle stimulating hormone (FSH)
Luteinizing hormone (LH)
Growth hormone (GH)
• Posterior pituitary hormones used in veterinary
practice include:
– Antidiuretic hormone (ADH)
– Oxytocin
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Anterior Pituitary Gland
Hormones
• TSH is used in the diagnosis of primary
hypothyroidism
• ACTH is used to stimulate the adrenal
cortex to secrete corticosteroids in the
diagnosis of adrenal cortex disease
• FSH and LH (see reproductive section)
• GH is used to increase growth rate and
feed use efficiency in livestock and
increase milk production in dairy cows
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Posterior Pituitary Gland
Hormones
• ADH is used to treat diabetes insipidus
(disease characterized by the inability to
concentrate urine due to insufficient
amounts of ADH)
• Oxytocin is used to aid in uterine
contraction and induce labor in animals at
term, expel the placenta, induce milk
letdown, and as an adjunct therapy for
animals with open pyometra
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Hormones of the Pancreas
• The pancreas secretes two hormones that
help regulate blood glucose
– Insulin responds to a rise in blood glucose and
promotes the uptake and use of glucose for
energy in cells
– Glucagon increases blood glucose levels by
promoting the breakdown of glycogen into
glucose
• Diabetes mellitus is a disease of fat,
carbohydrate, and protein metabolism
caused by lack of or inefficient use of
insulin
– Treated both with diet changes and medically
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Insulin
• Insulin is used to treat diabetes mellitus by
keeping blood glucose in the proper range
• Sources of insulin include pork, synthetic, and
recombinant forms
• Onset and duration of insulin action are
controlled by modifying the regular insulin
structure
– Short-acting is used for initial treatment of diabetic
ketoacidosis and keep blood glucose stable (regular
crystalline insulin, semilente)
– Intermediate-acting is used to control blood glucose in
uncomplicated cases of diabetes mellitus (NPH and
lente)
– Long-acting is used to control blood glucose for longer
periods of time, especially in cats (protamine zinc
insulin and ultralente)
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Oral Hypoglycemic Agents
• Oral hypoglycemic agents have been
used with some success in animals
• Work by stimulating pancreatic beta cells
to secrete insulin; therefore some
pancreatic function is needed
• Has been more successful in cats
• An example of an oral hypoglycemic
agent is glipizide
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Thyroid Hormones
• The thyroid gland
secretes two
hormones involved
in metabolism:
– Thyroxine or T4
– Triiodothyronine or
T3
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Diseases Involving Thyroid
Hormones
• Hypothyroidism is characterized by a deficiency
of thyroid hormone
• Signs of hypothyroidism include decreased coat
and hair luster, weight gain, listlessness,
intolerance to cold, and reproductive failure
• Diagnosed by measuring serum total T4 and T3 or
by a thyroid stimulation test or by the thyrotropin
releasing hormone response test
• Hypothyroid animals are treated with thyroid
replacement therapy
– levothyroxine (T4)
– liothyronine (T3)
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.
Diseases Involving Thyroid
Hormones
• Hyperthyroidism is characterized by an increased
production of thyroid hormone
• Signs of hyperthyroidism include increased thirst,
weight loss, increased stool production,
restlessness, and tachycardia
• Diagnosed by measuring serum total T4 and T3
• Hyperthyroid animals are treated with antithyroid
drugs or surgical removal
– Radioactive isotopes of iodine (I-131) destroy the
thyroid gland
– Methimazole: interferes with the incorporation of iodine
in the molecules of T4 and T3
– Propylthiouracil (PTU): interferes with the conversion of
T4 to T3
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Adrenal Cortex Hormones
• The adrenal cortex is the outer part of the
adrenal gland
• The hypothalamus regulates the adrenal
cortex by secreting releasing hormones
for ACTH, which stimulates the adrenal
cortex
• Hormones produced by the adrenal cortex
include mineralocorticoids (aldosterone;
covered in chapter 12) and glucocorticoids
(cortisol)
– Glucocorticoids regulate nutrient levels in
blood (increase blood glucose levels)
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Diseases of Adrenal Cortex
Hormones
• Adrenocortical insufficiency (Addison’s disease)
is a progressive condition associated with
adrenal atrophy
– Result is a deficient production of corticosteroids and
mineralocorticoids
• Signs of this disease include lethargy, weakness,
anorexia, vomiting, diarrhea, and PU/PD
• Diagnosed by the ACTH stimulation test
• Treatment involves a long-acting
mineralocorticoid and corticosteroids
– Desoxycorticosterone (DOCP): mineralocorticoid
– Corticosteroids (Chapter 16)
– Fludrocortisone: both glucocorticoid and
mineralocorticoid activity
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Diseases of Adrenal Cortex
Hormones
• Hyperadrenocorticism (Cushing’s disease) is
characterized by excessive glucocorticoid
production due to prolonged administration of
adrenocortical hormones, adrenocortical tumors,
or pituitary disorders
• Signs: PU/PD, hair loss, pendulous abdomen
• Diagnosed by the ACTH stimulation test or lowdose dexamethosone suppression test
• Treatment involves destroying part of the adrenal
cortex
– Mitotane (o, p’-DDD)
– Ketoconazole: antifungal that blocks the enzymes
needed to produce steroid compounds
– Selegiline: monoamine oxidase inhibitor
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Basic Anatomy and Physiology
• Reproductive system is responsible for the
process of producing offspring
• Males
– Testes, epididymis, ductus deferens, accessory sex
glands, urethra, penis
– Sperm are produced in the seminiferous tubules of the
testes
• Females
– Ovaries, uterine tubes, uterus, cervix, vagina, and vulva
– Ova are produced in the Graafian follicle of the ovary
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Drugs Affecting Reproduction
• Androgens are male hormones
– Testosterone:
• Made in the interstitial cells of the testes
• Used to treat conditions such as infertility and
hypogonadism, produce estrus detectors, and for
testosterone-responsive urinary incontinence in
dogs
• Examples:
–
–
–
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Testosterone cypionate in oil
Testosterone enanthate in oil
Testosterone propionate in oil
Danazol
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Drugs Affecting Reproduction
• Androgens are male hormones (cont.)
– Mibolerone:
• Blocks the release of LH from the anterior pituitary
gland; therefore the follicle does not fully develop
• Used to prevent estrus in adult female dogs and the
treatment of false pregnancies
– Zinc gluconate neutralized by arginine:
• Nonsurgical neutering drug
• Chemical sterilant approved for use in 3- to 10month-old male dogs
• Used as an intratesticular injection
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Drugs Affecting Reproduction
• Female hormones
– Estrogen:
• Promotes female sex characteristics and stimulates and
maintains the reproductive tract
• Synthetic estrogens are used in dogs to prevent
implantation of fertilized ova and to correct urinary
incontinence, vaginitis, and dermatitis
• Synthetic estrogens are used in cattle to treat persistent
corpus luteum, aid in expulsion of retained placentas and
mummified feti, and to promote weight gain
• Synthetic estrogens are used in horses to induce estrus in
the nonbreeding season
• See further information under the growth promotant
section
• Examples:
– Estradiol cypionate
– Diethylstilbestrol
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Drugs Affecting Reproduction
• Female hormones (cont.)
– Progesterone:
• Decreases uterine activity when a female is in estrus or
pregnant
• Progestins (a group of compounds similar in effect to
progesterone) are used in dogs to block estrus
• Progestins are used in cattle to synchronize breeding and
birth cycles
• Progestins may be used to treat behavior problems and
some forms of dermatitis
• Examples include:
–
–
–
–
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Megestrol acetate
Medroxyprogesterone acetate
Altrenogest
Progesterone
Melengestrol
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Drugs Affecting Reproduction
• Female hormones (cont.)
– Prostaglandins:
• In the reproductive system, prostaglandin F2α causes lysis
of the corpus luteum, which initiates a new estrus cycle
• In small animals, prostaglandins are used to treat
pyometra, cause abortion, and induce parturition
• In cattle, prostaglandins are used for estrus
synchronization and inducing uterine contractions to
facilitate emptying of the uterus (pus or fetus)
• In horses, prostaglandins are used for estrus
synchronization
• Examples:
– Dinoprost tromethamine
– Fluprostenol
– Cloprostenol sodium
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Gonadotropins
• Gonadotropins are hormones that
stimulate the gonads
• These drugs cause the release of LH and
FSH or simulate their activity
• Gonadotropins include LH (simulated by
the use of hCG), FSH (simulated by the
use of PMSG), and GnRH (made
synthetically)
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Gonadotropins
• Human chorionic gonadotropin (hCG) is used to
treat cystic ovaries in cattle, to detect
cryptorchidism in dogs, to get infertile bitches to
cycle, and to make breeding mares ovulate
• Pregnant mare serum gonadotropin (PMSG) is
used to produce estrus and ovulation in horses
and as a follicle stimulant in many species
• Gonadorelin (GnRH) is used to treat follicular
cysts in cattle, for estrus synchronization in cattle,
and to induce estrus in small animals
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Growth Promotants
• Always check label to make sure growth promotants can
be used in the species you are working with
• Hormonal growth promotants
– Estradiol (tablet or implant used in ruminants)
– Testosterone (used in combination with estradiol to slow the
release rate of estradiol)
– Progesterone (used in combination with estradiol)
• Synthetic hormones
– TBA (works like testosterone)
– MGA (works like progesterone)
– Zeranol (analog of plant estrogen)
• Anabolic steroids
– Stanozolol
– Boldenone undecylenate
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.