Chapter 10 Hormonal and Reproductive Drugs Copyright © 2011 Delmar, Cengage Learning.

Chapter 10

Hormonal and Reproductive Drugs

Copyright © 2011 Delmar, Cengage Learning

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


Regulation of the Endocrine System

• 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


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


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


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


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 medically and with diet changes


Hormones of the Pancreas

• Diabetes Mellitus is found mostly in dogs, especially older obese females

• Dogs with the condition often have a chronic pancreatic disorder– Other suspected causes include pancreatic atrophy

and immune-mediated destruction of the islets of Langerhans cells

– Persistent fasting hyperglycemia is the hallmark of diabetes mellitus


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)

– Ultra-long-acting can take a few days to achieve its maximal effect; appropriate for use in cats


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


Thyroid Hormones

• The thyroid gland secretes two hormones involved in metabolism:– Thyroxine or T4

– Triiodothyronine or T3


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)


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


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)


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


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 low-dose

dexamethasone 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



• 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


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:– Testosterone cypionate in oil

– Testosterone enanthate in oil

– Testosterone propionate in oil

– Danazol



• 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 10-month-old

male dogs• Used as an intratesticular injection



• 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



• 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:

– Megestrol acetate– Medroxyprogesterone acetate– Altrenogest– Progesterone– Melengestrol



• 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


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)


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


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


Chapter 10 Hormonal and Reproductive Drugs Copyright © 2011 Delmar, Cengage Learning.

Documents

Transcript of Chapter 10 Hormonal and Reproductive Drugs Copyright © 2011 Delmar, Cengage Learning.