Endocrine and Reproductive Drugs

Endocrine and Reproductive Drugs

Master Control Gland: Pituitary

• The pituitary gland is known as the master control gland of the endocrine system.

• It is divided into two parts:
    - Anterior Pituitary (Adenohypophysis):
      - Secretes hormones that regulate growth and the proper functioning of the thyroid, gonads, and other organs.
      - Key hormones secreted include:
        - TSH (Thyroid Stimulating Hormone)
        - ACTH (Adrenocorticotropic Hormone)
        - GH (Growth Hormone)
        - FSH (Follicle Stimulating Hormone)
        - LH (Luteinizing Hormone)
        - LTH (Lactogenic Hormone or Prolactin)
      - These hormones stimulate target organs to secrete secondary hormones.
    - Posterior Pituitary (Neurohypophysis):
      - Secretes:
        - ADH (Vasopressin)
        - OXY (Oxytocin)

Control of Reproductive System

• The estrus cycle is typically divided into four stages:
    - Proestrus:
      - The period of the cycle before the female is receptive; regulated by FSH.
    - Estrus:
      - The period when the female is receptive to the male, characterized by a decrease in FSH and an increase in LH; at this stage, the follicle ruptures.
    - Metestrus:
      - The stage following estrus where the female is no longer receptive; a Corpus Luteum (CL) forms that produces progesterone if pregnancy occurs.
    - Diestrus:
      - A short phase of inactivity between cycles in polyestrous animals.
    - Anestrus:
      - A phase of sexual quiescence; typically a long phase in seasonally polyestrous or monestrous animals.

Drugs Affecting Reproduction

• Types of Drugs:
    - Male Hormone-Like Drugs
    - Female Hormone-Like Drugs

Uses of Reproductive Drugs

• Food Production Animals and Horses:
    - Estrus synchronization.
    - Inducing ovulation.
    - Termination of pregnancy.

• Dogs and Cats:
    - Preventing unwanted pregnancy.
    - Altering the state and condition of the uterus.

Male Hormone-Like Drugs

• Androgens:
    - Male sex hormones produced in the testes (interstitial cells), ovaries, and adrenal glands.
    - Functions include:
      - Androgenic: Development of male sex organs and secondary sexual characteristics.
      - Anabolic: Promotes tissue building, such as weight gain and red blood cell production.

Testosterone

• Uses:
    - Treat infertility and hypogonadism.
    - Produce teaser cattle.
    - Treat urinary incontinence in male dogs.

• Side Effects:
    - Premature growth plate closure.
    - Vaginitis.
    - Development of male secondary sexual characteristics.

• Dosage Forms:
    - Testosterone (CIII controlled substance).

Mibolerone

• Mechanism: Blocks the release of LH from the pituitary; should be started 30 days prior to proestrus.

• Uses:
    - Prevent estrus.
    - Treat pseudocyesis.

• Side Effects:
    - Premature growth plate closure.
    - Vaginitis.
    - Development of male secondary sexual characteristics; should not be used in cats due to low safety margin and potential for diabetes.

• Dosage Form:
    - Cheque Drops®.

Female Hormone-Like Drugs

• Estrogen Production:
    - Primarily produced by the ovaries and placenta but also by the testes and adrenal glands.

• Functions of Estrogen: Promotes female sex characteristics, stimulates and maintains the female reproductive tract, and is necessary for the uterus to contract and respond to oxytocin.

Estrogens

• Uses:
    - Treat urinary incontinence in dogs.
    - Treat persistent CL in cattle.
    - Assist with expulsion of retained placenta in cattle.
    - Induce estrus in horses.

• Side Effects:
    - Pyometra.
    - Bone marrow suppression.
    - Follicular cysts.
    - Endometrial hyperplasia.

• Dosage Forms:
    - Estradiol (ECP®) injection.
    - Diethylstilbestrol (DES®) tablets.

Progestins

• Progesterone:
    - Secreted by the CL after ovulation.

• Uses:
    - Block estrus in the bitch.
    - Maintain pregnancy in cattle and horses.
    - Delay or synchronize estrus.

• Side Effects:
    - In dogs: hyperglycemia, adrenal suppression, pyometra.
    - In cattle and horses: fewer side effects.

• Dosage Forms:
    - Megestrol acetate (Ovaban®) for dogs.
    - Altrenogest for horses; caution as it can be absorbed through skin, so pregnant women should not handle it.

Prostaglandins

• PG F2α:
    - In the female reproductive tract, causes lysis of CL (corpus ledum) and contraction of uterine muscle.

• Uses:
    - Estrus synchronization in cattle and horses.
    - Treatment of pyometra.
    - Inducing abortion in animals with dead fetuses, twins, or young animals.
    - Induce parturition in small animals.

• Cautions:
    - Pregnant women and asthmatics should not handle.

• Dosage Forms:
    - Dinoprost (Lutalyse®).

Oxytocin

• Uses:
    - Induction of labor.
    - Managing retained placenta.
    - Inducing involution.
    - Inducing milk let-down.

• Response from oxytocin therapy depends on the stage of parturition and levels of estrogen and progesterone present.

Neutersol - Chemical Sterilization

• Description:
    - A nonsurgical neutering drug; a chemical sterilant approved for use in males aged 3-10 months.

• Administration:
    - Injected intratesticularly once in each testicle.

• Cautions:
    - Not to be used in cryptorchids.

• Effects:
    - Most testicles atrophy post-injection.
    - Testosterone production is not completely eliminated, leading to persistent male behaviors and potential prostatic disease.
    - Does not kill sperm, therefore still fertile up to 60 days post-injection.

• Side Effects:
    - Pain and vocalization upon injection.
    - Vomiting.

Thyroid Drugs

• Thyroid Gland Location:
    - Located in the neck near the larynx.

• Functions:
    - Necessary for normal growth, metabolic rate, immune function, heat production, and reproduction.

• Hormones Produced:
    - Two active hormones: tri-iodothyronine (T3) and thyroxine (T4).

• Iodine Utilization:
    - Iodine consumed is trapped by the thyroid gland, converted to T3 and T4, and stored until released.

Hypothyroidism

• Description:
    - Characterized by a deficiency of thyroid hormone.
    - Possible causes include disorders of iodine trapping, conversion of iodine to hormone, release of hormone, or pituitary disorders that prevent adequate release of TSH.

• Clinical Signs:
    - Decreased coat luster or alopecia.
    - Weight gain without appetite.
    - Listlessness.
    - Intolerance to cold.
    - Reproductive failure.
    - Susceptibility to skin infections.

• Drug Therapy:
    - Thyroid replacement therapy aims to achieve a euthyroid state.
    - Drug of Choice:
      - Levothyroxine sodium (T4).
    - Dosage Forms:
      - Soloxine®.

Hyperthyroidism

• Description:
    - Characterized by excessive function of the thyroid gland resulting in excessive hormone production and heat production, increased nervous activity, and increased metabolism.

• Most Common:
    - Seen in older cats.

• Clinical Signs:
    - Polyuria (PU).
    - Polydipsia (PD).
    - Polyphagia (PP) with weight loss.
    - Increased stool production.
    - Restlessness.
    - Tachycardia.

• Treatment Options:
    - Destruction (radioactive iodine, I-131).
    - Surgical removal of thyroid gland.
    - Antithyroid drugs.

Antithyroid Drugs

• Mechanism:
    - Block excessive production of hormones by interfering with the incorporation of iodine into T3 or T4.

• Drug of Choice:
    - Methimazole (Tapazole®).

• Side Effects:
    - Vomiting.
    - Diarrhea.
    - Lethargy.

• Compounding Option:
    - Methimazole can be compounded into a liquid or ointment

• Radioactive Iodine Treatment:
    - Can be an option for hyperthyroidism.

Diabetes Mellitus

• Hormones Produced by the Pancreas:
    - Insulin by beta cells.
    - Glucagon by alpha cells.

• Functions of Insulin:
    - Promotes uptake of glucose by cells and its storage in the form of glycogen.

• Functions of Glucagon:
    - Causes breakdown of glycogen and raises blood glucose levels.

• Disease Description:
    - A complex disease of carbohydrate, fat, and protein metabolism.
    - Diabetic animals often present with:
      - Hyperglycemia.
      - Glucosuria.
      - Polyuria (PU).
      - Polydipsia (PD).
      - Altered fat metabolism that can lead to toxic effects and coma.

• Affected Animals:
    - Occurs more frequently in dogs and cats, particularly in obese female middle-aged or older dogs.

• Management:
    - Medical and dietary management usually focuses on diets low in carbohydrates and high in protein.
    - Incorporation of high soluble fiber to slow down digestion.
    - Animals should be fed 30 minutes prior to insulin treatment.

Insulin

• Sources:
    - Traditionally extracted from beef or porcine pancreas; however, pork insulin is structurally similar to canine insulin and beef insulin to feline insulin.
    - Synthetically processed human insulin is available but is not as effective in veterinary medicine.

• Classification:
    - Insulin is classified based on onset and duration of action.

Insulin Concentration

• Insulin concentration is expressed in units of insulin per milliliter:
    - Available concentrations include:
      - U-40: 40 units/mL.
      - U-100: 100 units/mL.

• Usage Guidelines:
    - It is crucial to use the correct syringes:
      - Use U-100 syringes for U-100 insulin.
      - Use U-40 syringes for U-40 insulin.

Insulin Storage and Handling

• Insulin is stable at room temperature but is best stored in refrigeration.

• Precautions:
    - Never freeze or expose insulin to high temperatures.
    - Vials should be rolled (not shaken) to mix before each use.
    - Discard insulin if discolored or if precipitate forms.

• Overdose Symptoms:
    - Symptoms of insulin overdose may include weakness, ataxia, tremors, and seizures; treat by administering Karo syrup.

Categories of Insulin

• Short Acting Insulin (Regular):
    - Duration: 1½ to 2 hours.
    - Usage: Primarily for treating diabetic ketoacidosis, can be administered via IV (e.g., Humulin R).

• Intermediate Acting Insulin:
    - Includes NPH, Lente, Humulin-N.
    - Administration: Subcutaneous (SQ).
    - Duration: Lasts 4 to 24 hours, primarily used to treat uncomplicated diabetes in dogs and cats.

• Long Acting Insulin:
    - Includes Glargine (Lantus) and PZI.
    - Administration: SQ.
    - Duration: Lasts 6 to 28 hours.

Insulin Products Commonly Used in Dogs and Cats

Oral Hypoglycemic Agents

• Function:
    - Stimulate pancreatic beta cells to produce insulin.

• Effectiveness:
    - Effective in approximately 25% of diabetic cats but not effective in dogs.

• Dosage Form:
    - Glipizide (Glucotrol®) tablets.

SGLT2 Inhibitors

• Examples:
    - Bexacat® (Bexagliflozin).
    - Senvelgo® (Velagliflozin).

• Mechanism:
    - Sodium glucose co-transport inhibitors work at the kidney level to prevent glucose reabsorption.

• Dosage:
    - Administered once daily as oral medication for otherwise healthy diabetic cats not requiring insulin and who have never been on insulin.

• Advantages:
    - Does not cause hypoglycemia, making it safe to administer with or without food.

• Contraindications:
    - Ketoacidosis should be avoided.

Regulation of Adrenal Cortex

• The adrenal glands are paired organs located near the cranial portion of the kidneys.

• Each gland consists of:
    - Outer adrenal cortex
    - Inner adrenal medulla

• Regulation:
    - The hypothalamus regulates the adrenal cortex by secreting CRH, which influences ACTH release from the anterior pituitary.

• Hormones Produced:
    - Hormones produced by the adrenal cortex are steroid hormones, including mineralocorticoids and glucocorticoids.

Functions of Mineralocorticoids

• Regulate blood volume and electrolyte concentration in blood.

• Aldosterone: Causes sodium retention to maintain blood pressure and volume.

Functions of Glucocorticoids

• Regulate nutrient levels in blood:
    - Increase cellular utilization of energy sources (proteins and fats) while conserving glucose.
    - Stimulate liver to produce glucose from amino acids and fat.

• Main glucocorticoid: Cortisol.

• Elevated cortisol levels can lead to diseases such as:
    - Adrenocortical Insufficiency (Addison's Disease)
    - Hyperadrenocorticism (Cushing's Disease)

Adrenocortical Insufficiency

• Addison's Disease (Hypoadrenocorticism):
    - Characterized by progressive adrenal atrophy, which is typically immune-mediated.
    - Results in deficiencies in glucocorticoids and mineralocorticoids.

• Clinical Signs:
    - Lethargy.
    - Weakness.
    - Anorexia.
    - Vomiting.
    - Diarrhea.
    - Polyuria (PU).
    - Polydipsia (PD).

• Treatment Options:
    - Treat with mineralocorticoids and glucocorticoids:
      - Mineralocorticoid Dosage Forms:
        - Desoxycorticosterone, DOCP (Percorten-V®) given every 25 days by injection.
        - Prednisone/prednisolone.
        - Fludrocortisone acetate (Florinef®) - exhibits both mineralocorticoid and glucocorticoid activity.

Hyperadrenocorticism (Cushing's Disease)

• Description:
    - Caused by adrenal tumors, pituitary disorders, or prolonged administration of adrenocortical hormones.

• Clinical Signs:
    - Polyuria (PU).
    - Polydipsia (PD).
    - Alopecia. Bilaterial symmetrical alopecia
    - Pendulous abdomen due to abnormal nutrient metabolism.

• Treatment Options:
    - Can treat by destroying part of the adrenal gland.

• Dosage Form:
    - Mitotane - Lysodren® (medication for Cushing's Disease).

Drug Treatment Options for Cushing's Disease

• Alternative Options:
    - Vetoryl (Trilostane) that blocks cortisol production.

Anabolic Steroids

• Description:
    - Tissue-building substances labeled for use in dogs, cats, and horses.

• Uses:
    - Primarily for anorexia, weight loss, debilitation, and to promote hematopoiesis.

• Classification:
    - Classified as C-III controlled substances.

• Dosage Forms:
    - Stanozol (Winstrol-V®).