Hormonal & Reproductive Drugs

Hormonal & Reproductive Drugs

Introduction to Hormones

  • Definition of Hormones: Hormones are powerful chemical messengers that regulate various physiological processes in the body. Their profound effects can render individuals relatively helpless to their influence, as noted by author Meg Cabot.

Endocrine Anatomy and Physiology

Overview of the Endocrine System

  • Characteristics: The endocrine system comprises a network of ductless glands that secrete hormones directly into the bloodstream, where they travel to target tissues and organs.

  • Regulation: Hormonal release and activity are primarily controlled through negative feedback mechanisms to maintain homeostasis.

Major Endocrine Glands and Their Hormones

  1. Pituitary Gland: Divided into the posterior and anterior sections.

    • Posterior Pituitary: Releases hormones like oxytocin and antidiuretic hormone (ADH) which is also known as vasopressin.

    • Anterior Pituitary: Produces several hormones, collectively remembered by the acronym FLAGToP.

      • FSH (Follicle Stimulating Hormone)

      • LH (Luteinizing Hormone)

      • ACTH (Adrenocorticotropic Hormone)

      • GH (Growth Hormone)

      • TSH (Thyroid Stimulating Hormone)

      • other hormones (prolactin)

      • Progesterone

  2. Thyroid Gland: Secretes thyroxine (T4), triiodothyronine (T3), and calcitonin.

  3. Parathyroid Glands: Produce parathyroid hormone (parathormone), which regulates calcium levels in the blood.

  4. Pancreas: Secretes insulin, glucagon, and somatostatin which regulate glucose metabolism.

  5. Adrenal Glands: Composed of two parts:

    • Adrenal Cortex: Produces glucocorticoids and mineralocorticoids, including aldosterone.

    • Adrenal Medulla: Releases catecholamines like epinephrine and norepinephrine.

  6. Gonads: Include ovaries and testes, which secrete sex hormones:

    • Ovaries: Produce estrogen from follicles and progesterone from the corpus luteum.

    • Testes: Produce testosterone.

Hormones Used in Veterinary Practice

Overview of Hormonal Applications

  1. ADH (Vasopressin): Used in treating shock and cardiac arrest and managing diabetes insipidus.

  2. Oxytocin: Employed for managing dystocias (difficult births) and stimulating milk letdown during lactation. not used for breach delivery

Specific Hormones and Their Uses

  1. Gonadotropins (LH, FSH, GnRH): Used primarily for reproductive management in livestock. synchronization of estrus

  2. ACTH: Aids in diagnosing adrenal cortical diseases.

  3. Growth Hormone (GH): Increases growth rates and feed efficiency in livestock and enhances milk production. also know as Cosyntropin

  4. Thyroid Stimulating Hormone (TSH): Helps in diagnosing hypothyroidism in pets.

  5. Prolactin: Stimulates milk secretion and influences maternal behaviors post-partum.

  6. Levothyroxine: Used for treating canine hypothyroidism (T4) and managing metabolism.

  7. Insulin: Essential for managing diabetes mellitus in animals; regulates glucose levels in the blood.

  8. Glucocorticoids and Mineralocorticoids: Utilize differing dosages depending on treatment necessity such as for hypoadrenocorticism (Addison’s Disease).

Diagnosis and Management of Thyroid Disease

Hypothyroidism in Dogs

Diagnosis

  • Tests involved include measurements of T4, free T4 (FT4), and thyroid-stimulating hormone (TSH), assisted by history, physical examination, and complete blood count/biochemical profiles.

  • T4 can be artificially lowered by disease processes and other drugs - steroids

Treatment Options

  • Levothyroxine Sodium (Thyro-Tabs®): Cost-effective, with a long half-life and rare adverse effects. T4

  • Liothyronine Sodium (Cytobin®): A synthetic alternative with a shorter half-life and similar safety profile. T3

Hyperthyroidism in Cats

Diagnosis

  • Similar diagnostic approach as hypothyroidism, utilizing T4, FT4, and additional tests (UA, CBC).

  • drugs metabolized by the liver - monitor

Treatment Options

  1. Methimazole (Felimazole®): Not a cure but manages the condition by inhibiting T3/T4 synthesis, with potential GI adverse effects.

    1. can cause GI signs, blood cell abnormalities, and idiosyncratic facial pruritis

    2. monitor T4, liver enzymes, CBC, UA, other tests as indicated

  2. I131 (Radioactive Iodine): A long-term solution that destroys overactive thyroid cells, requiring special facilities for isolation following administration, with a small retracement rate back to hyperthyroidism.

    1. approxiamately 2% will revert to hyperthyroid cells

    2. kills thyroid cellls

    3. requires special isolation facility for about 2 months

    4. must try methimazole first - hyperthyroidism might be covering up kidney disease d

Management of Diabetes Mellitus

Overview of Types

  1. Insulin-Dependent Diabetes Mellitus (IDDM): Predominantly seen in dogs, requiring lifelong insulin therapy alongside dietary management (low carbohydrate, high fiber).

  2. Non-Insulin Dependent Diabetes Mellitus (NIDDM): Most common in cats, which may initially require insulin but potentially achieve remission.

Dietary Management

  • Cats should adhere to low carbohydrate and high protein diets to manage their condition effectively.

Insulin Management Principles

  • The aim is to eliminate clinical symptoms while preventing hypoglycemia.

  • Insulin Storage and Administration: Insulin suspension requires consistent storage (refrigeration), proper syringe usage, and timely administration aligned with meal schedules.

    • short term hyperglycemia is less dangerous than hypoglycemia

    • always follow manufactures instructions for mixing suspension

    • must be given with a meal    

      • skip dose if animal doesn’t eat well

      • very SQ injection location - scar tissue may develop

    • units - U40 - no mixing syringes

Adverse Effects of Insulin

  • Complications may include hypoglycemia, leading to lethargy, weakness, seizures, or even coma; hyperglycemia may occur as a reflex response.

Types of Insulin

  1. Regular Crystalline Insulin: Typically administered intravenously with a short-acting duration (onset: 0-30 minutes; duration: 1-10 hours). very potent

    1. owners will not be giving this at home - used in house for DKA animals

    2. think about the state the animal is in when they come in - dehydrated, lethargic

  2. FDA-Approved Veterinary Insulins:

    1. both insulins have zinc

      • ProZinc: A long-acting option for cats and dogs, with an onset of 1-4 hours. human recombinant + zinc

      • Vetsulin®: An intermediate-acting insulin option for both species. porcine recombinant + zinc

  3. Human-Approved Insulins: Include Neutral Protamine Hagedorn (NPH) which mimics veterinary insulins and Glargine, linked to possible remission in feline patients. U100

    1. cheaper?

  4. glargine - associated with good chance of diabetic remission in cats

Additional Diabetes Management Drugs

  • Oral Hypoglycemics such as glipizide and SGLT2 inhibitors (e.g. Bexagliflozin, velagliflozin) are utilized in non-insulin dependent diabetic cats to enhance renal glucose excretion with potential adverse effects, including GI distress.

  • oral hypoglycemic agents - glipizide

  • sodium glucose contransporter inhibitors - bexagliflozin and velagliflozin

  • bexagliflozin (bexacat) - newly diagnosed, non - insulin dependent, otherwise healthy diabetic cats

    • encourage renal excretion of glucose

    • adverse effects 0 vomiting, diarrhea most common

      • DKA, pancreatitis, hepatic lipidosis

  • drugs to raise blood sugar

    • diazoxide - off label in cats and ferrets with insulinoma

    • glucocorticoids, epinephrine, progesterone, sugar solutions - dextrose

Adrenocortical Disease Management

Hypoadrenocorticism (Addison's Disease)

Diagnosis

  • Determined through patient history, physical examination, and laboratory tests such as CBC, chemistry panels, and ACTH stimulation tests.

    • hard to diagnose due to vague signs and waxing and waning signs

    • must have a high index of suspicion

  • ACTH stim - corticotropin gel or cosyntropin solution

  • treatment usually requires both gluco - and mineralocorticoid replacement

Treatment Strategies

  1. Acute Management: Includes administering IV fluids (NaCl) and glucocorticoids.

  2. Chronic Management: Utilize mineralocorticoid replacements, such as Desoxycorticosterone Pivalate (DOCP), administered every 25 days, often paired with oral glucocorticoids (prednisone). FDA approved for dogs

    1. encourages water reabsorption

      1. adverse effects - edema and electrolyte imbalances

      2. caution in patients with CV or renal disease

fludrocortisone acetate 0 human approved

  • both gluco- and mineralocorticoid activity, but doesn’t appear as effective as DOCP + pred

    • oral    

    • edema, electrolyte imbalance

    • caution in patients w/ CV or renal disease

Common Adverse Effects

  • Potential side effects such as edema and electrolyte imbalances may occur; care is advised in patients with cardiovary or renal diseases.

Hyperadrenocorticism (Cushing's Disease)

Diagnosis

  • Diagnosis involves similar approaches with focus on history, physical evaluation, and specific tests (e.g., urine cortisol ratio, ACTH stimulation). Additional imaging may be required.

  • ACTH stim test - exaggerated response - high likelihood of false positive and negative

  • ± high dose dexamethasone suppression tests

  • +/- abdominal imaging - adrenal glands become mineralized or enlarged

Management of Hyperadrenocorticism

  1. Adrenal Tumors: Often treated surgically if medical management fails.

  2. Pituitary Dependent Hyperadrenocorticism (PDH): Treatment includes mitigatory agents like

  3. Mitotane (off-label)

    1. destroys adrenocortical cells

    2. adverse effects - GI, neurologic, hypoadrenocorticism

  4. Trilostane (FDA approved). Adverse effects include gastrointestinal issues and potential for dehydration.

    1. approved for both AT and PDH

    2. used off label for hyperadrenocorticism in cats and horses

    3. reversible, dose - dependent inhibition of adrenocortical hormone production

    4. adverse effects - GI, dehydration, electrolyte imbalances

    5. caution with hepatic or renal disease

ketoconazole

  • imidiazole antifungal

  • inhibits cortisol production - minimal effect on aldosterone

  • adverse effects - GI, hepatotoxicity

  • caution for pregnant women - teratogenic

Management in Horses

Equine Cushing’s Disease (PPID)

  • Treated with Pergolide Mesylate (Prascend®) to stimulate dopamine receptors, inhibiting ACTH secretion, with gradual dosage increases to mitigate potential adverse effects like anorexia and weight loss.

Reproductive Drugs

Male Hormonal Agents

  • Anabolic Steroids: tissue building drugs

    • Caution due to potential for abuse and are classified as controlled substances

    • none are currently marketed for veterinary use in the US.

  • Finasteride: An anti-androgen used off-label to treat benign prostatic hypertrophy (BPH) in dogs by inhibiting testosterone conversion.

    • blocks testosterone into dihydrotestosterone in prostate, liver, and skin

    • also used as part of management of hyperadrenocorticism in ferrets

Female Hormonal Agents

Use of Estriol (Incurin®)

  • A synthetic estrogen approved for managing estrogen-responsive urinary incontinence in spayed female dogs, with potential adverse effects including GI disturbances.

Use of Progesterones/Progestins

  • Indicated for suppressing estrus, synchronizing breeding cycles in livestock, and managing specific behavioral issues in dogs.

  • adverse effects - anorexia, vomiting, estrogenic effects

  • Examples include:

    • Eazi-Breed CIDR®: Utilized in bovine and sheep - vaginal insert

    • Medroxyprogesterone Acetate: Used in various situations including alopecia in dogs, prevent estrus in horses, urine spraying in cats but not recommended due to risks

    • Altrenogest: Approved for estrus suppression in mares, known for being absorbed through skin contact.

    • Melengestrol Acetate (MGA): Used to promote growth in cattle and manage estrus.

Prostaglandins

  • Hormone-like compounds involved in diverse bodily processes, particularly in reproductive functions:

    • Uses in Animals: Treating pyometra and inducing abortions in small animals, and induce parturition

    • cattle uses - synchronize estrus, induce uterine contractions

    • horses uses - synchronize estrus

    • Agents: Dinoprost Tromethamine and Cloprostenol Sodium are notable examples, with cautions including the potential adverse effects of vasoconstriction and bronchoconstriction when handled by pregnant individuals.

    • cautions - should not be handled by pregnant women - induce abortion or parturition, and vasoconstriction and bronchoconstriction

Gonadotropins

  • Indications include off-label for small animals and FDA approvals for synchronization and treatment of follicular cysts in livestock. Prominent examples:

    • Human chorionic gonadotropin (hCG): Simulates LH.

    • Pregnant Mare Serum Gonadotropin (PMSG): Simulates FSH release.

    • Gonadotropin Releasing Hormone (GnRH): Stimulates both LH and FSH release from the pituitary.

Hormonal Implants for Growth Promotion

  • FDA approved hormonal implants, such as natural estradiol combined with androgens or synthetic agents like Trenbolone Acetate, are utilized to promote weight gain and feed efficiency in livestock with specific adverse effects to monitor.