What's on Top or Is It? - The Use and Misuse of Systemic and Topical Medications in Breeding Animals
Frances O. Smith, DVM, PhD, DACT
Smith Veterinary Hospital, Burnsville, MN, USA

Many practitioners and owners use and prefer topical medications as an alternative to oral or injectable products. As with any medication, there are risks, benefits, and contraindications. It is very important that label directions and recommended applications be considered when making product selection. Equally important is addressing the potential reproductive status of any animal being treated with a topical medication, as some of these products can have a negative effect on future reproductive ability.

The following topical preparations such as antibiotic preparations, antifungals (zinc undecylenate), antivirals, capsaicin, sunscreens, topical corticosteroids, tanning lotions, and vitamin A or E all have potential for toxicity. When using any topical preparations, the package labeling and packaging insert require investigation. Of particular importance are the precautions and animal safety indication.

The hypothalamic-pituitary axis (HPA) of healthy dogs can be readily suppressed with any form of glucocorticoids. THE HPA axis controls development, reproduction, and aging in animals. Ocular, otic, and other topical products containing any glucocorticoid can be absorbed systemically and result in suppression of the HPA for weeks. The duration of action of many glucocorticoids administered either intravenously or orally is well documented; however, this information is scarce as it relates to topical usage. In a study published in Endocrinology, Beagle dogs were administered an otic preparation containing dexamethasone for twenty-one days. The treatment resulted in a marked suppression of resting plasma concentration within the first eleven days of treatment and these remained reduced during the entire treatment up to nineteen days. Additionally, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Eosinophils and lymphocytes were reduced. In this study, cortisol levels and hematologic parameters returned to baseline seven days post-treatment cessation while liver enzymes remained elevated.

One of the important functions of the HPA axis is to regulate reproduction. The hypothalamus is located in the brain and secretes GnRH (gonadotropin-releasing hormone). In females, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) activate the ovaries to produce estrogen and inhibin. In female dogs, the positive feedback loop between estrogen and LH help to prepare the follicle in the ovary and the uterus for ovulation and implantation. Once ovulation occurs, the ovary begins to produce progesterone to inhibit the hypothalamus and the anterior pituitary, thus stopping the estrogen-LH positive feedback loop. In males, the productions of these hormones are similar, but the effects are different. Follicle-stimulating hormone acts on Sertoli cells of the testicle to stimulate spermatogenesis. Luteinizing hormone acts on Leydig cells to stimulate steroidogenesis. The testosterone produced works on the Sertoli cells to stimulate spermatogenesis and on the hypothalamus and anterior pituitary to inhibit GnRH, LH, and FSH secretion.

Glucocorticoids affect both gonadotropin and gonadal function. Administration of corticosteroids to male dogs inhibits gonadotropin secretion as evidenced by decreased circulating testosterone concentrations and testicular atrophy. Blood levels of testosterone are two to three times lower than the levels of testosterone required for sperm production. Thus you cannot give enough systemic testosterone or any other anabolic steroid to improve sperm production. Instead, any exogenous steroid including topically applied but systemically absorbed corticosteroid will interfere with the HPG axis causing a decrease in hypothalamic activity and less testosterone in the testicle itself even though libido may be enhanced.


From: Ellington JE, Wilker CE. Reproductive toxicology of the male companion animal. In: Peterson ME, Talcott PA, eds. Small Animal Toxicology. Chapter 19. pages 354-355.
 

In female dogs, the same corticosteroids can suppress the HPA access as evidenced by interruption of estrus cycle activity. Glucocorticoid administration topically and systemically absorbed can be considered one of many xenobiotic compounds. A xenobiotic compound by definition is a pharmacologically, endocrinologically or toxicologically active substance which is not produced endogenously and is therefore foreign to an organism. The effects of these compounds can range from no effect to irreversible sterility. Other possible outcomes included premature reproductive aging and possibly increased neoplasia. In a mature female the effects are more likely to be temporary, whereas exposure prepuberally can disrupt reproductive function either by delaying or accelerating puberty.

When selecting topical preparations for use in our patients, reproductive status and potential reproductive demand should be considered. In patients with reproductive futures, topical preparations that contain a corticosteroid with the least potency and the shortest duration of action after withdrawal should be selected. Dexamethasone, flumethasone, betamethasone and cortisone administration to dams has been associated with increased incidence of cleft palate and other congenital malformation and may induce premature labor and abortion in dogs.

For topical parasiticides, it is important to read the package insert and to identify those products which have been tested safe for breeding animals. The indications, safety and precautions areas of the package insert are the most informative portion of the insert. Revolution® is one product that has many applications that are useful in reproducing animals. It has limited efficacy against several tick species but is very effective for control of heartworm, roundworm, hookworm, and fleas. While many other products may be safe even if not labeled for use in reproducing animals, the clinician recommending these products assumes any extra-label usage.

Many of the oral medications prescribed for dogs and cats have not been tested for their effect on the pregnancy itself or for the effect on fetal development. Antifungal drugs are known to be teratogenic, fluoroquinolones can inhibit cartilage formation, tetracyclines can inhibit dental enamel production, chloramphenicol can suppress bone marrow, and aminoglycosides may be neurotoxic. As would be expected, chemotherapeutic agents can be teratogenic or induce abortion. Cimetidine can decrease androgen production, which may contribute to cryptorchidism. Exogenous hormone administration by any route may affect sexual development. Glucocorticoids may cause fetal anasarca, cleft palates and may induce abortion. Pain medications should be used with caution - opioids are the analgesics of choice during pregnancy. The US Food and Drug Administration have developed a table which categorizes drugs into 5 categories based on the effects of each on pregnancy in women. Whenever a drug choice is made, the risk versus benefit ratio should be considered.


 


 

Potency of topical corticosteroids

Class

Generic name

Very high potency

I

Betamethasone dipropionate - augmented 0.05% - Ointment
Clobetasol propionate 0.05% - Cream and ointment

High potency

II

Betamethasone dipropionate 0.05% - Ointment
Desoximetasone 0.25% - Cream
Fluocinonide 0.05% - Cream and ointment
Mometasone furoate 0.1% - Ointment

III

Betamethasone dipropionate 0.05% - Cream
Betamethasone valerate 0.1% - Ointment
Fluticasone propionate 0.005% - Ointment

Mid-potency

IV

Fluocinolone acetonide 0.025% - Ointment
Mometasone furoate 0.1% - Cream
Triamcinolone acetonide 0.1% - Cream

V

Betamethasone valerate 0.1% - Cream
Fluocinolone acetonide 0.025% - Cream
Fluticasone propionate 0.05% - Cream

Low potency

VI

Alclometasone dipropionate 0.05% - Ointment
Clobetasone butyrate 0.05% - Cream
Desonide 0.05% - Cream and ointment

VII

Hydrocortisone or hydrocortisone acetate 1% - Cream and ointment
Hydrocortisone aceponate 0.127% - Cream

  

Speaker Information
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Frances O. Smith, DVM, PhD, DACT
Smith Veterinary Hospital
Burnsville, MN, USA


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