Veterinary Pharmacology

Endocrine System

Antiduretic Hormone, Growth

Hormone & Anabolic Steroids

Veterinary Pharmacology

Endocrine System

Antiduretic Hormone, Growth

Hormone & Anabolic Steroids

Goudarz Sadeghi, DVM, PhD, DSc

Associate Professor of Pharmacology

University of Tehran

Faculty of Veterinary Medicine

ADH – 1Introduction

� Full name: Anti-diuretic hormone

� Other name: Vasopressin

� Secretion: by the neurohypophysial system

� Receptors:– V1:

� VSM: vasoconstriction

� Hepatocytes: glycogenolysis

� Platelets: aggregation

– V2:

� Renal collecting ducts:

– ↑ permeability to water ⇒ concentrated urine

– ↑ the release of von Willebrand factor

ADH – 2Release & Effects

ADH – 3Desmopressin - 1

� Chemical name:

– DDAVP (l-desamino-8-D-arginine vasopressin)

� Pharmacodynamics:

– A long-acting synthetic analogue of ADH that

works primarily at V2 receptors.

� Main application:

– treatment of diabetes insipidus

ADH – 4Desmopressin - 2

� Administration:– Parenterally

– Intranasally

– Into the conjunctival sac�The minimum dose required by these latter routes is 5-

10 times the parenteral dose.

� The administration of 1-4 drops once or twice a day controls polyuria in most animals with diabetes insipidus.

ADH – 5Desmopressin - 3

� DDAVP is used to treat canine patients with von Willebrand disease.

– shortens the bleeding time in these dogs.

– The parenteral route is indicated, because

hemostatic effects require 5-10 times the dose needed to control polyuria.

ADH – 6Desmopressin - 4

� Side effects of therapy:

– Rare

– Conjunctival irritation

– excessive doses of DDAVP ⇒ ↓ excretion of a

free water load ⇒– fluid retention

– hyponatremia

– if severe overhydration develops ⇒ cerebral edema

GH – 1General

� Growth hormone (GH) is normally synthesized and secreted by the pituitary gland under the influence of GHRH produced by the hypothalamus.

GH – 2Bovine GH - 1

� Application: in cattle to enhance growth or milk production.

� Characteristics: a prolonged- release injectable formulation of a recombinant bovine GH.

� Administration: SC every 14 days

GH – 3Bovine GH - 2

� Adverse effects:– Mild hyperthermia

– Clinical and subclinical mastitis

– Reduced feed intake

– Swelling at the injection site

– Mild anemia

– Decreased fertility

– Increased gestational problems� Early birth, twinning, retained placenta

Anabolic Steroids – 1General

� The ASs are synthetic androgenic compounds that have been developed to have:– ↑ anabolic effects

– ↓ virilizing effects

� Veterinary applications:– 1) to treat nonregenerative anemias

– 2) to enhance growth and performance

– 3) to stimulate appetite

Anabolic Steroids – 2Compounds

Anabolic Steroids – 3Effects

� Useful in anemia:

– ↑ erythropoietin production ⇒ ↑ heme synthesis

⇒ ↑ red cell proliferation

� If adequate protein and calories ⇒

– ↑ nitrogen retention ⇒ ↑ lean body mass ⇒ ↑

body weight

� They are controlled drugs.

Anabolic Steroids – 4Applications - 1

� In small animals:

– Stanozolol

– Nandrolone decanoate

� In the horse:

– Stanozolol

– Boldenone undecylenate

Anabolic Steroids – 5Applications - 2

� Stanozolol:

– Oral or parenteral

– The anabolic effects persist for up to 1 week.

� Nandrolone:

– Parenteral, weekly

– Somewhat more effective in stimulating erythropoiesis

� Boldenone:

– IM, every 8 weeks to horses

Anabolic Steroids – 6Side Effects

� Hepatotoxicity (particularly in cats)

� Sodium, calcium, phosphate, potassium, and water retention

� ↑ Prostatic disease

� ↓ Spermatogenesis

� ↓ Estrus

� Contraindication:– in pregnant or breeding animals

Bile Acids – 1General

� Synthesized exclusively in the liver from cholesterol.

� The only bile acid used pharmacologically in small animals is ursodeoxycholic acid.

Bile Acids – 2Ursodeoxycholic Acid - 1

� Applications:

– to treat cholesterol gallstones

– as a hepatoprotective agent

� Lowers plasma and bile cholesterol by:

– ↓ cholesterol secretion into bile

– ↓ intestinal re-absorption of cholesterol

– ↓ hepatic synthesis of cholesterol

Bile Acids – 3Ursodeoxycholic Acid- 2

� Potential benefits in treating hepatic disease:

– ↑ bicarbonate-rich bile flow (chloresis).

– Chronic administration ⇒ replacement of the normal relatively hydrophobic pool of bile acids with the relatively

hydrophilic ursodeoxycholate.

� Hydrophobic bile acids are cytotoxic agents at high concentrations!

– Protection of mitocnondrial membrane integrity.

– Immune-modulating effects (interactions with the

corticosteroid receptor?)

WebSite

http://www.gsadeghi.com

E-Mail

gsadeghi@ut.ac.ir

خدايا چنان كن سرانجام كار تو خشنود باشي و ما رستگارخدايا چنان كن سرانجام كار تو خشنود باشي و ما رستگار