Hormones Flashcards
Growth hormone
- Protein (not PO),controlled by GHRH, GH plasma levels and Gherlin polypeptide (GI, hypothalamus)
- Inc. by sleep, excersice, stress , HYPOglycaemia, dopamine, alpha-agonists. => Giantism/acromegaly
- Dec. GC, HYPERglycaemia, beta-agonist=> dwarfism
- Stimulates IGF-1 secretion , anabolic hormone
- Use: inc. milk production and meat quality, alopecia in dog.
- Synthetic analogue: Octreotide, Lanreotide
- Dopaminergic agents: Cabergoline
- GH receptor antagonist:(IGF-1 inhib.)Pegvisomat (Somavert)
ACTH
- Protein, inc. synthesis of enzyme involved in steroid biosynthesis (cholesterol ->pregnenolone)-. Inc. cortisol and corticosterone levels.
- indications: dec. GC , cow ketosis, adrenal cortex atrophy, stimulation test, Adrenocortical hypo/hyperplasia.
Addison’s disease:
fludrocortisone. SE:increased blood pressure, inflammation, hypokalemia, hypernateamia
Cushing syndrome:
*Pituitary induced hypercortisolism:
Bromocriptine, Cyproheptadine
* Adrenal gland induced hypercortisolism :
1. Trilostane: selective inhibitor of 3B-hydroxysteroid dehydrogenase. SE: GI, lethargy, acute pancreatitis , addison’s crisis.
2.Ketoconazole weekly increasing dose.
3. Mitotane (must be avoided!)
TSH
*glycoprotein, no approved veterinary product in the market
*Effect: inc. iodine uptake by the thyroid gland, production and secretion of thyroid hormones.
*Used to diagnose primary hypothyroidism.
*inc. GH, GnRH, cortisol production + dec. prolactin
Hypothyroidism:
1. Iodine containing agents: iodised salt, Lgol solution
2. levothyroxine-Na
3.liothyronine (Lack of tissue deiodinase) overdose: hyperthyroidism like signs
Hyperthyroidism: mostly Cats!
1.Methimazol/Tiamazol
Side-effects: Liver damage, emesis, immune mediated haemolytic anaemia, facial pruritus
ADH
*protein hormome, responsible for water and Na retention , K excretion.
*Binds V1a (endothelium) -vasoconstriction
V2 (renal tubules) - inc. water absorption by aquaporin-2
*Use: diagnosis+ treatment of central diabetes insiphidus. Differential Diagnosis of diabetes mellitus
- Natural vasopressin nasal spray: short HL+BA, local irritation
- Desmopressin (synth. Analouge) - SC,PO,nasal, longer
- Chlorpropamide: PO, antidiabetic
- In syndrome of inappropriate ADH (overproduction): Conivaptan (IV, V1+V2 antagonist) , Tolvaptan , Lixivaptan (V2 antagonist)
Insulin
Protein, preproinsulin>proinsulin>insulin , stored in secretory granules in a complex with zinc (B-cells), exocytosis (ATP-dep K channels> inc. Ca>Ca-calmodulin protein kinase>fusion of granules with membrane)
- Inc. IC uptake of glu,AA,FA,K. Anabolic hormome- glycogenesis, lipogenesis, protein synthesis
- Degraded rapidly by insulinase
- Indications: DM in cat+dog, fatty liver+ ketosis in Bo
DM I: SC
- Caninsulin:Swine origin (lente insulin) - amorphous (intermediate duration) , crystalline (prolonged,12-24h) higher Zn content+acetate buffer
- Insuman® Rapid
- Human ProZinc®
DM II: PO
1. Acarbrose: alpha-glucosidase inhibitor (latent carbohydrate absorption- after meal) - dogs+cats
2. Sulfonylureas: increased insulin secretion.
Glipizide - cats, gliclazide ,glibenclamide
3.Biguanides decrease of insulin resistance. (metformin, Buformin)
4. Glinides: increased insulin secretion. (nateglinide)
5. Glitazones: activation of nuclear receptors, liver, adipose tissue and muscles increased insulin sensitivity. (pioglitazone)
Insulin: adverse effects and interactions.
- Adverse effects: acute hypoglycemia, Somogyi rebound effect (hypoglycemia->hyperglycaemia due to compensation by anti-insulin hormomes), allergy,Ab
- Interaction: hyperglycaemic (GC,dobutamin, oestrogen, progesterone,xylazine, thiazides diuretic)+hypoglycaemic drugs (,B-blockers,MAO inhibore, phenylbutazone, anabolic steroids, salicylates
Oral anti-diabetics warnings
- Mainly type-2 diabetes (NIDD, Insulin resistancy)
* Warnings: Hypoglycaemia, serious liver/kidney insufficiency
Oral antidiabetics: Sulphonylurea substances:
*Inc. insulin release, sensitivity in cells, receotors, binding, glucagon release.
*5 drugs:
Tolbutamide (short, CV SE)
Chloropropamide (long acting , also for Diabetes insiphidus)
Metahexamide, Glibenclamide, Glizipine
Oral antidiabetics: Biguqnides
- inc. utilization in cells, dec. Glu oral absorption
1. Fenformine (phenyl-ethyl)
2. Buformine (Butyl): ADEBIT
3. Methformine (Dimethyl)
Oral antidiabetics:
- Thiazolidine diones
- Acarbos
- Modulation of insulin dependent genes , reduction of blood sugar level
* No experience in veterinary (glitazones, troglitazones, draglitazone) - Inhibition of alpha-glycosidase (e.g alpha-amylase) activity; less rapid elevation of glu blood level after meal
Mineralocorticoids: Addison’s disease (hypoandrenocorticism)
- Aldosterone: in research
- Desoxycorticosterone pivalate: long acting, IM + hydrocortisone/GC replacement
- Fludrocortisone acetate: PO, slight GC effect
*SE: Hypokalemia (>muscle weakness), hypernatraemia, water retention (hypertension) , inflammation susp.
Mineralocorticoids: Cushing’s disease
Hyperadrenocorticism
K 9-85%
*Pitutary dependant:
Bromocriptine , Cyproheptadine-HCl (PERITOL)
*Pitutary/adrenal dependent:
Ketoconazole , Mitotane , Trilostane (selective inhibition of 3BHSD)
Thyroid hormones: hypothyroidism
More common, may arise from iodine def. , Feeding cabbage (ru), thyroid malfunction (primary), TSH def. (Secondary)
- L-thyroxine/Levothyroxine: PO
- L-thyroxine-Na : IV,SC
- L-tri-iodothyronine (T3): PO, only imducated when Levothyroxine had failed. Rapid onset , short durations
Calcitonin
Control hyperglycaemia (Paget’s disease, ergocalciferol , vit. D2 poisoning)
Salcatonin (from salmon)
Calcitonin
Control hyperglycaemia (Paget’s disease, ergocalciferol , vit. D2 poisoning)
Salcatonin (from salmon)
Thyroid hormones: hyperthyroidism
- Iodine (I131 isotope): before surgery, to block T3+4 release, highly radioactive, short HL
- Tiouracil: SE: Emesis, liver, liver, haemolytic anemia
- Propylthiouracil
- Thiamazole (methimazole): its prodrug is carbamazole which also used in therapy
GnRH
*Hypothalamus (Optic+suprachiasmatic areas), small amount in uterus+ovaries
*Pulsative release, same Composition in all mammals
*Action: stimulates the production of LH and FSH
1. Deslorelin: SUPRELORIN SC implant , make dogs for 6 months
2. Gonadorelin: cow+eq+su+rabbit
3.Buserelin: eq
4. Fertirelin: cow
5. Lencirelin: cow
SC,IM
*indications: reduce time interval btw calving to ovulation, treat ovarian follicilar cyst, control ovulation time+synchronization, induce ovulation in rabbit, inc. fertility in su, chemical castration in Hu+K9
- SE: hyperthermia, allergy, corpus luteum cyst.
- Don’t use in pregnant/starved animals
FSH
- inc. growth of follicles by granulosa cells (ovaries) *spermatogenesis by Seretoli cells (testis)
- Indications: super-ovulation in donor cows used for embryo transfer.
LH
- final maturation of the follicle and estrogen secretion
- Inc. testosterone secretion by Leydig cells
- Indications: to induce ovulation, lueinize follicilar cyst
PMSG, eCG
pregnant mare serum gonandotropin
- glycoprotein, secreted by endometrial cups of pregnant mares in early pregnancy in order to maintain the corpus luteum (which maintains high progesterone levels to sustain the pregnancy)
- Indications: follicular growth and ovulation, to induce super-ovulation. Males: inc. spermatogenesis+libido
- WERFASER inj.
- GONADOPHYL inj.
- SUIDAN inj.
* Combination with hCG to treat post weaning anoestrus in su
hCG
Human chronic gonandotropin
Glycoprotein, secreted from the chorionic portion of placenta , HL 12-24h
*Used as LH: female: ovulation (eq), nymphomania dye to cystic ovaries. Male: treating cryptorchidism
- WERFACHOR inj. , NYMFALON inj. (+Progesterone)
- P.G 600 inj.n, SUIDAN inj. (+PMSG)
- PROLAN inj. (+ oestradiol) - su, ovulatio
Sex hormone steroid pathway
Cholesterol=> Pregnenolone=> Progesterone=> Testosterone=> Estrogen
*Fat soluble , short HL, protein bound in blood
Natural estrogen: oestrone , oestradiol-17-B , oestriol
- produced by granulosa cells , corpus luteum, adrenal cortex,testis, placenta
- Effects: female sex organs development, 2ndary sex character, inc. cervical mucosa , Na +H2O retention, ossification, epiphyseal closure, GnRH release (dose dep)
- Pharmacokinetics: skin, mucous membranes, GI,SC,IM
*Use: female: dog-treatment for uterine infections, inhibition of nidation, urinary incontinence, dermatitis , stop lactation, presidtant CL in bo.
Male: anal adenoma , prostate hypertrophy/benign tumor
*SE: cow: prolapse vagina,uterus. Dog: anaemia, endometritis , ovarian supression and hypoplasia- ovarian cyst , feminisation in male.
NOT used in pregnancy or mammary tumours
- OESTRADIOL BENZOATE inj
- Estradiol bcypionate - ECP inj.
- Estradiol valerate
* Combinations: PROLA-s inj. (HCG) , SEROSAL tab. (Methyltestosterone) , CRESTAR sc implant
Anti-estrogen compounds
- Aromatase inhibitor of estrogen synthesis (anastrozole, letrozole)
- Estrigen receptor modulators:
i. Tamoxifen - treats estrogen-dep. Mammary tumors
ii. Raloxifene- antagonist in mammary gland and uterus, agonist in bones
iii. Clomiphene- only cebtrak (hypothalamic-pitutary)
Progesterone
Two effects:
- Nidation and maintanance of pregnancy
- Supression of oestrus and blocking ovulation
* Transforms proliferative endometrium to secretory endimetrium in pregnant animals, inhibits uterine contractions
* Main source: corpus luteum. But also produced in adrenal cortex, placenta.
Androgens:
Testosterone , Dihydrotestosterone, Androstenedione
- stimulate spermatogenesis , 2ndary make characteristics, muscle development
- Use: treatment for infertility, hypogonadism, aspermia , dec. Libido. Hormonal alopecia
- Andriol caps, Retandrol oil inj., Serosal tab.
i. Anabolic steroid
ii. Anti-andriogen
i. Stanozolol, Nandrolone, Methandienone
- Use: chronic disease accompanying with weight loss , erythropoietin stimulation, bone regeneration
- SE: vasoconstriction, heart faliure, impotence sperm
ii. Ciproterone , Delmadinon
Prostaglandins
Released in the endometrium, late in diestrus, near term pregnant animal
* Function: reproduction (PGF,PGE) and inflammation + membrane protection (PGE)
- Alfaprostol, PGF2alfa- Dinoprost
- Cloprostenol
- Luprostiol
- Use: oestrus synchronization, to induce parturition , abortion, pyometra
- SE: colic, nausea, vomiting , diarrhrea, bronchoconstriction, abortion
Oestrus synchronization: Progestogens/Progestagens
Type 1- strong gastagens (1st, MAP)
Type 2- weak gastagens (2nd Proligeston)
- Medroxy progesterone (MAP): control oestrus and ovulation, intravaginal sponge (VERAMIX) inhibits Oestrus in bitches (NEVER give in pro-oestrus).
SE: cystic endometrial hyperplasia, mammary tumours - Fluorogesterone (FGA): synchronization in ewe (CHRONOGEST intravaginal sponge)
- Norgestomet: string gestation, induce+sync ovulation in cow (CRESTAL imp)
- Proligestone and Megestol acetate: weak + antigonandotrophic effect , prevent or suppress ovulation (COVINAN inj. , OVARID inj.) Males: anal adenoma, …
- Anti-progestogens: abortion. Aglepristone (ALIZINE) , Dopamine receptot agonists: bromocriptine - prolactin inhibition- less prog. Secretion from corpus luteum
Oestrus synchronization: Prostaglandins
- Cloprostenol
- Dinoprost PGF-2Alpha
- Etiproston
- Luprostiol
Other uses: pyometra, endometritis Abortion, induction of parturition. Eosterus synchronisation
SE: vomiting, diarrhrea, colic disorders, nausea
Abortion induction
- Prostaglandins
- Antiprogesterone -Aglepriston, SC
Side-effects: swelling, skin enlargement at injection site, pyometra/metritis - Ergolines: cabergoline, bromocriptine Major indication pseudopregnancy in bitch Anti-prolactin effect Dopamine receptor modulators Emesis
Myometrial stimulants
- Prostaglandins
- oxytocin: dystocia, milk let down , uterine bleeding, retention of foetal membrane and eggs (reptiles too) Side-effects: GI and cardiovascular system! Oxytocin inj., Oxitocinainj., Oxytocineinj., Dila-Part inj., Perlactonnasal spray
- carbetocinDepotocininj. synthetic analogue, long duration of activity
- Ergometrine, methylergometrine Postpartum + vasoconstriction
Myometrial relaxants
- Beta2 adrenoreceptor agonists: clenbuterol, terbutaline
- Antispasmodics • papaverine, drotaverine ,denaverine
indications:
inhibition premature labour,difficult parturition ,intrauterine foetal procedures, reposition of uterus, -procurement of embryos from donors and implantation into the recipients
