Steroid Hormones. Steroid Hormones. Contraceptive agentsContraceptive agents

HormonesHormones

I I Protein-peptideProtein-peptide:: 1. 1. Hypothalamus Hypothalamus 2. 2. Pituitary glandPituitary gland 3. 3. Parathyroid glandsParathyroid glands 4. 4. Pancreas Pancreas 5. 5. IntestinalIntestinal II II Derivatives of amine acidsDerivatives of amine acids:: 1. 1. Thyroid glandThyroid gland – – derivatives of thyroninderivatives of thyronin 2. 2. Medulla of adrenal glandsMedulla of adrenal glands – – catecholaminescatecholamines

IIIIII SteroidSteroid::

1. 1. Adrenal cortexAdrenal cortex 2. 2. Sex glandsSex glands

Hormonal preparations Hormonal preparations of steroid structureof steroid structure

Natural hormones of adrenal cortex

Glucocorticosteroids

hydrocortisone (cortisole)corticosterone

cortisone11-dehydrocorticosterone

Mineral corticosteroids

aldosteronedesoxycorticosterone

11-desoxy-17-oxy-corticosterone

Hormones with sexual activity

androsteroneandrostendione

estroneprogesterone

Hypothalamus-adrenal axis

Hypothalamus-hypophysis-epinephral system

HypothalamusHypothalamusCRH Somatostatin GRH TRH PRH PIH GnRHCRH Somatostatin GRH TRH PRH PIH GnRH

Anterior pituitaryAnterior pituitaryGrowth hormone ACTH TSH FSH Growth hormone ACTH TSH FSH LH (male) LH (female) ProlactinLH (male) LH (female) Prolactin

Peripheral endocrine glandsPeripheral endocrine glandsAdrenal cortex Thyroid Gonads LiverAdrenal cortex Thyroid Gonads Liver

Feed-back mechanismFeed-back mechanism

Properties of glucocorticosteroides used in

clinics

• Anti-inflammatoryAnti-inflammatory

• Immune-suppressiveImmune-suppressive

• Anti-allergicAnti-allergic

• Anti-shockAnti-shock

• Anti-toxicAnti-toxic

Anti-inflammatory action of GCS

• Nonspecific inflammation

• Auto-immune component

• Hyperergic character

• Therapy of despair

Mechanism of anti-inflammatory action of GCS

GCS

activation of lipomoduline

decreasing of activity of phospholipase А2

slowing down of arachidonic acid metabolites production

(prostaglandins, leucotriens, thromboxan А2)

stabilization of cellular and

lyzosomalmembranes

decreasing of leucocytes’

migration processes, depression of

phagocytes activity

decreasing of capillaries’ wall permeability

depression of histamine, serotonin, bradykinine releasing

Administration of GCS• Insufficiency of adrenal cortexInsufficiency of adrenal cortex • Rheumatoid illnesses Rheumatoid illnesses ((rheumatoid arthritis, rheumatoid arthritis,

rheumatism, system red lupus etc.rheumatism, system red lupus etc.))• Chronic active hepatitisChronic active hepatitis• Bronchial asthmaBronchial asthma • Ulcerative colitisUlcerative colitis• Nephritic syndromeNephritic syndrome• Auto-immune hemolytic anemiaAuto-immune hemolytic anemia• Shock and collapse of any etiologyShock and collapse of any etiology• Brain, lungs, larynx edemaBrain, lungs, larynx edema• Acute allergic reactionsAcute allergic reactions • Transfusion reactionsTransfusion reactions• Heavy infectionsHeavy infections ( (hiding behind the etiotropic drugshiding behind the etiotropic drugs!)!)• Liver diseasesLiver diseases

Doses and terms of GCS therapy

Situation Daily dose Terms of treatment

Acute casesAcute cases ( (shock, shock, collapse, brain, lungs collapse, brain, lungs edema, septic shock, edema, septic shock, asthmatic condition etc.asthmatic condition etc.))

200-500-200-500-800-1000 800-1000 mg mg i.v.i.v.

1-3 1-3 daysdays

Subacute and acute Subacute and acute attacks of chronic attacks of chronic processesprocesses ( (rheumatoid rheumatoid diseases, ulcerative colitis, diseases, ulcerative colitis, bronchial asthma etc.bronchial asthma etc.))

20-50 20-50 mgmg((rarely tillrarely till 200 200 mgmg))

4-6 4-6 weeksweeks--several several monthsmonths

Primary and secondary Primary and secondary insufficiency of adrenal insufficiency of adrenal cortexcortex

2,5-10 2,5-10 mgmg life-longlife-long

Hydrocortisone acetate

Prednisolone

Prednisolone

Prednisolone

Becotide = Beclometh(beclomethasone dipropionate)

Kenalog(triamcinolone acetonide)

Kenalog(triamcinolone acetonide)

Fluocinar – Sinaflan – Sinalar(Fluocinole acetonide)

Dexamethasone

Dexamethasone

Dexamethasone

Lorinden A: flumethasone pivalate

(locacorten) + neomycin

Steroid diabetesSteroid diabetesimmune-suppressionimmune-suppressiondepression of resistance towards any infectionsdepression of resistance towards any infections atrophy of musclesatrophy of muscleshypopotassiumemiahypopotassiumemiapeptic ulcerspeptic ulcersdisturbance of regenerationdisturbance of regenerationosteoporosis, delay of growthosteoporosis, delay of growthmatronismmatronism ( (“buffalo hump”, “moonlike face” etc.)“buffalo hump”, “moonlike face” etc.)retention ofretention of NaNa++ , , HH22o edemao edemahypertensionhypertension hypercoagulation of bloodhypercoagulation of bloodchanges of psychical conditionschanges of psychical conditions disturbance of menstrual cycledisturbance of menstrual cyclehypothalamus-pituitary-epinephral insuffciencyhypothalamus-pituitary-epinephral insuffciency

Izenko-Cushing’s syndrome

Complications of GCS-therapyComplications of GCS-therapy

Controls and Actions of the Adrenal Glands

MINERALOCORTICOIDSDesoxycorticosterone acetate - DOXA

• Mode of actionMode of action

Acts on kidney tubules: causes the reabsorption of Acts on kidney tubules: causes the reabsorption of sodium and water, decreases the reabsorption of sodium and water, decreases the reabsorption of potassium,potassium,

regulates fluid-electrolyte metabolism, increases AP, regulates fluid-electrolyte metabolism, increases AP, enhances muscle workenhances muscle work

• AdministrationAdministration

For chronic adrenal insufficiency (Addison’s disease), For chronic adrenal insufficiency (Addison’s disease), myasthenia, adynamiamyasthenia, adynamia

• Side effectsSide effects

edema, AP increasing, pulmonary edema, cardiac edema, AP increasing, pulmonary edema, cardiac insufficiencyinsufficiency

Drugs of female sex Drugs of female sex hormoneshormones

Estrogens Estrogens

estron(oil solution of folliculin)estradiolethynilestradiol(microfollin)synestrol

Gestagens Gestagens

progesteroneoxyprogesterone caproatealilestrenol (turinal)

Estrogens

• UsesUses– Hormone replacement therapy (HRT)– Palliative and preventive therapy during

menopause

• Actions Actions – Protecting the heart from

atherosclerosis– Retaining calcium in the bones– Maintaining the secondary female sex

characteristics

Sites of Action of the Estrogens

Administration of drugs of female sex hormones

estrogensestrogens

1) Genital hypoplasia, primary and secondary amenorrhea2) Sexual underdevelopment of women3) After ovary-ectomia4) Climacteric disorders 5) Lactation depression6) Weak labor activity(estrogen background)7) Prostate cancer of men, breast cancer of women after the age of 608) A part of contraceptive agents

Effects of Progesterone on the Body

• Decreased uterine motility• Development of secretory

endometrium• Thickened cervical mucus• Breast growth• Increased body temperature• Increased appetite• Depressed T-cell function• Anti-insulin effect

Administration of gestagens

1) miscarriage, habitual abortion

2) dysfunctional uterus bleedings, algomenorrhea

3) as component of contraceptives

4) Climacteric disorders5) As part of fertility programs

6) Treat specific cancers with specific receptor site sensitivity

Hormonal contraceptivesHormonal contraceptives

1)1) combined estrogen-gestagencombined estrogen-gestagen aa)) monophased monophased ((bisecurin, non-ovlon, rigevidonbisecurin, non-ovlon, rigevidon, ,

marvelon, demulenmarvelon, demulen)) bb) ) double-phaseddouble-phased ( (anteovin, neo-eunominanteovin, neo-eunomin))

cc) ) triple-phasedtriple-phased ( (tri-regol, trisistontri-regol, trisiston))2)2) monohormonal gestagenmonohormonal gestagen ( (mini-pillimini-pilli))

exluton, ovret, continuinexluton, ovret, continuin3)3) postcoital hestagenpostcoital hestagen ( (postinorpostinor))

4)4) depot-contraceptivesdepot-contraceptives - - of prolonged actionof prolonged action norplantnorplant ( (levonorgestrellevonorgestrel))

depot-proveradepot-provera ( (medroxyprogesterone acetatemedroxyprogesterone acetate))

hypertension hypertension hypercoagulationhypercoagulationdyspeptic disordersdyspeptic disorders ( (nausea, vomitingnausea, vomiting))migraine migraine depressiondepressionobesityobesitycholestatic jaundicecholestatic jaundicebreast cancer, cancer of uterus cervixbreast cancer, cancer of uterus cervixischemic heart diseaseischemic heart diseasemyocardium infarctionmyocardium infarctionstrokestrokeembryotoxic and teratogenic actionembryotoxic and teratogenic action

thrombo-emboliathrombo-embolia

Complications in case of administration ofhormonal contraceptives

Focus on the Fertility Drug Prototype: Clomiphene

• Indications: Treat ovarian failure in patients with normal liver function and normal endogenous estrogens; unlabeled use: treat male sterility

• Actions: Binds to estrogen receptors, decreasing the number of available estrogen receptors, which gives the hypothalamus the false signal to increase FSH and LH secretion, leading to ovarian stimulation

• PO route: Onset 5–8 days; duration 6 weeks

• T½: 5 days, with hepatic metabolism and excretion in the feces

Abortifacients

• UseUse– Evacuate the uterus by stimulating

intense uterine contractions

• TypesTypes– Carboprost (Hemabate)– Dinoprostone (Cervidil, Prepidil Gel,

Prostin E2)– Mifepristone (RU-486, Mifeprex)

Androgens and Their Indications

• Testosterone (Duratest, Testoderm, others) – Hypogonadism; breast cancer

• Danazol (Danocrine)– Block the release of FSH and LH in women

• Fluoxymesterone (Halotestin)– Hypogonadism; breast cancer

• Testolactone (Teslac)– Breast cancers

ANABOLIC STEROIDSPhenobolinum, Retabolil, Methandrostenolonum

PHARMACOLOGICAL EFFECTSPHARMACOLOGICAL EFFECTS- Stimulation of protein synthesis- Depression of phosphor and Ca++ excretion- Increase of bones, muscles and parenchymatous

organs mass- Stimulation of regeneration

ADMINISTRATIONADMINISTRATION- Aplastic anemia (bone marrow suppression)- Osteoporosis, bone fractures- Exhausted diseases- Prolonged treatment with GCS

COMPLICATIONSCOMPLICATIONS Hepatitis, sexual disorders (impotence), edemas,

masculinization, nausea, vomiting