Upload
lambert-adams
View
224
Download
0
Tags:
Embed Size (px)
Citation preview
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
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
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
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
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