ClucocorticoidsClucocorticoids

Some characrteristics of synhetic Some characrteristics of synhetic

glukocorticoidsglukocorticoids

Effects of glucocorticoidsEffects of glucocorticoids

1. Physiologic effects1. Physiologic effects increase increase proteinprotein breakdown, leading to a negative nitrogen breakdown, leading to a negative nitrogen

balance,balance, stimulation of gluconeogenesis stimulation of gluconeogenesis increase of increase of blood glucosablood glucosa

level,level, increase plasma increase plasma fatty acidsfatty acids and ketone body formation, and ketone body formation, increase of increase of kaliumkalium excretion (increased protein catabolism), excretion (increased protein catabolism), increase of increase of Na+ and waterNa+ and water retention. retention.

2. Anti-inflammatory effect2. Anti-inflammatory effect inhibition of inhibition of antigen response,antigen response, inhibition of inhibition of PLA2PLA2 decrease of prostanoids production, decrease of prostanoids production, inhibition of inhibition of cytokine cytokine production (IL-1, IL-2, TNF-production (IL-1, IL-2, TNF-),), inhibition of inhibition of vascular permeabilityvascular permeability..

3. Immunologic effects3. Immunologic effects decrease of circulating lymphocytes, monocytes, decrease of circulating lymphocytes, monocytes,

eosinophils and basophils,eosinophils and basophils, increase of circulating increase of circulating neutrophils,neutrophils, chronic therapy results in ivolution of all chronic therapy results in ivolution of all lymphoid lymphoid

tissuetissue..

Other effectsOther effects inhibition of plasma inhibition of plasma ACTH ACTH and possible adrenal and possible adrenal

atrophy,atrophy, inhibition of inhibition of fibroblast growth and collagen fibroblast growth and collagen

synhesis,synhesis, stimulation ofstimulation of acid and pepsin secretion, acid and pepsin secretion, altered altered CNS responsesCNS responses, influencing mood and sleep , influencing mood and sleep

paterns,paterns, enhanced enhanced neuromuscular transmissionneuromuscular transmission

SIDE EFFECTS UF GCSIDE EFFECTS UF GC

iatrogenic Cushing´s diseaseiatrogenic Cushing´s disease adrenal suppresion,adrenal suppresion, hyperglycemia,hyperglycemia, osteoporosis,osteoporosis, peptic ulcer,peptic ulcer, cataracte and increased intraocular pressure,cataracte and increased intraocular pressure, edema,edema, hypertension,hypertension, increased susceptibility to infection and poor increased susceptibility to infection and poor

wound healing,wound healing, muscle weaknes and tissue loss,muscle weaknes and tissue loss,

Therapeutic uses of GCTherapeutic uses of GC

CVS:CVS: rheumatic carditis, myocarditisrheumatic carditis, myocarditis Respiratory system:Respiratory system: asthma, pulmonary fibrosisasthma, pulmonary fibrosis Gut:Gut: exacerbation of inflammatory bowel diseaseexacerbation of inflammatory bowel disease CNS:CNS: prevention of scarring and cerebral oedema prevention of scarring and cerebral oedema

produced by surgery, head injures and tumours, produced by surgery, head injures and tumours, exacerbation of sclerosis multiplexexacerbation of sclerosis multiplex

Renal:Renal: nephrotic syndromenephrotic syndrome Musculoskeletal system:Musculoskeletal system: rheumatoid arthritis and rheumatoid arthritis and

other collagen-diseasesother collagen-diseases Eye:Eye: prevention of scarring following surgery and prevention of scarring following surgery and

uveitisuveitis Skin:Skin: eczema, severe inflammatory skin conditionseczema, severe inflammatory skin conditions Endocrine:Endocrine: replacement therapy in Adison´s disease replacement therapy in Adison´s diseaseImmune system:Immune system: anaphylactic shock, prevention of anaphylactic shock, prevention of

transplanted organ rejectiontransplanted organ rejection Blood:Blood: autoimmune anaemia and thrombocytopenia, autoimmune anaemia and thrombocytopenia,

leukeamia and Hodkin´s disease leukeamia and Hodkin´s disease

Inhibitors of corticoid synthesisInhibitors of corticoid synthesis

Metyrapone, Trilostane- Metyrapone, Trilostane- predominantly inhibits terminal step in predominantly inhibits terminal step in cortisol and aldosterone productioncortisol and aldosterone production..

Ketoconazole, Ketoconazole, AminoglutethimideAminoglutethimide- inhibitors of - inhibitors of cytochrome P450.cytochrome P450.

Mitotane Mitotane - inhibits - inhibits steroidogenesis at the ACTH steroidogenesis at the ACTH regulated step.regulated step.

Estrogenes and androgenesEstrogenes and androgenes

ESTROGENS ESTROGENS

Naturaly estrogensNaturaly estrogens EstradioleEstradiole (most potent), testosterone is the (most potent), testosterone is the

precursorprecursor Estrone and EstrioleEstrone and Estriole are produced in the liver are produced in the liver

from 17 from 17 -estradiol-estradiol

Synthetic estrogensSynthetic estrogens EthinylestradiolEthinylestradiol MestranolMestranol Diethylstilbestrol Diethylstilbestrol (nonsteroidal)(nonsteroidal)

Mechanism of actionMechanism of action Estrogens bind to specific intracelular receptorsEstrogens bind to specific intracelular receptors Interacts with specific DNA sequences and alter the Interacts with specific DNA sequences and alter the

transcription rate of genestranscription rate of genes These changes leads to the specific protein synthesis These changes leads to the specific protein synthesis

within a target cellswithin a target cells

PharmacokineticPharmacokinetic Estradiol is extensively (98%) bound to sex Estradiol is extensively (98%) bound to sex steroid-binding steroid-binding

globulinglobulin and to serum albumin and to serum albumin Estrogens are metabolized in the liver (by conjugation)Estrogens are metabolized in the liver (by conjugation) Metabolites are excreted in the urine (10% undergou Metabolites are excreted in the urine (10% undergou

enterohepatic circulation)enterohepatic circulation)

ActionsActions Growth and developmentGrowth and development - - development and maturation of external genitalia, growth development and maturation of external genitalia, growth

of breast, myometriumof breast, myometrium Menstrual cycleMenstrual cycle Systemic metabolizmSystemic metabolizm - - promote positive nitrogen balance, increase triglycerides, promote positive nitrogen balance, increase triglycerides,

tend decrease cholesterotend decrease cholesteroll- decrease total serum proteins, increase level of transferin, - decrease total serum proteins, increase level of transferin,

and thyroid- binding globulins, plasminogen, fibrinogen and and thyroid- binding globulins, plasminogen, fibrinogen and coagulation factors ( VII-X) coagulation factors ( VII-X)

- decrease bone resorption- decrease bone resorption Influence libido andInfluence libido and

Therapeutic usesTherapeutic uses- Hypogonadism- Hypogonadism- Menstrual abnormalities- Menstrual abnormalities- Postmenopausal therapy- Postmenopausal therapy- Oral contraceptionOral contraceptionHormone replacement therapyHormone replacement therapy The principal indication for such therapy is to The principal indication for such therapy is to

suppress hot flashes and treat atrophy of the suppress hot flashes and treat atrophy of the urogenital tissues, which may manifest as urogenital tissues, which may manifest as dry vagina.dry vagina.

For women with a uterus, estrogen therapy For women with a uterus, estrogen therapy must be combined with progestin therapy to must be combined with progestin therapy to prevent the induction of endometrial cancer.prevent the induction of endometrial cancer.

Like contraceptives, hormone therapy is Like contraceptives, hormone therapy is available as oral tablets, transdermal available as oral tablets, transdermal patches, and vaginal rings and tablets. patches, and vaginal rings and tablets.

Oral contraception Oral contraception 1. 1. Combination Estrogen–Progestin Combination Estrogen–Progestin ContraceptionContraception

Side effectsSide effects (combined(combined pills)pills) Cardiovascular systemCardiovascular system venous thromboembolic disease,venous thromboembolic disease, myocardial infarction,myocardial infarction, hypertension.hypertension. CarcinomaCarcinoma increased risk of cervical and breast increased risk of cervical and breast

carcinoma,carcinoma, pill protects against endometrial and ovarian pill protects against endometrial and ovarian

malignancy.malignancy. Liver Liver rarely, cholestatic jaundice, hepatic tumours.rarely, cholestatic jaundice, hepatic tumours. OthersOthers headache, menstrual irregularity in the first headache, menstrual irregularity in the first

months of treatment months of treatment

ContraindicationContraindication

history of the thromboembolic disease,history of the thromboembolic disease,

breast, endometrial and liver carcinoma,breast, endometrial and liver carcinoma,

hyperlipidaemia.hyperlipidaemia.

Use with caution Use with caution

diabetes mellitus,diabetes mellitus,

hypertension, hypertension,

migraine.migraine.

1. Progestin-Only Contraception1. Progestin-Only Contraception The two progestin-only oral contraceptives The two progestin-only oral contraceptives

available, commonly referred to as the “mini-available, commonly referred to as the “mini-pill,” are norgestrel and norethindronepill,” are norgestrel and norethindrone. .

MedroxyprogesteroneMedroxyprogesterone acetate acetate 104 mg 104 mg for Subcutaneous injection or 150 mg for Subcutaneous injection or 150 mg intramuscular injection- can be given every 3 intramuscular injection- can be given every 3 monthsmonths

2. 2. Emergency (Morning-After) ContraceptionEmergency (Morning-After) Contraception

Oral levonorgestrel 0.75 mg, given as soon as Oral levonorgestrel 0.75 mg, given as soon as possible after the exposure and repeated in 12 possible after the exposure and repeated in 12 hours.hours.

3. 3. Male ContraceptionMale Contraception - - the goal of male the goal of male contraception would be to suppress endogenous contraception would be to suppress endogenous production of sperm reversibly, generating a state of production of sperm reversibly, generating a state of azoospermia (parenteral azoospermia (parenteral testosterone enanthatetestosterone enanthate plus plus daily oral levonorgestrel) daily oral levonorgestrel)

AndrogensAndrogens

Naturaly androgensNaturaly androgens Testosterone- is synthesised in the Leydig cellsunder Testosterone- is synthesised in the Leydig cellsunder

the influence of LHthe influence of LH

Synhetic androgensSynhetic androgens MethyltestosteroneMethyltestosterone FluoxymesteroneFluoxymesterone StanozololStanozolol Nandrolone-with highes anabolic actionNandrolone-with highes anabolic action

ActionsActions Stimulate the differentiation and development of Stimulate the differentiation and development of

wolffian structures: wolffian structures: epiddymis, seminal vesicles, epiddymis, seminal vesicles, prostate and penisprostate and penis

Stimulate the development and maintanance of male Stimulate the development and maintanance of male semale secundary semale secundary sexual characteristicssexual characteristics

Anabolic actions-Anabolic actions-growth at puberty, increase in growth at puberty, increase in muscle mass, positive nitrogen balance muscle mass, positive nitrogen balance

Behavioral effects-Behavioral effects-aggressiveness and icreased libidoaggressiveness and icreased libido

UsesUses -Prepubertal and postpubertal -Prepubertal and postpubertal hypogonadismhypogonadism --AnemiaAnemia-stimulate secretion of erythropoetine-stimulate secretion of erythropoetine - Androgen-dependent- Androgen-dependent breast cancers breast cancers --Illicit useIllicit use by athlets (increase the extent and rate of muscle by athlets (increase the extent and rate of muscle

formation)formation)

Adverse effectsAdverse effects -Decreased -Decreased testicular functiontesticular function, altered plasma lipids , altered plasma lipids

(increased LDL, decreased HDL)(increased LDL, decreased HDL) --MasculinizationMasculinization in women in women -Increase of plasma -Increase of plasma fibrinolytic activityfibrinolytic activity (bleeding with (bleeding with

concomitant anticoagulants)concomitant anticoagulants) -Long-term use is assotiated with -Long-term use is assotiated with liver tumorsliver tumors -Are contraindicated in patients with carcinoma of prostate, -Are contraindicated in patients with carcinoma of prostate,

or hepatic, renal and cardiovascular disease.or hepatic, renal and cardiovascular disease.AntiandrogensAntiandrogens Flutamide, FinasterideFlutamide, Finasteride-in the treatment of prostatic -in the treatment of prostatic

carcinomacarcinoma CyproteroneCyproterone-decrease sexual drive in men.-decrease sexual drive in men. Are usefulin treating precocious puberty.Are usefulin treating precocious puberty.

ProgestinsProgestins

Naturaly progestinsNaturaly progestins Progesterone-is synthesized by ovaries, testes Progesterone-is synthesized by ovaries, testes

and adrenalsand adrenalsSynhetic progestinsSynhetic progestins NorethisteroneNorethisterone MedroxyprogesteroneMedroxyprogesterone NorgestrelNorgestrelActionsActions Mechanism of action: as for estrogens. Prior Mechanism of action: as for estrogens. Prior

estrogen action is required for the synthesis of estrogen action is required for the synthesis of progesterone receptorsprogesterone receptors

Slow the mitotic activity of the estrogen Slow the mitotic activity of the estrogen stimulated uterus, cause the vascularization of stimulated uterus, cause the vascularization of the endometriumthe endometrium

Induce a more glandular appearance and Induce a more glandular appearance and functionfunction

Slightly decrease triglycerides and and HDL Slightly decrease triglycerides and and HDL and increase LDLand increase LDL

Progestins Progestins

Therapeutic usesTherapeutic uses- - Oral Oral contraceptioncontraception (alone or in the (alone or in the

combination)combination)- Treatment of - Treatment of endometrial cancerendometrial cancer- - To delay menstruationTo delay menstruation (for surgical (for surgical

or postoperative reasons)or postoperative reasons)- Combination with estrogenes – Combination with estrogenes –

replacement therapyreplacement therapy

Anti-progestinsAnti-progestins Mefepristone-Mefepristone-for use to induce for use to induce

medical abortion in the first trimestermedical abortion in the first trimester