GLUCOCORTICOIDS AND MINERALOCORTICOIDS

CorticosteroidsAdrenal glands produce glucocorticoids and mineralocorticoidsGlucocorticoids:Involved in cholesterol, fat, and protein metabolism

CorticosteroidsAdrenal glands produce glucocorticoids and mineralocorticoidsGlucocorticoids:Involved in cholesterol, fat, and protein metabolismMineralocorticoids:Involved in regulating electrolyte and water balance

CortisolPrincipal adrenal steroid hormoneResponsible for:GluconeogenesisProtein catabolismAnti-inflammatory reactionsStimulation of fat depositionSodium and water retention

CorticosteroidsAdrenal hormones excluding sex hormonesSteroid production follows a circadian rhythm

Properties of glucocorticosteroides used in clinicsAnti-inflammatoryImmune-depressiveAnti-allergicAnti-shockAnti-toxic

Anti-inflammatory action of GCSNonspecific inflammation Auto-immune componentHyperergic characterTherapy of despair

Mechanism of anti-inflammatory action of GCSGCSactivation of lipomodulinedecreasing of activity of phospholipase 2slowing down of arachidonic acid metabolites production (prostaglandins, leucotriens, thromboxan 2)stabilization of cellular andlyzosomalmembranesdecreasing of leucocytes migration processes, depression ofphagocytes activity decreasing of capillaries wall permeabilitydepression of histamine, serotonin, bradykinine releasing

Indications for administration of GCSInsufficiency of adrenal cortex Rheumatoid illnesses (rheumatoid arthritis, rheumatism, system red lupus etc.)Chronic active hepatitisBronchial asthma Ulcerative colitisNephritic syndromeAuto-immune hemolytic anemiaShock and collapse of any etiologyBrain, lungs, larynx edemaAcute allergic reactions Transfusion reactionsHeavy infections (hiding behind the etiotropic drugs!)Liver disesaes

Doses and terms of GCS therapy

Situation Daily doseTerms of treatmentAcute cases (shock, collapse, brain, lungs edema, septic shock, asthmatic condition etc.)200-500-800-1000 mg i.v.1-3 daysSubacute and acute attacks of chronic processes (rheumatoid diseases, ulcerative colitis, bronchial asthma etc.)20-50 mg(rarely till 200 mg)4-6 weeks-several monthsPrimary and secondary insufficiency of adrenal cortex2,5-10 mglife-long

CorticosteroidsAct as anti-inflammatory and immunosuppressive agents in treating diseases of different origins:HematologicAllergicInflammatoryNeoplasticAutoimmune

Administration of GCSInsufficiency of adrenal cortex Rheumatoid illnesses (rheumatoid arthritis, rheumatism, system red lupus etc.)Chronic active hepatitisBronchial asthma Ulcerative colitisNephritic syndromeAuto-immune hemolytic anemiaShock and collapse of any etiologyBrain, lungs, larynx edemaAcute allergic reactions Transfusion reactionsHeavy infections (hiding behind the etiotropic drugs!)Liver diseases

Doses and terms of GCS therapy

Situation Daily doseTerms of treatmentAcute cases (shock, collapse, brain, lungs edema, septic shock, asthmatic condition etc.)200-500-800-1000 mg i.v.1-3 daysSubacute and acute attacks of chronic processes (rheumatoid diseases, ulcerative colitis, bronchial asthma etc.)20-50 mg(rarely till 200 mg)4-6 weeks-several monthsPrimary and secondary insufficiency of adrenal cortex2,5-10 mglife-long

Hydrocortisone acetate

Prednisolone

Prednisolone

Prednisolone

Becotide = Beclometh(beclomethasone dipropionate)

Kenalog(triamcinolone acetonide)

Kenalog(triamcinolone acetonide)

Fluocinar Sinaflan Sinalar(Fluocinole acetonide)

Dexamethasone

Dexamethasone

Addisons DiseaseLife-threatening deficiency of glucocorticoids and mineralocorticoids

Treated with daily corticosteroids

Symptoms of Addisons DiseaseDebilitating weaknessHyperkalemiaHyperpigmentation of skinLow levels of serum sodium and glucoseReduced blood pressureWeight loss

Cushings DiseaseCaused by an overproduction of steroids or excessive administration of corticosteroidsSymptoms:Protruding abdomen; round, puffy face; fat over the shoulder blades

Reasons for Using CorticosteroidsInhibit inflammationUseful in treating asthma, rashes, and skin disordersAvailable in many different dosage forms

Problems with CorticosteroidsLessen the ability of leukocytes to destroy infection which decreases fever, redness, and swellingAlso may cause infection to spread

Corticosteroid Dispensing IssuesTake caution in patients with diabetes, uncontrolled hypertension, CHF, severe infection or altered immunity, or peptic ulcer disease with active GI bleeding

Warning!

CorticosteroidsUsage must be tapered off, not abruptly stoppedMay cause withdrawal symptomsAnorexia, nausea, vomiting, myalgia, arthralgia, lethargy, headache, sluggishness, weight loss, postural hypotension, fever and depressionDoses should be given in the morning

Adverse Effects of GlucocorticoidsCardiovascular effectsDermatologic effectsGastrointestinal effectsImmune system effectsMetabolic effectsMusculoskeletal effectsNeuropsychiatric effectsOphthalmic effects

Adrenal Sex HormonesAndrogens are produced by:The testesThe ovariesAdrenalsPeripheral fat tissueMost important male hormone is testosterone which is produced by the testes

Responsibilities of TestosteroneInitiating sperm productionBehavioral characteristicsLibidoSexual potencyMuscle mass and strengthFat distributionBone massErythropoiesisPrevention of baldness

HypogonadismDeficient hormone production and secretionAndrogens must be replaced by medicationsMay cause virilization, muscle building, and hematologic stimulation of erythropoiesisCan be used to treat anemia, breast cancer, or endometriosis

Androgens Side EffectsVirilizationHirsutismAcneHepatoxicityHigh levels of erythrocytesOily skinGynecomastiaPriapism

Male ImpotenceFailure to initiate or maintain an erection until ejaculationCauses:Testosterone deficiencyAlcoholismCigarette smokingPsychological factorsMedications

Drugs That May Cause Impotence

Alcohol (most significant)AmphetaminesAntihypertensivesCorticosteroidsEstrogens

H2 blockershaloperidollithiumOpiatesSome antidepressants

Agents for Male Impotencealprostadil (Caverject, Edex, Muse)danazol (Danocrine)methyltestosterone (Android, Testred)oxymetholone (Anadrol)papaverine testosterone (Androderm, AndroGel, Striant, Testoderm)Drug List

Agents for Male Impotence Phosphodiesterase Inhibitorssildenafil (Viagra)tadalafil (Cialis)vardenafil (Levitra)Drug List

sildenafil (Viagra)1st oral therapy for impotenceAllows an erection to occur naturallyTake at least 1 hour before activity

sildenafil Dispensing IssuesPotentially lethal interaction with nitratesWarning!

tadalafil (Cialis)Duration of action is 36 hoursFaster onset and longer duration than others in this class

tadalafil Dispensing IssuesPotentially lethal interaction with nitratesWarning!

Drugs of female sex hormonesEstrogens

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

progesteroneoxyprogesterone caproatealilestrenol (turinal)

Estrogens UsesHormone replacement therapy (HRT)Palliative and preventive therapy during menopauseActions Protecting the heart from atherosclerosisRetaining calcium in the bonesMaintaining the secondary female sex characteristics

Sites of Action of the Estrogens

Administration of drugs of female sex hormones

estrogens

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 BodyDecreased uterine motilityDevelopment of secretory endometriumThickened cervical mucusBreast growthIncreased body temperatureIncreased appetiteDepressed T-cell functionAnti-insulin effect

Administration of gestagens 1) miscarriage, habitual abortion2) dysfunctional uterus bleedings, algomenorrhea3) as component of contraceptives4) Climacteric disorders5) As part of fertility programs6) Treat specific cancers with specific receptor site sensitivity

Hormonal contraceptives

1) combined estrogen-gestagen a) monophased (bisecurin, non-ovlon, rigevidon, marvelon, demulen) b) double-phased (anteovin, neo-eunomin) c) triple-phased (tri-regol, trisiston)2) monohormonal gestagen (mini-pilli) exluton, ovret, continuin3) postcoital hestagen (postinor)4) depot-contraceptives - of prolonged action norplant (levonorgestrel) depot-provera (medroxyprogesterone acetate)

hypertension hypercoagulationdyspeptic disorders (nausea, vomiting)migraine depressionobesitycholestatic jaundicebreast cancer, cancer of uterus cervixischemic heart diseasemyocardium infarctionstrokeembryotoxic and teratogenic actionthrombo-emboliaComplications in case of administration ofhormonal contraceptives

Focus on the Fertility Drug Prototype: ClomipheneIndications: 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 stimulationPO route: Onset 58 days