Pharmacology of Endocrine System-nursing

8/6/2019 Pharmacology of Endocrine System-nursing

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Endocrine pharmacologyEndocrine pharmacology


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Human Endocrine SystemHuman Endocrine System

Principal organsPrincipal organs --Hypothalamus,Hypothalamus,

Pituitary gland (two lobes),Pituitary gland (two lobes),

Pineal gland,Pineal gland, Thyroid gland, Parathyroid glands (4),Thyroid gland, Parathyroid glands (4),

Thymus gland, Adrenal glands,Thymus gland, Adrenal glands,

Pancreas (islets ofPancreas (islets of LangerhansLangerhans),),

Ovaries orTestes.Ovaries orTestes.


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Endocrine SystemEndocrine System

A) FunctionA) Function

1) control systems, maintain homeostasis1) control systems, maintain homeostasis

(control chemical and water balance in body)(control chemical and water balance in body)

22-- Regulation of growth and development.(control embryonic development )Regulation of growth and development.(control embryonic development )

33-- Control of reproductive system processes (ovulation,Control of reproductive system processes (ovulation, mestruationmestruation,,

maintanencemaintanence of pregnancy)of pregnancy)

44-- Effects on Behavior (modification, modulation, initiation of specificEffects on Behavior (modification, modulation, initiation of specific

patterns)patterns)

55-- influence sexual behavior, stimulate growth andinfluence sexual behavior, stimulate growth and

maturation of the gonadsmaturation of the gonads


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PosteriorPituitaryPosteriorPituitary

a)a) OxytocinOxytocin -- stimulates uterine contractions, milk ejection reflex in the mammarystimulates uterine contractions, milk ejection reflex in the mammary

glandsglands

b)b) ADHADH -- antidiureticantidiuretic hormone, stimulates retention of water action blocked byhormone, stimulates retention of water action blocked by

caffeinecaffeine


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Adrenal GlandsAdrenal Glands (on top of kidneys)(on top of kidneys) -- hormones in the fight/fright responsehormones in the fight/fright response

a)a) GlucocorticoidsGlucocorticoids -- raises glucose levels in the blood, stimulates glucose productionraises glucose levels in the blood, stimulates glucose production

b) Epinephrineb) Epinephrine -- complement supply from the sympathetic system function is to give the bodycomplement supply from the sympathetic system function is to give the bodyan energetic boost, increase metabolic rate, dilates bronchioles in the lungs, increases heartan energetic boost, increase metabolic rate, dilates bronchioles in the lungs, increases heart

rate, etc.rate, etc.

TargetTarget -- most systems of the bodymost systems of the body

c)c) MineralocorticoidsMineralocorticoids -- retention of ionsretention of ions

PancreasPancreas (at junction of stomach and small intestine)(at junction of stomach and small intestine)a) Insulina) Insulin -- lowers blood sugar levels (secreted by beta cells)lowers blood sugar levels (secreted by beta cells)

Target organsTarget organs -- liver, skeletal, adipose (fat) tissuesliver, skeletal, adipose (fat) tissues

b) Glucagonb) Glucagon -- increases blood sugar levels (secreted by alpha cells)increases blood sugar levels (secreted by alpha cells)

Target organsTarget organs -- liver, skeletal, adipose (fat) tissuesliver, skeletal, adipose (fat) tissues

Male gonadsMale gonads -- testes (pelvic region on men)testes (pelvic region on men)a) testosterone, maintain secondary sexual characteristics,a) testosterone, maintain secondary sexual characteristics,

stimulate sperm productionstimulate sperm production

Female gonadsFemale gonads -- ovaries (pelvic region of women)ovaries (pelvic region of women)

a) estrogen and progesterone, maintain secondarya) estrogen and progesterone, maintain secondary

sexual characteristics,sexual characteristics,

regulate reproductive cycleregulate reproductive cycle


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HormonesHormones Hormones are chemical messengers that are producedHormones are chemical messengers that are produced

by the endocrine glands and are carried by theby the endocrine glands and are carried by thebloodstream.bloodstream.

They actually act as "messengers" to coordinateThey actually act as "messengers" to coordinatefunctions ofvarious body parts.functions ofvarious body parts.

Most hormones are proteins consisting of amino acidMost hormones are proteins consisting of amino acidchains. Some hormones are steroids.chains. Some hormones are steroids.

..


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Functions controlled by hormones include:Functions controlled by hormones include:

activities of entire organsactivities of entire organs growth and developmentgrowth and development

reproductionreproduction

sexual characteristicssexual characteristics

usage and storage of energyusage and storage of energy

levels of fluid, salt and sugar in the bloodlevels of fluid, salt and sugar in the blood


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Types ofHormonesTypes ofHormones

There are two main classes (chemical groups) into whichThere are two main classes (chemical groups) into which

hormones fall:hormones fall:

1.1. steriodssteriods

(in vertebrates(in vertebrates sythesizedsythesized from cholesterol by adrenal cortex,from cholesterol by adrenal cortex,

testis, ovary and placenta)testis, ovary and placenta)

[examples:[examples: cortisolcortisol,, estradiolestradiol]]

2. non2. non--steroidsteroid

-- amines [epinephrine andamines [epinephrine and norepinephrinenorepinephrine]]

--peptides [peptides [oxytocinoxytocin, ADH], ADH]

--proteins [growth hormone, insulin]proteins [growth hormone, insulin]

-- glycoproteinsglycoproteins [FSH, TSH][FSH, TSH]


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Adrenal steroidsAdrenal steroids


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Adrenal steroidsAdrenal steroids

The adrenal gland consists of the cortex and the medulla. TheThe adrenal gland consists of the cortex and the medulla. The

latter secretes epinephrine, whereas the cortex, synthesizeslatter secretes epinephrine, whereas the cortex, synthesizesand secretes two major classes of steroidand secretes two major classes of steroid hormonesthehormonesthe

adrenocorticosteroidsadrenocorticosteroids ((glucocorticoidsglucocorticoids andand mineralocorticoidsmineralocorticoids..

and the adrenal androgens.and the adrenal androgens.


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The adrenal cortex is divided into three zones thatThe adrenal cortex is divided into three zones that

synthesize various steroids from cholesterol and thensynthesize various steroids from cholesterol and then

secrete them .secrete them .The outerThe outer zonazona glomerulosaglomerulosa

producesproduces mineralocorticoidsmineralocorticoids (for example,(for example,

aldosteronealdosterone), which are responsible for regulating salt), which are responsible for regulating salt

and water metabolism. Production ofand water metabolism. Production of aldosteronealdosterone isisregulated primarily by theregulated primarily by the reninrenin--angiotensinangiotensin system .system .

The middleThe middle zonazona fasciculatafasciculata

synthesizessynthesizes glucocorticoidsglucocorticoids (for example,(for example,cortisolcortisol), which are involved with normal metabolism), which are involved with normal metabolism

and resistance to stress.and resistance to stress.

The innerThe inner zonazona reticularisreticularis secretes adrenal androgenssecretes adrenal androgens

(for example,(for example, dehydroepiandrosteronedehydroepiandrosterone..


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Mechanism of actionMechanism of action

They bind to specific intracellular cytoplasmicThey bind to specific intracellular cytoplasmic

receptors in target tissues, the receptorreceptors in target tissues, the receptor--

hormone complex then translocates into thehormone complex then translocates into the

nucleus where it acts as a transcription factornucleus where it acts as a transcription factor

to turn genes on or off, depending on the tissueto turn genes on or off, depending on the tissue

( this mechanism take a time for the effect to be( this mechanism take a time for the effect to be

obvious )obvious )


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Pharmacological actionPharmacological action

Promote normal intermediary metabolismPromote normal intermediary metabolism

Carbohydrate metabolismCarbohydrate metabolism: (: (increaseincrease gluconeogenicgluconeogenic enzymes)enzymes)

gluconeogenesisgluconeogenesis is increased and peripheral glucoseis increased and peripheral glucose

utilization may be decreased (insulin antagonism) so thatutilization may be decreased (insulin antagonism) so that

hyperglycaemiahyperglycaemia and sometimesand sometimes glycosuriaglycosuria result.result.

Latent diabetes becomes overt.Latent diabetes becomes overt.

Protein metabolismProtein metabolism: anabolism (conversion of amino acids to: anabolism (conversion of amino acids to

protein) is decreased but catabolism continues unabated orprotein) is decreased but catabolism continues unabated or

even faster, so that there is a negative nitrogen balance witheven faster, so that there is a negative nitrogen balance withmuscle wasting.muscle wasting.

stimulatestimulate lipolysislipolysis ..


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Increase resistance to stress:Increase resistance to stress:

increase blood glucose ( provide energy )increase blood glucose ( provide energy )

increase blood pressure ( potentateincrease blood pressure ( potentate vasoconstrictervasoconstrictereffect of adrenergic system on bloodeffect of adrenergic system on blood vesselavessela))

Alter blood cell levels in plasmaAlter blood cell levels in plasma

DecreaseDecrease inin eosinophilseosinophils ,, basophilsbasophils,, monocytesmonocytes andandlymphocytes by redistributing them to lymphoid tissuelymphocytes by redistributing them to lymphoid tissuefrom the circulation . The decrease in circulatingfrom the circulation . The decrease in circulatinglymphocytes and macrophages compromises the body'slymphocytes and macrophages compromises the body'sability to fight infections. However, this property isability to fight infections. However, this property is

important in the treatment of leukemiaimportant in the treatment of leukemia In contrast to this effect, theyIn contrast to this effect, they

IncreaseIncrease blood levels ofhemoglobin , erythrocytes,blood levels ofhemoglobin , erythrocytes,platelets andplatelets and polymorphonuclearpolymorphonuclear leukocytes .leukocytes .


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AntiAnti--inflammatory actioninflammatory action

The most important therapeuticThe most important therapeutic

property of theproperty of the glucocorticoidsglucocorticoids is their abilityis their abilityto dramatically reduce the inflammatoryto dramatically reduce the inflammatory

response and to suppress immunity byresponse and to suppress immunity by

11-- Lowering the number and inhibition ofLowering the number and inhibition of

peripheral lymphocytes and macrophages roleperipheral lymphocytes and macrophages role

22-- Indirect inhibition ofIndirect inhibition of phospholipasephospholipase A2A2

through elevation of lipocortin which blocks thethrough elevation of lipocortin which blocks the

release of arachidonic acid from the cellrelease of arachidonic acid from the cell

membrane .membrane .

33-- In addition, interference in mast cellIn addition, interference in mast cell

degranulation results in decreased histaminedegranulation results in decreased histamine

and capillary permeability.and capillary permeability.


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Effects on other systemEffects on other system

Excessive level ofExcessive level of glucocorticoidsglucocorticoids stimulate gastric acid and pepsinstimulate gastric acid and pepsinproduction .production .

Bone loss .(Bone loss .(Osteoporosis (reduction of bone protein matrix)Osteoporosis (reduction of bone protein matrix) occurs,occurs,growth slows in children).growth slows in children).

Myopathy leads to weakness .Myopathy leads to weakness .

-- Fat deposition: this is increased on shoulders, face andFat deposition: this is increased on shoulders, face and

abdomen.abdomen.

Anti

Anti--vitamin D action .vitamin D action .--Reduction ofReduction ofhypercalaemiahypercalaemia chiefly where this is due to excessivechiefly where this is due to excessive

absorption of calcium from the gut (absorption of calcium from the gut (sarcoidosissarcoidosis, vitamin D, vitamin D

intoxication).intoxication).

--Urinary calcium excretion is increased and renal stones form.Urinary calcium excretion is increased and renal stones form.

--SuppresionSuppresion ofhypothalamic /ofhypothalamic / pitutarypitutary adrenocorticaladrenocortical

feedback system (with delayed recovery) occurs withfeedback system (with delayed recovery) occurs with

chronic use, so that abrupt withdrawal leaves the patient in achronic use, so that abrupt withdrawal leaves the patient in a

state ofstate of adrenocorticaladrenocortical insufficiencyinsufficiency


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MineralocorticoidsMineralocorticoids

Help to control the bodys water volume andHelp to control the bodys water volume and

concentration of electrolytes speciallyconcentration of electrolytes specially

sodium and potassium .sodium and potassium .

AldosteroneAldosterone acts on kidney tubules andacts on kidney tubules and

collecting ducts, causing acollecting ducts, causing a reabsorptionreabsorption ofof

sodium, bicarbonate, and water.sodium, bicarbonate, and water.

Conversely,Conversely, aldosteronealdosterone decreasesdecreases

reabsorptionreabsorption of potassium, which, with H+,of potassium, which, with H+,

is then lost in the urine.is then lost in the urine.


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Commonly used corticosteroidsCommonly used corticosteroids

Short actingShort acting glucocorticoidsglucocorticoids ( 8( 8--12 hours )12 hours ) HydrocortisoneHydrocortisone

cortisonecortisone

Intermediate actingIntermediate acting glucocorticoidsglucocorticoids (18(18--36 hours )36 hours ) PrednisolonePrednisolone

PrednisonePrednisone

MethylprednisoloneMethylprednisolone

trimcinolonetrimcinolone

Long actingLong acting glucocorticoidsglucocorticoids ( 1( 1--3 days )3 days ) BetamethasoneBetamethasone

DexamethasoneDexamethasone ParamethasoneParamethasone

MiniralocorticoidsMiniralocorticoids FludrocortisoneFludrocortisone ( strong salt retaining effect( strong salt retaining effect

DeoxycorticosteroneDeoxycorticosterone ( only salt retaining effect )( only salt retaining effect )


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PharmacokineticsPharmacokinetics

-- They are readily absorbed from GIT , selectedThey are readily absorbed from GIT , selectedcompound can be given IV, IM, Topically or as ancompound can be given IV, IM, Topically or as anaerosol .aerosol .

-- Greater thanGreater than 9090% of absorbed corticosteroids are% of absorbed corticosteroids arebound to plasma protein mostly to corticosteroidbound to plasma protein mostly to corticosteroid--binding globulin (CBG) and the remainder tobinding globulin (CBG) and the remainder toalbumin .albumin .

-- They are metabolized in the liver their metabolitesThey are metabolized in the liver their metabolitesconjugated toconjugated to glucuronicglucuronic acid or sulfate which areacid or sulfate which areexcreted in the urine .excreted in the urine .


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Figure : Routes of administration and

elimination of corticosteriods.


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Therapeutic UsesTherapeutic Uses

II-- AntiAnti--inflammatory and antiinflammatory and anti--allergyallergy

22-- contact dermatitis, hives, drug allergies etccontact dermatitis, hives, drug allergies etc

33-- Asthma ( Inflammatory condition of theAsthma ( Inflammatory condition of the

airwaysairways Beclometh

asoneBeclometh

asone (inh

aled) focuses th

e(inh

aled) focuses th

edrug to the site.drug to the site.

((NOT FOR REVERSAL OF AN ACUTE ATTACKNOT FOR REVERSAL OF AN ACUTE ATTACK))

44-- Transplant rejectionTransplant rejection

55-- Autoimmune disorders ( Rheumatoid arthritis,Autoimmune disorders ( Rheumatoid arthritis,ulcerative colitis .ulcerative colitis .


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Therapeutic UsesTherapeutic Uses

IIII-- Other UsesOther Uses

11-- Replacement Therapy (Primary adrenalReplacement Therapy (Primary adrenalinsufficiency (Addisons disease) and Secondaryinsufficiency (Addisons disease) and Secondaryadrenal insufficiencyadrenal insufficiency

22-- Diagnostic (Diagnostic (DexamethasoneDexamethasone suppression test)suppression test)

33-- Stimulation of lung maturation in the fetus Up toStimulation of lung maturation in the fetus Up to3434 weeks gestationweeks gestation

44-- ShockShock

55-- Spinal cord injurySpinal cord injury

66-- AntiAnti--neoplasticsneoplastics agentagent


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Adverse EffectsAdverse Effects

11-- Osteoporosis (Common side effect of longOsteoporosis (Common side effect of long--term therapyterm therapyDue to direct actions onDue to direct actions on osteoblastsosteoblasts and impaired Caand impaired Caabsorption. Increased protein catabolism resulting fromabsorption. Increased protein catabolism resulting fromgluconeogenesisgluconeogenesis can consume the protein matrix of bones.can consume the protein matrix of bones.

22-- Skeletal muscle wasting and weakness (Results fromSkeletal muscle wasting and weakness (Results from

increased protein catabolism associated withincreased protein catabolism associated withgluconeogenesisgluconeogenesis..

33--Increased appetiteIncreased appetite

44-- Inhibition of growth in children Protein catabolism inInhibition of growth in children Protein catabolism inbonesbones

55-- Delayed wound healing Results from increased proteinDelayed wound healing Results from increased proteincatabolism in the skincatabolism in the skin


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Adverse EffectsAdverse Effects

66-- Peptic Ulceration (Suppression ofPG synthesis).Peptic Ulceration (Suppression ofPG synthesis).77-- Hyperglycemic action (Decreased glucoseHyperglycemic action (Decreased glucose

tolerance and insulin responsiveness.tolerance and insulin responsiveness.

88-- Moon face and buffalo humpMoon face and buffalo hump

99-- Increased susceptibility to infection CatabolicIncreased susceptibility to infection Cataboliceffect on lymphoid tissue.effect on lymphoid tissue.

1010-- Suppression of the HypothalamicSuppression of the Hypothalamic--PituitaryAxisPituitaryAxis


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Withdrawal of corticosteroidWithdrawal of corticosteroid

Withdrawal from these drugs can be a seriousWithdrawal from these drugs can be a seriousproblem, because if the patient has experienced HPAproblem, because if the patient has experienced HPA

suppression, abrupt removal of the corticosteroidssuppression, abrupt removal of the corticosteroids

causes an acute adrenal insufficiency syndrome thatcauses an acute adrenal insufficiency syndrome that

can be lethal. This, coupled with the possibility ofcan be lethal. This, coupled with the possibility ofpsychologicpsychologic dependence on the drug and the fact thatdependence on the drug and the fact that

withdrawal might cause an exacerbation of thewithdrawal might cause an exacerbation of the

disease, means the dose must be tapered according todisease, means the dose must be tapered according to

the individual, possibly through trial and error. Thethe individual, possibly through trial and error. Thepatient must be monitored carefully.patient must be monitored carefully.


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Inhibitors ofInhibitors of adrenocorticoidadrenocorticoid

biosynthesisbiosynthesis

Several substances have proven to be useful asSeveral substances have proven to be useful as

inhibitors of the synthesis of adrenal steroids:inhibitors of the synthesis of adrenal steroids:

aminoglutethimideaminoglutethimide,,

ketoconazoleketoconazole,,

metyraponemetyrapone,,

trilostanetrilostane,, spironolactonespironolactone, and, and eplerenoneeplerenone..

MifepristoneMifepristone competes withcompetes with glucocorticoidsglucocorticoids

for the receptor.for the receptor.


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Endocrine pharmacologyEndocrine pharmacology

Sex steroids andSex steroids andtheir inhibitorstheir inhibitors


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Figure : Summary of sex hormones


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Sex hormonesSex hormones

produced by the sex gonads are necessary forproduced by the sex gonads are necessary for

conception, embryonic maturation, and developmentconception, embryonic maturation, and developmentof primary and secondary sexual characteristics atof primary and secondary sexual characteristics at

puberty. Their activity in target cells is modulated bypuberty. Their activity in target cells is modulated by

receptors.receptors.

The gonadal hormones are used therapeutically inThe gonadal hormones are used therapeutically inreplacement therapy, for contraception, and inreplacement therapy, for contraception, and in

management of menopausal symptoms.management of menopausal symptoms.

Several antagonists are effective in cancerSeveral antagonists are effective in cancer

chemotherapy. All gonadal hormones are synthesizedchemotherapy. All gonadal hormones are synthesizedfrom the precursor, cholesterol.from the precursor, cholesterol.

These hormones regulate the menstrual cycle (follicularThese hormones regulate the menstrual cycle (follicular

phase , ovulatory phase and luteal phase)phase , ovulatory phase and luteal phase) ..


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EstrogenEstrogen

It is secreted from granulose cells of the follicles , theIt is secreted from granulose cells of the follicles , the

major ovarian estrogen ismajor ovarian estrogen is

estradiolestradiol , , estroneestrone, and , and estriolestriol..

All most all estrogens in the blood is bound to sexAll most all estrogens in the blood is bound to sex

hormone binding globulinhormone binding globulin

EstradiolEstradiol isis 8080XX more potent thanmore potent than estroneestrone, and it is, and it is

1212XX more potent th

anmore potent th

an estriolestriol.. It can be given orally but their bioIt can be given orally but their bio--availability is lowavailability is low

because of short half life and hepatic metabolism .because of short half life and hepatic metabolism .


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Pharmacological actionPharmacological action

Normal female sexual developmentNormal female sexual development

Capillary dilatationCapillary dilatation

Fluid retentionFluid retention

Protein anabolism

Protein anabolism

Enhance deposition of fat .Enhance deposition of fat .

Inhibit boneInhibit bone resorptionresorption


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Estrogens preparationEstrogens preparation

11-- Natural estrogen from animalNatural estrogen from animal

conjugated estrogen( premarin)conjugated estrogen( premarin)

22-- Synthetic estrogensSynthetic estrogens Stilbesterol used in Ca of prostateStilbesterol used in Ca of prostate

Ethinyl estradiolEthinyl estradiol

MestranolMestranol


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Clinical uses of estrogensClinical uses of estrogens

As replacement therapy in hypogonadism in girls .As replacement therapy in hypogonadism in girls .

As a component of contraceptive preparation (As a component of contraceptive preparation (

alone or in combination with progesterone)alone or in combination with progesterone)

As replacement therapy in post menopausalAs replacement therapy in post menopausal

women ( prevent osteoporosis, facial weakness andwomen ( prevent osteoporosis, facial weakness and

reduce vaginal dryness .reduce vaginal dryness .

Androgen dependent C

Aof prostate

Androgen dependent C

Aof prostate

To inhibit lactation ( rare)To inhibit lactation ( rare)

To reduce sexual activity in male.To reduce sexual activity in male.


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ContraindicationsContraindications of estrogensof estrogens

Pregnancy because it damage the fetus.Pregnancy because it damage the fetus.

InIn thromboembolicthromboembolic disease.disease.

CA of breast.CA of breast.

Hypertension ,Hypertension ,

migraine ,migraine ,

diabetes mellitus anddiabetes mellitus and

liver disease.liver disease.


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Adverse effectsAdverse effects of estrogensof estrogens

Nausea , vomiting and diarrhoeaNausea , vomiting and diarrhoea

Breast tendernessBreast tenderness

Retention of salt and fluid (edema).Retention of salt and fluid (edema). Increase incidence of gall bladder formationIncrease incidence of gall bladder formation

Increase incidence of endomaterialIncrease incidence of endomaterial

carcinoma.carcinoma. Vaginal adenocarcinoma in femaleVaginal adenocarcinoma in female


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Figure : Some adverse effects

associated with estrogen therapy


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Estrogen inhibitorsEstrogen inhibitors

TamoxifenTamoxifen

It is a non steroidal that acts as a competitiveIt is a non steroidal that acts as a competitive

inh

ibitors ofinh

ibitors of estradiolestradiol by binding to th

eby binding to th

eestrogen receptor .estrogen receptor .

It is used in treatment of breast cancer inIt is used in treatment of breast cancer in

post menopausal women .post menopausal women .

main adverse effectsmain adverse effects

Hot flush, nausea and vomiting .Hot flush, nausea and vomiting .


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Estrogen inhibitorsEstrogen inhibitors

ClomipheneClomiphene (( clomidclomid))

It is a partial agonist at estrogen receptors in theIt is a partial agonist at estrogen receptors in thepituitary gland, it prevent the normal feedbackpituitary gland, it prevent the normal feedback

inhibition and increase release of LH and FSHinhibition and increase release of LH and FSHfrom pituitary which subsequently stimulatefrom pituitary which subsequently stimulateovulation.ovulation.

It is used in treatment of infertility.It is used in treatment of infertility.

main adverse effectsmain adverse effects Hot flush, ovarian enlargement multipleHot flush, ovarian enlargement multiple

simultaneous births and visual disturbances .simultaneous births and visual disturbances .


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ProgesteronProgesteron

It is synthesized in the ovary, testes and adrenalIt is synthesized in the ovary, testes and adrenalgland from circulating cholesterol,gland from circulating cholesterol,

--It stimulate lipoprotein lipase activity and increaseIt stimulate lipoprotein lipase activity and increasefat deposition,fat deposition,

--It increase insulin response to glucose promotesIt increase insulin response to glucose promotesglycogen storage in the liver,glycogen storage in the liver,

Types of progestinsTypes of progestins

--Medroxyprogesterone acetate (provera)Medroxyprogesterone acetate (provera)-- NorethindroneNorethindrone

-- Norethindrone acetateNorethindrone acetate


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Therapeutic usesTherapeutic uses

--Contraception ( alone or with estrogen)Contraception ( alone or with estrogen)-- Hormone replacement therapyHormone replacement therapy


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Adverse effectsAdverse effects

Weight gainWeight gain

DepressionDepression

EdemaEdema AcneAcne

HypertensionHypertension

ThrombophlebitisThrombophlebitis Cholrestatic jaundiceCholrestatic jaundice


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Figure : Some adverse effects associated

with progestin therapy.


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ProgestineProgestine inhibitorsinhibitors

-- Mifepristone:Mifepristone:

--It is a competitive inhibitor of progestin at progesteroneIt is a competitive inhibitor of progestin at progesteronereceptors.receptors.

--It is used to induce abortion with prostaglandine E or F toIt is used to induce abortion with prostaglandine E or F toincrease myomaterial contraction .increase myomaterial contraction .

Adverse effects areAdverse effects are

heavy bleeding , nausea and vomiting anorexia andheavy bleeding , nausea and vomiting anorexia andabdominal pain .abdominal pain .

--

Danazol ( Danocrine)Danazol ( Danocrine)

It is a drug that acts as a partial agonist at progesterone ,It is a drug that acts as a partial agonist at progesterone ,androgen and glucocorticoid receptors .androgen and glucocorticoid receptors .

It is used clinically in treatment of endometriosis .It is used clinically in treatment of endometriosis .

Their main adverse effects areTheir main adverse effects are

weight gain , edema, acne, and reduced HDL cholesterolweight gain , edema, acne, and reduced HDL cholesterollevels .levels .


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ContraceptiveContraceptive

Types of contraceptiveTypes of contraceptive

11-- Combination estrogenCombination estrogen--progestin tablets inprogestin tablets inconstant doses throughout the menstrualconstant doses throughout the menstrualcycle .cycle .

22-- Combination estrogenCombination estrogen--progestin tablets inprogestin tablets inwhich the progestin concentration slowlywhich the progestin concentration slowly

increased to mimic th

e natural cycle .increased to mimic th

e natural cycle .

33-- ProgestinProgestin--only preparation .only preparation .


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Adverse effects of combination oral contraceptivesAdverse effects of combination oral contraceptives

-- Formation of blood clots .Formation of blood clots .

-- Increase risk of breast cancerIncrease risk of breast cancer

-- Breast tendernessBreast tenderness-- HeadacheHeadache

-- Gallbladder diseaseGallbladder disease

-- AcneAcne

-- Weight gainWeight gain


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Adverse effects

Most adverse effects are believed to be due to the

estrogen component, but cardiov

ascular effects reflectthe action of both estrogen and progestin.

Major adverse effects: The major adverse effects arebreast fullness, depression, fluid retention, headache,nausea, and vomiting.

Cardiovascular:

Including thromboembolism, thrombophlebitis,hypertension, increased incidence of myocardialinfarction, and cerebral and coronary thrombosis.

Carcinogenicity:

Oral contraceptives have been shown to decrease theincidence of endometrial and ovarian cancer.


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Absolute contraindication for combinationAbsolute contraindication for combination

oral contraceptiveoral contraceptive

pregnancypregnancy

history of thromboembolic diseasehistory of thromboembolic disease

MIMI Coronary artery diseaseCoronary artery disease

Cerebral vascular diseaseCerebral vascular disease

Congenital hyperlipidemiaCongenital hyperlipidemia Breast or endometrial cancerBreast or endometrial cancer


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AndrogensAndrogens

The androgens are a group of steroids that ha

ve

The androgens are a group of steroids that ha

veanabolic and/oranabolic and/or masculinizingmasculinizing effects in both maleseffects in both males

and females.and females.

Testosterone [Testosterone [tesstess--TOSSTOSS--tete--ronerone], the most important], the most important

androgen in humans, is synthesized byandrogen in humans, is synthesized by LeydigLeydig cells incells inthe testes and, in smaller amounts, by cells in thethe testes and, in smaller amounts, by cells in the

ovary of the female and by the adrenal gland in bothovary of the female and by the adrenal gland in both

sexes.sexes.

Other androgens secreted by the testes areOther androgens secreted by the testes aredihydrotestosteronedihydrotestosterone (DHT),(DHT),

androstenedioneandrostenedione, and, and

dehydroepiandrosteronedehydroepiandrosterone (DH

EA) in small amounts.(DH

EA) in small amounts.


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Regulation of secretion of testosterone. DHT =

dihydro testosterone; LH = luteinizing hormone


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Therapeutic usesTherapeutic uses

Androgenic effectsAndrogenic effects::

Androgenic steroids are used for males with inadequateAndrogenic steroids are used for males with inadequate

androgen secretion. [Note:androgen secretion. [Note: HypogonadismHypogonadism can be caused bycan be caused by

testicular dysfunction (primarytesticular dysfunction (primary hypogonadismhypogonadism) or due to) or due to

failure of the hypothalamus or pituitary (secondaryfailure of the hypothalamus or pituitary (secondary

hypogonadismhypogonadism). In each instance, androgen therapy is). In each instance, androgen therapy isindicated.]indicated.]

Anabolic effectsAnabolic effects::

Anabolic steroids can be used to treat senile osteoporosisAnabolic steroids can be used to treat senile osteoporosis

and chronic wasting associated with human immunodeficiencyand chronic wasting associated with human immunodeficiencyvirus or cancer.virus or cancer.

They may also be used as adjunct therapy in severe burnsThey may also be used as adjunct therapy in severe burns

and to speed recovery from surgery or chronic debilitatingand to speed recovery from surgery or chronic debilitating

diseases.diseases.


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EndometriosisEndometriosis::

DanazolDanazol , a mild androgen, is used in the treatment of, a mild androgen, is used in the treatment of

endometriosis (ectopic growth of theendometriosis (ectopic growth of the endometriumendometrium) and) andfibrocystic breast disease. It inhibits release of FSH and LHfibrocystic breast disease. It inhibits release of FSH and LH

but has no effect on thebut has no effect on the aromatasearomatase..

Adverse effects ofAdverse effects of danazoldanazol

weight gain, acne, decreased breast size, deepening

voice,weight gain, acne, decreased breast size, deepening

voice,increased libido, and increased hair growth .increased libido, and increased hair growth .

DanazolDanazol has been reported occasionally to suppress adrenalhas been reported occasionally to suppress adrenal

function.function.

Unapproved use of androgenUnapproved use of androgen::

Anabolic steroids are used to increase lean body mass, muscleAnabolic steroids are used to increase lean body mass, muscle

strength, and endurance in athletes and body builders.strength, and endurance in athletes and body builders.

Ad ff tAd ff t


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.. Adverse effectsAdverse effects

In femalesIn females::

Androgens can causeAndrogens can cause masculinizationmasculinization, with acne, growth of, with acne, growth of

facial hair, deepening of the voice, male pattern baldness, andfacial hair, deepening of the voice, male pattern baldness, andexcessive muscle development. Menstrual irregularities mayexcessive muscle development. Menstrual irregularities may

also occur. Testosterone should not be used by pregnantalso occur. Testosterone should not be used by pregnant

women because of possiblewomen because of possible virilizationvirilization of the female fetus.of the female fetus.

In malesIn males:: Excess androgens can causeExcess androgens can cause priapismpriapism, impotence, decreased, impotence, decreased

spermatogenesis, andspermatogenesis, and gynecomastiagynecomastia. Cosmetic changes such as. Cosmetic changes such as

those described for females may occur as well. Androgens canthose described for females may occur as well. Androgens can

also stimulate growth of the prostate.also stimulate growth of the prostate.

In childrenIn children::

Androgens can cause abnormal sexual maturation and growthAndrogens can cause abnormal sexual maturation and growth

disturbances resulting from premature closing of thedisturbances resulting from premature closing of the

epiphysealepiphyseal plates.plates.


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AntiandrogensAntiandrogens

AntiandrogensAntiandrogens counter male hormonal action by interfering with thecounter male hormonal action by interfering with the

synthesis of androgens or by blocking their receptors. For example, at highsynthesis of androgens or by blocking their receptors. For example, at high

doses, the antifungal drugdoses, the antifungal drug ketoconazoleketoconazole inhibits several of the cytochromeinhibits several of the cytochromePP450450 enzymes involved in steroid synthesis.enzymes involved in steroid synthesis.

FinasterideFinasteride andand dutasteridedutasteride used for the treatment of benignused for the treatment of benign

prostatic hypertrophy, inhibitprostatic hypertrophy, inhibit 55 reductase . The resultingreductase . The resulting

decrease in formation of DHT in the prostate leads to adecrease in formation of DHT in the prostate leads to a

reduction in prostate size.reduction in prostate size.

AntiandrogensAntiandrogens, such as, such as flutamideflutamide , act as competitive, act as competitive

inhibitors of androgens at the target cell.inhibitors of androgens at the target cell.

FlutamideFlutamide is used in the treatment of prostatic carcinoma inis used in the treatment of prostatic carcinoma in

males.males. Two other potentTwo other potent antiandrogensantiandrogens,,bicalutamidebicalutamide andand nilutamidenilutamide

are effective orally for the treatment of metastatic prostateare effective orally for the treatment of metastatic prostate

cancer.cancer.

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Pharmacology of Endocrine System-nursing