NeuroendocrineDrugs

FajarWahyuPribadi
FajarWahyuPribadi
Overview
EndocrineSystem

composedofhormonereleasingorganssuch
composedofhormone
asthe:
hypothalamus thymus
pituitarygland pancreas
thyroidgland gonads
parathyroid ovaries
adrenalglands testes
pinealgland
EndocrineSystem
EndocrineSystem
EndocrineSystem
iscontrolledbythehypothalamusand
iscontrolledbythehypothalamusand
thepituitarygland

alongwiththeNervousSystem,it
alongwiththeNervousSystem,it
coordinatesanddirectsbodyfunction

maintainshomeostasisbyreleasing
maintainshomeostasisbyreleasing
chemicalscalledhormones
hormones
Endocrinevs
EndocrinevsNervous
Nervous
thenervoussystemcommunicates
thenervoussystemcommunicates
locallybyelectricalimpulsesand
neurotransmittersdirectedthrough
neuronstootherneuronsortospecific
targetorganssuchasmuscleorglands

nerveimpulsesgenerallyactwithin
nerveimpulsesgenerallyactwithin
milliseconds
NervousSystem
NervousSystem
Endocrinevs
EndocrinevsNervous
Nervous
theendocrinesystemreleases
theendocrinesystemreleases
hormonesintothebloodstream
thehormonesarethencarriedbythe
thehormonesarethencarriedbythe
bloodstreamintotargetcellsthroughout
thebody
hormoneshavebroaderrangeof
hormoneshavebroaderrangeof
responsetimes(theyactfromseconds
responsetimes(theyactfromseconds
todaysorlonger)
Endocrinevs
EndocrinevsNervous
Nervous
NOTE:thereiscloseinterrelationship
betweentheendocrineandnervous
betweentheendocrineandnervous
systems
EndocrineSystem
Processescontrolledbytheendocrine
System:
1.growth&development
2.reproduction
3.bodydefenses
4.water,electrolyteandnutrient
balance
5.regulationofcellularmetabolism
andenergybalance
andenergybalance
Hormones
Hormones
Hormones
Greekword,toarouse
toarouse

chemicalsubstancessecretedbythe
chemicalsubstancessecretedbythe
cellsintotheextracellularfluidsthat
stimulateorregulatethemetabolic
activityofothercellsinthebody.

Gen.MOA:bindingofthehormoneto
Gen.MOA:bindingofthehormoneto
thetargetcellororganelicitsresponse.
thetargetcellororganelicitsresponse.
EndocrineDrugs
EndocrineDrugs
EndocrineDrugs
Hormonesarepharmacologically
Hormonesarepharmacologically
classifiedasdrugs
canbenatural(fromanimals),
(fromanimals),semi
syntheticorsynthetic
syntheticcompounds
Indications:
a.replacementtherapy
b.treatmentforcertaindisorders
c.diagnosticpurposes
c.diagnosticpurposes
EndocrineDrugs
I.Hypothalamic&PituitaryHormones
II.SteroidHormones
A.GonadalHormones
1.Estrogens
2.Progestins
3.Androgens
B.HormonesoftheAdrenalCortex
1.Adrenocorticosteroids
2.AdrenalAndrogens
III.ThyroidHormonesandDrugsforThyroid
Disorders
IV.AntidiabeticAgents
Hypothalamic&Pituitary
Hormones
Hormones
Hypothalamus
masterendocrineorgan
masterendocrineorgan
secretesreleasing/inhibitinghormones
secretesreleasing/inhibitinghormones
PituitaryGland
weighs600mgandrestsinthesella
weighs600mgandrestsinthesella
turcicaunderalayerofduramaterin
thebrain
composedof2lobes:
composedof2lobes:
a.anteriorlobe
b.posteriorlobe
b.posteriorlobe
 Hypothalamic&PituitaryHormones
H yp othalam icH orm o ne
1. G rowthHorm one G rowthHorm one(G H)
R eleasingHorm one
(G H RH )
aka:S erm orelin
2. G rowthHorm one InhibitsG rowthH orm one
InhibitingHorm one(G H IH )
aka:S om atostatin
3. C orticotropinR eleasing
H orm one(CR H)
4. T hyrotropinR eleasing
H orm one(T RH )
5. G onadotropinReleas ing
H orm one(G nRH )or
LuteinizingHorm one
R eleasingHorm one
(LH RH )
6. ProlactinR eleasing
H orm one(PRH )
7. ProlactinInhibiting
H orm one(PIH )
8. O xytocin
9. Vasopressin
Pituitary Targ etO rgan TargetO rgan
H orm o ne H orm o ne
Liver Som atom edins
aka:Som atotropin
Adrenocorticotropic AdrenalCortex G lucocorticoids
H orm one(A CT H ) M ineralocorticoids
aka:C orticotropin AdrenalAndrogens
T hyroidStim ulating T hyroidG land T 3(T riiodoth yronine)
H orm one(T SH ) T 4(T hyroxine)
aka:T hyrotropin
Gonadotropins O varies(Fem ales) E strogen(byF SH)
a. F ollicleStim ulating T estes(M ales) Progesterone(byLH
H orm one(F SH ) infem ales)
b. LuteinizingH orm one T estosterone(byLH
(LH ) inm ales)
Prolactin Breasts
InhibitsProlactin
StoredintheP osterior
PituitaryG land
StoredintheP osterior
PituitaryG land
land
GrowthHormone
GrowthHormone
GrowthHormone(GH)
aka:Somatotropin,Asellacrin
aka:Somatotropin,Asellacrin
alargepolypeptide:about191amino
alargepolypeptide:about191amino
acids(MW:21,500)
releasedbytheanteriorpituitaryin
releasedbytheanteriorpituitaryin
responsetoGHRH(Sermorelin)
producedbythehypothalamus
producedsyntheticallybyrecombinant
producedsyntheticallybyrecombinant
DNAtechnology
GrowthHormone(GH)
animalsourceisineffectiveinhumans
animalsourceisineffectiveinhumans
inducesthereleaseofsomatomedinsin
inducesthereleaseofsomatomedinsin
theliver
promotionofcellproliferationandbone
promotionofcellproliferationandbone
growthatopenepiphyses
openepiphyses
boostscartilagesynthesis
boostscartilagesynthesis
GrowthHormone(GH)
Indications:
forlongtermtreatmentingrowth
hormonedeficiencyinchildren
(Dwarfism)
fornonGHdeficientshortchildren(can
GHdeficientshortchildren(can
growupto2cmperyear)
growupto2cmperyear)
Dwarfism
Dwarfism
Somatrem
atherapeuticallyequivalentdrugofGH
atherapeuticallyequivalentdrugofGH
containsanextraterminalmethionyl
containsanextraterminalmethionyl
group
GrowthHormoneInhibiting
Hormone
Hormone
GrowthHormoneInhibiting
Hormone(GHIH)
aka:Somatostatin
inhibitsGrowthHormone
inhibitsGrowthHormone
Indications:
PituitaryGigantism(pre
PituitaryGigantism(prepubertal)
Acromegaly(post
Acromegaly(postpubertal)
PituitaryGigantism
PituitaryGigantism
Acromegaly
macrognathia(largejaw)
macrognathia(largejaw)
widespacedteeth
macroglossia
thickenedlips
broadnose
enlargedjoints
cardiomegaly
organomegaly
Octreotide
syntheticoctapeptideanalogof
somatostatin
45xmorepotentthanGHIH
45xmorepotentthanGHIH
AdrenocorticotropicHormone
AdrenocorticotropicHormone
AdrenocorticotropicHormone(ACTH)

aka:Corticotropin,Acthar
aka:Corticotropin,Acthar
singlechainpolypeptidecontaining39
chainpolypeptidecontaining39
aminoacids
precursor:proopiomelanocortin
opiomelanocortin
releasedbytheanteriorpituitaryin
releasedbytheanteriorpituitaryin
responsetoCRHproducedbythe
responsetoCRHproducedbythe
hypothalamus
AdrenocorticotropicHormone(ACTH)

stimulatestheadrenalcortextoproduce
stimulatestheadrenalcortextoproduce
adrenocorticosteroids&androgens
isusedprimarilyforthediagnosisand
isusedprimarilyforthediagnosisand
differentiationofprimary&secondary
adrenalinsufficiency
Primary:AddisonsDisease
AddisonsDiseaseassociated
withadrenalatrophy
Secondary:causedbyinadequate
Secondary:causedbyinadequate
secretionofACTHbythepituitary
secretionofACTHbythepituitary
AddisonsDisease
hyposecretionofadrenocorticosteroids

characterizedby:
anorexia
dehydration
weaknessandlethargy
hyperpigmentation(bronzecoloredskin)
hyperpigmentation(bronze
CushingsSyndrome
hypersecretionofadrenocorticosteroids

characterizedby:
moonface
buffalohump
pendulousabdomen
pendulousabdomen
hypertension
Cushing'sSyndrome
Cushing'sSyndrome
Cosyntropin
synthetichumanACTH
synthetichumanACTH
morepreferredsinceanimalACTHcan
morepreferredsinceanimalACTHcan
causeallergicreactions
causeallergicreactions
ThyrotropinStimulating
Hormone
Hormone
ThyrotropinStimulatingHormone(TSH)
Thyrotropin StimulatingHormone(TSH)

aka:Thyrotropin
releasedbytheanteriorpituitaryin
releasedbytheanteriorpituitaryin
responsetoTRH(aka:Protirelin)
producedbythehypothalamus
stimulatesthethyroidtoproduceT3and
stimulatesthethyroidtoproduceT3and
T4
T3:triiodothyronine(mostactive)
T3:triiodothyronine(mostactive)
T4:thyroxine
(convertedtoT3inthebody)
(convertedtoT3inthebody)
ThyrotropinStimulatingHormone(TSH)
Thyrotropin StimulatingHormone(TSH)

thethyroidhormonesT3andT4are
thethyroidhormonesT3andT4are
essentialforthenormalgrowthand
maturationofthebody
maturationofthebody
Conditions:
hypothyroidism
hyperthyroidism
Hypothyroidism
inabilityofthethyroidglandtosupply
inabilityofthethyroidglandtosupply
sufficientthyroidhormonetothebody
manifestations:
Cretinism (infant
(infantstate)
Myxedema (adult
(adultstate)
Cretinism
infantstatehypothyroidism
statehypothyroidism
characterizedbyphysicalandmental
characterizedbyphysicalandmental
retardation
Myxedema
adultstatehypothyroidism
statehypothyroidism
characterizedby:
bradycardia
weaknessandlethargy
weaknessandlethargy
dryskinandhair
coldness
goiter
Hyperthyroidism
overabundanceofthyroidhormonein
overabundanceofthyroidhormonein
thebody
thyrotoxicosis
Forms:
GravesDiseasemostcommon
mostcommon
PlummersDisease
PlummersDiseaselesscommon
withcardiacabnormalities
withcardiacabnormalities
Graves'Disease
Graves'Disease
AntithyroidDrugs
Antithyroid Drugs
1.Thioamides
2.InorganicAnions/AnionicInhibitors
3.Iodides
4.Radiocontrastdyes
4.Radiocontrastdyes
5.Betablocker
6.Dexamethasone
7.RadioactiveIodine
Thioamides
MOA:inhibitiodineorganificationand
MOA:inhibitiodineorganificationand
coupling
examples:
Propylthiouracil(PTU)
Methimazole
Carbimazole
S/E:
pruriticmaculopapularrash
pruriticmaculopapularrash
agranulocytosis
InorganicAnions
aka:AnionicInhibitors
aka:AnionicInhibitors
MOA:interferewiththeuptakeofiodine
MOA:interferewiththeuptakeofiodine
andcausethedischargeofintra
andcausethedischargeofintra
thyroidaliodine
examples:
Potassiumperchlorate
Potassiumthiocyanate
S/E:
aplasticanemia,nephroticsyndrome
aplasticanemia,nephroticsyndrome
Iodides
MOA:inhibitorganificationandhormone
MOA:inhibitorganificationandhormone
release
theydecreasethesizeandvascularityof
theydecreasethesizeandvascularityof
goiter
examples:
KISSPotassiumiodidesaturated
Potassiumiodidesaturated
solution
Lugolssolution
Lugolssolutionstrongiodine
solution
solution
RadiocontrastDyes
RadiocontrastDyes
MOA:inhibitperipheralconversionofT4
MOA:inhibitperipheralconversionofT4
toT3alsoinhibitproteolysis
toT3alsoinhibitproteolysis
examples:
Ipodate
Iopanoicacid
Beta
Beta
blocker
blocker
MOA:symptomaticreliefofthe
MOA:symptomaticreliefofthe
sympatheticmanifestationsof
hyperthyroidismmayalsoinhibit
peripheralconversionofT4toT3
peripheralconversionofT4toT3
Propranolol
Dexamethasone
MOA:inhibitsperipheralconversionof
MOA:inhibitsperipheralconversionof
T4toT3
Radioactiveiodine
131I
MOA:destructionofthyroidcellsby
MOA:destructionofthyroidcellsby
emissionofhighenergybetaradiation
energybetaradiation
canoffercure
Contraindicatedtopregnantwomenor
Contraindicatedtopregnantwomenor
womenwhowillbecomepregnant
womenwhowillbecomepregnant
Gonadotropins
Gonadotropins
Gonadotropins
include:
FollicleStimulatingHormone(FSH)
StimulatingHormone(FSH)
LuteinizingHormone(LH)
releasedbytheanteriorpituitaryglandin
releasedbytheanteriorpituitaryglandin
responsetoGnRH/LHRH
stimulatesthegonads(ovaries&testes)
stimulatesthegonads(ovaries&testes)
toproducesexhormones
Females:FSH estrogen
LH progesterone
Males: LH testosterone
testosterone
Gonadotropins
NOTE:Pituitarygonadotropins(FSH,LH)
arenotavailablefortherapeuticuse,
however,therearenon
however,therearenonpituitary
gonadotropinsthathaveFSH
gonadotropinsthathaveFSHlikeor
LHlikeactivityandaretheonesused
likeactivityandaretheonesused
therapeutically
Non
Non
PituitaryGonadotropins
PituitaryGonadotropins
1.Menotropins
2.Urofollitropin
3.HumanChorionicGonadotropin
3.HumanChorionicGonadotropin
Non
Non
PituitaryGonadotropins
PituitaryGonadotropins
Indications:
women:toinduceovulation&
pregnancy
men:toinducespermatogenesis

Adverseeffects:
ovarianenlargement
multiplebirths
gynecomastiainmen
gynecomastiainmen
Menotropin
aka:
HumanMenopausalGonadotropin
(hMG)
Pergonal
obtainedfromtheurineofpost
obtainedfromtheurineofpost
menopausalwomen
partiallybrokendownintoFSHandLH
partiallybrokendownintoFSHandLH
inthebody
Urofollitropin
Metrodin
obtainedfromtheurineofpost
obtainedfromtheurineofpost
menopausalwomen
highinFSHlikeactivity
likeactivity
HumanChorionicGonadotropin
aka:hCG,Follutein
aka:hCG,Follutein
aplacentalhormone
aplacentalhormone
LHagonisteffect
obtainedfromtheurineofpregnant
obtainedfromtheurineofpregnant
women
HormonesofthePosterior
PituitaryGland
PituitaryGland
HormonesofthePosterior
HormonesofthePosterior
PituitaryGland
1.Oxytocin
2.Vasopressin
Oxytocin
stimulatesuterinecontractionandplaysan
importantroleintheinductionoflabor
alsopromotesbreastmilkejection
alsopromotesbreastmilkejection
Indications:
toinducecontractionduringlabor
tocontrolpostpartumbleeding
Contraindications:
abnormalfetalpresentation
abnormalfetalpresentation
fetaldistress
prematurebirths
Oxytocin
Oxytocin
Vasopressin
aka:AntidiureticHormone(ADH)
aka:AntidiureticHormone(ADH)
hasbothantidiureticandvasopressor
hasbothantidiureticandvasopressor
activity
actsbybindingtoitsreceptorinthe
actsbybindingtoitsreceptorinthe
kidneyspromotingthereabsorptionof
waterinthecollectingtubules
Indications:
DiabetesInsipidus
PostoperativeAbdominalDistention
PostoperativeAbdominalDistention
DiabetesInsipidus
DiabetesInsipidus(DI)
Insipidus(DI)
adisorderduetothedeficiencyorlack
adisorderduetothedeficiencyorlack
ofresponsetoAntidiureticHormone
(ADH)
2Types:
a.CentralDIdeficiencyinADH
deficiencyinADH
b.NephrogenicDI
b.NephrogenicDIsufficientADH
butbodydoesnotrespond
tothehormone
tothehormone
Desmopressin
modifiedanalogofvasopressin
modifiedanalogofvasopressin
morepreferredforDIandnocturnal
morepreferredforDIandnocturnal
enuresisbecauseitislargelyfreeof
pressoreffectsandislonger
pressoreffectsandislongeracting
SteroidHormones
SteroidHormones
SteroidHormones
containthesteroidnucleus,CPPP
containthesteroidnucleus,CPPP
cyclopentanoperhydro
erhydrophenanthrene
SteroidHormones
Carbon3&Carbon17
Carbon3&Carbon17
OH(sterol)
=O(sterone)
Gonadal/SexHormones
Gonadal/SexHormones
SteroidHormones
A.Gonadal/SexHormones
1.Estrogens
2.Progestins
3.Androgens
B.HormonesoftheAdrenalCortex
1.Adrenocoticosteroids
a.Glucocorticoids
b.Mineralocorticoids
2.AdrenalAndrogens
2.AdrenalAndrogens
Gonadal/SexHormones
Gonadal/SexHormones
Estrogens
Estrogens
Estrogens
basicnucleus:estrane
basicnucleus:estrane

Estradiol
Estrogens
Effects:
1.normalfemalematurationand
development
2.inhibitboneresorption
3.increaseHDL,decreaseLDL
4.decreaseplateletadhesiveness
4.decreaseplateletadhesiveness
Estrogens
Indications:
contraception
postmenopausalhormonetherapy
primaryhypogonadism
primaryhypogonadism
osteoporosis
NaturalSteroidalEstrogens
NaturalSteroidal Estrogens
Estradiolmostpotentestrogen
mostpotentestrogen
producedbywomen
Estrone,Estriolhaveaboutonetenth
haveaboutonetenth
thepotencyofestradiol
*Premarinapreparationofconjugated
apreparationofconjugated
estrogens(sulfateestersofestrone&
equilin)
obtainedfrompregnantmaresurine
obtainedfrompregnantmaresurine
Premarin
Premarin
SyntheticSteroidalEstrogens
SyntheticSteroidal Estrogens
Ethinylestradiol
Mestranol
Quinestrol
SyntheticNonsteroidal
SyntheticNonsteroidalEstrogens
NonsteroidalEstrogens
Diethylstilbestrolpossiblecauseofa
possiblecauseofa
rare,clearcellcervicalorvaginal
adenocarcinomaamongdaughtersof
womenwhotookthedrugduringearly
womenwhotookthedrugduringearly
pregnancy
EstrogenAntagonists/
EstrogenAntagonists/
Antiestrogens

Clomiphenefertilitydrugitinduces
fertilitydrugitinduces
ovulationbynegativefeedback
mechanism

Tamoxifen&Toremifenepalliative
Tamoxifen&Toremifene
treatmentofadvancedbreastcancerin
postmenopausalwomen
postmenopausalwomen
EstrogenRelatedDrugs
EstrogenRelatedDrugs
AromataseInhibitors
SelectiveEstrogenReceptorModulators
SelectiveEstrogenReceptorModulators
AromataseInhibitors
arepotentandselectivenon
arepotentandselectivenonsteroidal
inhibitorsofaromatase,anenzyme
reponsiblefortheconversionof
androgenstoestrogens
usedtotreatadvancedbreastcancer
usedtotreatadvancedbreastcancer
Anastrozole,Letrozole
Anastrozole,Letrozole
SERMs
SelectiveEstrogenReceptorModulators
SelectiveEstrogenReceptorModulators
reduceboneresorptionanddecrease
reduceboneresorptionanddecrease
boneturnover
usedforthepreventionofosteoporosis
usedforthepreventionofosteoporosis
Raloxifene
Progestins
Progestins
Progestins
basicnucleus:pregnane
basicnucleus:pregnane
Progestins
Effects:
1.endometrialchanges
2.alveolobulardevelopmentof
secretoryapparatusinbreasts
3.hepaticglycogenesis&ketogenesis
4.increaselipoproteinlipaseactivity
andfatdeposition
andfatdeposition
Progestins
Indications:
contraception
formenstrualdisorders
dysfunctionaluterinebleeding
dysfunctionaluterinebleeding
dysmenorrhea
dysmenorrhea
endometriosis
 NaturalProgestin
Progesterone
endogenousprogestinproducedin
endogenousprogestinproducedin
responsetoluteinizinghormone(LH)
alsosynthesizedbytheadrenalcortex
alsosynthesizedbytheadrenalcortex
infemales,itpromotesthedevelopment
infemales,itpromotesthedevelopment
ofasecretoryendometriumthatcan
accommodateimplantationofanewly
accommodateimplantationofanewly
formingembryo
SyntheticProgestins
Synthetic Progestins
morestabletofirstpassmetabolism,
passmetabolism,
allowingforlowerdoseswhen
administeredorally
medroxyprogesterone
medroxyprogesterone
hydroxyprogesterone
hydroxyprogesterone
megestrol
norethindrone
norgestrel
ProgestinAntagonist/
Antiprogestin

Mifepristone
aka:RU486
progestinantagonistwithpartial
progestinantagonistwithpartial
agonistactivity
cancauseabortionofthefetusdueto
cancauseabortionofthefetusdueto
theinterferencewithprogesteroneand
theinterferencewithprogesteroneand
thedeclineinhCG
Oral&Implantable
Contraceptives
Contraceptives
MajorClasses
1.CombinationPills
2.ProgestinOnlyContraceptives
3.PostcoitalContraceptives
3.PostcoitalContraceptives
CombinationPills
containbothestrogenandprogestin
containbothestrogenandprogestin
providedas21dayor28day
providedas21dayor28daypacks
mostcommontypeoforalcontraceptives
mostcommontypeoforalcontraceptives
estrogen:suppressesovulation
estrogen:suppressesovulation
ethinylestradiol
ethinylestradiolmostcommon
mestranol
CombinationPills
progestin:preventsimplantationinthe
progestin:preventsimplantationinthe
endometriumandmakesthecervical
mucusimpenetrabletothesperm
mucusimpenetrabletothesperm
norethynodrel
norethindrone
norgestrel
ProgestinOnlyContraceptives
lesseffectivethancombinationpills
dosageforms/deliverysystems:
dosageforms/deliverysystems:
a.minipill lowdoseprogestins
lowdoseprogestins
350 mgnorethindroneor
gnorethindroneor
75 mgnorgestrel
b.progestinimplants subdermalimplant
of216mgofnorgestrel(Norplant)
effectivefor5years
effectivefor5years
ProgestinOnlyContraceptives
c.intramuscular givenevery3months
givenevery3months
150mgofmedroxyprogesterone
acetate(Depo
acetate(DepoProvera)
ProgestinOnlyContraceptives

d.intrauterinedevice(IUD)foryearly
d.intrauterinedevice(IUD)
insertionProgestasert
insertionProgestasert
PostcoitalContraceptives
PostcoitalContraceptives
called,morningafterpills
afterpills
highdoseestrogenadministeredwithin
highdoseestrogenadministeredwithin
72hoursaftercoitusandcontinued2x
for5days
ethinylestradiol
diethylstilbestrol
conjugatedestrogens
conjugatedestrogens
estrone
Androgens
Androgens
Androgens
basicnucleus:androstane
basicnucleus:androstane

Testosterone
Androgens

groupofsteroidsthathaveanabolic
groupofsteroidsthathaveanabolic
and/ormasculinizingeffectsinboth
and/ormasculinizingeffectsinboth
malesandfemales
EndogenousAndrogen
Testosterone
primarynaturalendogenousandrogen
primarynaturalendogenousandrogen
synthesizedbyLeydigcellsinthetestes
synthesizedbyLeydigcellsinthetestes
ofmalesandinsmalleramountsbythe
cellsintheovaryoffemales,andinthe
adrenalgland
producedinresponsetoLH
producedinresponsetoLH
SyntheticAndrogens
SyntheticAndrogens
Methyltestosterone
Danazol
Stanozolol
Nandrolone
TherapeuticUses
1.AndrogenicEffects
inhypogonadisminmales
inhypogonadisminmales
2.AnabolicEffects
insenileosteoporosis,severeburns,
insenileosteoporosis,severeburns,
speedyrecoveryfromsurgeryorfrom
chronicdebilitatingdiseases
3.Endometriosis(Danazol)
3.Endometriosis(Danazol)
UnapprovedUse
Usedtoincreaseleanbodymass,muscle
strengthandaggressivenessinathletes
andbodybuilders(Nandrolone&
andbodybuilders(Nandrolone&
Stanozolol)
Antiandrogens
inhibittheactionofandrogensby
inhibittheactionofandrogensby
interferingwithandrogensynthesisor
byblockingtheirreceptors
a.FinasterideusedinBenignProstatic
usedinBenignProstatic
Hypertrophy(BPH)
Hypertrophy(BPH)
Antiandrogens
b.Flutamideforprostaticcarcinoma
forprostaticcarcinoma

c.Cyproteroneacetateforhirsutismin
c.Cyproteroneacetate
females
HormonesoftheAdrenal
Cortex
Cortex
HormonesoftheAdrenalCortex
1.Adrenocorticosteroids
a.Mineralocorticoids
b.Glucocorticoids
2.AdrenalAndrogens
2.AdrenalAndrogens
AdrenalCortex
3Zones:
1.Zonaglomerulosa
producesmineralocorticoids
producesmineralocorticoids
2.Zonafasciculata
producesglucocorticoids
producesglucocorticoids
3.Zonareticularis
producesadrenalandrogens
producesadrenalandrogens
AdrenalCortex

Zonaglomerulosa

Zonafasciculata

Zonareticularis

Kidney
Mineralocorticoids
possesssodiumretainingand
retainingand
potassiumsecretingeffects
secretingeffects
essentialforfluidandelectrolytebalance
essentialforfluidandelectrolytebalance

endogenous:aldosterone
endogenous:aldosterone
desoxycorticosterone

synthetic: fludrocortisone
fludrocortisone
Glucocorticoids
Endogenous:Cortisol
Cortisol
Cortisone
Corticosterone
Hydrocortisone
essentialforthemetabolismof
essentialforthemetabolismof
carbohydrates,fatsandproteins
theyenhanceresponseofthevascular
theyenhanceresponseofthevascular
andbronchialsmoothmusclesto
andbronchialsmoothmusclesto
catecholamines
Glucocorticoids
OtherPreparations:
Prednisone Betamethasone
Methylprednisolone
MethylprednisoloneDexamethasone
Triamcinolone
antiinflammatory,anti
inflammatory,antiallergyand
immunosuppressanteffects
inhibitcellgrowthanddivision
inhibitcellgrowthanddivision
cataboliceffectsonproteinandbones
cataboliceffectsonproteinandbones
Glucocorticoids
TherapeuticUses:
Allergy
Inflammationofjointsandbones
Skindiseases
Organtransplantimmunosuppression
PulmonaryDiseases:BronchialAsthma
COPD
Glucocorticoids
Adverseeffects:
Cushingssyndrome
Adrenalsuppression
osteoporosis
PUD
impairedwoundhealing
increasedsusceptibilitytoinfection
increasedsusceptibilitytoinfection
hyperglycemia/DM
cataract
Anti
Anti
diabeticAgents
diabeticAgents
diabeticAgents
Pancreas
isamixedgland
Exocrineportion
releasespancrealipase&chymotrypsin
releasespancrealipase&chymotrypsin
Endocrineportion
1millionisletsofLangerhan
1millionisletsofLangerhan
haveatleast4hormone
haveatleast4hormoneproducing
cells
EndocrinePancreas
CellType %islet Hormone
A(alpha) 20 glucagon
proglucagon
B(beta) 75 insulin
proinsulin
D(delta) 35 somatostatin
F(PPcell) <2 pancreatic
polypeptide(PP)
DiabetesMellitus(DM)
diabetes=Greeksiphon
=Greeksiphon
mel=honey
somethingsweetispassingthroughor
somethingsweetispassingthroughor
siphoningfromthebody
ametabolicdisorderinwhichglucose
ametabolicdisorderinwhichglucose
levelsinthebloodaretoohighand
beginstospillintheurinebecausethe
kidneytubulecellscannotreabsorbit
kidneytubulecellscannotreabsorbit
fastenough
TypesofDM
Type1
Type2
GestationalDM
SecondaryDM
Diabetes

132
CreatedbyAmanda
CreatedbyAmanda
2TypesofDiabetes
2TypesofDiabetes

133
CONFIDEN
Type1
insulindependentDM(IDDM)
dependentDM(IDDM)
juvenileonsetDM
ketosispronediabetes
pronediabetes
mostcommoninchildren
mostcommoninchildren
insulinsecretionisdestroyed
insulinsecretionisdestroyed
dependentuponexogenousinsulinto
dependentuponexogenousinsulinto
sustainlife
Type2
noninsulindependentDM(NIDDM)
dependentDM(NIDDM)
adultonsetDM
notinsulindependent
notinsulindependent
endogenousinsulinlevelsmayappear
endogenousinsulinlevelsmayappear
normalorincreasedbutbeta
normalorincreasedbutbetacell
dysfunctionismanifestedbyarelative
insulininsufficiency
insulininsufficiency
GestationalDM
definedasanydegreeofglucose
definedasanydegreeofglucose
intolerancethathasitsonsetduring
intolerancethathasitsonsetduring
pregnancy
SecondaryDM
broadtermusedtoclassifypatientswho
broadtermusedtoclassifypatientswho
haveunusualcausesofDMdueto
certaindiseasesofthepancreas,
endocrinopathiesordrugs
endocrinopathiesordrugs
3CardinalSignsofDM
1.Polyuriaexcessiveurinationtoflush
excessiveurinationtoflush
outtheglucoseandketones

2.Polydipsiaexcessivethirstresulting
excessivethirstresulting
fromwaterloss

3.Polyphagiaexcessivehungerdueto
excessivehungerdueto
inabilitytousesugarsandthelossof
fatsandproteinsfromthebody
fatsandproteinsfromthebody
Insulin
isthestorageandanabolichormoneofthe
isthestorageandanabolichormoneofthe
body
producedbytheBeta
producedbytheBetacellsofthepancreas
principalhormonerequiredforproper
principalhormonerequiredforproper
glucoseuseinnormalmetabolic
processes
previouslyextractedfrombeef/pork
previouslyextractedfrombeef/pork
pancreas
nowisproducedviarecombinantDNA
nowisproducedviarecombinantDNA
technology
Insulin
InsulinEffects
Effects
1.Itfacilitatestransportofglucoseacross
cellmembrane
2.Intheliver,itpromotesglycogenesis
andgluconeogenesis
3.Inthemuscles,itincreasesaminoacid
transport,proteinsynthesisand
glycogenesis
4.Inadiposetissues,itincreases
4.Inadiposetissues,itincreases
triglyceridestorage
Insulin
InsulinIndications
Indications
DiabetesMellitusType1
DiabetesMellitusType2thatcannotbe
controlledbydiet,exerciseandoral
hypoglycemicagents(OHAs)
hypoglycemicagents(OHAs)
Ketoacidosis
Diabeticcoma
InsulinPreparations
Pharmakokinetic SpeciesType Activityinhours
Type Peak Duration
Ultrarapidacting Human
InsulinLispro (Modified) 0.250.50 34

Rapidacting
Insulininjection,USP Human,Pork 0.503 57
(Regular,Crystalline)
Intermediateacting
NPHInsulin Human,Pork 812 1824
(Isophane)
LenteInsulin Human,Pork 812 1824
(Insulinzincsusp)
Longacting
UltralenteInsulin Human 816 1828
(Insulinzincsusp
extended)
Ultralongacting
Insulinglargine Human Nopeak >24
(Modified)
OralHypoglycemic
OralHypoglycemicDrugs
Hypoglycemic Drugs
Insulinsecretagogues
Biguanides
Alphaglucosidaseinhibitors
glucosidaseinhibitors
Thiazolidinedionederivatives
Thiazolidinedionederivatives
InsulinSecretagogues
InsulinSecretagogues
Secretagogues
Sulfonylureas
Meglitinides
Sulfonylureas
MOA:
stimulatepancreaticreleaseofinsulin
stimulatepancreaticreleaseofinsulin
inhibitpancreaticreleaseofglucagons
inhibitpancreaticreleaseofglucagons
increaseinsulinreceptorbinding
increaseinsulinreceptorbinding
decreasehepaticextractionofinsulin
decreasehepaticextractionofinsulin
Sulfonylureas
IstGeneration
Chlorpropamide Acetohexamide
Tolbutamide Tolazamide

2ndGeneration
Glibenclamide Glipizide
Gliclazide Glimepiride
Sulfonylureas
Sideeffects:
hypoglycemia
blooddyscrasias
disulfiramlikereactionswith1stGen
likereactionswith1stGen
andglipizide
andglipizide
weightgain
Meglitinides
MOA:increasepancreaticinsulin
MOA:increasepancreaticinsulin
secretion
shortdurationofaction:1to3hours
shortdurationofaction:1to3hours
examples: Repaglinide
Nateglinide
Nateglinide
S/E:
hypoglycemia
weightgain
Biguanides
unknownMOA
reducebloodglucoseleveleveninthe
reducebloodglucoseleveleveninthe
absenceofbetacellfunction
provenasausefulinitialtherapyamong
provenasausefulinitialtherapyamong
DMType2patients,especiallyamong
obesepatients
notassociatedwithhypoglycemia
notassociatedwithhypoglycemia
ex.Metformin(mostproven)
ex.Metformin(mostproven)
Phenformin(nolongeravailable)
S/E:lacticacidosis,megaloblastic
S/E:lacticacidosis,megaloblastic
anemia
Alpha
Alpha
glucosidase
glucosidaseinhibitors
glucosidaseinhibitors
MOA:competitiveinhibitionofintestinal
MOA:competitiveinhibitionofintestinal
alphaglucosidaseenzyme,preventing
glucosidaseenzyme,preventing
digestionofdextrinsanddisaccharides
intoabsorbablemonosaccharides
examples: Acarbose
Voglibose
Miglitol
S/E:flatulence,potentialhepatotoxicity
S/E:flatulence,potentialhepatotoxicity
ofacarbose
Thiazolidinedionederivatives
MOA:insulinsensitizers
MOA:insulinsensitizersincrease
skeletalmusclesensitivitytoinsulin
theyalsodecreasehepatic
gluconeogenesis
examples: Rosiglitazone
Pioglitazone
S/E:Hepaticfailure(reasonforthe
S/E:Hepaticfailure(reasonforthe
withdrawalofTroglitazone),edemaand
withdrawalofTroglitazone),edemaand
mildanemia
Successistobemeasurednotsomuchbythe
positionthatonehasreachedinlife,butbythe
obstacleswhichhehasovercome.

BookerT.Washington
BookerT.Washington