Hypothalamic & Pituitary

Hormones
Most body functions are controlled by two
systems: namely

the nervous system & the endocrine system.

The endocrine system is composed of a number
of glands

that secrete chemicals called hormones directly

in blood
stream that affect body functions.ie they are
ductless
glands.

The control of metabolism, growth &

reproduction is

mediated through a combination of neural &

endocrine
systems located in hypothalamus & pituitary
glands.

The Endocrine
Glands

Control of petuitary hormones by

Hypothalamus

Hypothalamic
Hormones

Are called releasing factors or

hormones.

Regulate secretion of anterior pituitary

hormones. Some

are used for diagnosis or treatment of some

diseases.They
include:
1-GH-releasing factor or hormone-also
called somatorelin)

Main function is to stimulate AP to

release GH.

An analogue called sermorelin is used as a

diagnostic test

for GH secretion
2-Somatostatin inhibits release of GH &TSH
from anterior pituitary & insulin& glucagon from
pancreas, also deceases
release of most GIT hormones &
acid.
Octreotide is a long-acting analogue used
to treat

acromegally,carcinoid tumors & tumors

secreting

vasoactive intestinal
peptide,glucagonomas & various
pituitary adenomas. Lanreotide is an other
analogue that is
used also for thyroid
tumors.
3- Thyrotrohpin-releasing
hormone(TRH- protirelin)
Stimulates release of TSH from anterior piuitary.
Protirelin
is a synthetic analogue used for diagnosis of
thyroid
disorders.

4-Corticotropin-releasing factor
(CRF) or hormone
Releases ACTH & endorphin from anterior
pituitary.Acts

synergistically with antidiuretic hormone

(Vasopressin).
Both its action and release are inhibited by
glucocorticoids

Synthetic preparations were used to test ability of pituitary

to secrete

ACTH and to assess whether ACTH deficiency is due to

pituitary or

hypothalamic defect.

5-Gonadotropin releasing hormone(GnRH)

and analogs:
Drugs available include gonadorelin (natural
hormone).
Long-acting
analogs:
histrelin
(Suprelin), leuprolide (Leupron), gosrelin
(Zoladex), triptorelin(Trelstar), and nafarelin
(Synarel).
Gonadorelin is used for induction of ovulation in
infertility
Long acting analogs are used for treatment of
endometriosis,

prostate cancer, and central precocious puberty.

Experimental use
as male contraceptive.
GnRH antagonists ganirelix (Antagon) and
cetrorelix (Cetrotide)

Used to inhibit premature LH surges prior to harvesting

eggs for in

vitro fertilization
Also abarelix (Plenaxis) a GnRH receptor antagonist
used to

treat advanced prostate cancer. Danger of lifethreatening allergic

reactions in 4% of patients.

The Pituitary Gland:

Consists of two
lobes:

-The anterior
lobe(adenohypophysis) secrete
GH,TSH,ACTH, FSH,LH
& PRL
-The posterior
lobe(neurohypophysis)secrete
oxytocin &
vasopressin.

Drugs that mimic or block effects of

pituitary or
hypothalamus hormones are
used in:
-Replacement therapy for hormonal
deficiency
-As antagonists for diseases due to
production o
excess pituitary
hormones.
-As diagnostic tools for many
endocrine diseases

Pituitary Hormones

Pituitary Control
The pituitary is controlled by releasing factors
(hormones)

from hypothalamus, these

are:
-growth hormone releasing
hormone(GHRH)
-corticotropin releasing
hormone(CRH)

-gonadotropin releasing
hormone(GnRH)
-thyrotropin releasing
hormone(TRH)
Also pituitary hormones & their releasing
factors from

hypothalamus are subject to control by the

hormones they regulate their secretion,
namely T3,T4,cortisol & sex hormones
(estrogens & progesterone).This is called

negative feedback
control.

The hypothalamus secretes two hormones

that
regulate release of GH, these are
GHRH that stimulates GH production &
somatostatin(SST) which
inhibits its production.
GH and its peripheral mediator insulinlike growth
factor -1(IGF-1) inhibit release of GH by a
negative
feedback mechanism also.

Production of prolactin by AP is
inhibited by dopamine & dopamine
analogs acting on D2
receptor
s. No hypothalamic regulator for PRL
production or
release.

Anterior pituitary hormones

include:

-Growth hormone(GH, somatotropin

-Thyroid stimulating
hormone(TSH,thyrotopin
-Follicle stimulating hormone(FSH
-Lutinizing hormone(LH
-Adrenocorticotrophic hormone(ACTH
-Prolactin (PRL
All anterior pituitary hormones,except
prolactin, are

trophic hormones i.e. they regulate

production of
other hormones produced by other endocrine
glands &
promote growth of these
glands.

Mechanism of Action:
TSH,FSH,LH,and ACTH all act
through G

protein coupled receptors, while GH

and PRL act through JAK/STAT
superfamily receptors

1- Growth
Hormone(GH,Somatotropin)
A single chain polypeptide hormone of
191 aa.

Secretion is high in the new born,decreasing at

4yrs to an

intermediate level, maintained until after

puberty, then further declines.Secretion
is high during sleep. Secretion is
inhibited by somatostatin & IGF-1.

Significant differences in amino acid sequence

between

humans & other species prevent the use of

non-human
hormone.
Actions:is required in children & adolescents for
attainment

of normal adult size.

Also has important effects on CHO & lipid metabolism &
lean body

mass(
protein anabolism,
lipolysis,
glycogenolysis)
Effects are mediated through IGF-1
(somatomedin- c)

Congenital or aquired deficiency in

children

leads to failure to attain

normal adult size(dwarfism),
disproportionate increased body
fat & decreased muscle mass.
Increased release of GH before
closure of

epiphysis leads to gigantism.

Deficiency leads to short stature,
adposity,

hypoglycemia due to unopposed

action of
insulin.

Growth Hormone

Physiological Actions:

Promotes growth of bone& muscle

Has anabolic effects in muscle

& catabolic effects in lipid cells,
shifting the balance of body
mass to an increase in muscle
mass and reduction in lipids.
Promotes use of lipids for
energy production instead of
CHO
Reduces insulin sensitivity
leading to hyperinsulinemia
Effects mediated through IGF-

Growth Hormone

Physiological
actions:

Mechanism GH receptor stimulation

activates

an intracellular tyrosine kinase,

JAK/STAT cytokine superfamily type
recepors, resulting in phosphorylation
of proteins and gene regulation.
Growth-promoting effect is mediated
through

production of IGF-1 in liver,bone,muscle

&
kidneys.

Growth:almost all body tissues are

stimulated to

grow.
Nitrogen metabolism: increased
nitrogen

retention, amino acid transport into

tissues, and
incorporation into protein

Carbohydrate and lipid

metabolism: GH

appears to promote use of lipids as

energy
source instead of carbohydrates.
GH & IGF-1 have opposite effects on
insulin

sensitivity.
GH reduces insulin sensitivity
leading to

hyperinsulinem
ia

IGF-1 lowers serum glucose and

reduces

circulating insulin through action

on IGF-1
receptors and insulin receptors.

Growth Hormone

Physiological actions
(cont..

Conserves muscle at the expense of fat

during stress
Insulin-like growth factor-1 (IGF-1&
IGF-2,

somatomedins): are peptides produced by

liver and other
tissues in response to GH; appear to mediate
many GH
effects.

Some children with growth failure have severe

IGF-
1deficiency that is not responsive to exogenous
GH may
be due to mutation in GH receptor or
development of
antibodies to GH.
rhIGF-1 (mecasermin, Increlix) is now
available for

treatment of growth failure in GH-resistant

patients

Growth Hormone
Clinical applications one of the few
pituitary

hormones with long-term

therapeutic utility. Recombinant human
growth hormone (rhGH, somatropin) is
used clinically.
There are two
forms,
somatropin and
somatrem.
Hypopituitary dwarfism: in
children with

insufficient GH secretion, GH will

generally

produce an increased growth rate over

several
years.
Recently, FDA approved its use in children
with

idiopathic, non-GH-deficient short

stature.

Growth Hormone

Clinical applications
cont
Treatment of AIDS associated
wasting Treatment of adult onset growth
hormone deficiency.

Turners syndrome a genetic disease that occurs

in girls, in

combination with
gonadotropins.
Prader Willi syndrome a genetic disease due to GH
deficiency, is

associated with growth failure, obesity and

carbohydrate intolerance.GH decreases body
fat & increases lean body

mass,linear growth & energy

expenditure.
Idiopathic short
stature
Anti-aging supplements OTC supplements which
suggest they

contain hGH. Contain amino acids that are supposed to

release GH.

Growth Hormone
Problems associated with
therapy

possibility of intracranial hypertension

and visual
changes exist, so fundoscopic exams
needed.
Also possibility of type 2 diabetes and
respiratory

difficulties in patients with obesity or

sleep apnea

due to Prader-Willi
syndrome.
Possible contamination of humanderived GH
with Creutzfeldt-Jakob virus,thus
recombinant
form, somatropin is
preffered.

Growth Hormone
Acromegaly hypersecretion of GH in
adults after

closure of epiphysis, may result in

acromegaly.
Octreotide (Sandostatin) or other
somatostatin

analogs are most commonly used to

decrease GH
secretion in these patients.
Dopamine agonists such as
bromocryptine will

inhibit GH secretion from some GH

secreting
tumors.

Pegvisomant (Somavert), a GH receptor

antagonist,

is now available to treat acromegaly in

patients who have not responded to
other treatment. Pegvisomant
prevents GH stimulation of IGF-1
production.25/10/2016

2-Gonadotropins(LH &FSH)&Human
Chorionic
Gonadotropin(hCG)

Luteinizing hormone (LH,interstitial cell

stimulating hormone)

Chemistrya glycoprotein hormone with 2

peptide chains produced by the anterior
pituitary gonadotrophs under
stimulation of GnRH from
hypothalamus.
Mechanisms & Physiological actions in
women:
Mechanism FSH& LH act by stimulating Gs
protein

coupled receptors.

In ovary FSH promotes ovarian follicle

development.
Both FSH and LH are needed for ovarian
steroidogenesis

In women:the main function of FSH is to

direct ovarian

folicle
development.
Both FSH & LH are needed for ovarian
steroidogenesis. In ovary LH stimulates androgen
production by the theca cells in the follicular
stage of menstrual cycle, whereas FSH
stimulates the conversion by granulosa cells of
androgens
to estrogens.
In the luteal phase production of both
estrogen &

progesterone is first under control of LH

and then if pregnancy occurs under control

of human chorionic
gonadotropin(hCG),a placental protein identical
to LH and
acts on LH
receptors.
FSH,LH & hCG are used in infertility to
stimulate

spermatogenesis in men & ovulation in

women.

Follicle stimulating
hormone (FSH)

Chemistry a glycoprotein with 2

peptide chains. Agents available are
recombinant human FSH, follitropin
(Gonal-F and Follistim), and urinary
human FSH, urofollitropin obtained from
urine of
postmenopausal
women.
Physiological actions of
FSH:
Mechanism acts through Gs coupled
receptors.

FSH+LH regulate gonadal

function
In ovaryit promotes follicular development
to

produce oocyte.
FSH,LH & hCG are given s/c,im,t1/21040
hrs

In Testis: FSH stimulates

spermatogenesis,

whereas LH stimulates testosterone

synthesis by
Leydig cells.
FSH+LH are required for
steroidogenesis in

ovaries.
In women FSH stimulates
conversion of

androgens to estrogens in
granulosa cells
FSH enhance Sertoli cells in testes to
produce

androgen-binding proteins that

maintain high concentration of
androgens in the vicinity of
developing sperms.

FSH also stimulates conversion by Sertoli

cells of

testosterone to estrogen.
Clinical use:to enhance ovulation&
spermatogenesis

Menotropins:are FSH and LH -like products

isolated

from urine of postmenopausal women.

Also called human menopausal
gonadotropins (hMG)
FSH: three forms of purified FSH are
available:

-Urofollitropin(uFSH) isolated from

urine of post

menopausal
women
-Follitropin alfa and follitropin beta are
recombinant
forms of FSH(rFSH).They have shorter
duration of
action than human form but may be more
efficient

Luteinizing
hormone:
-Lutropin alfa is a recombinant form of
human LH.Is
given s/c with t1/2 of
10hrs
Used in combination with follitropin
alfa for
stimulation of follicular development in
infertile
women with profound LH
deficiency

Human chorionic gonadotropin(hCG):

is produced

by placenta and excreted in

urine
-Choriogonadotropin alfa(rhCG) is a
recombinant
form
Pharmacodynamics: the gonadotropins and
hCG act
through Gs protein coupled
receptors

Figure 56-4. The hypothalamicpituitary-gonadol axis

A single hypothalamic releasing factor,
gonadotropin-releasing hormone (GnRH),
controls the synthesis and release of both
gonadotropins (LH and FSH) in males and
females. Gonadal steroid hormones
(androgens, estrogens, and progesterone)
cause feedback inhibition at the level of
the pituitary and the hypothalamus. The
pre-ovulatory surge of estrogen also can
exert a stimulatory effect at the level of the
pituitary and the hypothalamus. Inhibin, a
polypeptide hormone produced by the
gonads, specifically inhibits FSH
production by the pituitary.

Luteinizing
hormone

Clinical application

Infertility menotropins (a mixture of

urinary
LH and
FSH) and chorionic gonadotropin have
been used to induce ovulation.
Recombinant
human LH lutropin alpha (Luveris) is
now

available.
Hyperstimulation of ovary may
occur
May also increase fertility in men

Kits available to predict time of ovulation

by

measuring urinary LH

Clinical use of
Gonadotropins&hCG
Ovulation
induction:

- To induce ovulation in women with

unovulatory cycles for many reasons,who
failed to respond to
other treatments such as
clomiphene
-For controlled ovarian over stimulation in
assisted
reproductive technology
procedures

Male infertility
Most signs and symptoms of hypogonadism in
males(eg

delayed puberty,retension of prepubertal

secondary sex characteristics after puberty)
can be treated by exogenous androgens ,but
infertility rquires the use of LH and FSH

Toxicity and contraindications

In women:
-Ovarian hyperstimulation
syndrome,characterized by ovarian enlargement,
ascites, hydrothorax, and hypovolemia that may
result in shock,hemoproteinemia, fever and
arterial
thromboembolism.
-Headache depression,edema,precocious
puberty an
production of antibodies against hCG(rare).
In men the risk of
gynecomastia

Gonadotropin-releasing
hormone(GnRH) and
its analogs:

Is a peptide hormone secreted by

hypothalamus

It acts on G protein coupled receptors on

gonadotrophs

in anterior pituitary to stimulate secretion of

LH and
FSH
Pulsatile iv or s/c (frequency every 1-4hrs)
of GnRH

secretion is required for release of

LH&FSH Sustained nonpulsatile
administration of GnRH or its

analogs(as depot formulations) inhibits

release of
LH&FSH resulting in
hypogonadism GnRH analogs are used to
produce gonadal supression

in men with advanced prostate cancer

Preparations:
Gonadorelin is an acetate form of a
synthetic

human
GnRH
Goserelin,histrelin,leuprolide,nafareli
n and

triptorelin are synthetic analogs of

GnRH Gonadorelin is administered iv
or s/c, GnRH

analogs are administered

s/s, im,

intranasal(nafarelin)or as s/c
implants
T1/2 for GnRH is 4 minutes and for
synthetic

analogs is
3hrs

Pharmacodynamics
Pulsatile release of GnRH stimulates LH FSH
release

during fetal and neonatal

period From age 2years until the onset of
puberty GnRH

secretion falls off and the pituitary

simultaneously
exhibits very low sensitivity to
GnRH
Just before puberty an increase in
frequency and

amplitude ofGnRH release occurs and the

sensitivity of pituitary to GnRH increases due

to released of steroidal
hormones
By the end of puberty the sysyetm is well
established so

that menstrual cycles proceed at constant

intervals

Clinical pharmacology of GnRH

Assessment of delayed puberty for (a)
constitutional delay or
(b)hypogonadotropic hypogonadism
LH response distinguishes between
causes:
Following s/c GnRH bolus:
-peak LH responses more than 15.6mU/ml
indicat
normal(ie puberty will occur soon)

-peak LH impaired suggests

hypogonadotrop
hypogonadism)

GnRH agonists are used for

stimulation of

gonadotropins production or their

suppression
A stimulation by pulsatile
administration:

-Female and male infertility to

stimulate pituitary
function.
Inhibition: management of
prostate

cancer,endometriosis,uterine
fibroids,polycystic ovary
syndrome and precocious
puberty
By continuous administration of
GnRH or its

analogs

Toxicity of GnRH

For diagnosis,occasional headache,

flushing,

GnRH analogs:initial bone

pain,exacerbation in

prostate cancer and hot flushes(both

sexes)
Increased risk of osteoporosis in
women if

treatment is more than 6

months

Human chorionic gonadotropin

Human Chorionic Gonadotropin (hCG) not a pituitary

hormone but is
similar to pituitary
gonadotropins
Chemistry glycoprotein with 2 polypeptide chains &
chains.

Produced by placenta & excreted in

urine.
- chain closely resembles FSH, LH, TSH -chain
- chain closely resembles LH -chain
Similar to LH structuraly
Used to treat women and men with LH deficiency
Recombinant human HCG, choriogonadotropin alfa
(Ovidrel) is

used clinically.

Physiological actions
stimulate and sustain function of ovarian corpus
luteum to
produce progesterone
-placenta
maintenance

Pharmacokineti
cs:

-im,administration, well
absorbed,
t1/2=8hrs(compared with LH t1/2=30
minutes)
Pharmacodynam
ics:

-hCG stimulates gonadal steroidal

hormone
production
Cells affected:

-Female interstitial & corpusluteum

cellsto produce
progeterone
-Male Leydig cells to produce
testosterone
-hCG administration stimulates
midcycle LH surge
which promotes ovulation in
hypogonadotropic
states

Clinical use of human chorionic

gonadotropin

(hCG)
Diagnostic
use:

Prepubertal boys with undescended

gonads:hCG

distinguishes between retained

testes(cryptorchid) and retracted
testes (pseudocryptorchid)
-If transient testicular descent occurs
eith hCG

administrationpermenant pubertal
descent
-If transient testicular descent does not occur with
hCG adminstration orchiopexy will be required to
insure spermatogenesis

Conistitutional puberty delay vs

hypogonadotropic hypogonadism distinuished
using repetitive hCG administration
-With hCG administration serum testosterone
and estradiol levels increase in conistitutional
puberty delay but not in hypogonadotropic
hypogonadism states
Presence of hCG inurine confirms diagnosis of

pregnancy

Therapeutic use of hCG

hCG+hMG produce ovulation in women with
hypogonadotropic hypogonadism or as part
of invitro
fertilization
approach
hCG testicular testosterone stimulation in men
with

hypogonadotropic hypogonadism(increased
intratesticular
testosterone)promotes spermatogenesis ;
menotropins
oftenalso required for
fertility
Toxicity of hCG

Headache,edema,gynecomastia,precocious
puberty , hCG

antibodies
production(rare).
Contraindication
s: Presence of androgen-dependent
neoplasia Presence of precocious
puberty 25/11/2014

3-Thyrotropin (TSH)

Chemistry glycoprotein with 2

polypeptide chains

produced by anterior pituitary . Thyrotropin

alpha is a
recombinant TSH used
clinically.
Physiological actions Receptor stimulation
activates Gs

protein coupled receptors which increases

function of
thyroid gland

Increases uptake of iodine by thyroid gland, synthesis and

release

of T3 and T4, & growth(enlargement) of

gland.
Pharmacokinetics : administered
im,or s/c
T1/2 1hr,renal
degradation
Pharmacodynami
cs:
TSH activates thyroid cells
T3&T4 production

cAMP

iodine uptake

Control of thyroid
function

Thyrotropin (TSH)
cont.
Clinical
application

Increases uptake of radioactive

iodine. Used as a diagnostic tool for
serum thyroglobulin testing or whole
body scanning in the follow-up of
patients with thyroid cancer.

4-Corticotropin(Adrenal cortex trophic

hormone,
ACTH)
Chemistry natural hormone is a single chain
polypeptide

of 39 amino acids secreted by anterior

pituitary.Stimulates
cortisol synthesis &
release.
A synthetic form (cosynotropin-tetracosactide)
containing

amino acids 1-24 is used to assess adrenal

cortical status.
Physiological actions stimulates adrenal
cortex to

synthesize & secrete cortisol, corticosterone,&

aldosterone
(slightly). Prevents atrophy of adrenal cortex
due to its
trophic effects on adrenal
cells.
Mechanism receptor interaction results in
activation of

adenylate cyclase &synthesis of cAMP. cAMP

activates
enzymes involved in steroid
synthesis.

Chemistry of ACTH:
A single peptide chain of
39 aa
aa from 1
24 is
required for full biological activity

aa from 25
39 is for species specificity

Synthetic human ACTH:is called

cosynotropin or

tetracosactide
Aminoacid terminal 1-13 is identical to
melanocyte
stimulating hormone(MSH)

With excess ACTH pituitary secretion,

hyperpigmentation
due to excess -MSH occurs

Pharmacodynamics:
ACTH stimulates adrenal cortex to
produce

glucocorticoids,mineralocorticoids and
androgens
ACTH stimulates cholesterol esters
activity:

(chlesterol pregnenolone step:rate limitingstep

in steroid hormone
production
ACTH promotes adrenal
hypertrophy and

hyperplasia
ACTH may cause increased skin
hyperpimentation

Clinical use of
ACTH:

treatment of adrenal
insufficiency

Cosynotropin may be used to rule out

adrenal

insuficienc
y Following cosynotropin plasma
cortisol should

exceed 18g/dl
-subnormal response means primary or
secondary

adrenocortical
insuficiency
-primary adrenocortical
insuficiency:increased

endogenous ACTH
-secondary adrenocortical
insuficiency:decreased

ACTH levels
Treatment of infantile spasms
(epilepsy)

Differentiation of late-onset congenital

hyperplasia from a

state of ovarian hyperandrogenesim: 21-hydroxylase

deficiency,ACTH stimulation leads to

increase in plasma 17- hydroxyprogesterone

(substrate for
the deficient
enzyme).
Hydroxylase deficiency: ACTH stimulation
leads to

increased 11deoxycortisol

3--hydroxy-5- steroid dehydrogenase deficiency.ACTH

stimulation leads to increased 17 hydroxypregnenolone
Therapeutics: corticotropin: no advantage over direct
glucocorticid administration

Melanocyte-stimulating
hormone(MSH):

,, and MSH are peptide hormones

structurally related to ACTH and are derived
from the same precursor.
They are called melanocortins because they
stimulate production of melanin by specialized
skin cells called melanocytes
They play an important part in determining

hair and skin colour and reaction to UV light

5-Prolactin(PRL)
Chemistry single chain polypeptide hormone
produced

by anterior pituitary mamotroph

cells,resembles GH
structurally.
Physiological
actions

Lactation causes growth and development of

breasts,

and increased synthesis of milk.Lactation

requires
appropriate secreting levels
of

progestins,estrogen,corticosteroids
&insulin.
Decreases release or effectiveness of
gonadotropins.
PRL deficiency may be associated with pituitary
states,

resulting in lactation failure and luteal phase

defect.

Regulation of Prolactin secretion

Its secretion is under tonic inhibitory control
by the

hypothalamus,the inhibitory mediator being

dopamine
The main stimulus fro release is
suckling.

Main function in women is to control milk

production.

At delivery,when oestrogen levels fall,prolactin

levels rise

and lactation is initiated.

Hypersecretion may occur due to hypothalamic

destruction

that reduces release of dopamine.

Hyperprolactinemia may cause galactorrhea,
amenorrhea

and infertility.
Bromocriptine, pergolide (Permax),&
cabergoline

(Dostinex) are dopamine agonists that are

useful in
suppressing PRL secreting
tumors.

Bromocriptine and other

Dopamine agonist
Bromocriptine and cabergoline are ergot
alkaloids with high
affinity for dopamine D2
receptors. Quinagolide,a nonergot compd has
similar properties. Dopamine agonists
suppress prolactin release in patients
with hyperprolactinemia &shrinks pituitary(PRL
secreting
tumors
). Bromocriptine also increases GH release in
normal subjects, but decreases it in pts with
acromegaly (paradoxical

response).
Cabergoline and bromocriptine are also used in
parkinsonism. Newer nonergot D2 agonists
used in parkinsonism include
pramipexole and ropinirole

Clinical uses:
Hyperprolactinemia in PRL secreting

adenomas
To supress physiological lactation
after

abortion
Treatmen of acromegaly alone or in
combination with other
agents

Treatment of parkinsons disease as

first-line

drugs

Adverse effects of
bromocriptine:

GIT:anorexia,nausea,vomiting(reduced by taking
medication with

food)
-Conistipation,dyspepsia due to reflux
oesophagitis
-Peptic ulceration with
bleeding
CVs effects:
-Postural hypotesion
-Digital spasm on long-term therapy
-Cardiac arrhythemias may require stopping therapy
Dyskinesia similar to
leavodopa

Mental
disorders:hallucinations,confusion,dellusions

Miscellaneous adverse effects:headache,nasal

congestion,pulmonary

infiltrates,erythromelalgia, increased
arousal

Posterior petuitary
Hormones

Posterior Pituitary Hormones:

They are synthesized in hypothalamus and transported

via their

axons to petuitary
Oxytocin: a nonapeptide hormone secreted by
posterior pituitary.

Physiological levels are required for milk ejection in

lactating

women
Pharmacologic doses: induce uterine contractions &
maintain

labor.
Pharmacokinetics:
-IV dose for labor
induction
-IM for control of postpartum
bleeding
-Nasal spray for postpartum lactation
induction

-Not bound to plasma

proteins
-Elimination: renal and hepatic,t1/2=5
minutes.

Pharmacodyna
mics:

Acts through G protein coupled

receptors

Influences ionic currents in myometrial

smooth muscle

which leads to uterine contraction.Also

promotes release of PGs and leukotriens that
increase uterine contraction
Uterine sensitivity to oxytocin increase in
pregnancy Inhibition of oxytocin-induced
uterine contraction can be achieved by
magnesium sulphate,-adrenergic agonists or

inhalational anesthetics
Oxytocin also promotes contraction of myoepithelial cell
surrounding mammary alveolia which leads to milk
ejection .Thus normal lactation requires oxytocin

Clinical uses of
oxytocin

-Labor induction
-Promotion of dysfunctional labor
-Control of post partum bleeding
-To enhance impaired milk ejection(nasal route)
Toxicity:
-Hypertensive reactions
-Uterine rupture
-Water intoxication
-Fetal death
-Afibrinogenemia
Contraindicatio
ns:

-Fetal dystress
syndrome
-Abnormal fetal
presentation
-Factors predisposing to uterine
rupure

Oxytocin
Antagonist: Atosiban is an oxytocin
receptor antagonist used to prevent
preterm labor ( tocolysis).It
is as effective as 2-adrenergic
agonists.
Is administered
IV

n:

Vasopressi

Is a nonapeptide hormone released by

posterior

piuitary in response
to:
-Rising plasma
tonicity,or
-Decreased blood
pressure

Has antidiuretic and vasopressor

properties

Vasopressin deficiency causes diabetic

insipidus
Route of
administration: iv,im,intranasal
T1/2=20 minutes
Renal and hepatic catabolism
Minimal amounts excreted unchanged in urine

Pharmacodynamics:
Receptor types:
-V1:in vascular smooth muscle mediate
vasoconistriction
-V2:in renal tubules,produce antidiuretic
effect by increasing water permeability and
increasing collecting
tubules water
reabsorption.
-Extrarenal V2 receptors..promote
coagulation factor VIII
and von Willebrand factor
release

Desmopressin acetate a long-acting synthetic

analog of

vasopressin derivative with limited V1

receptor activity
Has significant antidiuretic/vasopressin ratio
compared to

vasopressin(4000:
1)

Clinical uses of vasopressin:

Vasopressin and desmopressin are used
alternately in

treatment of diabetes
insipidus Nocturnal enuresis(desmopressin at
bed time) to reduce

night urine
production
IV vasopressinmay be effective in managing
esophageal

variceal bleeding and colonic diverticular

bleeding
Toxicity:

Vasopressin (not desmopressin)causes

vasoconistriction

issues in patients with coronary vascular

disease Unusual side effects
include:aggitation,allergic

reactions,abdominal cramping, headache&

nausea

Vasopressin
Antagonists:
Conivaptan and tolvaptan are a
group of

nonpeptide vassopressin receptor

antagonists that are investigated for pts
with hyponatremia or acute
heart failure that are usually associated
with
elevated concentrations of
vasopressin.

Conivaptan has high affinity for both V1a

and V2

receptors.
Tolvaptan has higher affinity to V2 than V1
receptors

Both agents relieved symptoms and reduced

signs of

hyponatremia and heart failure

Thank You
For
Attenti
on