Hypothalamic and pituitary hormones

Presented by
Sujit Kumar Sarker
Outcomes
After this session we will be able to analyze:
Basic pharmacology of hypothalamic and pituitary hormones
SUJIT KUMAR SARKER
Outlines
Brief anatomy & physiology
of hypothalamus & pituitary
GH: analog & antagonist
Gonadotropin: analog &
antagonist
Dopamine agonist
Oxytocin & its antagonist
Vasopressin: agonist &
antagonist
Summary
Study questions
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Brief anatomy & physiology
Pituitary weighs: 0.6 g and
Rests in the bony sella turcica near the optic chiasm and the
cavernous sinuses
Consists of an anterior lobe (adenohypophysis) and a posterior
lobe (neurohypophysis)
It is connected to the overlying hypothalamus by a stalk of
neurosecretory fibers and
Blood vessels, including a portal venous system that drains the
hypothalamus and perfuses the anterior pituitary
SUJIT KUMAR SARKER
Brief anatomy & physiology
SUJIT KUMAR SARKER
SUJIT KUMAR SARKER
Growth hormone
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Somatropin Recombinant form
of human GH. Acts
through GH
receptors to
increase
production of IGF-I.
Restores normal
growth
Replacement in GH
deficiency
Pseudotumor
cerebri, edema,
hyperglycemia,
scoliosis etc.
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IGF-I agonist
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Mecasermin Recombinant form of
IGF-I that stimulates
IGF-I receptors.
Improves growth and
metabolic IGF-I
effects in individuals
with IGF-I deficiency
Replacement in IGF-I
deficiency
Hypoglycemia,
Intracranial
hypertension,
Increased liver
enzymes
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Somatostatin analogs
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Octreotide
Other:
Lanreotide: long-
acting
Agonist at
somatostatin
receptors.
Inhibits
production of GH
Acromegaly
Esophageal
varices
Gastrointestinal
disturbances,
gallstones,
bradycardia etc.
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GH receptor antagonist
Drugs Mechanism of
action
Clinical uses Adverse effects
Pegvisomant Blocks GH
receptors.
Ameliorates
effects of excess
GH production
Acromegaly Increased liver
enzymes
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Gonadotropins: FSH analogs
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Follitropin alfa
Others:
Follitropin beta
Urofollitropin
Menotropins
Activates FSH
receptors. Mimics
effects of
endogenous FSH
Controlled
ovulation
hyperstimulation
in women
Male
hypogonadism
Multiple
pregnancies in
women,
gynecomastia in
men, headache,
depression, edema
SUJIT KUMAR SARKER
Gonadotropins: LH analogs
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Human chorionic
gonadotropin
Others:
Choriogonadotropin
alfa
Lutropin
Menotropins
Agonist at LH
receptor &
mimics effects of
endogenous LH
Controlled
ovulation
hyperstimulation
Male hypogonadism
Multiple
pregnancies in
women,
gynecomastia in
men, headache,
depression, edema
SUJIT KUMAR SARKER
Gonadotropin releasing hormone analogs
Drugs Mechanism of action
& effects
Clinical uses Adverse effects
Leuprolide
Others:
Gonadorelin
Goserelin, histrelin,
nafarelin, and
triptorelin
Agonist of GnRH
receptors.
Increased LH and FSH
secretion with
intermittent
administration.
Reduced LH and FSH
secretion with
prolonged continuous
administration
Controlled ovarian
hyperstimulation
Precocious puberty
Advanced prostate
cancer
Headache, nausea,
injection site reaction
etc.
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Gonadotropin releasing hormone receptor antagonist
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Ganirelix
Others: Cetrorelix:
controlled ovarian
hyperstimulation
Degarelix: advanced
prostate cancer
Blocks GnRH
receptors &
reduces
endogenous
production of LH
and FSH
Prevention of
premature LH
surges during
controlled ovu-
lation
hyperstimulation
Nausea, headache
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Dopamine agonist
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Bromocriptine
Cabergoline
Activates dopamine
(D2) receptors.
Suppresses pituitary
secretion of prolactin
and less effectively
GH. Dopaminergic
effects on CNS
Treatment of
hyperprolactinemia
Acromegaly
Parkinsons disease
Gastrointestinal
disturbances,
orthostatic
hypotension,
headache,
psychiatric
disturbances
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Oxytocin
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Oxytocin Activates
oxytocin
receptors.
Increased
uterine
contractions
Induction and
augmentation of
labor
PPH
Fetal distress,
placental
abruption,
uterine rupture
etc.
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Oxytocin receptor antagonist
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Atosiban Blocks oxytocin
receptors
Decreased
uterine
contractions
Tocolysis for
preterm labor
Concern about
increased rates
of infant death
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Vasopressin receptor agonists
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Desmopressin
Vasopressin:
diabetes insipidus
esophageal varices
Vasopressin
receptor agonist &
acts in the kidney
collecting duct cells
to decrease the
excretion of water
Diabetes insipidus
Nocturnal enuresis
Hemophilia A &
Von Willebrand
disease
Gastrointestinal
disturbances
Headache
Hyponatremia
Allergic reactions
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Vasopressin receptor antagonist
Drugs Mechanism of
action & effects
Clinical uses Adverse effects
Conivaptan
Others:
Tolvaptan
Antagonist of
vasopressin
receptors &
reduced renal
excretion of
water
Hyponatremia Infusion site
reactions
SUJIT KUMAR SARKER
Summary
Drug Group Clinical use
Somatropin Recombinant form of human
GH
Replacement in GH deficiency
Mecasermin Recombinant form of IGF-I Replacement in IGF-I deficiency
Octreotide Somatostatin analogs Acromegaly, Esophageal
varices
Pegvisomant GH receptor antagonist Acromegaly
Follitropin alfa FSH analogs Controlled ovarian
hyperstimulation
Male hypogonadism
Human chorionic gonadotropin LH analogs Controlled ovarian
hyperstimulation
Male hypogonadism
SUJIT KUMAR SARKER
Summary
Drug Group Clinical use
Leuprolide Gonadoropin releasing
hormone analogs
Controlled ovarian
hyperstimulation
Precocious puberty
Advanced prostate cancer
Ganirelix Gonadotropin releasing
hormone receptor
antagonist
Prevention of premature
LH surges during controlled
ovulation hyperstimulation
Bromocriptine Dopamine agonist Hyperprolactinemia
Acromegaly
Parkinsons disease
SUJIT KUMAR SARKER
Summary
Drug Group Clinical use
Oxytocin Activates oxytocin
receptors
Induction and
augmentation of labor
PPH
Atosiban Oxytocin receptor
antagonist
Preterm labor
Desmopressin Vasopressin receptor
agonists
Diabetes insipidus
Conivaptan Vasopressin receptor
antagonist
Hyponatremia
Study questions
List some drugs used for controlled ovarian
hyperstimulation.
Name some drugs used for esophageal varices.
Name drug used in hyperprolactinemia.
List some drugs used in acromegaly.
SUJIT KUMAR SARKER
Book references
Basic & Clinical Pharmacology, BG Katzung, 12
th
Ed.
Davidsons Principle and Practice of Medicine, 20
th
Ed.
Essentials of Medical Pharmacology, K D Tripathy, 6
th
Ed.
Pharmacology, Tara V Shanbhag & Smita Shenoy, 2nd Ed.
SUJIT KUMAR SARKER