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

SUJIT KUMAR SARKER

Brief anatomy & physiology

Pituitary weighs: 0.6 g andRests in the bony sella turcica near the optic chiasm and the cavernous sinusesConsists of an anterior lobe (adenohypophysis) and a posteriorlobe (neurohypophysis)It is connected to the overlying hypothalamus by a stalk of neurosecretory fibers andBlood vessels, including a portal venous system that drains thehypothalamus 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.

SUJIT KUMAR SARKER

IGF-I agonist

Drugs Mechanism ofaction & 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

SUJIT KUMAR SARKER

Somatostatin analogs

Drugs Mechanism ofaction & 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.

SUJIT KUMAR SARKER

GH receptor antagonist

Drugs Mechanism of action

Clinical uses Adverse effects

Pegvisomant Blocks GH receptors. Ameliorates effects of excess GH production

Acromegaly Increased liverenzymes

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Gonadotropins: FSH analogs

Drugs Mechanism of action & effects

Clinical uses Adverse effects

Follitropin alfa

Others:

Follitropin betaUrofollitropinMenotropins

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

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Gonadotropins: LH analogsDrugs Mechanism of

action & effectsClinical uses Adverse effects

Human chorionicgonadotropin

Others: Choriogonadotropin alfaLutropin 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:

GonadorelinGoserelin, 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.

SUJIT KUMAR SARKER

Gonadotropin releasing hormone receptor antagonist

Drugs Mechanism ofaction & 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

SUJIT KUMAR SARKER

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 ofhyperprolactinemia

Acromegaly

Parkinson’s disease

Gastrointestinal disturbances, orthostatic hypotension, headache, psychiatric disturbances

SUJIT KUMAR SARKER

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 ofaction & effects

Clinical uses Adverse effects

Atosiban Blocks oxytocin receptors Decreased uterine contractions

Tocolysis for preterm labor

Concern aboutincreased ratesof infant death

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Vasopressin receptor agonists

Drugs Mechanism ofaction & 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 Willebranddisease

Gastrointestinal disturbances

Headache

Hyponatremia

Allergic reactions

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Vasopressin receptor antagonist

Drugs Mechanism ofaction & effects

Clinical uses Adverse effects

Conivaptan

Others:Tolvaptan

Antagonist of vasopressin receptors & reduced renal excretion of water

Hyponatremia Infusion site reactions

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SummaryDrug 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 Parkinson’s 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 receptoragonists

Diabetes insipidus

Conivaptan Vasopressin receptor antagonist

Hyponatremia

Study questions

List some drugs used for controlled ovarianhyperstimulation.

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, 12th Ed.

Davidson’s Principle and Practice of Medicine, 20th Ed.

Essentials of Medical Pharmacology, K D Tripathy, 6th Ed.

Pharmacology, Tara V Shanbhag & Smita Shenoy, 2nd Ed.

SUJIT KUMAR SARKER