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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
SUJIT KUMAR SARKER
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
SUJIT KUMAR SARKER
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.
SUJIT KUMAR SARKER
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
SUJIT KUMAR SARKER
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
SUJIT KUMAR SARKER
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
SUJIT KUMAR SARKER
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