Chapter 18 Cholinoceptor Antagonists. Part A Muscarinic receptor antagonists.
Hormones & Hormones Antagonists
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Transcript of Hormones & Hormones Antagonists
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Hormones & Hormones
antagonists
• Anterior and Posterior Pituitary hormones
• Corticosteroids and corticosteroid antagonists
• Thyroid and antithyroid drugs, parathyroid hormones, drugs regulating
calcium homeostasis, Vitamin D
• Insulin, Oral hypoglycemic agents, glucagon
• Gonadal hormones and Oral contraceptives, antifertility agents
• Oxytocin and drugs acting on uterus.
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Hormone
It is a substance of intensebiological activity that is
produced by specific cells in
the body and is transported
through circulation to act onits target cells.
Hormones regulate body functions to bring about a
programmed pattern of life events and maintainhomeostasis
These are secreted by the endocrine glands. These are
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Pituitary Hormones
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Thyroid Hormones
Thyroid gland is responsible for the secretion of three
hormones essential for proper regulation of metabolism.
Thyroxine (T4)- Follicular cells
Triodothyronine (T3)- Follicular cells Calcitonin- Parafollicular cells
Parathyroid Hormones
Parathormone (PTH)
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Pancreas
The pancreas has two mainfunctions:
[1] to produce pancreatic
endocrine hormones
(e.g., insulin & glucagon)which help regulate many
aspects of metabolism and
[2] to produce pancreatic
digestive enzymes.
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Adrenal Gland
Cortex: Glucocorticoids (Hydrocortisone)
Mineralocorticoids (Aldosterone)
Sex steroids (Dehydroepiandrosterone)
Medulla: Adrenaline, Noradrenaline
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Gonads
Androgens (Testosterone)
Estrogens (Estradiol)
Progestins (Progesterone)
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In addition,
Hypothalamus produces many releasing and
inhibitory hormones which control the secretion ofanterior pituitary hormones
Placenta also secrets many hormones
Chorionic gonadotropin
Estrogens
Placental lactogen Prolactin
Progesterone
Chorionic thyrotropin
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Sites and mechanisms of hormone
action Hormones act on their specific receptors located
on or within their target cells
1. At cell- membrane receptor
2. At cytoplasmic receptor
3. At nuclear receptor
Hormone
Receptor
Response
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At cell membrane receptors A) Through alteration of intracellular cAMP conc.
Hormone
ReceptorAdenyl
cyclase
Mg++
Cyclic 3’,5’- AMP
ATP
• activate enzymes, alters cell permeability, protein synthesis, secretions
Protein kinase A Ca2+ acts as third
messenger
E.g. : Adrenaline, glucagon, TSH,FSH, LH, PTH, Calcitonin, ACTH,
some hypothalamic releasing hormones, vasopressin (V2)
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B) Through IP3/DAG Pathway:
Release intracellular Ca2+ and
Activates Protein kinase C
E.g.: Vasopressin (V1) & Oxytocin
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C) Direct Transmembrane
activation of tyrosine
protein kinase: Phosphorylation cascade
Regulation of various
enzymes
E.g.: Insulin,
growth hormone, Prolactin
1
2
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At cytoplasmic receptors
Penetrates cell membrane
Combines with cytoplasmic
receptor
Exposes DNA molecule forbinding site
Migrates to nucleus and binds
to specific genes
Mediates synthesis of mRNA
and functional proteins
E.g.: glucocorticoids, mineralocorticoids, androgens, Estrogens, progestins,
calcitriol
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At nuclear receptor
Penetrates the nucleus
Combines with receptor
Alters DNA-RNA mediated protein synthesis
Nuclear receptor
E.g.: Thyroxine, Triiodothyronine
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Anterior Pituitary (Adenohypophysis)
Hormones
Growth Hormone
A 191 amino acid, single chain peptide of MW 22000
Physiological functions Promotes growth of all organs by inducing hyperplasia
Promotes retention of nitrogen and other tissue
constituents
Promotes utilization of fats and spares carbohydrates
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GH acts on cell surface JAK-STAT protein kinase
receptors
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Indirect actions of GH
Growth promoting
Nitrogen retaining and
Metabolic actions
Are exerted through theelaboration of peptides called
somatomedins or Insulin like
growth factors (mainly IGF-1)
Like insulin, IGF-1 promotes
lipogenesis and glucose uptake
by muscles
(Major source
of IGF-1)
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Direct actions of GH
Induce lipolysis in adipose tissue
Glycogenolysis in liver
Decrease glucose utilization by muscles
Opposite
effects to
those of IGF-1
& Insulin
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Pathological involvement Excess production of GH –
Gigantism in childhood Acromegaly in adults
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Preparations & Use
Primary indication for GH is
Pituitary dwarfism- 0.03-0.07 mg/kg (0.06-0.16 units/kg) i.m. or
s.c. 3 times a week upto the age of 20-25 years
Two forms of human GH produced by recombinant DNAtechnique (rhGH) Somatropin (191AA) and Somatrem (192AA)
are available for clinical use
rhGH can also be used in Turner’s syndrome and in children with
renal failure
It is also approved for AIDS-related wasting: higher dose (0.05-
0.1 mg/kg/day)
Should not be given postoperatively, trauma, cancer and other
critically ill patients
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Adverse effects
Pain at injection site and lipodystrophy
Glucose intolerance
Hypothyroidism
Salt and water retention Hand stiffness
Myalgia (Pain in muscle or group of muscles)
Headache
Rise in intracranial pressure can occur in few cases
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GH inhibitors
Somatostatin 14 amino acid peptide
Inhibits the secretion of GH, TSH and Prolactin by pituitary
insulin and glucagon by pancreas and almost all GIT secretions
Side effect: steatorrhoea, diarrhoea, hypochlorhydria, dyspepsia
and nausea
Decreased GI mucosal blood flow helps in controlling bleeding
esophageal & peptic ulcer
Antisecretory action is beneficial in pancreatic , biliary orintestinal fistulae
Used as adjuvant in diabetic ketoacidosis
Use in acromegaly is limited due to short duration of action (t1/2 ~
2-3 min)
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Octreotide Synthetic Octapeptide 40 times more potent in suppressing GH secretion
Longer acting (t1/2 ~ 90 min)
It is preferred over somatostatin for acromegaly and secretory
diarrhoeas associated with carcinoid, AIDS, cancer chemotherapy or
diabetes
It controls diarrhoea due to suppression of hormones which enhance
intestinal mucosal secretions
Dose: initially 50-100 g s.c.twice daily, increased upto 500 g TDS
Adverse effects: abdominal pain, nausea, steatorrhoea, diarrhoea and gall stones
Octreotide i.v. injection (100 g followed by 25-50 g/hr)- reduces hepatic blood
flow and helps stop esophageal variceal bleeding
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Congenital disease due to absence or deficiency of normal
thyroid secretion, characterized by physical deformity,
dwarfism, mental retardation, and often by goiter
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