1 Pituitary and Thyroid Pharmacology
1 Pituitary and Thyroid Pharmacology
1 Pituitary and Thyroid Pharmacology
Pharmacology Team
Naim Kittana, Suhaib Hattab, Ansam Sawalha, Adham Abu Taha, Waleed Sweileh,
Ramzi Shawahneh
Hypothalamus (GHRH,
GnRH,CRH, TRH)
Direct action
Anterior Posterior
Growth
FSH & LH TSH ACTH Prolactin ADH Oxytocin
Hormone
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Hormones of the hypothalamus
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1. Agents Affecting Growth Hormone (Somatotropin)
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Growth-promoting and metabolic actions of GH
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Growth hormone (GH)
• Hypersecretion causes
gigantism in children and
acromegaly in adults
• Hyposecretion in children
causes pituitary dwarfism.
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1. Agents Affecting Growth Hormone (Somatotropin)
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1. Agents Affecting Growth Hormone (Somatotropin)
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2. Gonadotropin-releasing Hormone (GnRH) and Analogs
• GnRH Analogs
– GnRH Receptor Agonists
• Leuprolide
• Gonadorelin
• Triptorelin
• Nafarelin
• Goserelin
• Histrelin
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2. Gonadotropin-releasing Hormone (GnRH) and Analogs
Pulsatile administration
– Short-term or pulsatile administration of GnRH agonists (every 1–4 h)
increases the synthesis and release of both LH & FSH
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2. Gonadotropin-releasing Hormone (GnRH) and Analogs
Chronic administration
– 2–4 weeks of daily administration of GnRH inhibits the release of both
LH & FSH by causing a reduction in the number of GnRH receptors on
the anterior pituitary.
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2. Gonadotropin-releasing Hormone (GnRH) and Analogs
Chronic administration
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2. Gonadotropin-releasing Hormone (GnRH) and Analogs
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2. Gonadotropin-releasing Hormone (GnRH) and Analogs
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GnRH Receptor Antagonists
– Common example:
• Ganirelix
• Abarelix
• Cetrorelix
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GnRH Receptor Antagonists
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Clinical Uses of GnRH Receptor Antagonists
• Prostate cancer
• Hormone-sensitive breast cancer and some benign disorders such
as endometriosis and uterine fibroids
• Some cases of infertility: Prevents premature LH surge
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3. Prolactin-releasing factor (PRF) and prolactin-inhibiting
factor (PIF)
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Prolactin-releasing factor (PRF)
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Prolactin-inhibiting factor (PIF) (dopamine agonists)
– Cabergoline
A potent D2 agonist with greater D2 selectivity.
It is more effective in reducing hyperprolactinemia than bromocriptine
Has a long half-life that permits twice-weekly dosing.
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Prolactin-inhibiting factor (PIF) (dopamine agonists)
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Hormones of the anterior pituitary
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Growth hormone
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Growth hormone
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Growth hormone
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Growth hormone antagonists
– Pegvisomant
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Gonadotropins (LH & FSH)
• In men,
– LH induces testosterone production by the interstitial (Leydig) cells
of the testis
– FSH acts on the testis to stimulate spermatogenesis and the
synthesis of androgen-binding protein
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Regulation of the Ovarian Cycle
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Gonadotropins (LH & FSH)
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Gonadotropins (LH & FSH)
– hCG:
• hCG is nearly identical in activity to LH
• Produced by the placenta and can be isolated and purified from the
urine of pregnant women
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Gonadotropins (LH & FSH)
• Therapeutic uses:
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Gonadotropins (LH & FSH)
• Therapeutic uses:
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Gonadotropins (LH & FSH)
• Adverse effects
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Hormones of the posterior pituitary
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Anti-diuretic Hormone (ADH, Vasopressin)
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Anti-diuretic Hormone (ADH, Vasopressin)
• In renal tubules, ADH causes the permeability of water to increase and also
increases the transport of urea in the inner medullary collecting duct, which
increases the urine-concentrating ability of the kidney
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Anti-diuretic Hormone (ADH, Vasopressin)
– ADH preparations
• Aqueous vasopressin (Pitressin), a short-acting preparation that acts on
both V1 and V2 receptors, is administered parenterally and lasts 2–6 hours
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Anti-diuretic Hormone (ADH, Vasopressin)
– Therapeutic uses
• Desmopressin is the most effective treatment for severe central diabetes
insipidus because its V2 activity is 3,000 times greater than its V1 activity;
but it is not effective in the nephrogenic form of the disease
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Oxytocin
– Therapeutic uses
• Is used for induction and maintenance of labor.
• Stimulates milk ejection from the breast.
• Postpartum uterine bleeding.
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The Thyroid Gland
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Synthesis of thyroid hormones
• Thyroid hormones:
Triiodothyronine (T3)
Tetraiodothyronine (T4, thyroxine)
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Synthesis of thyroid hormones
• Steps:
1. Iodide (I-) is trapped by sodium-iodide
2. Iodide is oxidized by thyroidal peroxidase to iodine (I.)
3. Tyrosine in thyroglobulin is iodinated and forms MIT & DIT
4. Iodotyrosines condensation
MIT+DIT→T3; DIT+DIT→T4 44
Regulation of Thyroid Hormone
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Physiological actions of thyroid hormones
• Eitiology of hypothyroidism:
Hashimoto disease
Simple goiter
After surgery and ablation of thyroid after surgery
Congenital
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Myxedema
• Symptoms include:
Low metabolic rate
Feeling chilled
Constipation
Thick dry skin
Puffy eyes
Edema
Lethargy
Mental sluggishness (but not mental retardation)
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Goiter
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Cretinism
• Severe hypothyroidism in infants
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Physiological actions of thyroid hormones
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Graves’ disease
• The most common hyperthyroid disease
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Typical symptoms of Graves’ disease
• Sweating
• Rapid and irregular heartbeat
• Nervousness
• Weight loss despite adequate food
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• Mechanism of actions of thyroid
hormones
Clinical use:
1. Hypothyroidism: cretinism & myxedema;
2. simple goiter
3. Others
Adverse reactions:
Overdose leads to thyrotoxicosis and angina or MI (usually in ageds)
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Anti-thyroid drugs
Class Representative
Methimazole
Radioactive iodine I
131
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Thioamides
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Thioamides
• Methemazole is preferred over PTU because it has a longer t1/2 (given once
daily)
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Clinical use of Thioamides
• Mild hyperthyroidism and for those surgery & 131I are not permitted;
• Operation preparation
• Thyroid crisis (comprehensive therapy).
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Adverse effects of Thioamides
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Iodides (NaI, KI)
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Iodides (NaI, KI)
Clinical use
• Treatment of Thyroid Storm
Adverse reactions
• Acneiform rash
• Swollen salivary glands and mucous membrane ulcerations
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Radioactive iodine (131I)
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β-adrenoceptor blockers
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Anti-thyroid drugs
peroxidase
Perchlorates
Thiocynates.
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