REI Pharmacology

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REI Pharmacology

• Raymond W. Ke, MD
• University of Tennessee, Memphis

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Menstrual Cycle
Failure of implantation
Ovulation
Progesterone
Menses
Estradiol
Day 2
14
8
20
26
Endometrial Height
3
Cholesterol (27 carbons)
Pregnane (21 carbons)
Progesterone, Corticoids
Androstane (19 carbons)
Androgens
Estrane (18 carbons)
Estrogens
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Pharmacologic Estrogen and Progestogen

• Estrogen
• Natural hormones
• Ethinyl estradiol
• Mestranol
• Progestogen
• Natural progestins
• 17?-hydroxyprogesterone
• 19 nortestosterone

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Routes of Administration

• Oral
• Hepatic conversion
• Transdermal
• Vaginal
• Sublingual
• Parenteral

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Anti-Hormones

• Anti-estrogens
• Receptor antagonists or blockers
• SERMs
• Suppress ovarian sex hormone production
• Aromatase inhibitors
• GnRH agonists or antagonists
• Anti-progestogens
• Ru-486

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Selective Estrogen Receptor Modulator (SERMS)

• Binds to Er ? and Er ? receptors with varying
  affinities
• In order of increasing estrogen activity
• Clomiphene
• Tamoxifen
• Raloxiphene
• Bazedoxifene

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Hypothalmus

GnRH
estradiol progesterone
LH FSH
estradiol/progesterone
Ovaries
inhibin/activin
Pituitary
LH FSH
estradiol progesterone
Hypothalamic-Pituitary-Ovarian Axis

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Gonadotropin Releasing Hormone (GnRH) Agonists

• One to two amino acid substitutions in native
  decapeptide with longer and higher affinity for
  GnRH receptor
• Leads to initial flare effect followed by
  down-regulation of receptors
• Potent estrogen suppression

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Gonadotropin Releasing Hormone (GnRH) Antagonists

• Different polypeptide structure from true GnRH
• Pure antagonist of GnRH receptor
• High affinity for receptor
• Cetrotide, ganerelix

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Ovulation Induction

• Clomiphene citrate
• Letrozole
• Gonadotropin (FSH)
• Urinary
• Recombinant

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Were lost but were making good time.
Yogi Berra