Review of Pharmacology - 9E (2015)

Review of Pharmacology
Generation Examples Properties
1st Generation
(Estranes)
2nd Generation
(Gonanes)
3rd Generation
4th Generation
Norethindrone
Norethinodrel
Lynestrenol
Norgestrel
Levonorgestrel
Desogestrel
Norgestimate
Gestodene
Nomegestrol
Drospirenone
• Have weak estrogenic, androgenic and anabolic action
• Potent antiovulatory properties
• More potent than 1st generation
• Have reduced androgenic activity
• Levonorgestrel is more potent than norgestrel
• Very potent
• strong antiovulatory properties
• Reduced androgenic effects; thus
– ↓ risk of acne
– ↓ hirsutism
• Weak anti-androgenic property
• Less anti-ovulatory
• Strong antiestrogenic effects on endometrium
• Donot cause adverse effect on lipid profile or glucose
tolerance
• Drospirenone possess aldosterone receptor antagonistic
activity; preferred in woman who have fluid retention after
taking OCPs
Endocrinology
Actions
• Progesterone increases basal insulin levels and the insulin response to glucose.
• These can act as competitors of aldosterone causing decrease in Na + reabsorption.
• Progesterone increases LDL and opposes beneficial effect of estrogen on lipid profile.
• It has depressant effect on the brain.
• It causes growth of breast tissue and also participates in LH surge.
• Progestins decrease the chances of endometrial carcinoma and are added to HRT
to decrease this adverse effect of estrogens.
• Third generation agents are also known as impeded androgens because they lack
androgenic activity.
Uses
Major indications of progesterone are for oral contraception and hormone replacement
therapy, for which these are combined with estrogens. Progestins are added to decrease
the risk of endometrial and ovarian carcinoma. Progestins are also used for secondary
amenorrhea, abnormal uterine bleeding, premature labour and luteal phase support to treat
infertility.
Selective Progesterone Receptor Modulator (sprm)
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Uses of mifepristone
M – Morning after pill
I – Induction of abortion
F – Fibroid
E – Endometriosis
P – Progesterone receptor
R – +ve breast cancer and
meningioma
I – Increased steroids
S – (Cushing)
tone
Mifepristone, onapristone, ulipristal and asoprisnil are the drugs affecting progesterone
receptors.
• Mifepristone is a SPRM with mainly antagonistic activity and some agonistic
activity on progesterone receptors. It also has glucocorticoid and androgen
receptor blocking activity. It has a long t 1/2
of 20 hours. its uses are:
––
Medical termination of pregnancy: Oral dose of 600 mg mifepristone with
oral misoprostol (400 µg) effectively terminates pregnancy upto 49 days in
95% of patients. Most severe adverse effect is vaginal bleeding. Recently, low
dose mifepristone (200 mg) with oral misoprostol (800 µg) is indicated for termination
of pregnancy upto 63 days.
––
Single 600 mg dose is an effective emergency contraceptive.
––
It is recommended for treatment of cushing's syndrome for patients with
ectopic ACTH secretion or adrenal inoperable carcinoma who failed to
respond to other treatments.
––
Other potential uses include endometriosis, breast cancer, meningioma
(containing glucocorticoid or progesterone receptors), and fibroids.
• Onapristone is a pure progesterone antagonist in contrast to mifepristone.
Contd...
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