Progestins and anti progesterones and actions.ppt

Progestins and anti progesterones

1. Female sex hormones:
Progesterone

2. Female sex hormones
Progestrogens
•Synthesis& secretion
•Regulation
•Pharmacological actions
•Pharmacokinetics
•Preparations
•Therapeutic uses
•Adverse effects
Anti-progestrogens
Mifepristone

3. Cholesterol
Pregnenolone
Progesterone
17-α- Hydroxy
pregnenolone
17- Hydroxy
progesterone
Dehydro-epi
androsterone
Andro-
stenedione
Oestrone
Oestriol
TESTOSTERONE
OESTRADIOL

4. LH FSH
Progesterone
Oestrogen

5. http://anatomy.iupui.edu/courses/histo_D502/D502f04/lecture.f04/Female04/cycle.jpg

6. Type Hormonal activitiesProgestOestrogenAndrogAnabolic
Progesterone derivatives
Progesterone
+ - - -
Hydroxyprogesterone Capr.
+ -
slight
-
Medroxyprogesterone acet
+ - + -
Megesterol acetate
+ - - -
Testosterone derivative
Dimethisterone slight
- - -
Nor-testosterone derivative
Norethynodrel slight
+ - -
Lynestrenol slight
+ + +
Norethindrone
+
slight
+ +
Ethynodiol diacetate
+
slight
+
Norgesterol
+ - + -

7. Pharmacokinetics
•Absorption:
•progesterone undergoes high first pass
metabolism. Therefore synthetic
preparations are more commonly used.
•Progesterone esters in oily soln. for i.m.
admn.
•Metabolism:
– by liver enzymes
–excretion by urine after conjugation

8. Progestrogen: Actions
Uterus:
 secretray changes (with oestrogen)
 If ovum is fertilized
 prepare endometrium
 oxytocin & ergonovine actions
 FSH, LH ovulation
 cervical secretion – thick and viscid
Vagina: WBC infiltration & cornified epithelium
Breast
Body temperature
Respiration
Pituitary

9. •as OCP
•DUB
•HRT
•dysmenorrhea
•premenstrual
syndrome
•endometriosis
•threatened abortion
• post-partum
lactation
•endometrial cancer
Clinical uses of Progesterones

10. Adverse effects of Progesterone
• breast engorgement, headache, rise in body temp.,
oedema, acne & mood swings
• masculinization of external genitalia in the foetus
• Increased incidences of congenital abnormalities
• irregular bleeding or amenorrhea
• lower HDL (19-nortestosterone derivatives)
• hyperglycaemia

11. Antiprogestin
Mifepristone

12. Mifepristone
•19-nor-steroid derivative
Mechanism:
• Blocks progest. &
glucocorticoid receptors
•During luteal phase:
Pregest. PGs
Menstrual bleeding
•Sensitize myocardium to PGs.
•HCG production falls
ADME:
•F: 25 %, CYP3A4 metabolism’ t½: 20 h
Uses:
•Termination of early pregnancy –
along with prostaglandin
•As a cervical ripening agent
•Post-coital contraceptive
•Once a month contraceptive
•Progesterone sensitive tumors
•Cushing’s syndrome
Side effects:
Vomiting, diarrhoea, pelvic pain or
abdominal pain, about 5% have
severe vaginal bleeding

Precaution: Not to be given to a woman with suspected ectopic
pregnancy, hematological disorders, receiving oral anticoagulants,
Liver/renal diseases