23 Chemistry and formulation of contraceptives Flashcards
where do peptides come from
hypothalamus
where do glycoprotein gonadotrophin come from
the anterior pituitary
where do sex steroids come from
the gonads
action of gonadotrophin releasing hormone (GnRH) in follicular phase
- stimulation of anterior pituitary
- release of gonadotrophic hormones: FSH and LH
action of FSH and LH in ovaries in the follicular phase
- development of the follicle which contains and ovum and secretes oestrogen
- oestrogen is responsible for regeneration of endometrium
what happens before mid cycle
- high oestrogen secretion
- sensitisation of LH-releasing cells to action GnRH
- mid cycle increase of LH
- rupture of follicle
- ovulation
what does stimulation by LH cause in luteal phase
- formation of corpus luteum from ruptured follicle (produces oestrogen and progesterone)
- negative feedback exerted by progesterone on hypothalamus
- decrease of the release of LH
what does progesterone do to the endometrium in the luteal phase
make it suitable for implantation of a fertilised ovum
what does fall in oestrogen and progesterone in the luteal phase cause
- degeneration of the endometrium
- menstruation
what synthesises oestrogen
the ovaries and placenta
what does oestrogen come from
cholesterol
how do you go from cholesterol to oestrogen
hydroxylations and dehydrogenations
what are the main oestrogens
- oestradiol
- oestrome
- estriol
what secreted progestogens
corpus luteum and placenta
what does progestogen start as
cholesterol
how do you go from cholesterol to progestogen
successive hydroxylations and dehydrogenations
what is the main progestogen
progesterone
what does oestrogen do on its own in contraceptives
inhibit FSH secretion which suppresses development of ovarian follicle
what does progestogen on its own do as a contraceptive
inhibit secretion of LH which causes inhibition of ovulation and thickening of cervical mucus
what do oestrogen and progestogen combined do in contraception
thinning of the endometrium which prevents the implantation of fertilised ovum
advantages of pill form
- chemical, physical and microbiological stability
- accurate dosing
- convenient
- reliable
- reversible
disadvantages of pill form
- poor bioavailability of natural oestrogens and progestogens due to unfavourable drug properties
is there good absorption of natural and synthetic oestrogens in the GI
yes, but extensive first pass metabolise of estradiol in the liver
does progesterone undergo FPM
yes
advantage of progestogen only pill
used by menstruates with contra-indications to the combined pill (ie breast feeding)
disadvantages of progestogen only pill
- action mainly on alteration of cervical mucus (more viscous and impenetrable to sperm)
- ovulation is inhibited in only around 60% of cycles
what’s in parenteral injection suspensions
long acting progestogen in an aqueous suspension given IM
does parenteral injection suspensions work as well as combined oral pill
yes
advantages of parenteral injection suspensions
- slow release and long effect
- avoids FPM
- accurate dosing
- effective & convenient
- can be used during breast feeding
disadvantages of parenteral suspensions administration
- delayed return of fertility
- risk of weight gain
formulation of parenteral oily solution
long acting progestogen given as an oily injection (IM)
how long does parenteral oily injection last
8 weeks, used as short term contraception
advantages of transdermal patch form
- slow release and long effect
- avoids FPM
- accurate dosing
- oestrogen remains steady without peak and drops associated with oral administration
- effective and convenient
disadvantages of transdermal patch form
- both components are lipophillic so absorption affected by adiposity of skin
advantages of implant
- slow release and long lasting
- avoids FPM
- effective and convenient
- reversible
disadvantages of implant
- local reactions
- weight gain
- headache and acne
how does the ring work
releases a low does of oestradiol, drugs implanted in core of ring and slowly released
advantages of ring
- slow release and long effect
- avoids FPM
disadvantages of ring
- discomfort
advantages of IUD
- local contraceptive effect
- rapid return to fertility
- effective and convenient
- reduces blood loss and cramps
- doesn’t interact with other drugs significantly
disadvantages of IUD
- menstrual irregularities
- progestognenic side effects
- need for fitting
