23 Chemistry and formulation of contraceptives

Question 1

where do peptides come from

Answer 1

hypothalamus

Question 2

where do glycoprotein gonadotrophin come from

Answer 2

the anterior pituitary

Question 3

where do sex steroids come from

Answer 3

the gonads

Question 4

action of gonadotrophin releasing hormone (GnRH) in follicular phase

Answer 4

• stimulation of anterior pituitary
• release of gonadotrophic hormones: FSH and LH

Question 5

action of FSH and LH in ovaries in the follicular phase

Answer 5

• development of the follicle which contains and ovum and secretes oestrogen
• oestrogen is responsible for regeneration of endometrium

Question 6

what happens before mid cycle

Answer 6

• high oestrogen secretion
• sensitisation of LH-releasing cells to action GnRH
• mid cycle increase of LH
• rupture of follicle
• ovulation

Question 7

what does stimulation by LH cause in luteal phase

Answer 7

• formation of corpus luteum from ruptured follicle (produces oestrogen and progesterone)
• negative feedback exerted by progesterone on hypothalamus
• decrease of the release of LH

Question 8

what does progesterone do to the endometrium in the luteal phase

Answer 8

make it suitable for implantation of a fertilised ovum

Question 9

what does fall in oestrogen and progesterone in the luteal phase cause

Answer 9

• degeneration of the endometrium
• menstruation

Question 10

what synthesises oestrogen

Answer 10

the ovaries and placenta

Question 11

what does oestrogen come from

Answer 11

cholesterol

Question 12

how do you go from cholesterol to oestrogen

Answer 12

hydroxylations and dehydrogenations

Question 13

what are the main oestrogens

Answer 13

• oestradiol
• oestrome
• estriol

Question 14

what secreted progestogens

Answer 14

corpus luteum and placenta

Question 15

what does progestogen start as

Answer 15

cholesterol

Question 16

how do you go from cholesterol to progestogen

Answer 16

successive hydroxylations and dehydrogenations

Question 17

what is the main progestogen

Answer 17

progesterone

Question 18

what does oestrogen do on its own in contraceptives

Answer 18

inhibit FSH secretion which suppresses development of ovarian follicle

Question 19

what does progestogen on its own do as a contraceptive

Answer 19

inhibit secretion of LH which causes inhibition of ovulation and thickening of cervical mucus

Question 20

what do oestrogen and progestogen combined do in contraception

Answer 20

thinning of the endometrium which prevents the implantation of fertilised ovum

Question 21

advantages of pill form

Answer 21

• chemical, physical and microbiological stability
• accurate dosing
• convenient
• reliable
• reversible

Question 22

disadvantages of pill form

Answer 22

• poor bioavailability of natural oestrogens and progestogens due to unfavourable drug properties

Question 23

is there good absorption of natural and synthetic oestrogens in the GI

Answer 23

yes, but extensive first pass metabolise of estradiol in the liver

Question 24

does progesterone undergo FPM

Answer 24

yes

Question 25

advantage of progestogen only pill

Answer 25

used by menstruates with contra-indications to the combined pill (ie breast feeding)

Question 26

disadvantages of progestogen only pill

Answer 26

- action mainly on alteration of cervical mucus (more viscous and impenetrable to sperm) - ovulation is inhibited in only around 60% of cycles

Question 27

what's in parenteral injection suspensions

Answer 27

long acting progestogen in an aqueous suspension given IM

Question 28

does parenteral injection suspensions work as well as combined oral pill

Answer 28

yes

Question 29

advantages of parenteral injection suspensions

Answer 29

- slow release and long effect - avoids FPM - accurate dosing - effective & convenient - can be used during breast feeding

Question 30

disadvantages of parenteral suspensions administration

Answer 30

- delayed return of fertility - risk of weight gain

Question 31

formulation of parenteral oily solution

Answer 31

long acting progestogen given as an oily injection (IM)

Question 32

how long does parenteral oily injection last

Answer 32

8 weeks, used as short term contraception

Question 33

advantages of transdermal patch form

Answer 33

- slow release and long effect - avoids FPM - accurate dosing - oestrogen remains steady without peak and drops associated with oral administration - effective and convenient

Question 34

disadvantages of transdermal patch form

Answer 34

- both components are lipophillic so absorption affected by adiposity of skin

Question 35

advantages of implant

Answer 35

- slow release and long lasting - avoids FPM - effective and convenient - reversible

Question 36

disadvantages of implant

Answer 36

- local reactions - weight gain - headache and acne

Question 37

how does the ring work

Answer 37

releases a low does of oestradiol, drugs implanted in core of ring and slowly released

Question 38

advantages of ring

Answer 38

- slow release and long effect - avoids FPM

Question 39

disadvantages of ring

Answer 39

- discomfort

Question 40

advantages of IUD

Answer 40

- local contraceptive effect - rapid return to fertility - effective and convenient - reduces blood loss and cramps - doesn't interact with other drugs significantly

Question 41

disadvantages of IUD

Answer 41

- menstrual irregularities - progestognenic side effects - need for fitting