Chemistry and Formulation of Contraceptives- 22

Question 1

What are the main oestrogens

Answer 1

Oestradiol
Oestrome
Oestriol

Question 2

How are oestrogens syntheiszed

Answer 2

Starting substance is cholesterol and through hydroxylations and dehydrogenations they are synthesized.

Question 3

How are progestogens synthesised.

Answer 3

Starts with chloesterol which is hydroxylated and dehydrogenated to produce it.

Question 4

What is the mode of action of oestrogen drugs

Answer 4

Inhibits the secretion of FSH which prevents the development of a mature follicle.

Question 5

Mode of action of progestogen drugs

Answer 5

Inhibits the secretion of LH therefore preventing ovulation and thickening of cervical mucus.

Question 6

Mode of action of progesterone and oestrogen combination drugs.

Answer 6

Thinning of the endometrium which prevents the implantation of fertilised ovum.

Question 7

Advantages of oral administration of steroidal contraceptives.

Answer 7

Chemical physical and microbiological stability
Accurate dosing of the drug

For the patient-
Convenient
Reliable if taken correctly
Reversible.

Question 8

Disadvantage of oral admin of steroidal contraceptives.

Answer 8

Problem of poor bioavailability of natural oestrogens and progestogens due to unfavourable drug properties ie metabolism in the liver.

Question 9

Advantages and disadvantages of synthetic oestrogens.

Answer 9

Good absorption of natural and synthetic oestrogens in GI tract.

Extensive first pass metaolism of oestradiol in the liver.

Question 10

Disadvantages of using synthetic progestogens.

Answer 10

Virtually inactive orally, extensive first pass metabolism in the liver, short half life.

Question 11

dosage of the combined pill and examples

Answer 11

Once a day, at the same time, for 21 consecutive days followed by 7 pill-free days or inactive pills.

Norhisterone, desogestrel

Question 12

Dosage of progesterone pill and examples

Answer 12

Taken daily, at the same time without interuption.

Levonorgestrel, cerelle, cerazette

Question 13

Advantages and disadvantages of progesterone only pill.

Answer 13

Used by menstruators with contra-indications to combined pill ie cardio risks, breast feeding.

Action may alter cervical mucus, less reliable than combined pill.

Question 14

What are the two main types of contraceptives by parenteral administration.

Answer 14

Suspensions and Oily solutions.

Question 15

What is the dosage of depo-provera and whats in it.

Answer 15

Progesterone only.

Administered on a regular basis every 12 weeks.

Question 16

Advantages and disadvantages of parenteral suspensions.

Answer 16

Advantages- Slow release, long lasting effect.
Avoidance of hepatic first pass.
Can be used during breast feeding and very effective.

Disadvantages- Delayed return of fertility, risk of weight gain (up to 3kg in a year).

Question 17

What is the dose and indications for oily solution parenteral contraceptives.

Answer 17

Provides contraception for up to 8 weeks, usually used as a short term interim contraceptive for example before a partners vasectomy becomes effective.

Noristerat

Question 18

What are the two main types of transdermal contraceptives

Answer 18

Patches and Implants

Question 19

What is the dosage and examples of contraceptive patches.

Answer 19

Matrix patches, Progestogen (norelgestromin) Oestrogen (ethinylestradiol)
Application of a new patch once weekly for 3 weeks, followed by a 7 day no patch interval.

Question 20

Advantages and disadvantages of contraceptive patches.

Answer 20

Advantages- slow release and long lasting effects, avoidance of first pass, accurate dosing, very effective and convenient.

Disadvantages- both components are lipophillic, absorption affected by adiposity of the skin.

Question 21

Dosage and examples of contraceptive implants.

Answer 21

Progestogen (nexplanaon)

Consists of a single flexible rod which is inserted subdermally into the lower surface of the upper arm.

Provides contraception for up to 3 years.

Question 22

Advantages and disadvantages of the implant.

Answer 22

Slow release and long lasting effects.
Avoidance of first pass metabolism
Reversible

Local reactions(itching)
Weight Gain
Headache and acne

Question 23

Examples and dosage of vaginal administration.

Answer 23

Oestrogen: ethinylestradiol
* Progestogen: etonogestrel (NuvaRing®)

• Silicone ring, with drugs implanted to the core of the ring released slowly
• The ring releases a lower dose of oestradiol compared to pills (15µg oestradiol compared to 20-25 µg in oral pills)
• Insertion of ring in the vagina on Day 1 of the cycle, for 3 weeks, followed by a 7-day ring-free interval

Question 24

Advantages and disadvantages of vaginal administration

Answer 24

Slow release and long lasting effects.
avoidance of first pass metabolism.

Discomfort

Question 25

Dosage and examples of intra uterine administration.

Answer 25

Progestogen: Levonogestrel (Mirena®)

• Releases the drug directly into the uterine cavity
• Use as a contraceptive for the treatment of heavy menstrual periods
• Effective for 5 years

Question 26

Advantages and disadvantages of intrauterine administration.

Answer 26

Advantages:
* Local contraceptive effect
* Rapid return to fertility after removal
* Very effective and convenient
* Reduces blood loss and dysmenorrhoea
* Does not significantly interact with other drugs (local action)

Disadvantages:
* Menstrual irregularities (amenorrhoea, light bleeding)
* Progestogenic side-effects
* Need for fitting (larger than normal IUCDs, may require cervical dilatation with local anesthesia)