ORAL CONTRACEPTIVES

1. ADITYA INSTITUTE OF PHARMACY
(DEPARTMENT OF PHARMACOLOGY)
ADVANCED PHARMACOLOGYAND TOXICOLOGY
TOPIC ON
ORAL CONTRCEPTIVES
SUBMITTED TO :DR N VENKATESAN
SUBMITTED BY :RAJESH YADAV

2. History of Oral Contraceptives
• 1937- discovery of effects of progesterone on
ovulation
• 1940’s- Russell Marker isolates progesterone from
Mexican yams
• 1951- Luis Miramontes synthesizes 1st progestin
• 1960- FDA approves “the pill”
• 1963- 1st oral contraceptive put on drug market
• 1965- number one form of birth control
• Late 1970’s- FDA mandated warning that indicated
oral contraceptives carried risks of cancer and blood
clots

3. Definition
• Oral contraceptives are medicines taken by mouth to help
prevent pregnancy.
• They are also known as “birth control pills”.
• Birth control pills (oral contraceptives) are prescription
medications that prevent pregnancy.
• Birth control(contraceptive) medications contain hormones
(estrogen and progesterone, or progesterone alone).
• Birth control pills may also be prescribed to reduce menstrual
cramps or prevent anemia.
• Some women experience various levels of side effects of birth
control pills.

4. How birth control medications works
Hormonal birth control medications prevent pregnancythrough the following
ways:
• By blocking ovulation(release of an egg from the ovaries), thus preventing
pregnancy
• By altering mucus in the cervix, which makes it hard for sperm to travel
further
• By changing the endometrium (lining of the uterus) so that it cannot
support a fertilized egg
• By altering the fallopian tubes (the tubes through which eggs move from
the ovaries to the uterus) so that they cannot effectively move eggs toward
the uterus

5. General mechanism of action
All formulations act on other areas of the reproductive tract by
altering the following:
• Cervical mucus: making it viscid, thick, and scanty, thus
preventing sperm penetration and inhibiting capacitation of the
sperm.
• Decreasing motility of the uterus and oviduct thus inhibiting
ova and sperm transport.
• Diminishing endometrial glandular production of glycogen
making less energy available for the blastocyst to survive in
the uterine cavity.
• Decreasing ovarian responsiveness to gonadotropin
stimulation.

6. TYPES
• THE COMBINED PILL
• THE PROGESTOGENONLY PILL

7. ORAL CONTRACEPTIVE PILL TYPES,
FORMULATIONS, AND PILL-USE PATTERNS
A. There are two types of oral contraceptives:
1. Combined oral contraceptives (COCs), which contain
an estrogen and a progestin
2. Progestin-only contraceptives (POPs), which contain
a progestin but no estrogen. This pill is often
referred to as “the minipill”

8. B. Combined oral contraceptives are available in
2 basic formulations:
1. The monophasic formulation, in which each
active pill contains the same doses of estrogen
and progestin.
2. The multiphasic formulations can have
varying amounts of estrogen and/or progestin
in the active pills.

9. C. There are multiple different patterns of combined oral
contraceptive pill use that are options
• 1. 28-Day Cycling – Most pill packs have 21 active hormone
pills and 7 inactive (placebo) pills.
• 2. Shortened pill-free interval – Starting the new pack of pills
on the first day of menstruation usually decreases the pill-free
interval thus allowing less time for a new follicle to develop.
Pill-free interval should not be more than 7 days.

10. 3. Extended regimens
• There is no biological reason to have monthly
withdrawal bleeding on oral contraception.
• There are multiple extended regimens, and there are
some pills that are formulated and packaged
specifically for this type of extended regimen.
• If a client chooses an extended regimen, a
monophasic, combined oral contraceptives must be
used.
• Extended regimens in one form or another provide
options for women who need to control the timing of
their bleeding or have severe symptoms when
bleeding.

11. All clients using extended regimens have the potential for breakthrough
bleeding and must be counseled as such.
a. Bi-Cycling – Skipping the placebo pills at the end of every other pack of
pills yields one period after 6 weeks of active pills.
b. Tri-Cycling – Skipping the placebo pills at the end of 2 out of every 3
packs of pills yields one period after 9 weeks of active pills.
c. Other Extended Regimens (e.g. Seasonale) - COCs may be packaged by
manufacturers as extended regimens. Seasonale, for example, has 84
active pills followed by 7 inactive pills. The progestin and estrogen are
the same as Nordette.
d. Continuous – The client takes only active pills daily continuously.
Breakthrough bleeding will occur.
• D. The progestin-only contraceptive pill is taken every day without
interruption.

12. • The combined pill (combinations of an oestrogen with a
progestogen)
Formulations may be :
1. Monophasic (each tablet contains a fixed amount of estrogen
and progestin).
2. Biphasic (each tablet contains a fixed amount of estrogen,
while the amount of progestin increases in the second half of
the cycle).
3. Triphasic (the amount of estrogen may be fixed or variable,
while the amount of progestin increases in 3 equal phases).

13. • The oestrogen in most combined preparations
(second-generation pills) is ethinylestradiol, although
a few preparations contain mestranol instead.
• The progestogen may be norethisterone,
levonorgestrel, ethynodiol, or-in 'thirdgeneration'
pills-desogestrel or gestodene, which are more potent,
have less androgenic action and cause less change in
lipoprotein metabolism, but which probably cause a
greater risk of thrombo embolism than do
secondgeneration preparations.

14. • The oestrogen content is generally 20-50μg of
ethinylestradiol or its equivalent, and a preparation is
chosen with the lowest oestrogen and progestogen
content that is well tolerated and gives good cycle
control in the individual woman.
• This combined pill is taken for 21 consecutive days
followed by 7 pill-free days, which causes a
withdrawal bleed. Normal cycles of menstruation
usually commence fairly soon after discontinuing
treatment.

15. Mode of action
• Oestrogen inhibits secretion of FSH via negative feedback on
the anterior pituitary, and thus suppresses development of the
ovarian follicle
• Progestogen inhibits secretion of LH and thus prevents
ovulation; it also makes the cervical mucus less suitable for the
passage of sperm
• Oestrogen and progestogen act in concert to alter the
endometrium in such a way as to discourage implantation.
• They may also interfere with the coordinated contractions of
cervix, uterus and fallopian tubes that facilitate fertilisation
and implantation.

16. Common adverse effects
• Weight gain, owing to fluid retention or an anabolic
effect, or both.
• Mild nausea, flushing, dizziness, depression or
irritability
• Skin changes (e.g. acne and/or an increase in
pigmentation)
• Amenorrhoea of variable duration on cessation of
taking the pill.

17. POTENTIALADVERSE EFFECTS
• Cardiovascular: Although rare, the most serious adverse effect of oral
contraceptives is cardiovascular disease, including thromboembolism,
thrombophlebitis, hypertension, increased incidence of myocardial
infarction, and cerebral and coronary thrombosis. These adverse effects are
most common among women who smoke and who are older than 35 years,
although they may affect women of any age.
• Carcinogenicity: Oral contraceptives have been shown to decrease the
incidence of endometrial and ovarian cancer. Their ability to induce other
neoplasms is controversial. The production of benign tumors of the liver
that may rupture and hemorrhage is rare.

18. • Metabolic: Abnormal glucose tolerance (similar to the
changes seen in pregnancy) is sometimes associated with oral
contraceptives. Weight gain is common in women who are
taking the nortestosterone derivatives.
• Serum lipids: The combination pill causes a change in the
serum lipoprotein profile: Estrogen causes an increase in HDL
and a decrease in LDL (a desirable occurrence), whereas
progestins may negate some of the beneficial effects of
estrogen.

19. Beneficial effects
• The combined pill markedly decreases
menstrual symptoms such as irregular periods
and intermenstrual bleeding.
• Iron deficiency anaemia and premenstrual
tension are reduced, as are benign breast
disease, uterine fibroids and functional cysts of
the ovaries.

20. The progestogen-only pill
• The drugs used in progestogenonly pills
include norethisterone, levonorgestrel or
ethynodiol.
• The pill is taken daily without interruption.

21. Mode of action
• The mode of action is primarily on the cervical
mucus, which is made inhospitable to sperm.
• The progestogen probably also hinders
implantation through its effect on the
endometrium and on the motility and
secretions of the fallopian tubes

22. Potential beneficial and unwanted effects
• Progestogen-only contraceptives offer a suitable alternative to
the combined pill for some women in whom oestrogen is
contraindicated, and are suitable for women whose blood
pressure increases unacceptably during treatment with
oestrogen.
• However, their contraceptive effect is less reliable than that of
the combination pill, and missing a dose may result in
conception.
• Disturbances of menstruation (especially irregular bleeding)
are common.

23. POSTCOITAL (EMERGENCY) CONTRACEPTION
• Oral administration of levonorgestrel, alone (1.50 mg
usually) or combined with oestrogen, is effective if
taken within 72 hours of unprotected intercourse,
repeated 12 hours later.
• Nausea and vomiting are common. (replacement
tablets can be taken with an antiemetic such as
domperidone).
• A single dose of mifepristone has also been used for
emergency contraception

24. Ormeloxifene
• Ormeloxifene is a selective estrogen receptor
modulator (SERM).
• Marketed as Centchroman, Centron, or Saheli, it is
pill that is taken once per week.
• Ormeloxifene is legally available only in India.

25. Pharmacokinetics of oral contraceptives
• Combined and progestogen-only oral contraceptives are
metabolised by hepatic cytochrome P450 enzymes.
• Because the minimum effective dose of oestrogen is used (in
order to avoid excess risk of thromboembolism), any increase
in its clearance may result in contraceptive failure, and indeed
enzyme-inducing drugs can have this effect not only for
combined but also for progesterone-only pills.
• Such drugs include rifampicin and rifabutin, as well as
carbamazepine, phenytoin, griseofulvin and others.

26. • Broad-spectrum antibiotics such as amoxicillin
can disturb Enterohepatic recycling by
altering the intestinal flora, and cause failure of
the combined pill.
• This does not occur with progesterone-only
pills.

27. …….THANK YOU…….