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Oral contraceptives

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An all round solution to whatever you want to know about oral contraceptives.

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Oral contraceptives

  1. 1. ORAL CONTRACEPTIVES ANKIT A. GILANI DEPT. OF PHARMACOLOGY AND TOXICOLOGY SEMISTER-2 NIPER AHMEDABAD (NIPERA1113PC03)
  2. 2. Definition Oral contraceptives are medicines taken by mouth to help prevent pregnancy. They are also known as “birth control pills”.
  3. 3. FROM FERTILIZATION TO IMPLANTATION
  4. 4. TYPES THETHE COMBINED PROGESTOGEN- PILL ONLY PILL
  5. 5. 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); or3. Triphasic (the amount of estrogen may be fixed or variable, while the amount of progestin increases in 3 equal phases).
  6. 6. The combined pill (combinations of an oestrogen with a progestogen) 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 third- generation 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 thromboembolism than do second- generation preparations.
  7. 7. The combined pill 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.
  8. 8. 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.
  9. 9. Negativefeed back
  10. 10. 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.
  11. 11. POTENTIAL ADVERSE 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.
  12. 12. POTENTIAL ADVERSE EFFECTS 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. [Note: The potent progestin norgestrel causes the greatest increase in the LDL:HDL ratio. Therefore, estrogen-dominant preparations are best for individuals with elevated serum cholesterol.]
  13. 13. 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.
  14. 14. The progestogen-only pill The drugs used in progestogen- only pills include norethisterone, levonorgestrel or ethynodiol. The pill is taken daily without interruption.
  15. 15. 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
  16. 16. 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.
  17. 17. Pharmacokinetics of oralcontraceptives 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.
  18. 18. Broad-spectrum antibiotics such as amoxicillin candisturb Enterohepatic recycling by altering theintestinal flora, and cause failure of the combinedpill. This does not occur with progesterone-onlypills.
  19. 19. 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.
  20. 20. 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.
  21. 21.  From Fertilization to Implantation Figure 1 (click to enlarge) To understand and evaluate chemical methods of birth control, it is helpful to have a basic grasp of the mechanism and timing of the biological events that bring a new human life into the world. (For more complete coverage of this topic see the DVD Fearfully and Wonderfully Made.) About every 28 days, a woman with a normal menstrual cycle will release an egg (occasionally more than one) from her ovary (see Figure 1). This process, called “ovulation,” is under the control of hormones produced in the pituitary and ovary. Once ejected from the ovary, the egg enters a tube called the “oviduct” (or “fallopian tube”) which transports the egg to the uterus. If fertilization occurs, it normally occurs in the first third of the oviduct and typically within 12 to 24 hours after ovulation. Fertilization is completed when the genetic material of male germ cell (the sperm) combines with genetic material of the female germ cell (the egg)—a momentous event called “conception.” After fertilization, the fertilized egg (now called a “zygote”) continues on its passage toward the uterus, where it will arrive about three days from the time of ovulation. Along the way the zygote will divide a few times to produce a ball of cells called a “morula” (see Figure 1). Once in the uterus the morula continues to divide and by the fifth day becomes a hollow ball of cells called a “blastocyst,” which contains the embryo (an outer layer of cells will form the placenta). By about the sixth day, the blastocyst burrows into the wall of the uterus, a process called “implantation,” and here it will continue to grow. During the first two months of development after fertilization, the developing baby is called an “embryo” (later in development called a “fetus”). Despite all the name changes, the whole process from fertilization to birth is a continuous and marvelously complex development of a human baby.
  22. 22.  Major adverse effects: The major adverse effects are breast fullness, depression, fluid retention, headache, nausea, and vomiting. 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. 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. [Note: The potent progestin norgestrel causes the greatest increase in the LDL:HDL ratio. Therefore, estrogen-dominant preparations are best for individuals with elevated serum cholesterol.] Contraindications: Oral contraceptives are contraindicated in the presence of cerebrovascular and thromboembolic disease, estrogen-dependent neoplasms, liver disease, and pregnancy. Combination oral contraceptives should not be used in patients over the age of 35 who are heavy smokers.
  23. 23.  The endometrium slowly gets built up before ovulation (the proliferative phase) and then reaches its peak in the secretory phase (shortly after ovulation{and conception if it has occurred}). The endometrium is "ready for the newly conceived child to implant" when it reaches its peak in the secretory phase a few days after ovulation. We note that the blood flow and thus the oxygen and nutrients to the glandular cells of the endometrium increases through the cycle as the spiral arteries enlarge during the secretory phase. The size of the endometrial glands also enlarge in the secretory phase. The glands contain important nutritional building blocks for the unborn child who is about to implant, including glycogen (a type of sugar), mucopolysaccharides (ie, they supply certain building blocks for a cells growth) and lipids (fats) 5.

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