Contraceptive

مادة االدوية –المرحلة الثالثة: د. عماد نعمان شريف • • Objective :- • - Know the contraceptive drugs types and how to uses..- • - Know the pharmacokinetic, pharmacodynamic , indication, side effect, contraindication for contraceptive drugs.

• Male contraceptive classification: • Possible modes and sites of action: • 1- Direct inhibition of spermatogenesis: This presents many problems including the lag in onset of effect due to storage of mature spermatozoa until they are ejaculated or die from old age. • 2- Indirect inhibition of spermatogenesis by suppression of hypothalamus-pituitary activity, which control it, ex. by - combination; gonadorelin. • 3- Immunological techniques (vaccines): To induce antibodies to pituitary gonadotropins, sperm. • 4- Use of condoms. • 5- Vasectomy is a surgical procedure for male sterilization and/or permanent birth control. • 6- Vas-occlusive contraception consists of partially or completely blocking the vas deferens. • 7- Pharmacological drugs are : • - Risug (reversible inhibition of sperm under guidance)/vasal gel consists of injecting a polymer styrene maleic anhydride into the vas deferens. The polymer has a positive charge, and when negatively charged sperm pass through the vas deferens, the charge differential severely damages the sperm. • - channel blockers such as nifedipine may cause reversible infertility may cause reversible infertility by altering the lipid metabolism of sperm so that they are not able to fertilize an egg. • - Injections of depo-provera to prevent spermatogenesis. • - Phenoxybenzamine has been found to block ejaculation. • - Silodosin, an alpha 1-adrenoreceptor antagonist with high uroselectivity, has been shown to completely block ejaculation in human males while permitting the sensation of orgasm. • - : Is anabolic that has been show to significantly reduce sperm count. • Female contraceptive: • Possible modes and sites of action: • 1- Inhibition of ovulation present as different and easier biological problem. • 2- Prevention of fertilization: By altering cervical mucus or fallopian tube function. • 3- Antizygotic drugs: Compounds effective in the rate have been developed. • 4- Inhibition of implantation. • 5- Use of spermicidal in the vagina (in combination with barrier methods). This is strictly chemical rather than hormonal contraception, as also are intrauterine devices that contain copper, which is gametocidal. • 6- Immunological techniques (vaccines): To induce antibodies to pituitary gonadotropins, sperm or other components of the reproductive process in either sex, these are being developed. • There are numerous contraceptives classification available to women, some with greater protection from pregnancy than others. • 1- Birth Control Pills: • Take a birth control pills daily to prevent pregnancy. The pills are made up of hormones, and there are two types of pills: Combination pill (containing estrogen and progestin) or progestin-only pill. if a woman takes birth control pills as prescribed (every day), this form of contraception is 99 percent effective. • 2- Hormone Shots: • There are two types of birth control shots. The shot used is called Depo-Provera, or DPMA. • DPMA shot is given every 3 months, which many women find much more convenient than taking a daily pills. The shot works in the same way that birth control pills do. Also like pills, the DPMA shot is 99 percent effective. The other type of birth control shot is called Lunelle, which protects from pregnancy for up to a month, instead of three. • 3- Ring: • The ring is also known as a vaginal ring, or by its brand name, NuvaRing. The vaginal ring is flexible, and is inserted into the vagina, where it sites against the vaginal wall. The ring contains the hormones estrogen and and releases them into the body. The ring should stay inserted for 3 weeks, then removed for the week of your period. After, insert a new one. It is 99 percent effective when used properly. • 4- Patch: • The patch, also known by brand name Ortho Evra, is placed on the skin of the lower abdomen and, like the ring, releases estrogen and progestin into the body, working as a birth control method the same way that the ring does. The wearing the patch for 3 weeks before removing it in order to have a period. Then, a new patch is placed back on the skin. It is 99 percent effective in preventing pregnancy. • 5- Barrier Methods: • The barrier methods include the female condom, diaphragm, cervical cap and the sponge. All of the barrier methods are designed to prevent sperm from getting past the cervix. The female condom lines the vaginal walls, the diaphragm and cervical cap are cup-shaped latex devices that cover the cervix. The sponge also covers the cervix, but contains spermicidal to help kill the sperm. Spermicidal should also be added with use of the diaphragm, cervical cap and female condom. Barrier methods have an average effectiveness rate of 85 percent. • 6- Implantation: • Implantation devices include the IUD or the rod. Unlike other forms of contraception, implantation devices do not prevent sperm from passing the cervix, The IUD is a T-shaped device implanted into the uterus. One type releases copper, which prevents the sperm from fertilizing the egg. If the egg does become fertilized, it is prevented from implanting into the uterine wall. The other type of IUD releases progestin, which works like the hormonal contraceptives above. The rod is implanted into the arm, and it also releases progestin. Both the rod and IUD are 99 percent effective. • = Oral contraceptive are ease of use, high efficacy rate, and not interfere with sex. • Combined contraceptives (OC) pill: • Combined estrogen-progestogen oral contraceptive is conveniently started on the first day of the cycle (first day of menstruation) and continued for 21 days (this is immediately effective, inhibition the first ovulation) it followed by a period of 7 days when no pill is taken, and during which bleeding usually occurs. Thereafter, regardless of bleeding a new 21-day occurs is begun, and so on, and should be take the same time daily. • It preferred in most women because: • * Are controlled by the women. • * Can be stopped at any time without a providers help. • * Do not interfere with sex. • Progestogen: • Progestogen-only pill (POP) are indicated where estrogen is contraindicated and in lactating women. It is taken daily continuously without any gap. It is contains 75microgram inhibit ovulation in 97- 99% of cycles. • Injectable contraception: = • - progesterone only injectable contraceptive: The two widely used hormonal preparations are depomedroxy progesterone acetate (DMPA) and enanthate (NET-EN) which must be injected every 2-3 months. These are depot preparations given by deep intramuscular injections. • DMPA: It is administered at a dose of 150mg every three months. It is available in both intramuscular and subcutaneous injection formulation. Following IM injection, there is an initial rise of progestin delivery into the blood stream • NET-EN: It is highly effective when given at a dose of 200mg every 60 ± 14 days to minimize the contraceptive protection. The mechanism of it is exerted at the central neuroendocrine and peripheral target organ levels. • The most side effect: • 1- It is complete disruption of menstrual bleeding pattern • 2- Total amenorrhoea. • 3- Return of fertility may take 6-30 months. • 4- After discontinuation, permanent sterility may occur in some women. • 5- Weight gain and headache occur in > 5% . • 6- Bone mineral density may decrease in long term users due to low estrogen levels caused by gonadotropin suppression and predispose patients to osteoporosis and /or fracture.. • = Postcoital contraceptive: • - : 0.5 mg + 100microgram ethinyl taken orally as early as possible, within 72 hours of unprotected intercourse and repeated after 12 hours. This regimens is called as Yuzpe method and is losing its property as nearly 50% women experience nausea and 20% are unable to tolerate the vomiting. • - Levonorgestrel alone: 0.75mg taken twice with 12hours gap within 72hours of intercourse is very effective in preventing unwanted pregnancy. • - 1.5mg levonorgestrel one time dose within 120hours of intercourse. • - : a 10mg single dose taken within 120 hours of intercourse. • Mechanism of action of contraceptive: • Estrogen and progestin in combination or alone prevents ovulation conception in following ways: • 1- Estrogen inhibits the release of FSH from pituitary, thus suppressing the folliculogenesis in ovaries. • 2- Progesterone inhibits the LH secretion and prevents ovulation when combination pill is used both FSH and LH are reduced and the midcycle surge is abolished. As a results follicles fail to rupture. • 3- Progesterone in addition also thickens the cervical mucus so that sperm cannot pass through it. • 4- Both estrogen and progestin when used alone or in combination makes the lining of the uterus to become thinner so that it will be harder for a fertilized egg to embed there. • 5- Emergency contraception or postcoital pill acts by preventing fertilization and implantation. • Adverse effect of contraceptive: Most of them is dose dependent and were more common with high older generation of oral contraceptive pills. The recent low dose pills are relatively safe and have minimal side effects. • Minor: • - Nausea, rarely vomiting. • - Weight gain. • - Discomfort in breast. • - Headache. • - Migraine may be precipitate. • * Change in bleeding patterns including: • - frequent bleeding. • - irregular bleeding. • - infrequent bleeding. • - prolong bleeding. • - no monthly bleeding. • - Chloasma or pigmentation over check, nose and forehead similar to that occurring during pregnancy. • - Impair glucose tolerance leading to development of diabetes in few cases. • - Mood swings more so with progesterone containing pills. • Major: • - Hypertension: 5-10% women using high dose OC pills . This effect due to increase in plasma angiotensinogen level and rennin activity which induces salt and water retention. Blood pressure returns to normal within 3-6 months of stopping therapy. • - Leg vein and pulmonary thrombosis: The estrogens increase the coagulability of blood and are seen more with higher dose estrogen pills. The risk more in obese and smokers. • - Coronary and cerebral infarction: The risk of fatal or nonfatal myocardial infarction is two to five times higher and that of stroke is two to ten time higher in women using OC pills. The estrogen are mainly responsible for this adverse effect as they: • a- decrease antithrombin 111 and plasminogen activator in endothelium. • b- increase platelet aggregation. • c- enhance the coagulability of blood. • - Gallstones. • Contraindication of contraceptive: • = Absolute include:- • 1- A person history of thromboembolic venous, arterial or cardiac disease, coronary artery disease, and myocardial infarction. • 2- Hypertension. • 3- Active liver disease or history of jaundice. • 4- Carcinoma of reproductive tract. • 5- Known or suspected breast carcinoma. • 6- undiagnosed of vaginal bleeding. • 7- Porphyria. • = Relative contraindication or uses with caution, include:- • 1- Family history of venous thromboembolism, arterial disease or a known prothrombotic condition. • 2- Diabetic mellitus, which may be precipitated or become more difficult to control (avoid if there are diabetic complication). • 3- Smoking more than 40 cigarettes per day. • 4- Hypertension (avoid if blood pressure exceeds 160/100mmHg). • 5- Obesity (avoid if body mass index exceeds 39kg/m2). • 6- Gall bladder disease. • 7- Fibroids in uterus. • Oral contraceptive interaction: • Oral contraceptive interact with many drugs as follows: • - Antibiotics (erythromycin, griseofulvin, penicillins, rifampin, tetracyclines). May be decrease oral contraceptive effectiveness. • - Anticonvulsants (carbamazepine, felbamate, Phenobarbital, , primidone). Decrease oral contraceptive action due to increased metabolism of hormones. • - Antifungal (fluconazole, itraconazole, ). May decrease oral contraceptive action. • - Bronchodilator (theophylline). Theophylline metabolism may be decreased, increased side effect. • - Corticosteroids (hydrocortisone, methylprednisolone, prednisolone, prednisone). Effects may be increased owing to inhibition of metabolism by oral contraceptive. • - Lipid-lowering agent (clofibrate). Metabolism of clofibrate may be increased, decreased oral contraceptive effect. • - Tricyclic antidepressants (amitriptyline, imipramine). Tricyclic antidepressant metabolism may be decreased, increasing the side effect. Reference

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