The reproductive systems of men and women consist of those organs that produce and release sperm (male), or store and release eggs, and then nurture a fertilized egg until it develops into a baby (female).
The urinary system filters wastes and water from the blood, producing urine, which is then expelled from the body. The reproductive and urinary systems of men are partially linked, but those of women form two physically close but functionally separate systems.
The female reproductive organs comprise the ovaries, fallopian tubes, and uterus (womb). The uterus opens via the cervix (neck of the uterus) into the vagina. The principal male reproductive organs are the two sperm-producing glands, the testes (testicles), which lie within the scrotum, and the penis. Other structures of the male reproductive tract include the prostate gland and several tubular structures – the tightly coiled epididymides, the vas deferens, the seminal vesicles, and the urethra.
The urinary organs in both sexes comprise the kidneys, which filter the blood and excrete urine, the ureters down which urine passes, and the bladder, where urine is stored until it is passed out of the body through the urethra.
WHAT CAN GO WRONG
The reproductive and urinary tracts are both subject to infection. Such infections (apart from those transmitted by sexual activity) are relatively uncommon in men because the long male urethra prevents bacteria and other organisms passing easily to the bladder and upper urinary tract, and to the male sex organs. The shorter female urethra allows urinary tract infections, especially of the bladder (cystitis) and of the urethra (urethritis), to occur commonly. The female reproductive tract is also vulnerable to infection, which, in some cases, is sexually transmitted.
Reproductive function may also be disrupted by hormonal disturbances that lead to reduced fertility. Women may be troubled by symptoms arising from normal activity of the reproductive organs, including menstrual disorders as well as various problems associated with childbirth.
The most common urinary problems apart from infection are those related to bladder function. Urine may be released involuntarily (incontinence) or it may be retained in the bladder. Such disorders are usually the result of abnormal nerve signals to the bladder or sphincter muscle. The filtering action of the kidneys may be affected by alteration of the composition of the blood or the hormones that regulate urine production, or by damage (from infection or inflammation) to the filtering units themselves.
WHY DRUGS ARE USED
Antibiotic drugs are used to eliminate infections of the urinary and reproductive tracts (including sexually transmitted infections). Certain infections of the vagina are caused by fungi or yeasts and require antifungal drugs.
Hormone drugs are used both to reduce fertility deliberately (oral contraceptives) and to increase fertility in certain conditions in which it has not been possible for a couple to conceive. Hormones may also be used to regulate menstruation when it is irregular or excessively painful or heavy. Analgesic drugs are used to treat menstrual period pain and are also widely used for pain relief in labour. Other drugs used in labour include those that increase contraction of the muscles of the uterus and those that limit blood loss after the birth. Drugs may also be employed to halt premature labour.
Drugs that alter the transmission of nerve signals to the bladder muscles have an important role in the treatment of urinary incontinence and retention. Drugs that increase the kidneys’ filtering action are commonly used to reduce blood pressure and fluid retention (see Diuretics). Other drugs may alter the composition of the urine – for example, the uricosuric drugs that are used in the treatment of gout increase the amount of uric acid.
THE MENSTRUAL CYCLE
A monthly cycle of hormone interactions allows an egg to be released and, if it is fertilized, creates the correct environment for it to implant in the uterus. Major changes occur in the body, the most obvious of which is monthly vaginal bleeding (menstruation). The menstrual cycle usually starts between the ages of 11 and 14 years and continues until the menopause, which occurs at around the age of 50. After the menopause, childbearing is no longer possible. The cycle is usually 28 days, but this varies from one individual to another.
Menstruation If no egg is fertilized, the endometrium is shed (days 1–5).
Fertile period Conception may take place in the two days after ovulation (days 14–16).
MAJOR DRUG GROUPS
· Drugs used to treat menstrual disorders
· Oral contraceptives
· Drugs for infertility
· Drugs used in labour
· Drugs used for urinary disorders
Drugs used to treat menstrual disorders
The menstrual cycle results from the actions of female sex hormones that cause ovulation (the release of an egg) and thickening of the endometrium (the lining of the uterus) each month in preparation for pregnancy. Unless the egg is fertilized, the endometrium will be shed approximately two weeks later during menstruation (see also The menstrual cycle).
The main problems associated with menstruation that may require medical treatment are excessive blood loss (menorrhagia), pain during menstruation (dysmenorrhoea), and the distressing physical and psychological symptoms that sometimes occur before menstruation (premenstrual syndrome).
The absence of periods (amenorrhoea) is commonly due to pregnancy in women of childbearing age or to the menopause in older women; other causes are discussed under female sex hormones).
The drugs most commonly used to treat the menstrual disorders described in this section include oestrogens, progestogens, danazol, and analgesics (painkillers).
WHY THEY ARE USED
Drug treatment for menstrual disorders is undertaken only when the doctor has ruled out the possibility of an underlying gynaecological disorder, such as a pelvic infection or fibroids. In some cases, especially in women over the age of 35, a D and C (dilatation and curettage) may be recommended. When no underlying reason for the problem is found, drug treatment aimed primarily at the relief of symptoms is usually prescribed.
Dysmenorrhoea Painful menstrual periods are usually treated initially with a simple analgesic. Non-steroidal anti-inflammatory drugs (NSAIDs) are often most effective because they counter the effects of prostaglandins, chemicals that are partly responsible for transmission of pain to the brain. The NSAID mefenamic acid has the additional ability to reduce the excessive blood loss of menorrhagia.
When these drugs are not sufficient to provide adequate pain relief, hormonal drug treatment may be recommended. If contraception is also required, treatment may involve an oral contraceptive pill containing both an oestrogen and a progestogen, or a progestogen alone. Non-contraceptive progestogen preparations may also be prescribed. These are usually taken for only a few days during each month.
Menorrhagia Excessive loss of blood during menstruation can sometimes be reduced by some NSAIDs. Tranexamic acid, an antifibrinolytic drug, is an effective treatment for menorrhagia. Alternatively, danazol, a drug that reduces production of the female sex hormone oestrogen, may be prescribed to reduce blood loss.
Premenstrual syndrome This is a collection of psychological and physical symptoms that affect many women to some degree in the days before menstruation. Psychological symptoms include mood changes such as increased irritability, depression, and anxiety. Principal physical symptoms are bloating, headache, and breast tenderness. Combined oral contraceptives may be prescribed and, for severe premenstrual syndrome, SSRI antidepressants are sometimes given. Other drugs sometimes used include pyridoxine (vitamin B6), diuretics if bloating due to fluid retention is a problem, and bromocriptine when breast tenderness is the major symptom.
Endometriosis is a condition in which fragments of endometrial tissue (uterine lining) occur outside the uterus in the pelvic cavity. It causes severe pain during menstruation, often causes pain during intercourse, and may sometimes lead to infertility. Drugs used for this disorder are similar to those prescribed for heavy periods (menorrhagia). In this case, however, the intention is to suppress endometrial development for an extended period so that the abnormal tissue eventually withers away. Progesterone supplements that suppress endometrial thickening may be prescribed throughout the menstrual cycle. Alternatively, danazol, which suppresses endometrial development by reducing oestrogen production, may be prescribed. Any drug treatment usually needs to be continued for a minimum of six months. When drug treatment is unsuccessful, surgical removal of the abnormal tissue is usually necessary.
HOW THEY WORK
Drugs used to treat menstrual disorders act in a variety of ways. Hormonal treatments are aimed at suppressing the pattern of hormonal changes that is causing troublesome symptoms. Contraceptive preparations override the woman’s normal menstrual cycle. Ovulation does not occur, and the endometrium does not thicken normally. Bleeding that occurs at the end of a cycle is less likely to be abnormally heavy, to be accompanied by severe discomfort, or to be preceded by distressing symptoms.
Non-contraceptive progestogen preparations taken in the days before menstruation do not suppress ovulation. Increased progesterone during this time reduces premenstrual symptoms and prevents excessive thickening of the endometrium.
Danazol, a potent drug, prevents the thickening of the endometrium, thereby correcting excessively heavy periods. Blood loss is reduced, and in some cases menstruation ceases altogether during treatment.
Oestrogens and progestogens
NSAID analgesics Aspirin, Dexibuprofen, Dexketoprofen, Diclofenac, Flurbiprofen, Ibuprofen, Indometacin, Ketoprofen, Mefenamic acid, Naproxen
Other drugs Bromocriptine, Buserelin, Danazol, Gestrinone, Goserelin, Leuprorelin, Nafarelin, Pyridoxine, Tranexamic acid, Triptorelin
There are many different methods of ensuring that conception and pregnancy do not follow sexual intercourse, but for many women oral contraception is the preferred method because it is highly effective, convenient and unobtrusive during sexual intercourse. About 30 percent of the women who seek contraceptive protection in Britain choose a form of oral contraceptive.
There are three main types of oral contraceptive: the combined pill, the progestogen-only pill (POP), and the phased pill. All three types contain a progestogen (a synthetic form of the female sex hormone, progesterone). Both the combined and phased pills also contain a natural or synthetic oestrogen (see also Female sex hormones).
The following list indicates the number of pregnancies occurring with each method of contraception per 100 women using that method in a year. The figures are for correct usage; if a contraceptive is used incorrectly, the failure rate will be higher. The variation that occurs with some of these methods takes into account pregnancies that occur through incorrect use of the method (e.g. the wide variation in figures for the “morning after” pill reflects the difference in effectiveness depending on how soon it is taken after unprotected sex).
· Combined and phased pills Less than 1
· IUD (Intrauterine device) Less than 1
· IUS (Intrauterine system) Less than 1
· Contraceptive implant Less than 1
· Contraceptive injection Less than 1
· Progestogen-only pill About 1
· Male condom About 2
· Female condom About 5
· Diaphragm with spermicide 4–8
· Cap with spermicide 4–8
· “Morning after” pill About 2–42
WHY THEY ARE USED
The combined pill This is the most widely prescribed form of oral contraceptive and has the lowest failure rate in terms of unwanted pregnancies. It is referred to as the “pill” and is the type thought most suitable for young women who want to use a hormonal form of contraception. The combined pill is particularly suitable for those women who regularly experience exceptionally painful, heavy, or prolonged periods (see Drugs used to treat menstrual disorders).
There are many different products available containing a fixed dose of an oestrogen and a progestogen drug. They are divided generally into three groups according to their oestrogen content (see table). Low-dose products are chosen when possible to minimize the risk of adverse effects.
Progestogen-only pill (POP) The progestogen-only pill (POP) is often recommended for women who react adversely to the oestrogen in the combined pill or for whom the combined pill is not considered suitable because of their age or medical history (see Risks and special precautions). It is also prescribed for breast-feeding women, since it does not reduce milk production. The progestogen-only pill has a higher failure rate than the combined pill and, for maximum contraceptive effect, must be taken at precisely the same time each day. It works by changing the quality of the endometrium (the lining of uterus), making implantation of a fertilized egg less likely. However, Cerazette (a brand of the progestogen, desogestrel) also inhibits ovulation, making it more reliable than other progestogen-only pills.
Phased pills The third form of oral contraceptive is a pack of pills divided into two or three groups or phases. Each phase contains a different proportion of an oestrogen and a progestogen. The aim is to provide a hormonal balance that closely resembles the fluctuations of a normal menstrual cycle. Phased pills provide effective protection for many women who suffer side effects from other available forms of oral contraceptive.
HOW THEY WORK
In a normal menstrual cycle, the ripening and release of an egg and the preparation of the uterus for implantation of the fertilized egg are the result of a complex interplay between the natural female sex hormones, oestrogen and progesterone, and the pituitary hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The oestrogen and progestogens in oral contraceptives disrupt the normal menstrual cycle in such a way that conception is less likely.
With combined and phased pills, the increased levels of oestrogen and progesterone produce similar effects to the hormonal changes of pregnancy. The actions of the hormones inhibit the production of FSH and LH, thereby preventing the egg from ripening in the ovary and from being released.
The progestogen-only pill has a slightly different effect. It does not always prevent release of an egg; its main contraceptive action may be to thicken the mucus that lines the cervix, preventing sperm from crossing it. This effect occurs to some extent with combined and phased pills. Cerazette, additionally, inhibits ovulation.
HORMONE CONTENT OF COMMON ORAL CONTRACEPTIVES
The oestrogen-containing forms are classified according to their oestrogen content as follows: low: 20 micrograms; standard: 30–35 micrograms; high: 50 micrograms; phased pills: 30–40 micrograms. Morning after: 1.5 milligrams (levonorgestrel), 30 milligrams (ulipristal).
HOW THEY AFFECT YOU
Each course of combined and phased pills lasts for 21 days, followed by a pill-free seven days, during which time menstruation occurs. Some brands contain additional inactive pills. With these, the new course directly follows the last so that the habit of taking the pill daily is not broken. Progestogen-only pills are taken for 28 days each month. Menstruation usually occurs during the last few days of the menstrual cycle.
Women taking oral contraceptives, especially drugs that contain oestrogen, usually find that their menstrual periods are lighter and relatively pain-free. Some women cease to menstruate altogether. This is not a cause for concern in itself, provided no pills have been missed, but it may make it difficult to determine if pregnancy has occurred. An apparently missed period probably indicates a light one, rather than pregnancy. However, if you have missed two consecutive periods and you feel that you may be pregnant, it is advisable to have a pregnancy test.
All forms of oral contraceptive may cause spotting of blood in mid-cycle (breakthrough bleeding), especially at first, but this can be a particular problem with the progestogen-only pill.
Oral contraceptives that contain oestrogen may produce any of a large number of mild side effects, depending on the dose. Symptoms similar to those experienced early in pregnancy may occur, particularly in the first few months of pill use: some women complain of nausea and vomiting, weight gain, depression, altered libido, increased appetite, and cramps in the legs and abdomen. The pill may also affect the circulation, producing minor headaches and dizziness. All these effects usually disappear within a few months, but if they persist it may be advisable to change to a brand containing a lower dose of oestrogen or to some other contraceptive method.
RISKS AND SPECIAL PRECAUTIONS
All oral contraceptives need to be taken regularly for maximum protection against pregnancy. Contraceptive protection can be reduced by missing a pill (see What to do if you miss a pill). It may also be reduced by vomiting or diarrhoea. If you vomit within two hours of taking a pill, take another one. If vomiting and diarrhoea persist, follow the packet instructions or consult your doctor or pharmacist. Many drugs may also affect the action of oral contraceptives and it is essential to tell your doctor that you are taking oral contraceptives, before taking additional prescribed medications.
Oral contraceptives, particularly those containing an oestrogen, have been found to carry a number of risks (see Balancing the risks and benefits of oral contraceptives). One of the most serious potential adverse effects of oestrogen-containing pills is development of a thrombus (blood clot) in a vein or artery. The thrombus may travel to the lungs or cause a stroke or heart attack. The risk of thrombus formation increases with age and other factors, notably obesity, high blood pressure, and smoking. Doctors assess these risk factors for each person when prescribing oral contraceptives. A woman who is over 35 may be advised against taking a combined pill, especially if she smokes or has an underlying medical condition such as diabetes. Some studies have found that women taking a combined oral contraceptive containing either desogestrel or gestogene are at greater risk of developing a venous thromboembolism. The risk is still very small, however, and is lower than the risk of developing a venous thromboembolism during pregnancy. The combined oral contraceptive pills that contain desogestrel include Marvelon and Mercilon; those that contain gestodene include Femodene, Femodette, and Triadene.
High blood pressure is a possible complication of oral contraceptives for some women. Measurement of blood pressure before the pill is prescribed and every six months after the woman starts taking oral contraceptives is advised for all women taking oral contraceptives.
Some very rare liver cancers have occurred in pill-users, and breast cancer and cervical cancer may be slightly more common, but cancers of the ovaries and uterus are less common.
Although there is no evidence that oral contraceptives reduce a woman’s fertility or that they damage the babies conceived after the oral contraceptives are discontinued, doctors recommend that you wait for at least one normal menstrual period before you attempt to become pregnant.
BALANCING THE RISKS AND BENEFITS OF ORAL CONTRACEPTIVES
Oral contraceptives are safe for the vast majority of young women. However, every woman who is considering oral contraception should discuss with her doctor the risks and possible adverse effects of the drugs before deciding whether or not a hormonal contraception is the most suitable method in her case. A variety of factors must be taken into account, including the woman’s age, her own medical history and that of her close relatives, and factors such as whether or not she is a smoker. The importance of such factors varies depending on the type of oral contraceptive. The principal advantages and disadvantages of oestrogen-containing and progestogen-only pills are listed here.
Advantages of oestrogen-containing combined and phased pills Very reliable; convenient and unobtrusive; regularize menstruation; reduce menstrual pain and blood loss; reduce risk of benign breast disease, endometriosis, ectopic pregnancy, ovarian cysts, pelvic infection, ovarian and endometrial cancer.
Advantages of progestogen-only pill Very reliable; convenient and unobtrusive but the timing of doses is more critical than in the case of combined and phased pills; suitable for use during breast-feeding; avoids any oestrogen-related side effects and risks; allows rapid return to fertility; suitable for women in whom use of oestrogen-containing contraception is not possible.
Side effects of oestrogen-containing combined and phased pills Weight gain; depression; breast swelling; reduced sex drive; headaches; increased vaginal discharge; nausea.
Side effects of progestogen-only pill Irregular menstruation; nausea; headaches; breast discomfort; depression; changes in libido; weight changes.
Risks of oestrogen-containing combined and phased pills Thromboembolism; heart disease; high blood pressure; liver impairment/cancer of the liver (rare); gallstones; breast and/or cervical cancer (risk is low).
Risks of progestogen-only pill Ectopic pregnancy; ovarian cysts; breast cancer (risk is low).
Factors that may prohibit use of oestrogen-containing combined and phased pills Previous thrombosis*; heart disease; high levels of lipid in blood; liver disease; blood disorders; high blood pressure; unexplained vaginal bleeding; migraine; otosclerosis; presence of several risk factors.
Factors that may prohibit use of progestogen-only pill Previous ectopic pregnancy; heart or circulatory disease; unexplained vaginal bleeding; history of breast cancer.
Factors that increase risks of oestrogen-containing combined and phased pills Smoking*; obesity*; increasing age; diabetes mellitus; family history of heart or circulatory disease*; current treatment with other drugs.
Factors that increase risks of progestogen-only pill As for oestrogen-containing pills, but to a lesser degree.
*Products containing desogestrel or gestodene have a higher excess risk with these factors than other progestogens.
HOW TO MINIMIZE YOUR HEALTH RISKS WHILE TAKING THE PILL
· Do not smoke.
· Maintain a healthy weight and diet.
· Have regular blood pressure and blood lipid checks.
· Have regular cervical screening tests.
· Remind your doctor that you are taking oral contraceptives before taking other prescription drugs.
· Stop taking oestrogen-containing oral contraceptives four weeks before any planned major surgery (use alternative contraception).
WHAT TO DO IF YOU MISS A PILL
Contraceptive protection may be reduced if blood levels of the hormones in the body fall due to missing a pill. It is particularly important to ensure that the progestogen-only pills are taken punctually. If you miss a pill, the action you take depends on the degree of lateness and type of pill being used.
Combined and phased pills If you are less than 24 hours late (12 hours for Qlaira), take the missed pill now and the next on time. If you are over 24 hours late (12 hours for Qlaira), the pill may not work. For Qlaira, refer to packet instructions. For others, take the missed pill now and the next on time. If more than one pill has been missed, just take one then the next on time (even if on the same day); take additional precautions for the next 7 days. If the 7 days extends into the pill-free (or inactive pill) period, start the next packet without a break (or without taking inactive pills).
Progestogen-only pills If you are less than 3 hours late (12 for Cerazette), take the missed pill now and the next on time. If you are over 3 hours late (12 for Cerazette), take the missed pill now and the next on time. If more than one pill has been missed, just take one then the next on time (even if on the same day). In either case, you are not protected and will need to take additional precautions for the next 2 days.
Pregnancy following intercourse without contraception may be avoided by taking a postcoital (morning after) pill. The drugs for this (levonorgestrel and ulipristal) are synthetic progestogens that work by inhibiting ovulation and also by changing the endometrium (uterine lining) to reduce the likelihood of a fertilized egg implanting.
The drugs should be taken as soon as possible after unprotected intercourse; levonorgestrel is only effective if taken within 72 hours, ulipristal if taken within 120 hours. The high progestogen dose required make this method unsuitable for regular use. It also has a higher failure rate than the usual oral contraceptives.
Progestogens Desogestrel, Dienogest, Drospirenone, Etynodiol, Gestodene, Levonorgestrel, Nomegestrol, Norelgestromin, Norethisterone, Norgestimate, Ulipristal
Oestrogens Estradiol, Ethinyloestradiol, Mestranol
Drugs for infertility
Conception and the establishment of pregnancy require a healthy reproductive system in both partners. The man must be able to produce sufficient numbers of healthy sperm; the woman must be able to produce a healthy egg that is able to pass freely down the fallopian tube to the uterus. The lining of the uterus must be in a condition that allows the implantation of the fertilized egg.
The cause of infertility may sometimes remain undiscovered, but in the majority of cases it is due to one of the following factors: intercourse taking place at the wrong time during the menstrual cycle; the man producing too few or unhealthy sperm; the woman either failing to ovulate (release an egg) or having blocked fallopian tubes, perhaps as a result of previous pelvic infection. Alternatively, production of gonadotrophin hormones – follicle-stimulating hormone (FSH) and luteinizing hormone (LH) – needed for ovulation and implantation of the egg may be affected by illness or psychological stress.
If no simple explanation can be found, the man’s semen will be analysed. If these tests show that abnormally low numbers of sperm are being produced, or if a large proportion of the sperm produced are unhealthy, drug treatment may be tried.
If no abnormality of sperm production is discovered, the woman will be given a thorough medical examination. Ovulation is monitored and blood tests may be performed to assess hormone levels. If ovulation does not occur, the woman may be offered drug treatment.
WHY THEY ARE USED
In men, the evidence is poor for treating low sperm production with gonadotrophins – FSH or human chorionic gonadotrophin (HCG) – or a pituitary-stimulating drug (for example, clomifene) and corticosteroids.
In women, drugs are useful in helping to achieve pregnancy only when a hormone defect inhibiting ovulation has been diagnosed. Treatment may continue for months and does not always result in pregnancy. Women in whom the pituitary gland is producing some FSH and LH may be given courses of clomifene for several days during each month. Usually, up to three courses may be tried. An effective dose produces ovulation 5 to 10 days after the last tablet is taken.
Clomifene may thicken the cervical mucus, impeding the passage of sperm, but the advantage of achieving ovulation outweighs the risk of this side effect. If treatment with clomifene fails to produce ovulation, or if a disorder of the pituitary gland prevents the production of FSH and LH, treatment with FSH and LH together, FSH alone, or HCG may be given. In menstruating women, FSH is started within the first 7 days of the menstrual cycle.
HOW THEY WORK
Ovulation (release of an egg) and implantation are governed by hormones produced by the pituitary gland. FSH stimulates ripening of the egg follicle. LH triggers ovulation and ensures that progesterone is produced to prepare the uterus for the implantation of the egg. Drugs for female infertility raise the chance of ovulation by boosting levels of LH and FSH. Clomifene stimulates the pituitary gland to increase its output of these hormones. Artificially produced FSH and HCG mimic the action of naturally produced FSH and LH respectively. Both treatments, when successful, stimulate ovulation and implantation of the fertilized egg.
HOW THEY AFFECT YOU
Clomifene may produce hot flushes, nausea, headaches, and, rarely, ovarian cysts and visual disturbance, while HCG can cause tiredness, headaches, and mood changes. FSH can cause the ovaries to enlarge, producing abdominal discomfort. These drugs increase the likelihood of multiple births, usually twins.
DRUGS FOR ERECTILE DYSFUNCTION
Erectile dysfunction (also known as impotence) is a common male disorder defined as inability to achieve or maintain an erection. The penis contains three cylinders of erectile tissue: the two corpora cavernosa and the corpus spongiosum. Normally, when a man is sexually aroused, the arteries in the penis relax and widen, allowing more blood than usual to flow into the organ, filling the corpora cavernosa and corpus spongiosum. As these tissues expand and harden, the veins that carry blood out of the penis are compressed, reducing outflow and resulting in an erection. In some forms of erectile dysfunction, this does not happen. Drugs can be used to increase blood flow into the penis to produce an erection.
Sildenafil and tadalafil not only increase the blood flow into the penis but also prevent the muscle wall from relaxing, so the blood does not drain out of the blood vessels and the penis remains erect.
Alprostadil is a prostaglandin drug that helps men achieve an erection by widening the blood vessels, but it must be injected directly into the penis, or applied into the urethra using a special syringe.
Bromocriptine, Buserelin, Cetrorelix, Chorionic gonadotrophin (HCG), Clomifene, Follitropin (FSH), Ganirelix, Goserelin, Lutropin (LH), Menopausal gonadotrophins (Menotrophin), Nafarelin, Tamoxifen
Drugs for erectile dysfunction Alprostadil, Papaverine, Sildenafil/tadalafil, Vardenafil
Drugs used in labour
Normal labour has three stages. In the first stage, the uterus begins to contract, initially irregularly and then gradually more regularly and powerfully, while the cervix dilates until it is fully stretched. During the second stage, powerful contractions of the uterus push the baby down the mother’s birth canal and out of her body. The third stage involves the delivery of the placenta.
Drugs may be required during one or more stages of labour for any of the following reasons: to induce or augment labour; to delay premature labour (see Uterine muscle relaxants); and to relieve pain. The administration of some drugs may be viewed as part of normal obstetric care; for example, the uterine stimulants ergometrine and oxytocin may be injected routinely before the third stage of labour to prevent excessive bleeding. Other drugs are administered only when the condition of the mother or baby requires intervention. The possible adverse effects of the drug on both mother and baby are always carefully balanced against the benefits.
DRUGS TO INDUCE OR AUGMENT LABOUR
Induction of labour may be advised when a doctor considers it risky for the health of the mother or baby for the pregnancy to continue – for example, if natural labour does not occur within two weeks of the due date or when a woman has pre-eclampsia. Other common reasons for inducing labour include premature rupture of the membrane surrounding the baby (breaking of the waters), slow growth of the baby due to poor nourishment by the placenta, or death of the fetus in the uterus.
When labour needs to be induced, oxytocin may be administered intravenously. Alternatively, a prostaglandin pessary may be given to soften and dilate the cervix. If these methods are ineffective or cannot be used because of potential adverse effects (see Risks and special precautions), a caesarean delivery may have to be performed.
Oxytocin may also be used to strengthen the force of contractions in labour that has started spontaneously but has not continued normally.
A combination of oxytocin and another uterine stimulant, ergometrine, is given to most women as the baby is being born or immediately following birth to prevent excessive bleeding after the delivery of the placenta. This combination encourages the uterus to contract after delivery, which restricts the flow of blood.
RISKS AND SPECIAL PRECAUTIONS
When oxytocin is used to induce labour, the dosage is carefully monitored throughout to prevent the possibility of excessively violent contractions. It is administered to women who have had surgery on the uterus only with careful monitoring. The drug is not known to affect the baby adversely. Ergometrine is not given to women who have suffered from high blood pressure during the course of pregnancy.
DRUGS USED FOR PAIN RELIEF
Opioid analgesics Pethidine, morphine, or other opioids may be given once active labour has been established (see Analgesics). Possible side effects for the mother include drowsiness, nausea, and vomiting. Opioid drugs may cause breathing difficulties for the new baby, but these problems may be reversed by the antidote naloxone.
Epidural anaesthesia This provides pain relief during labour and birth by numbing the nerves leading to the uterus and pelvic area. It is often used during a planned caesarean delivery, thus enabling the mother to be fully conscious for the birth.
An epidural involves the injection of a local anaesthetic drug into the epidural space between the spinal cord and the vertebrae. An epidural may block the mother’s urge to push during the second stage, and a forceps delivery may be necessary. Headaches may occasionally occur following epidural anaesthesia.
Oxygen and nitrous oxide These gases are combined to produce a mixture that reduces the pain caused by contractions. During the first and second stages of labour, gas is self-administered by inhalation through a mouthpiece or mask. If it is used over too long a period, it may produce nausea, confusion, and dehydration in the mother.
Local anaesthetics These drugs are injected inside the vagina or near the vaginal opening and are used to numb sensation during forceps delivery, before an episiotomy (an incision made to enlarge the vaginal opening), and when stitches are necessary. Side effects are rare.
UTERINE MUSCLE RELAXANTS
When contractions of the uterus start before the 34th week of pregnancy, doctors usually advise bed rest and may also administer a drug that relaxes the muscles of the uterus, and thus halts labour. Initially, the drug is given in hospital by injection, but it may be continued orally at home. These drugs work by stimulating the sympathetic nervous system (see Autonomic nervous system) and may cause palpitations and anxiety in the mother. They have not been shown to have adverse effects on the baby.
DRUGS USED TO TERMINATE PREGNANCY
Drugs may be used to terminate pregnancy up to the end of the 23rd week, or to empty the uterus after the death of the baby. The principal drugs used are mifeprostone and a prostaglandin (usually gemeprost or misoprostol). The effect of these drugs is to stimulate a miscarriage. Mifeprostone blocks progesterone, which is necessary for continuation of pregnancy, and ripens the cervix. The prostaglandin causes the uterine lining to break down and be shed, causing bleeding. Other methods of termination, such as suction termination or surgical dilation and evacuation, can be used either instead of or when a drug-induced termination is unsuccessful; these may be carried out under local or general anaesthesia.
Prostaglandins Carboprost, Dinoprostone, Gemeprost, Misoprostol
Pain relief Entonox (oxygen and nitrous oxide), Fentanyl, Morphine, Pethidine
Uterine muscle relaxants Atosiban, Salbutamol, Terbutaline
Uterine stimulants Ergometrine, Oxytocin
Local anaesthetics Bupivacaine, Lidocaine (lignocaine)
Drugs used for urinary disorders
Urine is produced by the kidneys and stored in the bladder. As the urine accumulates, the bladder walls stretch and pressure within the bladder increases. Eventually, the stretching stimulates nerve endings that produce the urge to urinate. The ring of muscle (sphincter) around the bladder neck normally keeps the bladder closed until it is consciously relaxed, allowing urine to pass via the urethra out of the body.
A number of disorders can affect the urinary tract. The most common of these disorders are infection in the bladder (cystitis) or the urethra (urethritis), and loss of reliable control over urination (urinary incontinence). A less common problem is inability to expel urine (urinary retention). Drugs used to treat these problems include antibiotics and antibacterial drugs, analgesics, drugs to increase the acidity of the urine, and drugs that act on nerve control over the muscles of the bladder and sphincter.
DRUGS FOR URINARY INFECTION
Nearly all infections of the bladder are caused by bacteria. Symptoms include a continual urge to urinate, although often nothing is passed; pain on urinating; and pain in the lower abdomen.
Many antibiotics and antibacterials are used to treat urinary tract infections. Among the most widely used, because of their effectiveness, are cephalosporins, amoxicillin, and trimethoprim (see Antibiotics, and Antibacterial drugs).
Measures are also sometimes taken to increase the acidity of the urine, thereby making it hostile to bacteria. Ascorbic acid (vitamin C) and acid fruit juices have this effect, although making the urine less acidic with potassium or sodium citrate during an attack of cystitis helps to relieve the discomfort. Symptoms are commonly relieved within a few hours of the start of treatment.
For maximum effect, all drug treatments prescribed for urinary tract infections need to be accompanied by increased fluid intake.
DRUGS FOR URINARY INCONTINENCE
Urinary incontinence can occur for several reasons. A weak sphincter muscle allows the involuntary passage of urine when abdominal pressure is raised by coughing or physical exertion. This is known as stress incontinence and commonly affects women who have had children. Urgency – the sudden need to urinate – stems from oversensitivity of the bladder muscle; small quantities of urine in the bladder stimulate the urge to urinate frequently.
Incontinence can also occur due to loss of nerve control in neurological disorders such as multiple sclerosis. In children, the inability to control urination at night (nocturnal enuresis) is also a form of urinary incontinence.
Drug treatment is not necessary or appropriate for all forms of incontinence. In stress incontinence, exercises to strengthen the pelvic floor muscles or surgery to tighten stretched ligaments may be effective. In urgency, regular emptying of the bladder can often avoid the need for medical intervention. Incontinence caused by loss of nerve control is unlikely to be helped by drug treatment. Frequency of urination in urgency may be reduced by anticholinergic and antispasmodic drugs. These drugs reduce nerve signals from the muscles in the bladder, thereby allowing greater volumes of urine to accumulate without stimulating the urge to pass urine.
Tricyclic antidepressants, such as imipramine, have a strong anticholinergic action and have been prescribed for nocturnal enuresis in children, but many doctors believe the risk of overdosage is unacceptable. Desmopressin, a synthetic derivative of antidiuretic hormone, is also used to treat nocturnal enuresis.
DRUGS FOR URINARY RETENTION
Urinary retention is the inability to empty the bladder. This usually results from the failure of the bladder muscle to contract sufficiently to expel the accumulated urine. Possible causes include an enlarged prostate gland or tumour, or a long-standing neurological disorder. Some drugs can also cause urinary retention.
Most cases of urinary retention need to be relieved by inserting a tube (catheter) into the urethra. Surgery may be needed to prevent a recurrence of the problem.
Drugs that relax the sphincter or stimulate bladder contraction are now rarely used in the treatment of urinary retention, but two types of drug are used in the long-term management of prostatic enlargement: finasteride and alpha blockers. Finasteride prevents production of male hormones that stimulate prostate growth, and alpha blockers, such as prazosin, tamsulosin, and terazosin, relax prostatic and urethral smooth muscle, thereby improving urine outflow. Long-term drug treatment of urinary retention can relieve symptoms and delay the need for surgery.
Antibiotics and antibacterials
Anticholinergics Flavoxate, Imipramine, Oxybutynin, Propantheline, Propiverine, Solifenacin, Tolterodine, Trospium
Parasympathomimetics Bethanechol, Distigmine
Alpha blockers Alfuzosin, Doxazosin, Indoramin, Prazosin, Tamsulosin, Terazosin
Other drugs Desmopressin, Dimethyl sulfoxide, Duloxetine, Finasteride, Potassium citrate, Sodium bicarbonate/citrate, Vitamin C