21.11.09

answer to the saudi medical council question exami...

Drug Use During Pregnancy

http://www.merck.com/mmhe/print/sec22/ch259/ch259a.html


More than 90% of pregnant women take prescription or nonprescription (over-the-counter) drugs or use social drugs (such as tobacco and alcohol) or illicit drugs at some time during pregnancy. In general, drugs, unless absolutely necessary, should not be used during pregnancy because many can harm the fetus. About 2 to 3% of all birth defects result from the use of drugs other than alcohol.

Sometimes drugs are essential for the health of the pregnant woman and the fetus. In such cases, a woman should talk with her doctor or other health care practitioner about the risks and benefits of taking the drugs. Before taking any drug (including over-the-counter drugs) or dietary supplement (including medicinal herbs), a pregnant woman should consult her health care practitioner. A health care practitioner may recommend that a woman take certain vitamins and minerals during pregnancy.

Drugs taken by a pregnant woman reach the fetus primarily by crossing the placenta, the same route taken by oxygen and nutrients, which are needed for the fetus's growth and development. Drugs that a pregnant woman takes during pregnancy can affect the fetus in several ways:

They can act directly on the fetus, causing damage, abnormal development (leading to birth defects), or death.
They can alter the function of the placenta, usually by causing blood vessels to narrow (constrict) and thus reducing the supply of oxygen and nutrients to the fetus from the mother. Sometimes the result is a baby that is underweight and underdeveloped.
They can cause the muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply or triggering preterm labor and delivery.



How Drugs Cross the Placenta


Some of the fetus's blood vessels are contained in tiny hairlike projections (villi) of the placenta that extend into the wall of the uterus. The mother's blood passes through the space surrounding the villi (intervillous space). Only a thin membrane (placental membrane) separates the mother's blood in the intervillous space from the fetus's blood in the villi. Drugs in the mother's blood can cross this membrane into blood vessels in the villi and pass through the umbilical cord to the fetus.



How a drug affects a fetus depends on the fetus's stage of development and the strength and dose of the drug. Certain drugs taken early in pregnancy (within 20 days after fertilization) may act in an all-or-nothing fashion, killing the fetus or not affecting it at all. During this early stage, the fetus is highly resistant to birth defects. However, the fetus is particularly vulnerable to birth defects between the 3rd and the 8th week after fertilization, when its organs are developing. Drugs reaching the fetus during this stage may have no effect, or they may cause a miscarriage, an obvious birth defect, or a permanent but subtle defect that is noticed later in life. Drugs taken after organ development is complete are unlikely to cause obvious birth defects, but they may alter the growth and function of normally formed organs and tissues.

The Food and Drug Administration (FDA) classifies drugs according to the degree of risk they pose for the fetus if they are used during pregnancy. Some drugs are highly toxic and should never be used by pregnant women because they cause severe birth defects. One example is thalidomide. Several decades ago, this drug caused extreme underdevelopment of arms and legs and defects of the intestine, heart, and blood vessels in the babies of women who took the drug during pregnancy. Some drugs cause birth defects in animals, but the same effects have not been seen in people. One example is meclizine, frequently taken for motion sickness, nausea, and vomiting.




Categories of Risk for Drugs During Pregnancy
CATEGORY
DESCRIPTION

A
These drugs are the safest. Well-designed studies in people show no risks to the fetus.

B
Studies in animals show no risk to the fetus, and no well-designed studies in people have been done.

OR

Studies in animals show a risk to the fetus, but well-designed studies in people do not.

C No adequate studies in animals or people have been done.

OR

In animal studies, use of the drug resulted in harm to the fetus, but no information about how the drug affects the human fetus is available.

D
Evidence shows a risk to the human fetus, but benefits of the drug may outweigh risks in certain situations. For example, the mother may have a life-threatening disorder or a serious disorder that cannot be treated with safer drugs.

X
Risk to the fetus has been proved to outweigh any possible benefit.


Often, a safer drug can be substituted for one that is likely to cause harm during pregnancy. For an overactive thyroid gland, propylthiouracil is usually preferred. For prevention of blood clots, the anticoagulant heparin is preferred. Several safe antibiotics, such as penicillin, are available.

Some drugs can have effects after they are stopped. For example, isotretinoin, a drug used to treat skin disorders, is stored in fat beneath the skin and is released slowly. Isotretinoin can cause birth defects if women become pregnant within 2 weeks after the drug is stopped. Therefore, women are advised to wait at least 3 to 4 weeks after the drug is stopped before they become pregnant.

Vaccines made with a live virus (such as the rubella and varicella vaccines) are not given to women who are or might be pregnant. Other vaccines (such as those for cholera, hepatitis A and B, plague, rabies, tetanus, diphtheria, and typhoid) are given to pregnant women only if they are at substantial risk of developing that particular infection. However, all pregnant women who are in the 2nd or 3rd trimester during the influenza (flu) season should be vaccinated against the influenza virus.

Drugs to lower high blood pressure (antihypertensives) may be needed by pregnant women who have had high blood pressure before pregnancy or who develop it during pregnancy. Either type of high blood pressure increases the risk of problems for the woman and the fetus (see Pregnancy Complications: Preeclampsia and Pregnancy Complicated by Disease: High Blood Pressure During Pregnancy). However, antihypertensives can markedly reduce blood flow to the placenta if they lower blood pressure too rapidly in pregnant women. So pregnant women who have to take these drugs are closely monitored. Two types of antihypertensives?angiotensin-converting enzyme (ACE) inhibitors and thiazide diuretics?are usually not given to pregnant women because these drugs can cause serious problems in the fetus.

Digoxin, used to treat heart failure and some abnormal heart rhythms, readily crosses the placenta. But it typically has little effect on the baby before or after birth.

Most antidepressants appear to be relatively safe when used during pregnancy.




Some Drugs That Can Cause Problems During Pregnancy*
Type
Examples
Problem

Antianxiety drug
Diazepam
When the drug is taken late in pregnancy, depression, irritability, shaking, and exaggerated reflexes in the newborn

Antibiotics
Chloramphenicol
Gray baby syndrome

In women or fetuses with glucose-6-phosphate dehydrogenase (G6PD) deficiency, the breakdown of red blood cells

Fluoroquinolones (such as ciprofloxacin, ofloxacin, levofloxacin, and norfloxacin)
Possibility of joint abnormalities (seen only in animals)

Kanamycin
Damage to the fetus's ear, resulting in deafness

Nitrofurantoin
In women or fetuses with G6PD deficiency, the breakdown of red blood cells

Streptomycin
Damage to the fetus's ear, resulting in deafness

Sulfonamides (such as sulfasalazine and trimethoprim- sulfamethoxazole)
When the drugs are given late in pregnancy, jaundice and possibly brain damage in the newborn (much less likely with sulfasalazine)

In women or fetuses with G6PD deficiency, the breakdown of red blood cells

Tetracycline
Slowed bone growth, permanent yellowing of the teeth, and increased susceptibility to cavities in the baby

Occasionally, liver failure in the pregnant woman

Anticoagulants
Heparin
When the drug is taken a long time, osteoporosis and a decrease in the number of platelets (which help blood clot) in the pregnant woman

Warfarin
Birth defects

Bleeding problems in the fetus and the pregnant woman

Anticonvulsants
Carbamazepine
Some risk of birth defects

Bleeding problems in the newborn, which can be prevented if pregnant women take vitamin K by mouth every day for a month before delivery or if the newborn is given an injection of vitamin K soon after birth

Phenobarbital
Same as those for carbamazepine

Phenytoin
Same as those for carbamazepine

Trimethadione
Increased risk of miscarriage in the woman

High (70%) risk of birth defects, including a cleft palate and defects of the heart, face, skull, hands, or abdominal organs

Valproate
Some (1%) risk of birth defects, including a cleft palate and defects of the heart, face, skull, spine, or limbs

Antihypertensives
Angiotensin-converting enzyme (ACE) inhibitors (see High Blood Pressure: Antihypertensive Drugs.)
When the drugs are taken late in pregnancy, kidney damage in the fetus, a reduction in the amount of fluid around the developing fetus (amniotic fluid), and defects of the face, limbs, and lungs

Beta-blockers
When some beta-blockers are taken during pregnancy, a slowed heart rate and low blood sugar level in the fetus and possibly slowed growth

Thiazide diuretics
A decrease in the levels of oxygen, sodium, and potassium and in the number of platelets in the fetus's blood

Slowed growth

Chemotherapy drugs
Actinomycin
Possibility of birth defects (seen only in animals)

Busulfan
Birth defects such as underdevelopment of the lower jaw, cleft palate, abnormal development of the skull bones, spinal defects, ear defects, and clubfoot

Slowed growth

Chlorambucil
Same as those for busulfun

Cyclophosphamide
Same as those for busulfun

Mercaptopurine
Same as those for busulfun

Methotrexate
Same as those for busulfun

Vinblastine
Possibility of birth defects (seen only in animals)

Vincristine
Possibility of birth defects (seen only in animals)

Mood-stabilizing drug
Lithium
Birth defects (mainly of the heart), lethargy, reduced muscle tone, poor feeding, underactivity of the thyroid gland, and nephrogenic diabetes insipidus in the newborn

Nonsteroidal anti-inflammatory drugs (NSAIDs)
Aspirin and other salicylates

Ibuprofen

Naproxen
When the drugs are taken in large doses, a delay in the start of labor, premature closing of the connection between the aorta and artery to the lungs (ductus arteriosus), jaundice, and (occasionally) brain damage in the fetus and bleeding problems in the woman during and after delivery and in the newborn

When the drugs are taken late in pregnancy, a reduction in the amount of fluid around the developing fetus

Oral antihyperglycemic drugs
Chlorpropamide
A very low level of sugar in the blood of the newborn

Inadequate control of diabetes in the pregnant woman

When the drug is taken early in pregnancy by a woman with type 2 diabetes, possibility of increased risk of birth defects

Tolbutamide
Same as those for chlorpropamide

Sex hormones
Danazol
When this drug is taken very early in pregnancy, masculinization of a female fetus's genitals, sometimes requiring surgery to correct

Diethylstilbestrol (DES)
Abnormalities of the uterus, menstrual problems, and an increased risk of vaginal cancer and complications during pregnancy in daughters

Abnormalities of the penis in sons

Synthetic progestins (but not the low doses used in oral contraceptives)
Same as those for danazol

Skin treatments
Etretinate
Birth defects, such as heart defects, small ears, and hydrocephalus (sometimes called water on the brain)

Isotretinoin
Same as those for etretinate

Mental retardation

Risk of miscarriage

Thyroid drugs
Methimazole
An enlarged or underactive thyroid gland in the fetus

Scalp defects in the newborn

Propylthiouracil
An enlarged or underactive thyroid gland in the fetus

Radioactive iodine
Destruction of the thyroid gland in the fetus

When the drug is given near the end of the 1st trimester, very overactive and enlarged thyroid gland in the fetus

Triiodothyronine
An overactive and enlarged thyroid gland in the fetus

Vaccines (live virus)
Vaccine for German measles (rubella) and chickenpox (varicella)
Potential infection of the placenta and developing fetus

Vaccines for measles, mumps, polio, or yellow fever
Potential but unknown risks

* Unless absolutely necessary, drugs should not be used during pregnancy. However, drugs are sometimes essential for the health of the pregnant woman and the fetus. In such cases, a woman should talk with her health care practitioner about the risks and benefits of taking the drugs.


Social Drugs

Cigarette (Tobacco) Smoking: Although cigarette smoking harms both pregnant women and the fetus, only about 20% of women who smoke quit during pregnancy. The most consistent effect of smoking on the fetus during pregnancy is a reduction in birth weight: The more a woman smokes during pregnancy, the less the baby is likely to weigh. The average birth weight of babies born to women who smoke during pregnancy is 6 ounces less than that of babies born to women who do not smoke. The reduction in birth weight seems to be greater among the babies of older smokers.

Birth defects of the heart, brain, and face are more common among babies of smokers than among those of nonsmokers. Also, the risk of sudden infant death syndrome (SIDS) may be increased. A mislocated placenta (placenta previa), premature detachment of the placenta (abruptio placentae), premature rupture of the membranes (containing the fetus), preterm labor, uterine infections, miscarriages, stillbirths, and premature births are also more likely. In addition, children of women who smoke have slight but measurable deficiencies in physical growth and in intellectual and behavioral development. These effects are thought to be caused by carbon monoxide and nicotine. Carbon monoxide may reduce the oxygen supply to the body's tissues. Nicotine stimulates the release of hormones that constrict the vessels supplying blood to the uterus and placenta, so that less oxygen and fewer nutrients reach the fetus.

Pregnant women should avoid exposure to secondhand smoke because it may similarly harm the fetus.

Alcohol: Drinking alcohol during pregnancy is the leading known cause of birth defects. Because the amount of alcohol required to cause fetal alcohol syndrome is unknown, pregnant women are advised to abstain from drinking any alcohol regularly or on binges; avoiding alcohol altogether may be even safer. The range of effects of drinking during pregnancy is great.

The risk of miscarriage almost doubles for women who drink alcohol in any form during pregnancy, especially if they drink heavily. Often, the birth weight of babies born to women who drink regularly during pregnancy is substantially below normal. The average birth weight is about 4 pounds for babies exposed to large amounts of alcohol, compared with 7 pounds for all babies. Newborns of women who drank during pregnancy may not thrive and are more likely to die soon after birth.

Fetal alcohol syndrome is one of the most serious consequences of drinking during pregnancy. Binge drinking as few as three drinks a day can cause this syndrome. It occurs in about 2 of 1,000 live births. This syndrome includes inadequate growth before or after birth, facial defects, a small head (probably caused by inadequate growth of the brain), mental retardation, and abnormal behavioral development. Less commonly, the position and function of the joints are abnormal and heart defects are present.

Babies or developing children of women who drank alcohol during pregnancy may have severe behavioral problems, such as antisocial behavior and attention deficit disorder. These problems can occur even when the baby has no obvious physical birth defects.

Caffeine: Whether consuming caffeine during pregnancy harms the fetus is unclear. Evidence seems to suggest that consuming caffeine in small amounts (for example, one cup of coffee a day) during pregnancy poses little or no risk to the fetus. Caffeine, which is contained in coffee, tea, some sodas, chocolate, and some drugs, is a stimulant that readily crosses the placenta to the fetus. Thus, it may stimulate the fetus, increasing the heart rate. Caffeine also may decrease blood flow across the placenta and decreases the absorption of iron (possibly increasing the risk of anemia (see Pregnancy Complicated by Disease: Anemia During Pregnancy). Some evidence suggests that drinking more than seven cups of coffee a day may increase the risk of having a stillbirth, premature birth, low-birth-weight baby, or miscarriage. Some experts recommend limiting coffee consumption and drinking decaffeinated beverages when possible.

Aspartame: Aspartame, an artificial sweetener, appears to be safe during pregnancy when it is consumed in small amounts, such as in amounts used in normal portions of artificially sweetened foods and beverages. Pregnant women with phenylketonuria, an unusual disorder, should not consume any aspartame.












Taking Drugs While Breastfeeding
When mothers who are breastfeeding have to take a drug, they wonder whether they should stop breastfeeding. The answer depends on the following:

How much of the drug passes into the milk
Whether the drug is absorbed by the baby
How the drug affects the baby
How much milk the baby consumes, which depends on the baby's age and the amount of other foods and liquids in the baby's diet
Some drugs, such as epinephrine, heparin, and insulin, do not pass into breast milk and are thus safe to take. Most drugs pass into breast milk but usually in tiny amounts. However, even in tiny amounts, some drugs can harm the baby. Some drugs pass into breast milk, but the baby usually absorbs so little of them that they do not affect the baby. Examples are the antibiotics gentamicin, kanamycin, streptomycin, and tetracycline.

Drugs that are considered safe include most nonprescription (over-the-counter) drugs. Exceptions are antihistamines (commonly contained in cough and cold remedies, allergy drugs, motion sickness drugs, and sleep aids) and, if taken in large amounts for a long time, aspirin and other salicylates. Acetaminophen and ibuprofen, taken in usual doses, appear to be safe.

Drugs that are applied to the skin, eyes, or nose or that are inhaled are usually safe. Most antihypertensive drugs do not cause significant problems in breastfed babies. Women may take beta-blockers during breastfeeding, but the baby should be checked regularly for possible side effects, such as a slow heart rate and low blood pressure. Warfarin can be taken if the baby is full-term and healthy, but its use should be monitored. Caffeine and theophylline do not harm breastfed babies but may make them irritable. The baby's heart and breathing rates may increase. Even though some drugs are reportedly safe for breastfed babies, women who are breastfeeding should consult a health care practitioner before taking any drug, even an over-the-counter drug, or a medicinal herb. All drug labels should be checked to see whether they contain warnings against use during breastfeeding.

Some drugs require a doctor's supervision during their use. Taking them safely while breastfeeding may require adjusting the dose, limiting the length of time the drug is used, or timing when the drug is taken in relation to breastfeeding. Most antianxiety drugs, antidepressants, and antipsychotic drugs require a doctor's supervision, even though they are unlikely to cause significant problems in the baby. However, these drugs stay in the body a long time. During the first few months of life, babies may have difficulty eliminating the drugs, and the drugs may affect the baby's nervous system. For example, the antianxiety drug diazepam (a benzodiazepine) causes lethargy, drowsiness, and weight loss in breastfed babies. Babies eliminate phenobarbital (an anticonvulsant and a barbiturate) slowly, so this drug may cause excessive drowsiness. Because of these effects, doctors reduce the dose of benzodiazepines and barbiturates as well as monitor their use by women who are breastfeeding.

Some drugs should not be taken by mothers who are breastfeeding. They include amphetamines, chemotherapy drugs (such as doxorubicin and methotrexate), chloramphenicol, ergotamine, lithium, radioactive drugs for diagnostic procedures, and illicit drugs such as cocaine, heroin, and phencyclidine (PCP). Drugs that may suppress milk production should not be taken. They include bromocriptine, estrogen, oral contraceptives that contain high-dose estrogen and a progestin, and levodopa.

If women who are breastfeeding must take a drug that may harm the baby, they must stop breastfeeding. But they can resume breastfeeding after they stop taking the drug. While taking the drug, women can maintain their milk supply by pumping breast milk, which is then discarded.

Women who smoke should not breastfeed within 2 hours of smoking and should never smoke in the presence of their baby whether they are breastfeeding or not. Smoking reduces milk production and interferes with normal weight gain in the baby.

Alcohol consumed in large amounts can make the baby drowsy and cause profuse sweating. The baby's length may not increase normally, and the baby may gain excess weight.


Illicit Drugs

Use of illicit drugs (particularly opioids) during pregnancy can cause complications during pregnancy and serious problems in the developing fetus and the newborn. For pregnant women, injecting illicit drugs increases the risk of infections that can affect or be transmitted to the fetus. These infections include hepatitis and sexually transmitted diseases (including AIDS). Also, when pregnant women take illicit drugs, growth of the fetus is more likely to be inadequate, and premature births are more common.

Babies born to mothers who use cocaine often have problems, but whether cocaine is the cause of those problems is unclear. For example, the cause may be cigarette smoking, use of other illicit drugs, deficient prenatal care, or poverty.

Hallucinogens, such as methylenedioxymethamphetamine (MDMA, or Ecstasy), rohypnol, ketamine, methamphetamine, and LSD (lysergic acid diethylamide) may, depending on the drug, lead to an increased incidence of spontaneous miscarriage, premature delivery, or fetal/neonatal withdrawal syndrome.

Opioids: Opioids, such as heroin, methadone, and morphine, readily cross the placenta. Consequently, the fetus may become addicted to them and may have withdrawal symptoms 6 hours to 8 days after birth (see Drug Use and Abuse: Opioids). However, use of opioids rarely results in birth defects. Use of opioids during pregnancy increases the risk of complications during pregnancy, such as miscarriage, abnormal presentation of the baby, and preterm delivery. Babies of heroin users are more likely to be small.

Amphetamines: Use of amphetamines during pregnancy may result in birth defects, especially of the heart.

Marijuana: Whether use of marijuana during pregnancy can harm the fetus is unclear. The main component of marijuana, tetrahydrocannabinol, can cross the placenta and thus may affect the fetus. However, marijuana does not appear to increase the risk of birth defects or to slow the growth of the fetus. Marijuana does not cause behavioral problems in the newborn unless it is used heavily during pregnancy.

Drugs Used During Labor and Delivery

Local anesthetics, opioids, and other analgesics usually cross the placenta and can affect the newborn. For example, they can weaken the newborn's urge to breathe. Therefore, if these drugs are needed during labor, they are given in the smallest effective doses (see Normal Labor and Delivery: Pain Relief

1 comment:

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