Vaginal therapeutics

The vagina mucosa absorbs pharmacologically active compounds readily Antibiotics and antifungals are commonly used in the form of suppositories and douches. If the compound can be used systematically for other infections, it is safe via the vagina. Trichomoniasis is usually treated with metronidazole, vaginally or orally. In general, anti-infective treatment is more effective systemically than locally. Of considerable concern is the use of iodine preparations, includ ing providone-iodine...

Vitamin E tocopherol

Vitamin E is not essential for human beings, and deficiencies are unknown. The usual requirement for vitamin E is provided by a normal diet (10-20 1U). There have not, as yet, been any observations of vitamin E deficiency during pregnancy. Among 82 prospectively ascertained pregnancies exposed to high doses of vitamin E during the first trimester (400-1200 IU daily), the birth weight was significantly lower than among non-exposed controls. However, it was not clear whether the authors adjusted...

Gout interval therapy

For women of childbearing age, therefore, gout therapy is only a minimal issue. Gout is caused by an elevated level of uric acid in the blood and in the tissue. Uric acid is the end product of purine metabolism. Interval treatment between gout attacks with uricosurics and allopurinol aims to lower uric acid levels. Uricosurics, like benzbromaron and probenecid, promote the excretion of uric acid by inhibiting renal absorption. Allopurinol causcs a decrease...

Antineoplastic drugs

Corinna Weber-Sch ndorfer and Christof Schaefer 2.13.1 Cancer and pregnancy 33S 2.13.2 Classification of the drugs 2.13.3 Vinca alkaloids and structural analogs 339 2.13.4 Podophyllotoxin derivatives 340 2.13.5 Nitrogen mustard agents 340 2.13.6 Nitrogen mustard analogs 341 2.13.7 Other alkylating agents 342 2.13.8 Cytotoxic anthracyciine antibiotics 343 2.13.9 Other cytotoxic antibiotics 345 2.13.10 Folate antagonistic antimetabolites 346 2.13.11 Purine-derived antimetabolites (purine...

Injectable anesthetics

Etomidate, ketamine, methohexital, propofol, and thiopentone (ithiopental) are among the injectable anesthetics. If administered intravenously, injectable anesthetics reach their maximum concentrations immediately. The concentration in plasma falls rapidly due to rapid redistribution and excretion. After use in labor, the longer the time between the injection of the anesthetic and the infant's birth, the lower the concentration in the newborn, and the less the possible transient effects of...

Coal tar and slate oil preparations

Coal tar as treatment for neurodermatitis has not been suspected of having a teratogenic effect. A retrospective study of 23 exposed women revealed nothing notable (Franssen 1999). Experimentally, coal tar products have, to some extent, demonstrated mutagenic or carcinogenic properties, but there has not yet been any indication of this in the longstanding and well-tried use of the group of substances employed therapeutically in humans. The slate oil extracts ammonium bitumen sulfonate and...

Hepatitis C

Hepatitis C is transmitted in a similar way to hepatitis B. Contaminated syringes and blood products are the most critical sources of infection, although the latter has become significantly less of a risk factor since 1993 due to mandatory testing of all blood donations. Hepatitis C infection is typically asymptomatic or mild. Drug addicts are not infrequently infected simultaneously with HIV. hepatitis B, and hepatitis C. Concomitant HIV infection is linked with higher risk of vertical...

Insulin and oral antidiabetics

Insulin as a proteohormone does not reach the mother's milk, and is not absorbed intestinally. Any effect on the infant can therefore be ruled out. Neither glibenclamide nor glipizide were detected in the breast-milk of three mothers. Hypoglycemia was not observed in any of the children. In another eight women receiving a single dosage of gliben clamide, no substance was found in milk. A high protein-binding of 98 could explain these results (Feig 2005). Only small amounts of metformin are...

Fluorescein

Fluorescein (fluorescein sodium) has yellow coloring, and is used as a diagnostic agent as topical, ophthalmic and intravenous solutions, ft is excreted into breast milk. Fluorescein is photosensitive and there is a risk of phototoxicity, especially in neonates who may require phototherapy (i.e. extensive light exposure). There is a case reported of a premature infant who received the compound directly, and had a skin reaction (Kearns 1985). A woman was given 5 ml intravenous dose of a 10...

Dermatological medications and local therapeutics

2.17.1 Typical skin changes during pregnancy 441 2.17.2 Anti-infective agents 442 2.17.3 Antiseptics and disinfectants 444 2.17.6 Camphor and menthol 448 2.17.7 Coal tar and slate oil preparations 448 2.17.8 Local immunomodulators and neurodermatitis therapy 449 2.17.12 Sex hormones and cyproterone 2.17.15 Scabies and lice medications 458 2.17.16 Diethyltoiuamide and icaridin 458 2.17.17 Eye, nose, and ear drops 459 2.17.18 Hemorrhoid medications 461 2.17.19 Vein thetapeutfcs 462 In this...

Efficacy of immunization in breastfed infants

Many myths have circulated regarding the efficacy of immunization of the infant during breastfeeding. Actually, the immunogenicity of some vaccines is increased by breastfeeding, but long-range enhancement of efficacy has not been studied. In any case the response to vaccines while breastfeeding is not diminished, and the usual vaccination schedules should be followed. Hepatitis A vaccine is available in two preparations which are prepared from cell culture-adapted hepatitis A virus which has...

Selective adrenergic agonists

.- -adrenergic drugs specifically act at . -receptors. The intermediate-acting -adrenergic agonists bitolterol, fenoterol, metaproterenol, pir-buterol, reproterol, salbutamol (albuterol), terbutaline, and tulobuterol, and the long-acting -adrenergic agonists formoterol and salmeterol, belong to this group and are used for the treatment of asthma. . -agonists cause bronchodilation. They also inhibit uterine contractions in the second and third trimesters, and therefore are effective in the...

Amphotericin B

Amphotericin B can be applied locally or can be used as a systemic therapy for mycosis - for instance, in systemic Candida infection, cryptococcosis, and coccidiomycosis. Amphotericin B is bound to ergosterol in the fungal cell membrane, and causes a disturbance in the permeability of the ceil membrane. This antimycotic can cause febrile reactions, electrolyte disorders, and nephrotoxicity, when administered parenterally. Amphotericin B crosses the placenta and may be retained in the placenta...

Phnobarbital and primidone

Among barbiturates, ph nobarbital and primidone have proven themselves as AEDs. These probably achieve their anticonvulsant effect by stabilizing the neuron membranes. Primidone is converted to the metabolites ph nobarbital and phenylethylmalonamide, which have an anticonvulsant action. Because the indications, effectiveness, half-lives, and undesirable side effects of primidone and ph nobarbital in pregnancy are similar, only ph nobarbital will be described extensively. Barbiturates used as...

Hallucinogens

Marijuana (cannabis, Indian hemp, hashish), along with alcohol, nicotine, and ecstasy, is among the drugs most commonly used during pregnancy. The carbon monoxide concentration in the blood caused by marijuana is thought to be five times higher than that caused by tobacco, and the coal tar content in the blood is three times higher. Tetrahydrocannabinol, the active ingredient in marijuana, crosses the placenta and can lead to a decline in the baby's heart frequency. The rate of birth defects is...

Camphor and menthol

A small amount of camphor applied to the skin has a cooling and local anesthetic effect. Rubbing it in vigorously enhances the circulation to the skin. Because of these effccts, camphor and other essential oils arc included in a large number of hyperemia-causing dcrmatological products. Menthol is used topically for itching. No teratogenic action has, as yet, been observed in either animal or human studies for topical application. Recommendation. Camphor and other essential oils may be used...

Herbs frequently used during pregnancy

Herbs are frequently used as teas or infusions. Although there are no clinical trials available, and there is no evidence-based proof in terms of Western medical standards, some herbal teas infusions have been used for many years without adverse effects, and arc considered to be safe. The evidence of their safety comes from their traditional use and from traditional evidence passed down through history by traditional users. Although there are no data to suggest how much is safe, it is suggested...

Counseling a pregnant woman about herbs

For the above reasons, it is difficult even for an experienced healthcare provider to counsel a pregnant woman on the use of herbal preparations. As providers, evidence-based medicine is expected. However, few herbs and natural therapies even have good scientific evidence, never mind the evidence-based medicinc that people expect today. RaLher, herbal therapies use more traditional evidence as their proof of safety. This is evidence passed down by culture and tradition, and is often only oral....

Herbs during pregnancy

2.19.1 The safety of herbs during pregnancy 485 2.19.2 Counseling a pregnant woman about herbs 486 2.19.3 General concepts regarding the use of herbs during 2.19.4 Herbs used as foods 489 2.19.5 Essential oils that are safe during pregnancy 489 2.19.6 Herbs frequently used during pregnancy 490 2.19.7 Herbs controversially used during pregnancy 491 2.19.8 Herbs contraindlcated during pregnancy 491 Plants and plant extracts have been used for medicinal purposes since before recorded time. Many...

Radiation associated with the nuclear industry

Although background ionizing radiation is a known mutagen, few studies have examined transgenerational effects in human beings. Chernobyl, in the former USSR, was the site in 1986 of probably the worst accident ever to have occurred at a nuclear plant. Considerable quantities of radioactivity were released into the atmosphere, much of which was dispersed over the former Soviet Union and Western and Northern Europe. The radioactivity from the accident was washed from the skies and entered the...

Diuretics

With therapy using diuretics, milk production can decrease, especially if there was already some lactational deficiency. Displacement of bilirubin from the plasma protein binding in newborns was discussed for furosemide and the thiazides. A risk of kernicterus as a result should not, however, be considered a realistic possibility (see also section 3.6). Chlorthalidone has a half-life of 44 hours or more. Long-term treatment with 50 mg daily leads to an accumulation with values of up to 0.86 mg...

Antiemetics

Antihistaminics and other compounds are used as antiemetics. Very rarely, mild restlessness, sedation or weak sucking - none of which require treatment - have been described in the breastfed infant (see, for example, Moretti 1995). There is no detailed knowledge regarding the effects during breastfeeding of the following substances betahistine, cinnarizine, dimenhydrinate, diphenhydramine, flunarizine, meclizine, and scopolamine patches, nor of the newer serotonin-(5-HT3) antagonists...

General concepts regarding the use of herbs during pregnancy

There are a few points that are important for consideration of the use of herbs in pregnancy 1. Herbs should only be recommended by a competent and qualified provider caring for the pregnant woman, and one who is comfortable with and knowledgeable about the efficacy and risk assessment of herbs in pregnancy. IL is well worth becoming familiar with Blumcnthal (2003), Rotblatt (2002), and ConsumerLab.com. 2. Herbs are extracts of plants or plant roots, and they contain numerous compounds....

Ivermectin and diethylcarbamazine

Ivermectin is a highly effective drug in the treatment of onchocerciasis (river blindness) and lymphatic filiriasis. Reports from animal studies do not indicate a teratogenic potential of this drug. In some cases inadvertent exposure during pregnancy has occurred without apparent adverse effects (Gyapong 2003), but data are not sufficient for risk estimation. Diethylcarbamazine is used for the treatment of filiriasis and onchocercosis. No teratogenicity was reported in animal studies. No...

Other fibrinolytics

Urokinase is a plasminogen activator that is normally found in mammalian blood and urine. It plays an important role in the solution of physiologic clotting - for instance, in menstrual bleeding. It also is thought to play a role in preventing microthrombi in the placental circulation. There are insufficient data on the use of urokinase during pregnancy. In a few cases, the therapeutic use of urokinase during pregnancy was followed by the delivery of a healthy infant (la Valleur 1996,...

Antiestrogens antiandrogens and danazol

Bicalutamide, cyproterone, and flutamide belong to the group of antiandrogens. Aminoglutethimide, anastrozole, formestan, raloxifene, and tamoxifen are antiestrogen drugs. Danazol is a gonadotropin inhibitor with androgenic activity. (Foraminoglutethimide and tamoxifen, see Chapter 2.13.) Cyproterone acetate is the antiandrogen most commonly used during the reproductive years. It is available in combination with ethinylestradiol. This preparation is frequently prescribed as the pill, especially...

Parkinson drugs

Apart from the more widely used ergotamine derivatives, bromocriptine and cabergoline, there is little experience regarding the use of Parkinson drugs in breastfeeding. There is insufficient experience on the use of amantadine, benserazide, benzatropine, biperiden, bor-naprine, budipin, carbidopa, n-dihydroergocryptine, entacapon, lev-odopa, lisurid, metixen, pergolide, pridinol, pramipexol, procyclidine, ropinirol, tiaprid, trihexyphenidyl, and the monoaminooxydase-B (MAO-B) inhibitors...

Essential oils that are safe during pregnancy

Some essential oils can be safely used as aromatherapy during pregnancy, based on traditional and historic use. There are no evidenced-based studies that will assure their safety. They should always be used carefully, in a well-diluted form, and should not be ingested. They should be used in an aromatherapy diffuser. Such oils, and their uses, are listed in Table 2.19.1. (See Low Dog 2005, Fleming 2004, Blumenthal 2003, Weed 1986.) Table 2.19.1 Essential oils considered to be safe during...

Vitamin K antagonists

Coumarin derivatives (4-hydroxycoumarin compounds) are oral anticoagulants (OA) that prevent vitamin K from acting as a cofac-tor in the hepatic synthesis of the vitamin K-dependcnt coagulation factors II. VII, IX, and X (as well as the anticoagulants, proteins C and S). They arc also called vitamin K antagonists (VKA). Available coumarin derivatives are acenoeoumarol, phenprocoumon, and warfarin. Apart from coumarins, the indanediones, fluindione and phenidione, are used as a VKA for the same...

Hemorrhoid medications

Hemorrhoid medications (salves and suppositories) are local therapeutics which, for the most part, contain local anesthetics, glucocorticoids, antibiotics, and disinfectants, either as individual substances or in combination. These preparations are also used following surgical procedures in the rectal-anal area. Substantial absorption is not to be expected. There are no reports on fetal toxicity of the usual hemorrhoid medications. Recommendation. The usual hemorrhoid medications have proved to...

Dopamine antagonists

The dopamine antagonists used to treat NVP are metoclopramide, phenothiazines, domperidone, droperidol, and trimethobenzamide. Metoclopramide is an effective antiemetic that acts both centrally (causing dopamine blockade in the chemoreceptor trigger zone and decreasing sensitivity of the visceral nerves that transmit G1 impulses to the central emetic center) and peripherally by stimulating motility of the upper gastrointestinal tract and increasing the lower esophageal sphincter basal tone....

Other prokinetic agents

Metoclopramide, bromopride, cisapride, and domperidon are licensed for treating motility disturbances in the upper intestinal tract. Dexpanthenol is used for intestinal atonia. Metoclopramide is discussed in Chapter 2.4. In a prospective, controlled multicenter study, the authors concluded that exposure to cisapride during pregnancy was not associated with an increased risk of malformations or other adverse effects, although the sample size (88 first-trimester exposures) is too small to draw...

Valproic acid

Valproic acid (valproate, VPA) is effective for different forms of epilepsy, and apparently leads to an increase in the concentration of the inhibiting transmitter substance, -ramino butyric acid (GABA), in the brain. Valproic acid is well-absorbed after oral intake, and up to 95 is found in the plasma bound to the proteins. The lipophilia explains valproic acid's ability to cross the blood-brain barrier and the placenta. Towards the end of pregnancy, valproic acid is metabolized rapidly via...

Benzodiazepines

Benzodiazepines arc among the most commonly used anxiolytic drugs by women of reproductive age and pregnant women. They have anxiolytic, anticonvulsant, hypnotic-sedating, and muscle-relaxing properties. They are structurally related, and act on specific benzodiazepine receptors. The half-life may vary considerably, and depends mainly on the biologic activity of the metabolites, which are formed in the liver via oxidation. Benzodiazepines cross the placenta. The rate of metabolism in the...

Herpes simplex

Perinatal herpes infections are transmitted during birth because of the presence of the virus in the birth canal. When lesions are present near the anticipated time of delivery, a cesarian section is performed immediately when labor starts or the membranes rupture, to avoid infection of the infant. With the exception of one case (Dunkle 1979), no herpes simplex virus has been detected in mother's milk. This is as would be expected, because the infection in adults is usually a local one that...

Aciclovir and other herpes antivirals

Aciclovir (acyclovir) is an acyclic nucleoside analog, highly specific for HSV-infected cells. It inhibits viral ribonucleotide production in Herpes 1 and 2 and in varicella zoster infections. Valaciclovir is the prodrug of aciclovir, with the benefit of a greater bioavailability and a longer half-life (less frequent dosing). Aciclovir can cross the placenta, and fetal aciclovir levels arc comparable to maternal levels once a steady state is reached. It is concentrated in the amniotic fluid,...

Typical skin changes during pregnancy

The adaptation of the organism during pregnancy leads to typical morphological and functional changes in the skin. These are completely normal and do not need treatment. They include the following Pigmentation. Spotty hyperpigmentation (melasma) may appear on the face, and usually disappears spontaneously after birth. This is intensified by exposure to UV light (i.e. to direct sunlight), and using sun block can minimize it. Additionally, pigmentation of the nipples and the areola, the area...

Sex hormones and cyproterone acetate

Pharmacology and toxicology Androgens, such as testosterone, act directly on hair growth and the sebaceous glands this explains juvenile acne during puberty. Because of their anti-androgenic properties, a great many sex hormones, such as many progestins gestagens and estrogens and, in particular, the inhibiting substance cyproterone acetate, have an anti-acnc action. This cffcct is used therapeutically. Most widely used is the combination of ethinylestradiol and...

Tricyclic and tetracyclic antidepressants

Tricyclic antidepressants (TCAs) inhibit the reuptake of the neurotransmitters, noradrenaline and serotonin, in the adrenergic neurones, which results in increased concentrations of those neurotransmitters at the receptor. Imipramine, a tertiary amine, is the prototype of a TCA. Other members of this group are amitriptyline, clomipramine, dibenzepin, dosulepine, dothiepin, doxepin, imipramine, lofepramine, protripty-line, and trimipramine. Desipramine and nortriptyline are secondary amines,...

Dimeticon and plantbased carminatives

Substances that relieve meteorism are collectively referred to as carminatives. Among these are caraway, anise, and peppermint with their active essential oils. They are viewed as safe in pregnancy (see also Chapter 2.19). Dimeticon simethicone is a silicone product that is used as an antiflatulcnt. It dcfoams and disperses gas bubbles that accumulate in the gastrointestinal tract, causing meteorism. In this way, it makes transport of the intestinal contents easier. It is not absorbed, and is...

Other drugs

With a 20-mg intake of amphetamines daily, levels of 55-138 ig l were detected in breast milk. An M P ratio ranging from 2.8 to 7.5 was calculated (Steincr 1984). A relative infant dose of up to 3 would result from these values. Another study could not find any symptoms among 103 infants whose mothers took various amounts of amphetamines (Ayd 1973). Two publications report on phencyclidine in breast milk (Kaufman 1983, Nicholas 1982). However, these data are insufficient to assess its risk....

References

American Academy of Pediatrics, Committee on Drugs. The transfer of drugs and other chemicals into human breast milk. Pediatrics 2001 108 776-89. Anderson E, Held N, Wright K. Raynaud's phenomenon of the nipple a treatable cause of painful breastfeeding. Pediatrics 2004 113 360-64. Begg E). Robson RA. Gardiner S et al. Quinapril and its metabolite quinaprilat in human milk Br Clin Pharmacol 2001 51 478-81. Bennett PN (ed.). Drugs and Human Lactation, 2nd edn. Amsterdam Elsevier. 1996. Boutroy...

Cytotoxic anthracydine antibiotics

Daunorubicin interferes with DNA synthesis. The molecular size and relative hydrophilia of daunorubicin considerably restrict and delay its transfer to the placenta. According to Germann (2004), the concentrations in fetal tissues are between 100-fold and a 1000fold lower than in adult and tumor tissues, respectively. In his review, Briggs (2005) describes 29 pregnant women, of whom 4 had been exposed during the first trimester (Feliu 1988, Alegrc 1982). The 22 children born alive did not show...

Herbs contraindicated during pregnancy

There are numerous herbs that are thought to be contraindicated during pregnancy, or that traditional herbalists consider potentially contraindicated during pregnancy. Studies are minimal, however. (See Low Dog 2005, Blumenthal, 2003, 1998, Weed 1986.) These herbs can be classified into five subgroups for an understanding of their potential effect on a pregnant woman 1. Herbs used traditionally to stimulate menstruation (Table 2.19.4). Herbs that may stimulate the smooth muscle of the uterus...

Peristaltic stimulators

The antiemetic metoclopramide eases the emptying of the stomach and increases the milk production via its central antidopaminergic action. It may be used for a few days at a dosage of 3 x 10 nig per day to promote milk production see also section 3.7). The young infant whose mother takes 3xl0mg daily over many weeks receives a maximum of 4.7 of a weight-related child's dosage. Only in one case among more than 20 mother-child pairs could the substance be measured in the infant's plasma (Kauppila...

Development and health

The care of pregnant women presents one of the paradoxes of modern medicine, Women usually require little medical intervention during an (uneventful) pregnancy. Conversely, those at high risk of damage to their own health, or that of their unborn, require the assistance of appropriate medicinal technology, including drugs. Accordingly, there are two classes of pregnant women the larger group requires support but little intervention, while the other requires the full range of diagnostic and...

Constipation during pregnancy

Constipation is common during pregnancy, occurring in up to one-third of women. Constipation during pregnancy is probably caused by progesterone-related changes in both small bowel and colon motility, and by the increased absorption of water and electrolytes during pregnancy. The subjective experience of the pregnant woman (a feeling of fullness due to the growing uterus) ccrtainly also plays a role. Therefore, before prescribing laxatives it must be determined whether there is, in fact, any...

Hyperosmotic and saline laxatives

Lactulose, a poorly absorbed disaccharide, and its analog, lactitol, increase osmolar tension, creating an increase in water collection, distension, peristalsis, and evacuation. Lactulose is widely used, and in moderate use it is well tolerated. Poorly absorbed alcohols such as mannitol and sorbitol are used with the same effect. Macrogol works similarly macrogols with a molecular weight of more than 3000 arc not absorbed. Saline laxatives are poorly absorbed as well they work in a similar way...

Anthraquinone derivatives

Anthraquinone derivatives with a laxative action occur in a number of plants folia sennae, rhizoma rhei, cortex frangulae, and aloe. They have a laxative effect by directly stimulating colonic smooth muscles. Anthraquinone derivatives occur as glycosides. After the sugar portion is cleaved in the intestine, these agents are partially absorbed and excreted in the urine (colored ). Anthraquinone derivatives do not appear to be teratogenic. Reported experience is the most extensive with senna...

Arterial hypertension and pregnancy

Different kinds of arterial hypertension should be distinguished from one another as follows (for pulmonary hypertension, see section 2.8.14) m Chronic hypertension (with or without proteinuria) which was diagnosed before, during or after pregnancy Pre eclampsia, eclampsia that is proteinuria (> 300mg d), and newly diagnosed hypertension (edemas are no longer necessary symptoms) Pre-eclampsia in a pregnant woman with pre-existing chronic hypertension, which occurs in 20-25 percent of all...

Monoaminoxidase inhibitors MAOIs

MAOIs inhibit the enzyme, monoaminoxidase, which is responsible for the metabolism of neurotransmitters. The inhibition is either reversible, as with the newer MAOIs (e.g. moclobemide), or irreversible, as with the older MAOIs (e.g. isocarboxazid, phenelzine, and tranylcypromine). MAOIs have been associated with a high incidence of toxicity in man. There is a possible interaction between tyramine (which is present in high-protein food and drinks) and MAOIs, which may manifest itself as an acute...

Selective immunosuppressants

Tacrolimus is a macrolide obtained from Streptomyces, and is widely used as an immunosuppressant in transplant medicine. Skin diseases such as neurodermatitis are another indication this will be discussed elsewhere (see Chapter 2.17). Certain advantages and disadvantages of tacrolimus in pregnancy are discussed compared to cyclosporine rejection and hypertension are less common with tacrolimus, and the necessary dosage of prednisolone is lower. On the other hand, gestational diabetes occurs...

Diabetes mellitus and pregnancy

Diabetes mellitus is the collective name for heterogeneous disturbances of metabolism which all are characterized by chronic hyperglycemia. In essence, there are three different types. While type I is caused by a disturbed secretion of insulin, type II and gestational diabetes are characterized by a disturbed action of insulin. Both causes can also occur simultaneously. A poor glyccmic control in prcgestational diabetes, as measured by glycosylated hemoglobin (HbAlc > 6.5 ), is correlated...

General and local anesthetics and muscle relaxants

2.16.1 Halogenated inhalation agents for general anesthesia 424 2.16.2 Ether (diethyl ether) 426 2.16.4 Injectable anesthetics 427 2.16.5 Local anesthetics 431 2.16.6 Epidural and spinal analgesia anesthesia in pregnancy 432 2.16.7 Muscle relaxants 433 2.16.8 Occupational exposure to inhalation anesthetics 434 Due to their lipid solubility, general anesthetic agents rapidly cross the placenta. They also rapidly cross the blood-brain barrier - hence their instantaneous effects on the brain....

Griseofulvin

Griseofulvin is an organically derived antifungal agent it is used as an oral preparation for the treatment of dermatophytosis of skin, hair and nails. Because it is deposited in keratine, it is suitable for the therapy of nail mycoses. In animal experiments it has a teratogenic effect and, moreover, a carcinogenic effect in high doses. Experience in human pregnancy is limited. In one report, two pairs of conjoined twins were observed after use of griseofulvin in pregnancy (Rosa 1987) however,...

Other contaminants

A case report describes obstructive icteric liver disease in a breastfed baby after exposure to the volatile organochlorine tetrachloroethene (PER), which is used as a cleaning agent. The mother had visited her husband every day at his workplace, which was apparently strongly contaminated. This also led to neurological symptoms in the mother (Bagneli 1977). A milk sample given an hour after maternal exposure had 10 mg tetrachloroethene . After 24 hours, the level was still 3 mg l. The baby's...

Chenodeoxycholic acid and ursodeoxycholic acid

Ursodeoxycholic acid (UDCA) is a naturally occurring bile acid that has been used to change the composition of bile in an effort to dissolve gallstones, and in the management of chronic cholestatic disorders. It also has been used as a therapy for intrahepatic cholestasis of pregnancy. Intrahepatic cholestasis of pregnancy is characterized by maternal pruritis with elevated serum bile acids and liver-function test abnormalities, and associated with an increased rate of fetal distress,...

Gastritis and peptic ulcer during pregnancy

During prcgnancy, motility changes occur throughout the gastrointestinal tract. These changes are largely attributed to increased levels of progesterone and estrogen. The mechanisms promoting gastroesophageal reflux during gestation primarily involve decreased lower esophageal sphincter (LF.S) pressure and a decrease in the sphincter's adaptive responses, but mechanical factors may also be important. Gastroesophageal reflux and heartburn are common during pregnancy. In mild cases, lifestyle and...

Intrauterine devices

In women who use a copper IUD as a contraceptive, the copper concentration in the fallopian tubes is elevated, but copper and cerulo-plasmin levels in the serum are not changed (Wollen 1994). A number of reports suggest thaL pregnancy in association with copper IUDs results in an increased rate of spontaneous abortions and preterm birth in the group in which the IUD remained in the uterus, compared with the group in which the IUD was removed or expelled. No increase in the rate of birth defects...

Quinolones

Quinolones impair bacterial DNA metabolism by inhibiting DNA gyrase. They have bactericidal activity at normal doses at higher doses they have also bacteriostatic properties by inhibiting bacterial RNA and protein synthesis. Quinolones have a high affinity for cartilage and bone tissue this affinity is highest in immature cartilage. Pipemidic acid, cinoxacin, and nalidixic acid belong to the group of older quinolones. They concentrate in the urinary tract. Few data on their safety during...

Dihydroergotamine and other antihypotensives

Dihydroergotamine could not be detected in mother's milk. Generally speaking, ergotainine derivatives, as prolactin inhibitors, could inhibit the milk production. There is insufficient experience with the antihypotonics, etilefrine and norfenefrine, as weli as with amezinium, gepefrin, midodrin, and pholedrin. Recommendation. The use of dihydroergotamine during breastfeeding is considered safe. However, non-drug measures (sports, the use of cold water and brushes, moderate coffee consumption)...

Nonselective 3adrenergic agonists

Non-selective -adrenergic agonists are not recommended for asthma treatment. Some of these drugs are used in oral OTC drugs for the common cold. These combinations do not follow good therapeutic practiccs, and arc not recommended during pregnancy. Hexoprenaline, isoprenaline, and orciprenaline Hexoprenaline, isoprenaline (isoproterenol), and orciprenaline have a stimulating cffect on .Vreceptors. They are non-selective . -adrenergic agents that act on both ,5p and ( -receptors, and therefore...

Acetylsalicylic acid

The half-life of salicylates in mother's milk is more than 7 hours, which is decidedly longer than in plasma. The highest values are reached in just about 3 hours. Following a single dose of 500 mg acetylsalicylic acid, a maximum of 7.8 mg 1 was measured in the milk after 1000 mg this rose to 21 mg I, and after 1500 mg it was 48 mg 1 (Jamali 1981). If these high concentrations apply, an infant can consume between 0.2 and 1.4 mg acetylsalicylic acid per kg bodyweight at each breastfeed. This...

Photochemotherapy and fumaric acid

Photochemotherapy (PUVA therapy) for extremely severe psoriasis is given either orally or - as preferred today - by external application of 8-methoxypsoralen followed by long-wave UVA irradiation. The psoralen is activated chemically through the UV light, binds more strongly to the DNA, and damages the cells. The cytotoxic effect of PUVA treatment is minimal because of the limited depth of penetration. The European Network of Teratology Information Services (ENTIS) analyzed 41 pregnancies in...

Herpes zoster shingles chickenpox

Perinatal varicella infection can lead to severe infection in the infant if the maternal rash develops 5 days or less before delivery, or within 2 days after delivery. Illness in the infant usually develops before 10 days of age, and is more severe because of lack of maternal antibodies. The infant should receive varicella zoster immunoglobulin (VZIG). The infant can be infected by aerosolized virus from lesions or the maternal respiratory track. Postnatal varicella can develop from...

Methylergometrine methylergonovine

With therapy using 2 x 0.125 mg methylergometrine up to l.Ipg 1 was measured in the milk. This is a maximum of 0.16 pg kg of the infant's bodyweight, or 3.1 of the maternal weight-related dosage. In a more rccent study on 20 women with postpartum uterine atony, either 250 ng methylergometrine or 200 pg misoprostol were applied 4.11.3 Bromocriptine and other prolactin inhibitors orally (see also section 4.11.13). The maximum methylergometrine concentration in milk was reached at 2 hours. It has...

Other cytotoxic antibiotics

Bleomycin is a glycopcptidc antibiotic. These antineoplastic drugs appear to affect DNA binding, and act via radical formation. Isolated clinical reports are available on cases of Hodgkin's lymphoma, non-Hodgkin's lymphoma, and teratoma treated during the second and third trimesters of pregnancy. No fetal anomalies or chromosome changes were reported in these cases (Lowenthal 1982). Transient neonatal leukopenia and neutropenia were observed in a premature infant born to a woman who had been...

Quinine

Quinine is the oldest antimalarial agent. It has a good and rapid sch-izonticide activity against the erythrocytic forms of all Plasmodium species. In spite of relatively high toxicity and a narrow therapeutic range, it is used more often for the treatment of chloroquine-resistant malaria today. Concentrations in the fetus are just as high as in the mother, and arc potentially toxic. There are some reports describing eye defects and hearing loss in children after use of quinine in pregnancy....

Phenothiazines and thioxanthenes

Phenothiazines are effective in the treatment of psychosis and of hyperemesis, as they also block histamine receptors. They readily cross the placenta elimination is much slower by the fetus and the neonate than by adults. Chlorpromazine is the prototype of phenothiazines, and is structurally related to promethazine, which is used as an antihistamine. Phenothiazines block the dopamine receptors in the basal ganglia, the hypothalamus, and the limbic system. Due to their effect on dopamine...

Acetylcysteine and other mucolytics

Acetylcysteine, ambroxol, and bromhexine are widely used and well-tolerated during breastfeeding. There are no details available on their kinetics. Carbocisteine, guaiacol, guaifenesin, mesna, and preparations with essential oils such as cineol, myrtle, lime, and eucalyptus are probably also well-tolerated during breastfeeding, but here too there are no systematic studies to date. Essential oils can change the taste of the milk and lead to feeding problems. Iodine from potassium iodate...

Dapsone nitrofurantoin and other drugs for urinary tract infections

In the case of therapy with dapsone, 10-20 of the weight-related dosage can pass into the milk (Edstein 1986, Sanders 1982). In a case description, dapsone and its primary metabolite, monoacetyl-dapsone, were documented in the child's serum. The infant developed hemolytic anemia (Sanders 1982). After a single dose of lOOmg nitrofurantoin to four women, an average of 1.3 ng ml was measured in the milk the maximal measurement (about 5 hours after administration) was 3.2 ng ml. The M P ratio was 6...

European Israelian and Latin American Teratology information centers collaborating in the European Network of

Additional information and addresses not presented below can be found at www.entis-org.com L nea Salud Fetal, Servicio de Informaci n de Agentes Teratog nicos Health care professionals and general public Institut f r Zellbiologie, Histologie und Embryologie Harrachgasse 21 7 Medizinische Universit t 8010 Graz Tel, +43 316 3804256 Fax +43 316 3809625 E-mail herbert.juch meduni-graz.at Health care professionals and general public Sistema de informato sobre Agentes Teratogenicos (SIAT) Hospital de...

Local immunomodulators and neurodermatitis therapy

Tacrolimus and pimecrolimus are used as local treatment for neurodermatitis. Although there arc no studies regarding topical use, these exist for systemic use of tacrolimus in transplant medicine (see Chapter 2.12). The results do not indicate a risk of developmental disorders. Obviously, serum levels after local treatment with tacrolimus are much lower than in transplant patients. Therefore, this substance can be used topically when there are no acceptable alternatives. There are no data...

Vein therapeutics and other local therapeutics

Local sclerosing therapy to treat varicose veins usually involves sodium tetradecyl sulfate or polidocanol, which irritates the intima of the vein. It is injected into the empty vein and compression bandages are applied, keeping the leg elevated. It takes about 3 weeks for the vein to sclerose. The chemical is removed from the vein within a few hours. It is not circulated or absorbed, and is safe during lactation (Beers 1999). Aescein preparations (horse-chestnut extract) are insufficiently...

Amount of medication in the milk and relative dose

The simple calculation to determine the amount of the drug which the infant would consume via the milk in a day's time can be calculated by multiplying the concentration in the mother's milk (CM) by the volume of milk consumed (VM). The amount of milk produced daily is between 500 and 900 ml. This amount is achieved about 4 days after birth, in order to better compare the different medications, the average daily amount per kg bodyweight that the infant takes in, rather than the individual total...

Hydralazine and dihydralazine

Hydralazine and dihydralazine are structurally similar vasodilator drugs that have been used for the treatment of hypertension in pregnancy for over 40 years. Following oral administration, up to 80 percent absorption occurs, and approximately 66 percent of the drug is deactivated in the liver. The half-life is 2-8 hours. Hydralazine and dihydralazine cross the placenta well, and cord-blood drug concentrations may exceed those in the mother (Franke 1986). Although results from animal studies...

Conazole antimycotics for systemic use

Itraconazole and miconazole are systemically used antimycotics belonging to the group of imidazole derivatives. These agents inhibit the ergosterol biosynthesis, thereby causing disturbances in the permeability and functions of the fungal cell membrane. In animal experiments, they cross the fctal-placental barrier easily. Fluconazole and ketoconazole are triazole derivates. Their activity matches that of the structurally related imidazole derivatives. In animal experiments, teratogenic effects...

Vitamin K antagonists coumarin derivatives and indanediones

Acenocoumarol, phenprocoumon, and warfarin are the coumarin derivatives used as oral anticoagulants fluindione and phenindione belong to the group of indanediones with vitamin K antagonistic effects. The most widely used substances (warfarin, phenprocoumon, and acenocoumarol) have a very high protein binding (> 95 ), and thus only very small amounts would be expected in the mother's milk. Acenocoumarol and warfarin could not be detected in the milk at all (survey in Bennett 1996). In women...

Recommendations newer antiepileptics

As monotherapy, new antiepileptics are compatible with breastfeeding. However, close observation of the infant is recommended regarding drugs where there has been little experience or where substantial transfer has been documented. If there are any symptoms that could be associated with maternal drug therapy, the serum concentration in the child should be measured. To limit exposure, it may be necessary to supplement with formula or cease breastfeeding. In cases of prematurity,...

Reproductive and developmental toxicology

Reproductive toxicology is the subject area dealing with the causes, mechanisms, effects and prevention of disturbances throughout the entire reproductive cycle, including fertility induced by chemicals. Teratology (derived from the Greek word -repos which originally meant star later meanings were wonder, divine intervention and, finally, terrible vision, magic, inexplicability) is the science conccrned with the birth defects of a structural nature. However, the terminology is not strict, since...

Caffeine and other xanthine derivatives

The methyl xanthine derivatives caffeine and theobromine act as stimulants on the central nervous system as well as on the heart, circulation, and respiration. They are the pharmacologically effective components in a number of drinks, such as coffee, tea, cocoa, and coia beverages. Caffeine is also an ingredient in many over-the-counter pain and cold medications (see also Chapter 1.19). Theophylline is one of the methyl xanthines. The action of this asthma medication is described in Chapter...

Scabies and lice medications

Benzyl benzoate, lindane, and the pyrethroid allethrin are available for external use in treating scabies. Ivermectin is indicated for oral usage. For lice, coconut oil, pyrethrum extract, the pyrethroids allethrin and pyrethrin, and lindane are used. Crotamiton and the pyrithroid permethrin are used for both scabies and lice infestations. Benzyl benzoate was banned in the USA because its metabolite, benzyl alcohol, was associated with neonatal fatal intoxication (the gasping syndrome, with...

Circulatory drugs and vasodilators

A hearing loss, or so-called sudden deafness, occasionally appears in the weeks after the birth. Therapeutically, intravenous hydroxy ethyl starch and other medications are prescribed that are said to promote circulation in the inner ear, None of these therapeutic measures have, as yet, been proven effective. Naftidrofuryl and its primary metabolite LS74 appear only in traces in the milk. Within 72 hours, only about 300 ig of the total administered 3500mg had been excreted in the milk. With...

Occupational exposure to inhalation anesthetics

Pregnant women employed in operating rooms (ORs) may be chronically exposed to physical work load as well as to low doses of waste anesthetic gases. Volatile and gaseous inhalation anesthetics are administered as mixtures in different combinations, and can be delivered to the patient through an endotracheal tube or via a face-mask. Until several years ago, ventilation systems were apparently not efficient enough in preventing exposure to relatively high levels of anesthetics. Modern ORs are...

Myotonolytics

Among the myotonolytics, in the broadest sense, there are very different agents, such as baclofen, carisoprodol, quinine ethyl carbon-ate, chlormezanone, Clostridium botulinum toxin, dantrolene, fenyramidol, mephenesin, methocarbamol, orphenadrine, pridinol, tetrazepam, tizanidine, and tolperisone. For antiepileptics used for the treatment of neuropathic pain, see Chapter 4.8. There is one case report on baclofen in which a maximum of 0.13 mg 1 was measured in the mother's milk following a...

Folate antagonistic antimetabolites

As early as the 1950s malformations were being described resulting from treatment with aminopterin, a substance related to methotrexate (Warkany 1959, Meltzer 1956, Thiersch 1952). There are reports about failed terminations of pregnancies using aminopterin, in which malformations such as the following have been described CNS anomalies (meningo-encephaiocele, hydrocephalus, brachy-cephaly, anencephaly) anomalies of the facial cranium (micrognathia, cheiloschisis, and cleft palate,...

Muscle relaxants

Muscle relaxants are usually used in surgical anesthesia because most anesthetics alone do not produce sufficient relaxation of the skeletal muscles. In contrast to general and local anesthetics, muscle relaxants cross the blood-brain barrier and the placenta only in limited amounts due to their high degree of ionization and limited lipid solubility. Thus, in fetal tissue these agents achieve only 5-10 of the concentration measured in the maternal blood (Demetriou 1982, Abouleish 1980). Hence,...

Other antihypertensives

With long-term clonidine therapy using 240-290 ng d, up to 2.8(ig l of milk was measured. For the infant, this means a maximum of 8 of the weight-related maternal dosage. With 0.3-0.6 ng 1 in the infant's plasma, a near-therapeutic concentration was reached (Hartikainen-Sorri 1987). In another study involving ongoing therapy with 75 ng daily, a maximum of 7 was measured for the fully breastfed infant in whose plasma no active ingredient could be detected (< 0.096 ig ml). There was 0.6 Mg I in...

Bromocriptine and other prolactin inhibitors

Bromocriptine is an ergotamine derivative. As a prolactin inhibitor, it reduces the milk production and is used to treat prolactinoma. Because of the possible cardiovascular side effects in the mother, particularly the threat of cerebral angiopathy (Hopp 1996, Iffy 1996), it has a very limited use in stopping lactation (see also section 3.7). 4.11.4 Thyroid hormones and thyroid receptor antibodies The American Food and Drug Administration (FDA) has withdrawn permission to use bromocriptine for...

Antacids and sucralfate

Antacids are basic compounds which neutralize hydrochloric acid in the gastric secretions. For this purpose, the following arc used sodium hydrogen carbonate, aluminum hydroxide, aluminum phosphate, algeldrate, calcium carbonate, magnesium(hydr)oxide, magnesium carbonate, and magnesium trisilicate u combination preparations of aluminum, magnesium, and carbonate m the structurally newer aluminum-magnesium complexes almasi-late, hydrotalcite, and magaldrate and the aluminum saccharide...

Alcohol ethanol

About 30 years ago, a clinical picture that has been well-known for centuries (and was noted during the gin epidemic in England between 1720 and 1750) was rediscovered. Alcoholism during pregnancy causes a specific complex of congenital organic and functional developmental defects known as fetal alcohol syndrome (FAS) (Jones 1973, Lemoine 1968, Rouquette 1957). The milder version, in which there is primarily functional damage, is referred to as fetal alcohol effects (FAE). There is still debate...

Stimulants

Cocaine (coke, snow) is an alkaloid (benzoecgonine methyl ester) of the coca bush (Erythroxylon coca), which grows primarily in the Andes. The leaves contain about 1 cocaine. Cocaine was first used as an anesthetic in 1884. It is chemically related to local anesthetics, but has only been proven to be of value for external use in treating eyes, ears, nose, and throat conditions. Crack is the free base of cocaine Lhis is smoked. Cocaine blocks the reuptake of noradrenaline and dopamine at the...

Nifedipine and other calcium antagonists

Nifedipine is a frequently prescribed calcium antagonist for the treatment of hypertension (Easterling 1999B, Levin 1994). A recent meta-analysis of trials involving 27743 patients has shown that calcium antagonists are inferior to other types of antihypertensive drugs as first-line agents in reducing the major complications of hypertension, although they are equally effective in reducing blood pressure (Pahor 2000). Nifedipine and verapamil have been studied in the most detail. There is little...

Eye nose and ear drops

Eye, nose, and ear drops may generally be used during pregnancy for the appropriate indications. However, medication should be chosen carefully, and questionable combination preparations as well as (pscudo)-innovations should be avoided during pregnancy. Where there is some doubt, the recommendations on systemic therapy in the appropriate chapters can serve as guidance. With eye drops, quantitative absorption of the medication via the conjunctiva should be considered. For this reason, the...

Selective cyclooxygenase2 COX2 inhibitors

Because of their selective inhibition of COX-2, which is released in inflammatory processes, these newer agents arc thought to have significantly fewer gastrointestinal side effects than the classic S l Ds. and not to exert any antiplatelet effect. Celecoxia Jicoxii jnm-coxib, parecoxib, rofecoxib, and valdecoxib are affiong themTThcre are few case reports on their use in pregnancy (such as those collected by the producer of rofecoxib), and these do not to date indicate a teratogenic effect in...

Radionuclides

Iodine131 (,5II) accumulates in mother's milk at the same levels as normal iodine (see Chapter 4.11). Among 31 radionuclides studied for their appearance in mother's milk, 13II had the highest transfer (with 30 of the maternal dose), followed by 45Ca and lJCs (both 20 ) and *JSr (10 ) (Harrison 2003). In their review on 131I, Simon and co-workers (2002) found a median half-life in milk of 12 hours. When the mother received stable iodine to block her thyroid before administration of1311, the...

Adrenergic receptor blockers

i-blockers (acebutolol, alprenolol, atenolol, betaxolol, bisoprolol, Celiprolol, Carvedilol, esmolol, labetalol, rnetoprolol, nadolol, nebivolol, oxprenolol, pindolol, propranolol, sotalol, and timolol) have a wide spectrum of activity, and are often used to treat hypertension. There are two types of (3-receptors i -receptors predominate in the heart, and -receptors mediate relaxation (dilatation) of vascular and other smooth muscle (e.g. in the airways and blood vessels). Metoprolol is...

Antineoplastics

There are only a few ease reports on antineoplastics during lactation. The results of three reports on cisplatin are controversial Egan (1985) could not detect cisplatin in breast milk, while de Vries (1989) found identical levels in milk and maternal blood. Ben-Baruch (1992) measured 10-fold lower concentrations in the milk compared to maternal plasma. Cyclophosphamide passes into mother's milk in large quantities, and thus acute toxic effects on the breastfed infant are possible. Relative...

North American Teratology Information Services collaborating in the Organisation of Teratogen Information Specialists

Additional information and addresses not presented below can be found at www.otispregnancy.org Hamilton Health Science Corporation 2100 Main Street West L8N 3Z5 Canada Tel. (905) 521 2100 ext. 76788 serves Ontario open M-F 8-4 EST accepts calls from health carc providers by referral only. Does not handle breastfeeding. Department of Pediatrics c o Dr Michael Rieder Children's Hospital of Western Ontario 800 Commissioners Road East London, Ontario N6C 2V5 Tel. (519) 685 8293 serves Southwestern...

Reproductive stages

The different stages of reproduction are, in fact, highlights of a continuum. These stages concern a different developmental time-span, each with its own sensitivity to a given toxic agent. Table 1.1. Reproductive stages organs and functions potentially affected by toxicants Germ cell formation Oogenesis (occurs during fetal development of mother) Gene replication Cell division Egg maturation Hormonal influence on ovary Ovulation contractility secretions Hormonal influence on secretory and...