219 Fentanyl alfentanil remifentanil and sufentanil
Fentanyl is used very commonly in obstetrics today. It is generally given intravenously and by epidural, but it is also available in oral, oromucosal and transdermal forms for analgesia. Placental transfer of fentanyl in early pregnancy has been demonstrated Cooper 1999 . There are no reports of teratogenic effects, but use during the first trimester or prolonged use during pregnancy is scarcely documented. A mild withdrawal syndrome without apparent long-term effects was observed after...
2118 Gout interval therapy
Gout seldom occurs before menopause. 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...
241 Nausea and vomiting in pregnancy
Of all pregnant women, 50-80 suffer from nausea and vomiting of pregnancy NVP , also known as morning sickness - although symptoms may persist throughout the whole day. Usually limited to the first trimester, NVP may continue for the entire pregnancy. NVP may range from mild discomfort to severe vomiting and nausea, weight loss, dehydration and metabolic compromise. In severe cases, NVP can be fatal. The death of the famous Charlotte Bronte, author of fane Eyre 1855 , reflects the potential...
2649 Mebendazole and flubendazole
Most infections of adults with common nematodes like ascaris and trichuris will be asymptomatic, and there is rarely an indication for treatment during pregnancy. Severe infections with hookworms may cause anemia, responsible, if during pregnancy, for increased perinatal mortality and morbidity worldwide. The WHO estimates that as many as 44 million pregnant women throughout the world are infected with hookworms WHO 1996B . Mebendazole is a highly effective and well-tolerated drug against...
248 Dopamine antagonists
The dopamine antagonists used to treat NVP are metoclopmmide, phenothiazines, domperidone, droperidol, and trimethobenzamide. Metocloprarnide 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....
18 Passage of drugs to the unborn and fetal kinetics
Most studies of drug transfer across the maternal and embryonic fetal barrier are concerned with the end of pregnancy. Little is known about the transport of substances in the early phases of pregnancy, in which, morphologically and functionally, both the yolk sac and the placenta develop and change in performance Miller 2005, Carney 2004, Garbis-Berkvens 1987 . This is not a major issue with single doses, but becomes a matter of concern with long-term therapy. The placenta is essentially a...
References Nxn
Alexander S, Dodds L, Armson BA. Perinatal outcomes in women with asthma during pregnancy. Obstet Gynecol 1998 92 435-40. Baker HK. Flanagan MK Felal atrial flutter associated with maternal beta-sympatho-mimetic drug exposure. Obstet Gynecol 1997 89 861. Bakhireva LN. ones KL. Schatz M et ai. Asthma medication use in pregnancy and fetal growth. J Allergy Clin Immunol 2005 116 503-9. Bakhireva LN, ones KL, Chambers CD. Safety of leukotriene receptor agonists in pregnancy. Birth Def Res A 2006 76...
253 H2receptor antagonists
Cimetidine, famotidine, nizatidine, ranitidine, and roxatidine promote the healing of stomach and duodenal ulcers by blocking the H2-receptors in the gastric mucosa. In this way, the stimulation by histamine, which induces the secretion of hydrochloric acid, is prevented. Pepsin production is reduced as well. H2-receptor antagonists are used to treat gastroesophageal reflux and peptic ulcer disease. These agents are all well-absorbed and cross the placenta. Cimetidine showed weak...
2311 Antitussives
Codeine is the most widely used antitussive. It is a derivative of morphine, and has strong antitussive and analgesic properties. Because of its analgesic action, it is also used in compound antitussive preparations. An association between the prenatal use of codeine and congenital malformations has not been shown. When codeine is used in high doses for longer periods, or near term, respiratory depression and withdrawal symptoms can occur in the neonate see also Chapter 2.1 . Dextromethorphan...
224 Immunotherapy
Allergen immunotherapy allergy shots is an antiallergy therapy in which continuously increasing doses of an allergen arc injected sub-cutaneously. This therapy stimulates the production of immunoglobulins that bind the allergen before it can react with the mast cells. After immunotherapy, the allergic reaction on exposure to the allergen will be diminished because less histamine will be released by the mast cells. Immunotherapy is often effective for those allergic patients in whom the symptoms...
252 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...
References Wzr
Atanackovic G, Navioz Y, Moretti ME ct at. The safety of higher than standard dose of duxylamine pyridoxins Dicleclin for nausea and vomiting of pregnancy, Clin Pharmacol 2001 41 842-5. Backon J. Ginger in preventing nausea and vomiting or pregnancy a caveat due to its thromboxane synthetase activity and effect on testcstcrone binding. Rur Obstet Gynecol Reprod Biol 1991 42 163-4. Barash CI, l.asagna L. The Benedectin saga voluntary discontinuation. Clin Res DrugDev 1986 1 277-92. Berkovitch M,...
262 Cephalosporins
Cephalosporins also belong to the -lactam antibiotics, but their pharmacokinetic and antibacterial properties are different from those of penicillins. They may cause hypersensitivity reactions. Some patients with penicillin allergy also react with cephalosporins. Cephalosporins are classified according to their antimicrobial activity. First-generation cephalosporins are cefaclor, cefradin, Cefadroxil, cefalexin, cefalotine, and cefazolirt. Second-generation cephalosporins are cefamandole,...
2525 Cholestyramine and other lipid reducers
Cholestyramine is an anion-cxchangc resin which is not absorbed systemically. It binds bile acids, producing an insoluble complex which is excreted in the stool. This leads to a reduction of cholesterol and the low-density LD lipoproteins in the serum. Cholestyramine is used in pregnancy for the treatment of obstetric cholestasis to relieve the itching. Ursodeoxycholic acid is, however, more effective than cholestyramine in intrahepatic cholestasis of pregnancy see ursodeoxycholic acid...
251 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...
221 Antihistamines blocker
Antihistamines are substances that competitively block the action of histamine on the histamine rcceptors. Histamine release results in the stimulation of H -receptors located on the smooth muscles of many organs, or H2-receptors located in the mucosa of the stomach, producing an increase in acid secretion. Only the blocking of the Hrreceptors is essential in antiallergy therapy. Hj-antihistamines are mostly used in antiallergy therapy some are used as antiemetics and some as sedatives. The...
2413 Other agents with antiemetic properties
With respect to the antiemetics such as alizapride and aprepitant, used primarily in oncology, there is insufficient experience to estimate prenatal risk. Betahistine, a histamine analog, and the antihistamines cinnarizine and flimarizin have long been in use, and no increase in birth defects after clinical use has been shown. However, the absence of controlled studies on the use of these agents during pregnancy argues against their routine use. Betahistine and cinnarizine are both effective...
2511 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...
259 Atropine and other anticholinergic spasmolytics
Atropine, a belladonna-alkaloid, is a classic parasympatholytic, which inhibits the action of acetylcholine by competitively blocking muscarine rcccptors. With local application in the eye , systemic availability is negligible when applied properly. I-Atropinc is the biologically active enantiomer, and is sometimes encountered under the name hyoscyarnine. Atropine reaches concentrations in the fetus equivalent to those in the mother within a few minutes. Although atropine may alter fetal heart...
2526 Appetite suppressants obesity and weight loss
Amjepramone synonym diethylpropion , clobenzorex, dexfen-fluramine, fenfluramine, fenproporex, mazindol, mefenorex, norpseu-doephedrine, phentermine. and sibutramine are used as appetite suppressants. Amfepramone, clobenzorex, fenproporex, mefenorex, and phentermine share the pharmacological properties of amphetamines dexfenfluraminc, fenfluramine, and sibutramine stimulate the release of serotonin and block its reuptake norpseudoephedrine is a sympathomimetic amine mazindol is a tricyclic drug...
2514 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 are not absorbed. Saline laxatives are poorly absorbed as well they work in a similar way...
Gastrointestinal and antilipidemic agents and spasmolytics
Gastritis arid peptic ulcer during pregnancy Atropine and other anticholinergic spasmolytics Drugs for chronic Inflammatory bowel disease Dimeticon and plant-based carminatives Chenodeoxycholic acid and ursodeoxycholic acid Cloiibrine acid derivatives and analogs Cholesterol synthesis-enzyme inhibitors Cholestyramine and other lipid reducers Appetite suppressants, obesity and weight loss
242 Diet manipulations and treatment
Nausea and vomiting is a common predicament in early pregnancy. Patients can be reassured of the benign nature of their condition and should be encouraged to use the various treatment options that have been proven efficacious with little risk to the fetus. The treatment options for NVP range from conservative measures such as reassurance and diet manipulations in the mildly symptomatic women to drug therapy and, if necessary, in severe and intractable cases, intravenous rehydration and total...
2310 Expectorants and mucolytic agents
Expectorants and mucolytic agents enhance or facilitate the clearance of mucus in the respiratory tract. Ambroxol is a metabolite of bromhexine, and has been used in the prevention of neonatal respiratory distress syndrome with no reported maternal or fetal neonatal side effects. N-acetylcysteine is a derivative of the amino acid L-cysteine, and is used as a mucolytic agent and an antidote in paracetamol acetaminophen poisoning. Although the documented data on its use as a mucolytic during...
218 Pethidine meperidine
Because of its unparalleled spasmoanalgesic action during labor, pethidine is the analgesic of choice for this indication. When it is used during labor, the labor is not lengthened and the strength of the contractions is not diminished. Pethidine does not appear to influence either the severity of bleeding or the involution of the uterus postpartum. During pregnancy, pethidine passes unimpeded to the fetus and can reach higher concentrations there than in the maternal serum. Because of the...
2110 Other narcoanalgesics and centrally acting analgesics
Pentazol js an opioid analgesic with weak antagonistic activity. It crossesthe placenta readily at term. In combination with the antihistamine fr pe e aw ei Jitazocine has been abused under the name T's and Blues aWn intravenously injectable drug. In rats, this combination was associated with intrauterine growth restriction, and behavior abnormalities have been observed similar effects have also been seen in humans after prenatal exposure von Almen 1986 . Gross malformations have not been...
13 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 muscle...
General commentary on drug therapy and drug risks in pregnancy
Richard K. Miller, Paul W. Peters, and Christof E. Schaefer 1.2 Development and health 3 1.4 Reproductive and developmental toxicology 6 1.5 Basic principles of drug-induced reproductive and developmental toxicology 9 1.6 Effects and manifestations 10 1.7 Pharmacokinetics in pregnancy 12 1.8 Passage of drugs to the unborn and fetal kinetics 13 1.9 Causes of developmental disorders 14 1.10 Embryo fetotoxic risk assessment 15 1.11 Classification of drugs used in pregnancy 19 1.12 Paternal use of...