Women are blessed by god with a precious gift like conceiving the pregnancy. Pregnancy is the beginning of new life, it starts with conception and continues through the fetus and finally ends at birth. Pregnancy is the normal physiological process which results into continuation of species.
Women are blessed by god with a precious gift like conceiving the pregnancy. Pregnancy is the beginning of new life, it starts with conception and continues through the fetus and finally ends at birth. Pregnancy is the normal physiological process which results into continuation of species.
The pharmacokinetics during pregnancy include, drug absorption, drug distribution, drug metabolism, drug excretion. Effects of drug on pregnancy depends on four major stages i.e Pre-implantation stage, period of organogenesis, the second and third trimester, and a short delivery stage. During pregnancy the mother and fetus form a non-separable functional unit. Drugs can have harmful effects on the fetus at any time during pregnancy. It is important to remember this when prescribing medicine for women of child bearing age. Counseling of women before a planned pregnancy should be carried out including discussion of risks associated with therapeutic agents. Medication during pregnancy is very important, so, caution should be maintained while prescribing them to pregnant women.
Introduction
Pregnancy is the beginning of new life. It starts with conception and continues through the fetus and finally ends at birth. It is not an illness. Pregnancy is a process, which results into the continuation of the species. Furthermore, pregnancy has a positive influence on the female organism, both physically and psychologically. During gestation, the woman reaches her full physical and mental potential. Offcourse, we are referring here to normal pregnancies. In women who suffer from physical or mental anomalies, pregnancy can be the cause of various complications.
Pregnancy cycle1
Month | Fetal development | Weight | Height |
1 | The ovum is fertilized by a spermatozoid. The egg begins to divide and moves to the uterus where it implants itself around the 7th day. At the end of this month the heart begins to beat. | 0.8g | 0.7 cm |
2 | The embryo is characterized by its large head in relationship to the rest of the body. The head is the same size as the rest of the body. The face can be seen with eyes, nose and mouth. Arms and legs begin to grow. | 10g | 2 cm |
3 | It is now called a fetus.The internal organs begin to develop and the nasal orifice and genital structures can now be seen. The fetus moves but the mother cannot feel it yet. | 35g | 6.5 cm |
4 | The digestive and urinary begin to function. The baby is now covered with a fine coating of hair. The eyelashes and eyebrows begin to grow. | 50g | 15 cm |
5 | The volume of head is now only a third of the total body size. The eyes have centered, and hair begins to grow. The fingers are more formed, and they now have nails and fingertips. Movement increases and is now noticeable. | 250g | 25 cm |
6 | Muscles develop, and the nervous system is maturing.This means that the fetus can begin to coordinate its movements. Sometimes it is able to suck its thumb. This helps to develop its sucking instinct. It is now able to open its eyes. | 700g | 32 cm |
7 | The head is now only a quarter of body size. Ts skin is winked, and the fine hair disappears. If it is born now it has good chance of survival. | 1,500g | 38 cm |
8 | The outer layer of fat grows and the fetus’s form becomes rounded. It tends to move into the birth position with its head down. The position is the one which best fits the size of the uterus. | 2,300g | 43 cm |
9 | The fetus continues to mature. It receives the greatest amount of antibodies from its mother at this time, but its kicks and elbow movements are visible to the eye. | 3,000g | 50 cm |
Drugs, Pregnancy And Newborn1
Drugs are likely to be self administered or prescribed by the physician during pregnancy. For various reasons, studies on the proper use of drugs during human pregnancy are few, and drugs prescribing during pregnancy are often arbitrary rather than rational. Intelligent use of drugs during pregnancy requires that the physician casts the pregnant mother in the role of a therapeutic organ. It must be remembered that most of the drugs prescribed during pregnancy are given for benefit of the mother and that we must nit deny her adequate treatment for a serious illness. In addition to drugs, the pregnant women is likely to be exposed to a variety of environmental, therapeutic or illicit agents which can affect the fetal health.
Pharmacokinetics During Pregnancy1
Most of the available information on the Pharmacokinetics of the drugs during pregnancy has been obtained from animal experiments and cannot applied directly and in vivo to humans. Although pregnant women do not differ quantitatively from the non pregnant ones in their response to drugs, certain quantitative differences do not occur because of physiological changes and the consequent alteration in pharmacokinetics lead to the changes in drug absorption, distribution, metabolism and excretion. Further, the fetus has its own pharmacokinetic peculiarities.
Drug absorption:
High circulating levels of progesterone slow the gastric emptying as well as gut motility, thus increasing the intestinal transit time. One might expect slower drug absorption during pregnancy for the reason. However, this does not occur except at term when parental drug administration is preferred in order to obtain a quick response. Administration of iron and antacids may also interfere with the absorption of certain drugs. Drugs compliance may be poor because of nausea and fear of possible adverse effects.
Drug distribution:
Pregnancy is accompanied by an increase in total body water by upto 8 liters and a 30% increase in plasma volume, with consequent decrease in plasma albumin due to hemodilution. Drugs, which have low lipid solubility and are also highly plasma protein bound, have a low apparent volume of distribution. The Vd of such drugs increases markedly during pregnancy. The protein bound fraction of the drug in the plasma. Although the fraction of unbound drug increases, a greater pharmacodynamic effect is prevented by more rapid elimination of drug by metabolism and excretion. The therapeutic range for drugs whose use is monitored by measurement of total plasma concentration must be adjusted downwards to make allowance for the mentioned changes during pregnancy.
Drug metabolism :
Hepatic drug metabolizing enzymes are induced during pregnancy, probably by high concentration of circulating progesterone. This can lead to more rapid metabolic degradation, especially of high lipid soluble drugs. The contribution of placenta and fetal liver to the clearance of drugs from maternal body is thought to be small.
Drug excretion :
During pregnancy, the renal plasma flow increases by 100% and the glomerular filtration rate by 70%. Add to this the increase in the unbound fraction of the drug in the plasma. Hence, drugs which depend for their elimination mainly kidney are eliminated more rapidly than in the non-pregnant state. Examples of such drugs are ampicillin, gentamycin, cephalexin and digoxin.
Drugs and fetus:
Placental transfer of drugs:
The placenta acts as an intravenous portal for entry of entry of drugs into the fetus. Such entry of drugs is governed by several considerations. As pregnancy progresses and the placenta develops, the surface available for transfer between the maternal and fetal circulation increases; at the same time, the placenta-fetal barrier becomes progressively thinner. Transfer across this barrier is governed by the same properties of the drugs which regulate the transfer across other biological membranes: unbound, non-ionized, lipid soluble molecules of low molecular weight across the barrier more easily than those which do not posses these attributes; most of the drugs in use, fulfil these criteria and are able to cross the placental barrier. However, because of differences in the plasma protein concentration and the pH between the maternal and fetal blood, the concentration of drugs in the two circulation, even at equilibrium, may differ considerably. Add to this the differences in pharmacokinetics between the mother and the fetus. Further the placenta is capable of metabolizing drugs; this is of little relevance to the mother but can protect the fetus from the entry of many drugs. Prednisolone and hydrocortisone which are metabolized by the placenta to inactive compounds prednisone and cortisone, are safer for the fetus than dexamethasone and betamethasone, which are not so metabolized. The method of drug administration to the mother may also decide the fetal concentration. For example, at term, antibiotics given by intermittent intravenous infusion can achieve higher concentrations in the fetal growth and amniotic fluid than when the same total dose is given by continuous infusion; this may be important in the treatment of intrauterine infections. In spite of above considerations, the fetal: maternal ratio of unbound drug concentration is generally close to unity. Further, the placenta is always available to the fetus as a route of drug elimination. However, after birth, the placenta route of drug elimination is no longer available and the neonate is on its own; and that is when the possible inadequacies of fetal-neonatal drug handling start hurting.
Fetal- neonatal pharmacokinetics:
The fetal liver and the adrenals are capable of metabolizing many substrates by oxidation. Oxidative dealkylation is more efficient than hydroxylation. Reduction and hydrolysis are rudimentary at that age and so is glucurodnation. Conjucation with glycine or sulphate are as efficient as in adult life.drug metabolised by hydroxylation such as phenytoin, phenobarbitone, tolbutamide, nalidixic acid, nortriptiline and amulobarbitone have a longer half life in a neonate than in adults. Impaired conjugation of salicylates and chloramphenicol in the neonate can cause serious toxicity.
Because of low renal plasma flow and GFR and the more acidic urine, drugs such as aminoglycosides, digoxin, chloropromide, penicillin, salicylic acid, indomethacin, paracetamol and several sulfonamides are cleared very slowly by the neonate. Repeated administration of these drugs to the mother at term can cause neonatal toxicity. The same is true about pethidine; the capacity of the neonate to hydroxylate norpethidine and to excrete it via kidney is low.
Effects of drugs on pregnancy:
Effective treatment of maternal illness with drugs such as insulin, tryroxine, antibiotics and antihypertensives may be said to have a beneficial effect on the course of pregnancy. On the other hand, in certain situations, drugs can cause harm to the concepts. These harmful effects depend upon the nature of the drug and its dose and route of administration; the stage of pregnancy at which the drug is used; and the genetic constitution and susceptibility of the fetus, which in turn, depend upon the age, nutritional status and health of the mother. Gestation may be divided into four major stages.
Pre- implantation stage: which lasts about 16 days from conception to implantation. Exposure to harmful drugs can kill the embryo or else the damaged cells are replaced by undifferentiated cells which have the potential to develop normally. This is an all -or- none effect.
Period of organogenesis: from 17th to 56th day. Pre- implantation stage and the stage of organogenesis together constitute the trimester. Exposure to harmful drugs during the period of organogegesis can cause congenital malformations or abortion.
The second and third trimesters: are periods during which considerable growth and development occurs in teeth, bones and in central nervous, endocrine, genital and urine systems. During this period drugs can cause either teratogenesis or a variety of other effects such are retardation of physical and brain growth, behavioral teratogenecity, premature labour, neonatal toxicity and even late post natal effects such as cancer.
A short labour- delivery stage: drug administration during this period is mainly fraught with the danger of toxicity in the neonatal period for reasons already discussed.
Table no. 1 Medication During Pregnancy6
Drugs | Status | Effects |
Antibiotics | | |
Penicillin | Permitted | |
Cephalosporins | Permitted | |
Tetracyclins | Not permitted | If given from the 4th month on., it can effect the bone and dental development of the fetus. |
Glucosamines· Streptomycin · Kanamcyin · Gentamycin · Erythromycin | Not permittedNot permittedPermittedPermitted | Affects the auditory nerve of the fetus producing hypoacusis and Deafness |
Sulfonamides | Not permitted | Administered just before birth it produces jaundice and hemolytic anemia in the infant. |
Chloramphenicol | Not permitted | If administered during third trimester of pregnancy it can cause “gray syndrome” in the unborn baby. |
Analgesics and anti-inflammatories | | |
Acetaminophen | Permitted | |
Acetyl salicylic acid | Permitted | Closes the arteries prematurely. Prolonged gestation. Increase of length of labor. Increase in maternal hemorrhaging during birth. |
Digestive pathology | | |
Antihistamines | Permitted | |
Antacids: · Aluminium hydroxide and trisilicate magnesium | Permited | |
Vascular pathology | | |
Digoxin | Permitted | |
Antiarhytmics: · Qunidine · Amiodarone · Propanolol | Permitted Not permitted Not permitted | Miscarriages and premature births. |
Nitroglycerin | Permitted | |
Nifidipine | Permitted | |
Antihypertensives: · Hydrazine · Methyldopa · Reserpine | Permitted Permited Not permited | Neonatal ileus meconium. The fetus can get microcephaly, hydronephrosis, etc |
Diuretics: · Mercurials · Ethacrinic acid · Thiazides | Not permitted Not permitted Permitted | Nephrotoxicity Fetal deafness. Can cause thrombpcytopenia and hyperbilirobinemia. |
Central nervous system: | | |
Anticonvulsants | Not permitted | Fetal deformalities |
Phenitoin | Not permitted | Can produce cranial/facial abnormalities, slow growth, mental retardation, ungula and digital hypoplasia, palatal groove and congenital cardiopathy. |
Carbamazepine | Not permitted | |
Benzodiazepine | Not permitted | If given at the of pregnancy it can cause hypotonia, lethargy, hypothermia, respiratory diffulty and sucking difficulty in the newborn baby. |
Antipsychotic drugs: · Haloperidol · Phenothiazine | Not permitted Not permitted | |
Antidepressives: · Amitryptilin · Imipramine · Desipramine · Lithium | Permitted Permitted Permitted Not permitted | Can cause cardiac and circulatory malformations in the fetus. |
Hormones: · Estrogens · Progestagens | Not permitted. Not permitted | In male fetus it causes testicular cysts and ologospermia. In female fetus it causes masculinization. |
Drugs Harmful In Pregnancy1
During pregnancy the mother and fetus form a non-separable functional unit. Maternal well being is an absolute prerequisite for the optimal functioning and development of both parts of this unit, consequently, it is important to treat the mother whenever need while protecting the unborn to the greatest possible extent.
Drugs can harmful effects on the fetus at any time during pregnancy. It is important to remember this when prescribing for a woman of childbearing age. However, irrational fear of using drugs during pregnancy can also result into harm. This includes untreated illness, impaired maternal compliance, suboptimal treatment and treatment failures.
During the first trimester drugs may produce congenital malformations, and the greater risk is from third to eleventh week of pregnancy. During the second and third trimester drug may effect the growth and functional development of the fetus or have toxic effect on the fetal tissue. Drugs given shortly before term of during may have adverse effect on labour or on teratogenic in man but no drug is safe beyond all doubts in early pregnancy. Screening procedures are available where there is a known risk of certain defects.
Drugs Prescribing During Pregnancy
If possible counseling of women before a planned pregnancy should be carried out including discussion of risks associated with specific therapeutic agents, traditional medicines and abuse of substances such as smoking and alcohol. Folic acid supplements should be given in pregnancy planning because periconceptual use of folic acid reduces neural tube defects.
Well-known single component drugs should usually be preferred to multicomponent drugs. Certain vaccines should not be given during pregnancy. These vaccines are the “live vaccines”: MMR vaccine prevents rubella infection in moms, injecting the inactivated rubella virus may adversely affect the growing fetus.
The following list includes drugs which may have harmful effects in pregnancy and indicates the trimester of risk. It is based on human gata but information on animal studies has been included for some newer drugs when its omission might be misleading.
Drugs should be prescribed in pregnancy only if expected benefit to the mother is thought to be greater than the risk to the fetus, and all drugs should be avoided if possible during first trimester. Drugs, which have been extensively used in pregnancy, and drugs, which are safe, should be prescribed in preference of new or untried drugs; and the smallest effective dose should be used. Few things have been shown conclusively to be teratogenic in man but no drug is safe beyond all doubt in early pregnancy. Screening procedures are available where there is known risk of certain defects. Absence of a drug from a list dose not imply safety. The list may not include all drugs reported to have some toxicity in a pregnancy and therefore caution should be exercised at all times while prescribing in pregnancy.
Precautions To Be Taken While Prescribing Drug To A Pregnant Women1:
· Treat minor ailments without drugs.
· If a drug must be prescribed, it should be one, which is known to be safe during pregnancy.
· Prefer a drug, which has been in use for long periods of time to a newly introduced drug as the safety of the latter for the fetus, is not likely to be known completely.
· Adjust the dose of the drug to the pregnant state ; with most drugs, it is generally at the lower end of the therapeutic range. However, because of pharmacokinetic factors, the dose of certain drugs such as lithium, digoxin and phenitoin is likely to be higher than in the non-pregnant state of women.
· Discourage the patient from self-administering over-the –counter drugs.
· Advise the patient that absolute safety of the fetus cannot be guaranteed even by not prescribing any drug to women between the ages of 15 to 45. Therefore, do not sacrifice the mother’s interest for the sake of fetus.
Nausea and vomiting:
It can be treated without drugs in most women. Reassurance and high carbohydrate diet will help them. If required, an antihistaminic, antiemetic or chlorpromazine may be prescribed. Metoclopramide is safe in third trimester of pregnancy and may be prescribed in resistant cases.
Heartburn:
It is very common in pregnancy and is relived by a small carbohydrate meal; by avoiding fatty food, smoking and alcohol; and by maintenance of upright posture. Consumption of aerated lemonade 2-3 times a day is also effective. Non-systemic antacids and metoclopramide may be needed in some cases. Anticholinergics usually worsen the heartburn by relaxing the lower esophageal sphincter.
Peptic ulcer:
It should be treated with dietary modification and non systemic antacids. Sucralfate which is not absorbed, H2 receptor blockers and bismuth subsalicylate are safe during pregnancy.
Constipation:
Generally responds to high fibre diet, plenty of liquids and a mild laxative such as milk of magnesia, docusate sodium, glycerin, sorbuitol, mineral oil or bisacodyl.
Antimicrobial drugs :
Betalactum antibiotics are safe during pregnancy. Ampicillin acheives very high concentrations in the fetal circulation and amniotic fluid and is very suitable for treatment of uterine infections during pregnancy. Erythromycin base is safe but erythromycin estolate should be avoided for fear or hepatotoxicity. Nitrofurantoin and methanamine mandelate are safe during pregnancy. So is nystatin and miconazole; bit ketokonazole and 5-flucytosine should be avoided.
Aminoglycosides are ototoxic to the fetus and should be avoided; if one is neede to treat a serious systemic infection in the mother, gentamycin or tobramycin should be preferred .Tetracyclins damage the fetal teeth and bones and should be avoided. High doses of Tetracycline intravenously have been associated with serious hepatotoxicity in the mother. Chloramphenicol is absolutely contraindicated during pregnancy; it can cause fetal bone marrow toxicity and “Grey baby syndrome” in the neonate. Co-trimoxazole should be avoided. The use of sulfonamides at term can cause kernicterus in the neonate by displacing bilirubin from binding with albumin; the other drugs which displace bilirubin from albumin are aspirin, tolbutamide and water soluble vitamin K analogues.
Tuberculosis:
Isoniazid and ethambutal are during pregnancy. Rifampicin should be avoided as far as possible but may be used if a third drug is required. Streptomycin is ototoxic to the fetus and should never be used in pregnant women.
Parasitic diseases:
Ameobiasis should be treated with the usual drugs like metronidazole, diodoquin and diloxanide. However, large dose, short-term therapy with metronidazole should be avioded.
Primaquine pyrimethamine and mefloquine are contraindicated. Chronic suppressive use of chlroquine and its use to treat acute attacks of malaria during pregnancy are safe. Quinine may be used to treat acute attacks of chloroquine resistance malria. Fansidar has been used in-patients with exceptionally heavy parasitization of the red blood cells.
Piperazine, bephenium and pyrantel are safe for use during pregnancy. Unless the parasite load load is heavy, the treatment of intestinal parasitic infections is best postponed till after delivery.
NSAID:
Aspirin is not teratogenic but high dose aspirin treatment during the last six months is associated with increased gestation time, higher incidence of postmaturity and increased duration of labor. Further it can also cause severe postpartum haemorrage, bleeding in the neonate and premature closure of ductus arteriosus with pulmonary hypertension in the fetus and the newborn. Aspirin and other NSAID are, therefore, best avoided during pregnancy.
Hypertension:
Methyl-dopa isn usually safe and preferred. Betablockers in the second and third trimester can cause general retardation, whereas ACE inhibitors can cause abnormalities of renal functions and skull development. These drugs probably interfere with the maturation of specific organ system.
Heart diseases:
This is treated as in non-pregnant women. Digoxin clearance by the kidney increases during pregnancy, if the dosage remains unchanged by the end of the pregnancy, the serum concentration will have fallen to about half the value before pregnancy.
At the therapeutic concentration, quinidine appears to be safe and the dryg has only mild oxytoxic activity. Quinidine is normally 80%bound to plasma protein. Changes in plasma protein concentratuon during pregnancy cause total plasma quinidine concentration to fall and free concentration to be underestimated. After delivery, total concentration of quinidine increases by about half.
Vasopressor agents:
All decreases the uterine flow and may stimulate uterine contraction. Their use in pregnancy is justified only if the mother’s survival is at stake.
Anticoagulants:
Warfarin is best avoided in pregnant women, except those who have an artificial heart value; in these latter subjects, heparin dose not give adequate anticoagulant cover. In other patients subcutaneous heparinshould be used if anticoagulation is required. One dose of heparin should be omitted when labor is imminent, so as to avoid post-partum haemorrage.
Deep vein thrombosis:
It may be treated with heparin. The use of streptokinase is associated with risk of bleeding.
Allergic rhinitis:
This may be treated either locally or systemically.
Cough:
Diphenhydramine, codein and dextromethorphan may be used safely to treat cough during pregnancy.
Pruritus:
This may be treat locally or systematically.
Bronchial asthma:
This is usual manner with beta adrenergic agonists, aminophylline and glucocorticoids. However, intravenous salbutamol used to delay labor is known to cause pulmonary edema especially in individuals with mitral stenosis and when corticosteroids are administered concurrently to promote fetal lung maturation. This therapy should not be used in hypertensive subjects. Further, in diabetic subjects IV salbutamol can cause severe hyperglycemia and ketoacidosis, which can be resistant even to the most aggressive insulin therapy.
Headache:
It may be treated with paracetamol, codein and benzodiazepines. Aspirin and NSAID may be used in the first and second but not in the third trimesters.
Migrane:
It may be treated with analgesics, propanalol, dimenhydrinate and amitryptilline.
Diabetes Mellitus:
It should be treated with dietary restriction and insulin, if required; the use of oral hypoglycemic agents is contraindicated. In insulin dependent diabetics who become pregnant, the insulin requirement drops somewhat during the first trimester, then rises progressively to 2-3 times the pregnancy level upto 36 weeks, and then drops again upto term. After delivery, insulin requirement dives dramatically ton pre-pregnancy level. If diabetes is detected in pregnancy for the first time, it is advisable to prescribed a highly insulin preparation.
Thyrotoxicosis:
Thionamides are the therapy of choice for thyrotoxicosis during pregnancy; proply-thiouracil is preferred to carbimazole. The dose should be kept as low as possible. Stable iodine and radioactive iodine are contraindicated.
Epilepsy:
Adequate seizure control is important during pregnancy as convulsions themselves are harmful to the fetus. Phenobarbitone , phenytoin and carbamazepine may be used during pregnancy; as discussed earlier, their dose may have to be increased slightly in order to maintain seizure control. All pregnant women on antiepileptic drugs should be prescribed folic acid 5mg per day throughout pregnancy. Vitamin K1 should be administered to such patients routinely, before delivery and to their newborn babies at birth. The use of valproic acid is contraindicated during pregnany.
Drugs acting on CNS:
Barbiturates, benzodiazepines and antidepressants have not been shown to have any significant teratogenic effects. Lithium has been reported to be teratogenic and also to be deleterious to the fetus in the last trimester.
The use of CNS depressants such as diazepam, antidepressants, phenothiazines and opoids at term and specially during labor, exposes the neonate to the risk of serious CNS depression. Benzodiazepines are best avoided towards the end of pregnancy. Phenothiazines and tricyclic antidepressants can be continued during pregnancy in minimum possible doses. Antiparkinsonian drugs commonly prescribed together with phenothiazines and should not be used during first trimester. MAO inhibitors are contraindicated during pregnancy. Further, it is desirable to taper and omit tricyclic antidepressants in the last few of pregnancy and to restart them after delivery.
Table no 2: Drugs To Be Avoided Or Used With Caution In Pregnancy4
First trimester |
Drug | Comment and advice |
Acetazolamide | Avoid |
Albendazole | Avoid in nematode infection |
Alcohol | Regular daily drinking is teratogenic and may cause growth retardation; occasional single drinks are probably safe |
Amitriptyline | Avoid unless essential |
Artemether | Avoid |
Artesunate | Avoid |
Benznidazole | Avoid |
Carbamazepine | Risk of teratogenesis including increased risk of neural tube defects; risk of teratogenicity greater if more than one antiepileptic used. |
Chloroquine | Benefit of prdphylaxis and treatment in malaria out weighs risk |
Ciprofloxacin | Avoid arthropathy in animal studies; safer alternative available |
Clomipramine | Manufacturer advises avoid unless essential |
Didanosine | Avoid if possible |
Diloxanide | Defer treatment until first trimester |
Doxycycline | Effect on skeletal development in animal studies |
Efavirenz | Avoid |
Eflornithine | Avoid |
Enalapril | Avoid; may adversely affect fetal and neonatal blood pressure control and renal function; also possible skull defects and oligohydramnios; toxicity in animal studies |
Ergotamine | Oxytocic effect on the pregnant uterus |
Ethosuximide | May possible be teratogenic; risk of teratogenicity greater if more than one antiepileptic used |
Heparin | Osteoporosis has been reported after prolonged use; multidose vials may contain benzyl alcohol avoid |
Hydralazine | Avoid |
Indinavir | Avoid if possible |
Insulin | Insulin requirement should be assessed frequently by an experienced diabetic clinic |
Lithium | Avoid if possible |
Lopinavir + ritonavir | Avoid |
Mebendazole | Avoid in nematode infection |
Malarsoprol | Avoid |
Metformin | Avoid; insulin is normally substituted in all diabetics |
Nalidixic acid | Avoid arthropathy in animal studies; safer alternatives available |
Nelfinavir | Avoid |
Nevirapine | Avoid |
Nifurtimox | Avoid |
Ofloxacin | Avoid arthropathy; safer alternatives available |
Penicillamine | Fetal abnormalities reported rarely; avoid if possible |
Phenobarbital | Congenital malformations; risk of teratogenicity greater if more than one antiepileptic used. May possibly cause vitamin A deficiency and risk of neonatal bleeding; if vitamin K not given at birth, neonate should be monitored closely for signs of bleeding |
Phenytoin | Congenital malformations; adequate folate supplements should be given to mother; risk of teratogenicity greater if more than one antiepileptic used. May possibly cause vitamin A deficiency and risk of neonatal bleeding; if vitamin K not given at birth, neonate should be monitored closely for signs of bleeding. Caution in interpreting plasma concentrations bound may be reduced but free unchanged |
Podophyllum resin | Avoid neonatal death and teratogenis have been reported |
Pyrimethamine | Theoretical teratogenic risk; adequate fetal supplements should be given to the mother. |
Quinin | High dose are teratogenic; but in malaria benefit of treatment out weighs risk |
Retinal | Excessive dose may be teratogenic |
Rifampicin | Very high doses teratogenic in animal studies |
Stavudine | Avoid |
Streptokinase | Possibility of premature separation of placenta in first 18 weeks; theoretical possibility of fetal hemorrhage throughout pregnancy; risk of maternal hemorrhage on postpartum use |
Sulfadiazine | Avoid |
Sulfamethoxazole + trimethoprim | Teratogenic risk |
Testosterone | Masculinization of female fetus; avoid |
Tetracycline | Effect on skeletal development in animal studies |
Trimethoprim | Teratogenic risk |
Vaccine, BCG | Theoretical risk of congenital malformations, but need for vaccination may out weigh possible risk to fetus |
Vaccine, Measles | Theoretical risk of congenital malformations, but need for vaccination may out weigh possible risk to fetus-avoid MMR |
Vaccine, poliomyelitis, live | Theoretical risk of congenital malformations, but need for vaccination may out weigh possible risk to fetus |
Vaccine, yellow fever | Theoretical risk of congenital malformations, but need for vaccination may out weigh possible risk to fetus |
Valproic acid | Increased risk of neural tube defects; risk of teratogenicity greater if more than one antiepileptic used; neonatal bleeding and neonatal hepatotoxicity also reported |
Warfarin | Congenital malformations; fetal and neonatal hemorrhage |
Zidovudine | Avoid |
Lamivudine | Avoid if possible |
Second trimester |
Alcohol | Regular daily drinking is teratogenic and may cause growth retardation; occasional single drinks are probably safe |
Ciprofloxacin | Avoid arthropathy in animal studies; safer alternative available |
Doxycycline | Dental discoloration; maternal hepatootxicity with large doses |
Efavirenz | Avoid |
Enalapril | Avoid; may adversely affect fetal and neonatal blood pressure control and renal function; also possible skull defects and oligohydramnios; toxicity in animal studies |
Ergotamine | Oxytocic effect on the pregnant uterus |
Gentamicin | Auditory or vestibular nerve damage; risk probably very small with gentamicin, but avoid unless essential |
Heparin | Osteoporosis has been reported after prolonged use; multidose vials may contain benzyl alcohol avoid |
Hydralazine | Avoid |
Insulin | Insulin requirement should be assessed frequently by an experienced diabetic clinic |
Iodine | Neonatal goiter and hypothyroidism |
Eflornithine | Avoid |
Lithium | Dose requirements increased; close monitoring of serum-lithium concentration advised |
Malarsoprol | Avoid |
Metformin | Avoid; insulin is normally substituted in all diabetics |
Nalidixic acid | Avoid arthropathy in animal studies; safer alternatives available |
Ofloxacin | Avoid arthropathy; safer alternatives available |
Penicillamine | Fetal abnormalities reported rarely; avoid if possible |
Podophyllum resin | Avoid neonatal death and teratogenis have been reported |
Polyvidoneiodine | Sufficient iodine may be absorbed to affect the fetal thyroid |
Potassium iodide | Neonatal goiter and hypothyroidism- Avoid |
Propylthiouracil | Neonatal goiter and hypothyroidism- Avoid |
Streptokinase | Possibility of premature separation of placenta in first 18 weeks; theoretical possibility of fetal hemorrhage throughout pregnancy; risk of maternal hemorrhage on postpartum use |
Streptomycin | Auditory or vestibular damage; avoid unless essential |
Testosterone | Masculinization of female fetus; avoid |
Tetracycline | Dental discoloration; maternal hepatotoxicity with large doses |
Warfarin | Congenital malformations; fetal and neonatal hemorrhage |
Lamivudine | Benefit of treatment considered to outweighs risk |
Third trimester |
Alcohol | Withdrawal may occur in babies of alcoholic mother |
Aminophylline | Neonatal irritability and apnoea have been reported |
Amitriptyline | Avoid unless essential |
Bupivacaine | With large doses; neonatal respiratory depression, hypotonia, and bradicardia after paracevical or epidural block |
Chloramethine | Neonatal ‘gray’ syndrome |
Carbamazepine | May possibly cause vitamin K deficiency and risk of neonatal bleeding; if vitamin K not given at birth, neonate should be monitored closely for signs of bleeding |
Chloroquine | Important |
Chlorpromazine | Extrapyramidal effects in neonatal occasionally reported |
Ciprofloxacin | Avoid arthropathy in animal studies; safer alternative available |
Clomipramine | Manufacturer advises avoid unless essential |
Codeine | Depresses neonatal respiration; withdrawal effects in neonates of dependent mothers; gastric stasis and risk of inhalation pneumonia in mother during labour |
Dapsone | Neonatal haemolysis and methaemoglobinaemia; folic acid 5mg daily should be given to mother |
Doxycycline | Dental discoloration; maternal hepatootxicity with large doses |
Efavirenz | Avoid |
Eflornithine | Avoid |
Enalapril | Avoid; may adversely affect fetal and neonatal blood pressure control and renal function; also possible skull defects and oligohydramnios; toxicity in animal studies |
Ergotamine | Oxytocic effect on the pregnant uterus |
Ether, anaesthetic | Depression neonatal respiration |
Fluphenazine | Extrapyramidal effects in neonatal occasionally reported |
Gentamicin | Auditory or vestibular nerve damage; risk probably very small with gentamicin, but avoid unless essential |
Glibenclamide | Neonatal hypoglycaemia; insulin is normally substituted in all diabetics; if oral drugs are used therapy should be stopped at least 2days before delivery |
Haloperidol | Extrapyramidal effects in neonate occasionally reported |
Halothane | Depresses neonatal respiration |
Heparin | Osteoporosis has been reported after prolonged use; multidose vials may contain benzyl alcohol avoid |
Hydralazine | No reports of serious harm |
Hydrochlorothiazine | May cause neonatal thrombocytopenia |
Ibuprofen | With regular use closure of fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of the newborn. Delayed onset and increased duration of labour |
Insulin | Insulin requirement should be assessed frequently by an experienced diabetic clinic |
Iodine | Neonatal goiter and hypothyroidism |
Ketamine | Depresses neonatal respiration |
Levamisole | Avoid |
Lamivudine | Benefit of treatment considered to outweighs risk |
Lidocaine | With large doses, neonatal respiratory depression, hypotonia, and bradicardia after paracervical or epidural block |
Lithium | Dose requirements increased; close monitoring of serum-lithium concentration advised |
Magnesium sulfate | Not known to be harmful but observe caution for short-term intravenous administration in eclampsia but excessive doses may cause neonatal respiratory depression |
Malarsoprol | Avoid |
Metformin | Avoid; insulin is normally substituted in all diabetics |
Morphine | Depresses neonatal respiration; withdrawal effects in neonates of dependent mothers; gastric stasis and risk of inhalation pneumonia in mother during labour |
Nalidixic acid | Avoid arthropathy in animal studies; safer alternatives available |
Neostigmine | Neonatal myasthenia with large doses |
Nitrofurantoin | May produce neonatal haemolysis if used at term |
Nitrous oxide | Depresses neonatal respiration |
Ofloxacin | Avoid arthropathy; safer alternatives available |
Penicillamine | Fetal abnormalities reported rarely; avoid if possible |
Phenytoin | Congenital malformations; adequate folate supplements should be given to mother; risk of teratogenicity greater if more than one antiepileptic used. May possibly cause vitamin A deficiency and risk of neonatal bleeding; if vitamin K not given at birth, neonate should be monitored closely for signs of bleeding. Caution in interpreting plasma concentrations bound may be reduced but free unchanged |
Phenobarbital | Congenital malformations; risk of teratogenicity greater if more than one antiepileptic used. May possibly cause vitamin A deficiency and risk of neonatal bleeding; if vitamin K not given at birth, neonate should be monitored closely for signs of bleeding |
Podophyllum resin | Avoid neonatal death and teratogenis have been reported |
Polyvidoneiodine | Sufficient iodine may be absorbed to affect the fetal thyroid |
Potassium iodide | Neonatal goiter and hypothyroidism- Avoid |
Primaquine | Neonatal haemolysis and methaemoglobinaemia. Delay treatment until after delivery |
Propylthiouracil | Neonatal goiter and hypothyroidism- Avoid |
Pyridostigmine | Neonatal myasthenia with large doses |
Salbutamol | For use in premature labour |
Rifampicin | Risk of neonatal bleeding may be increased |
Silver sulfadiazine | Neonatal haemolysis and methaemoglobinaemia; fear of increased risk of kernicterus in neonates appears to be unfounded |
Streptokinase | Possibility of premature separation of placenta in first 18 weeks; theoretical possibility of fetal hemorrhage throughout pregnancy; risk of maternal hemorrhage on postpartum use |
Streptomycin | Auditory or vestibular damage; avoid unless essential |
Sulfadiazine | Neonatal haemolysis and methaemoglobinaemia; fear of increased risk of kernicterus in neonates appears to be unfounded in toxoplasmosis |
Sulfasalazine | Theoretical risk of haemolysasis; adequate fotal supplements should be given to mother |
Sulfadoxine + Pyrimethamine | Neonatal haemolysis and methaemoglobinaemia; fear of increased risk of kernicterus in neonates appears to be unfounded |
Sulfamethoxazole + Trimethoprim | Neonatal haemolysis and methaemoglobinaemia; fear of increased risk of kernicterus in neonates appears to be unfounded |
Testosterone | Masculinization of female fetus; avoid |
Tetracycline | Dental discoloration; maternal hepatotoxicity with large doses |
Theophylline | Neonatal irritability and apnoea have been reported |
Thiopental | Depresses neonatal respiration |
Valproic acid | Increased risk of neural tube defects; risk of teratogenicity greater if more than one antiepileptic used; neonatal bleeding and neonatal hepatotoxicity also reported |
Warfarin | Congenital malformations; fetal and neonatal hemorrhage |
Miscellaneous |
Abacavir | Toxicity in animal studies |
Acetylsalicylic acid | Impaired platelet function and risk of hemorrhage; delayed onset and increased duration of labour with increased blood loss; avoid analgesic drugs if possible in last few weeks; with high doses, closure of fetal ductus arteriosus in utero and possibly persistent pulmonary hypertension of newborn; kernicterus in jaundiced neonate |
Aciclovir | Not known to be harmful but observe caution; limited absorption from topical preparation |
Albendazole | Contraindicated in cestode infections |
Alcuronium | Does not cross placenta in significant amounts; use only if potential benefit out weighs risk |
Allopurinol | Toxicity not reported; use only if no safer alternatives and diseases carried risk for mother or child |
Amiloride | Nit used to treat hypertension in pregnancy |
Amodiaquine | Use only if no safer alternative |
Amoxicillin | Not known to be harmful but observe caution |
Amoxicillin + Clavulanic acid | Not known to be harmful but observe caution |
Amphotericin B | Not known to be harmful but observe caution but use only if potential benefit out weighs risk |
Artemather + Lumefantrin | Avoid. Toxicity in animal studies with artemether |
Asparaginase | Avoid |
Atenolol | May cause intrauterine growth restriction, neonatal hypoglycaemia, and bradycardia; risk greater in sever hypertension |
Atropine | Not known to be harmful but observe caution |
Azathioprine | Transplant patient should be discontinue azathioprine on becoming pregnant; use in pregnancy should be supervised in specialist units; there is no evidence that azathioprine is teratogenic |
Azithromycin | Use only if potential benefit out weighs risk |
Beclometasone | Benefit of treatment, for example in asthma, out weighs risk |
Benzathine benzylpenicillin | Not known to be harmful but observe caution |
Benzylpenicillin | Not known to be harmful but observe caution |
Betamethasone | Benefit of treatment, for example in asthma, out weighs risk |
Bleomycin | Avoid |
Calcium folinate | Use only if potential benefit out weighs risk |
Ceftazidime | Not known to be harmful but observe caution |
Chlirmethine | Avoid |
Ceftriaxone | Not known to be harmful but observe caution |
Chlorambucil | Avoid; use effective contraception during administration to men or women |
Chlorphenamine | No evidence of teratogenicity |
Ciclosporin | There is less experience of ciclosporin in pregnancy but it does not appear to be any more harmful than azathioprine; use in pregnancy should be supervised in specialist units |
Cisplatin | Avoid |
Clindamycin | Not known to be harmful but observe caution |
Clomifene | Possible effects on fetal development |
Clonazepam | Avoid regular use; use only if clear indication such as seizure control |
Cloxacillin | Not known to be harmful but observe caution |
Contraceptives, oral | Epidemiological evidence suggests no harmful effects on fetus |
Cytarabin | Avoid |
Cyclophosphamide | Avoid |
Dacarbazin | Avoid; ensure effective contraception during and for at least 3 months after administration to men or women |
Dactinomycin | Avoid |
Daunorubicin | Avoid |
Deferoxamine | Teratogenic in animal studies; manufacturer advises use only if potential benefit outweighs risk |
Dexamethasone | Benefit of treatment, for example in asthma, out weighs risk; risk of intrauterine growth retardation or prolonged or repeated systemic treatment; corticosteroid cover required by mother during labour; monitor closely if fluid retention |
Diazepam | Avoid regular use; use only if clear indication such as seizure control |
Diethylcarbamazine | Avoid; delay treatment until after delivery |
Digoxin | May need dosage adjustment |
Doxorubicin | Avoid; with liposomal product use effective contraception during and for at least 6 months after administration to men or women |
Ephedrine | Increased fetal heart rate reported with parenteral ephedrine |
Ergocalciferol | High doses teratogenic in animals but therapeutic doses unlikely to be harmful |
Erythromycin | Not known to be harmful but observe caution |
Ethambutol | Not known to be harmful but observe caution |
Ethinylestradiol | Epidemiological evidence suggests to harmful effects on fetus |
Etoposide | Avoid |
Fluconazole | Avoid |
Flucytosine | Teratogenic in animal studies; use only if potential benefit outweighs risk |
Fluorouracil | Avoid |
Furosemide | Not used to treat hypertension in pregnancy |
Griseofulvin | Avoid; effective contraception required during and for at least 1 month after administration; also men should avoid fathering child during and for at least 6 months after administration |
Hydrocortisone | Benefit of treatment, for example in asthma, out weighs risk; risk of intrauterine growth retardation or prolonged or repeated systemic treatment; corticosteroid cover required by mother during labour; monitor closely if fluid retention |
Ibuprofen | Avoid unless potential benefit outweighs risk |
Idoxuridine | Teratogenic in animal studies |
Imipenem + cilastatin | Use only if potential benefit out weighs risk |
Isoniazid | Not known to be harmful but observe caution |
Ivermectin | Delay treatment until after delivery |
Levodopa + carbidopa | Toxicity in animal studies |
Levonogestrel | In oral contraceptives, epidemiological evidence suggest no harmful effect on fetus |
Levothyroxine | Monitor maternal serum-thyrotrophin concentration dosage adjustment may be necessary |
Medroxyprogesterone | Avoid; inadvertent use of depot medroxyprogesterone acetate contraceptive injection in pregnancy unlikely to harm fetus |
Mefloquine | Use only if other antimalarials inappropriate |
Mercaptopurine | Avoid |
Methotrexate | Avoid; use effective contraception during and for at least 6 months after administration to men or women |
Methyldopa metoclopramide | Not known to be harmful but observe caution |
Metronidazole | Avoid high-dose regimens |
Naloxone | Use only if potential benefit out weighs risk |
Niclosamide | T. solium infections in pregnancy should be treated immediately |
Nifedipine | May inhibit labour; some dihydropyridines are teratogenic in animals; but risk to fetus should be balanced against risk of uncontrolled maternal hypertension |
Norethisterone | In oral contraceptives, epidemiological evidence suggests to harmful effects on fetus in higher dosage mascilinization of female fetuses and other defects are reported |
Nystatin | No information available; but absorption from gastrointestinal tract negligible |
Oxaminiquine | If immediate treatment not required schistosomiasis treatment should be delayed until after delivery |
Paracetamol | Not known to be harmful but observe caution |
Pentamidine isetionate | Potentially fetal visceral leishmaniasis must be treated without delay. Should not be withheld in trypanosomiasis even if evidence of meningoencephalitic involvement potentially fetal P. carinii pneumonia must be treated without delay |
Pentavalent antimony compounds | Potentially fetal visceral leishmaniasis must be treated without delay |
Phenoxymethyl penicillin | Not known to be harmful but observe caution |
Phytomenadione | Use only if potential benefit out weighs risk |
Praziquantel | T. solium infections in pregnancy should be treated immediately; benefit of treatment in schistosomiasis outweighs risk if immediately treatment not considered essential for fluke infections, treatment should be delayed until after delivery |
Prednisolone | Benefit of treatment, for example in asthma, out weighs risk; risk of intrauterine growth retardation or prolonged or repeated systemic treatment; corticosteroid cover required by mother during labour; monitor closely if fluid retention |
Procarbazine | Avoid |
Proguanil | Benefit of prophylaxis and of treatment outweighs risk. Adequate fetal supplements should be given to mother |
Promethazine | No evidence of teratogenicity |
Propranolol | May cause intrauterine growth retardation, neonatal hypoglycaemia, and bradycardia; risk greater in sever hypertension |
Pyrazinamide | Use only if potential benefit out weighs risk |
Ranitidine | Not known to be harmful but observe caution |
Sodium cromoglicate | Not known to be harmful but observe caution |
Spironolactone | Toxicity in animal studies |
Suramin sodium | In onchocerciasis, delay treatment until after delivery. In T.b rhodesiense treatment should be given even of meningoencephalopatic involvement |
Suxamethonium | Mildly prolonged maternal paralysis may occur |
Tamoxifen | Avoid possible effects on fetal development; effective contraception must be used during treatment and for 2 months after stopping |
Vaccine, measles | Avoid; pregnancy should be avoided for 1 month after immunization |
Vaccine, rubella | Avoid; pregnancy should be avoided for 1 month after immunization |
Vancomycin | Use only if potential benefit out weighs risk. Plasma-vancomycin concentrating monitoring essential to reduce risk of fetal toxicity |
Vecuronium | Use only if potential benefit out weighs risk |
Vinblastine | Avoid |
Vincristine | Avoid |
Verapamil | Animal studies have not shown teratogenic effect; possibility that verapamil can relax uterine muscles should be considered at term; risk to fetus should be balanced against risk of uncontrolled maternal hypertension |
LORATADINE is not recommended during pregnancy. The European Committee for Proprietary Medicinal Products (CPMP) has finalized a EU-wide review of loratadine due to safety concern of hypospadias in newborn baby born to mothers receiving loratadine during pregnancy.
Eating well balanced meals in important at all times, but it is even more essential when you are pregnant. There are essential nutrients, vitamins, and minerals that your developing baby needs. Most foods are safe; however there are some foods that you should avoid during pregnancy.
Table no 3 Foods To Be Avoided During Pregnancy2
Food | Examples | Reason to be Avoided. |
Raw materials: | Sushi, uncooked seafood, rare or uncooked beef or poultry. | Should be avoided because of the risk of contamination with coliform bacteria, taxoplasmosis, and salmonella. |
Fish : | Fishes exposed to industrial pollutants. Fish in local lakes and streams. | Avoid fish from contaminated lakes and rivers that may be exposed to high levels of polychlorinated biphenyls. |
Raw eggs: | Raw eggs or food containing raw eggs. | Should be avoided because of potential exposure to salmonella. |
Soft cheeses: | Imported soft cheeses. | These may contain bacteria called called listeria which can cause miscarriage. Listeria has the ability to cross the placenta and infect the baby leading to infection, or blood poisoning which can be life threatening. |
Milk: | Unpasteurized milk: | Unpasteurized milk may contain bacteria called Listeria which can cause miscarriage. |
Caffeine: | Caffeinated beverages: | Although most studies show that caffeine intake in moderation is okay, there are others that show that caffeine intake may be related to miscarriages. Avoid caffeine during the first trimester to reduce the likelihood of miscarriage. As a general rule in the later stages of your pregnancy, caffeine should be limited to fewer than 300mg per day. Caffeine is a diuretic, which means it helps eliminate fluids from the body. This can result in water and calcium loss. It is important that u drink plenty of water, juice and milk rather than caffeinated beverages. |
Vegetables: | Unwashed vegetables. | Yes, vegetables are safe to eat, so you still need to eat them. However, it is essential to make sure they arw washed, to avoid potential exposure to toxoplasmosis. Toxoplasmosis may contaminate the soil, which the vegetables were grown in. |
Herbal remedies: | --- | Don’t take anything without consulting with your doctor or pharmacist. |
Conclusion:
Pregnancy, brings with it important concerns about prescription and over the counter drugs. Not every medication possesses a risk to unborn baby but they too its necessary to talk to the family doctor, discuss the relative risks and benefits of any prescribed drug therapy and should not take over-the-counter drugs or naturopathic remedies without consulting the physician.
During pregnancy drugs are not to be administered. However drugs are required for the treatment of various diseases present in the mother. Therefore during the treatment of diseases during pregnancy becomes a very critical issue and only safe drugs are to be administered during pregnancy.
Based on this information I would like to conclude that though there is enough awareness in India presently regarding the safety and precautions during pregnancy, I feel that there is a need or a scope or improvement in this field and we all should contribute in taking initiative in conducting awareness programmes for the common mass from the point of view of both social and medical ground.
References:
1) Satoskar R.S., Bhandarkar S.D., Rege N.N., Popular prakashan – Mumbai. Pharmacology and pharmacotherapeutics, 19th edition. Page no.1091-1101.
2) Isrido Equilar and Hermina Galbes, Education and health library Editorial Safeliz. Encyclopedia of health and education for the family, volume 3. page no74- 126
3) Tripathi K.D., Essemtials of medical pharmacology, 5th Edition. Page no 849- 852.
5) Speight T.M., Halford NHG., Auckland, NewZealand, Adis International limited, 1997. A Very,s drug treatment 4th edition. Page no 74- 126, 684-698.
6) Young LY., Koda-Kimble MA, Appliedtherapeutics: the clinical use of drugs, Vancouver, WA, 6TH edition. Page no 2,3,5,10,12,14,45.
7) Behram R.E., Nelson, Textbook of pediatrics, Philadelphia: WB. Saunders, 1996, 15th edition. Page no 448 – 451
8) Briggs G.G, Etal drugs in pregnancy and lactation. A reference guide of fetal and neonatal risk. Balimore, M.D: Williams and Wilkins, 1994, 4th edition. Page no74-126
9) Maharashtra state pharmacy council’s drug information center.