DRUGS USED IN PREGNANCY

UNDER THE GUIDANCE OF: DR. ANSHUL AGARWAAL

SUBMITTED BY: MOHAMMAD ZUBAIR ANSARI

Introduction Drug use during pregnancy and lactation requires

special consideration because both the mother and the child are affected.

Few drugs are considered safe, and drug use is generally contraindicated.

Many pregnant or lactating women take drugs for acute or chronic disorders or habitual use of alcohol and tobacco.

Two main concerns must be addressed when considering whether to give a drug to pregnant women. that the drug may be teratogenic drug can affect near term fetus.

One must always be aware of the teratogenic, toxic or otherwise harmful effects of the drug on the developing fetus.

The physiologic changes during pregnancy and the consequent alteration in the pharmacokinetics lead to changes in drug absorption, distribution, metabolism and excretion.

As a general rule, it is best that no drug should be given during pregnancy, especially during the first trimester as it is period of organogenesis.

Fortunately, most of drugs commonly used in dentistry are not contraindicated during pregnancy.

Tetracycline and streptomycin are notably exceptions.

Pregnancy Trimesters

First trimester: in this trimester, different body organs in the fetus are forming.

It is most critical time for teratogenicity. Dental prophylaxis with detailed instructions and a visual

examination of the oral cavity without X-rays should be performed if the patient is pregnant.

Elective dental treatment should be avoided in the morning as women may feel nauseated in the morning.

Second trimester: it is an excellent time for the patient to undergo dental prophylaxis if needed.

The patient’s periodontal status should be carefully evaluated during this period.

Third trimester: the women begin to feel uncomfortable and it is difficult for her to lie in prone position for long period time.

Drugs that may affect the newborn should not be given during this trimester.

Positioning of patient on dental chair can cause hypotension due to compression of gravid uterus on the inferior vena cava,resulting in syncope.

Stress can precipitate premature labor. Due to hormonal changes, gingival tissue shows exaggerated

response to local irritants.

Pharmacokinetics in Pregnancy

Drug absorption: high circulating levels of progesterone slow the gastric emptying as well as gut motility resulting in slower drug absorption.

Parenteral drug administration is preferred in order to obtain a quick response.

Drug compliance may be poor because of nausea and fear of adverse effect.

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 highly lipid soluble drugs.

Drug excretion: during pregnancy the renal plasma flow increases by 100% and glomerular filtration rate by 70%.

Hence, drugs which depend for their elimination mainly on kidney are eliminated more rapidly than in non-pregnant stage, e.g. ampicillin, gentamicin and cephalosporin.

Increase total blood volume: there is increased total blood volume, because of increased fluid retention.

This leads to change in cardiac output, blood pressure and glomerular filtration rate.

This results in change in volume of distribution of drug, change in metabolism,

change in absorption, change in excretion of drug, change in protein binding of drugs and passage of drug

through placenta.

Teratogenicity: it refers to capacity of a drug to cause fetal abnormalities when administered to pregnant mother.

Drug can affect fetus at three stages,

1. stage of fertilization and implantation

2. stage of organogenesis

3. stage of growth and development

Drugs Abnormalities

Thalidomide Phocomelia

Anticancer drug Multiple defect, Fetal death

Tetracycline Discolored and deformed tooth, Retarded bonegrowth.

Phenytoin Craniofacial and limb defect, cleft lip, cleft palate

Phenobarbitone Various malformations

Carbamazepine CNS defect

Retinoids Various abnormalities

Alcohol Fetal alcohol embryopathy

Normal physiologic changes that occur during pregnancy may alter medication effects, resulting in the need to monitor and, sometimes, adjust therapy.

1. maternal plasma volume, cardiac output, and glomerular filtration increase by 30% to 50%.

2. As body fat increases during pregnancy.

3. Plasma albumin concentration decreases.

MATERNAL PHARMACOKINETIC CHANGES IN PREGNANCY

4. Nausea and vomiting, as well as delayed gastric emptying, may alter the absorption of drugs.

5. Likewise, a pregnancy-induced increase in gastric pH may affect the absorption of weak acids and bases.

6. Higher levels of estrogen and progesterone alter liver enzyme activity and increase the elimination of some drugs but result in accumulation of others.

A teratogen is defined as any agent that results in structural or functional abnormalities in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy.

The teratogenic mechanism for most drugs remains unclear(idiosyncratic), but may be due to the direct effects of the drug on the fetus and/or as a consequence of indirect physiological changes in the mother or fetus.

Teratogen

Teratogenic risk is determined largely by timing of drug expo- sure.

Establishment of full implantation of the fertilized egg takes 1 to 2 weeks.

Teratogenic exposure during this stage elicit an ‘all-or-nothing’ response, leading either to death of the embryo or completely normal development of the fetus.

Pathophysiology

• Embryonic stage (weeks 3-8 post-conception) The critical time for organogenesis is during the first 8

weeks of pregnancy. Organogenesis occurs predominantly during the

embryonic stage and, with the exception of the central nervous system, eyes, teeth, external genitalia and ears, is complete by the end of the 10th week of pregnancy.

Exposure to drugs during this critical period therefore represents the greatest risk of major birth defects.

For this reason, women are often advised to avoid or minimize all drug use in the first trimester whenever possible.

After 8 weeks, most teratogenic effects are related to fetal growth restriction or functional deficits such as mental retardation.

FDA Drug Categories Used in Pregnancy Category A:

Adequate studies in human demonstrate no risk. Category B:

Animal studies indicate no risk, but there are no adequate studies in human.

Animal studies show adverse effects, but adequate studies in human have not demonstrated a risk.

Category C:

A potential risk, when:Animal studies have been performed or,Animal studies indicated adverse effects and,There are no data from human studies.

These drugs may be used when potential benefits outweigh the potential risks.

Category D: There is evidence of human fetal risk, but the potential

benefits to the mother may be acceptable.

Category X:

Studies in animals or humans show adverse reaction reports or both have demonstrated fetal abnormalities.

The risk of use in a pregnant woman clearly outweighs any possible benefit.

DRUGS CATEGORYAnalgesics and antipyretics B and CAcetaminophen B Aspirin BPhenacetin CAntiemetics B and CAntibiotics B,C and DPenicillin,ampicillin,amoxicillin B Cephalosporin BErythromycin BGentamycin CStreptomycin ,Tetracycline DMetronidazole B

Commonly used drugs and their categories

DRUGS CATEGORY

Antimalarial C

Antifungal C

Antitubercular B and C

Ethambutol B

Rifampicin C

Pyrizinamide C

Vitamin B,C,D,E and folic acid A

Local anesthesia

Local anesthesia are not teratogenic, and may administered to pregnancy patient is usual clinical doses.

Large dose of prilocaine are know to cause methemoglobinemia which could cause maternal & fetal hypoxia.

Vasoconstrictors Local vasoconstriction Delay uptake from the site of injection Increase the effectiveness & duration There is no specific contraindication to these

vasoconstrictors in a pregnant patient although it is prudent to use minimal effective dose.

AntibioticsPenicillin FDAB All trimester are safe No teratogenic Pass the placenta Inhibit cell wall synthesis

Tetracycline

Contraindication Chelation with calcium & deposited in the skeleton of

the fetus resulting in depression of bone growth Discoloration Maternal fatty liver degeneration FDAD

Chloramphenicol

Bone marrow depression irreversible aplastic anemia agranulocytosis

FDAC Gray-baby syndrome

Aminoglycoside

Ototoxicity Nephrotoxity FDAD

Acetaminophen

No teratogenesis Most frequency used Analgesic and antipyretic but no anti-inflammation

activity

Aspirin Oral clefts and other defects Intrauterine death,growth retardation,pulmonary

hypertention Longer pregnancies & longer the average period of labor Tetralogy of Fallot (Raot, RVhyperatrophy,Vsep

def,Pula.steno) Increase the risk of antepartum and postpartum

hemorrhage.

NSAID

Contraindication Inhibit synthesis of postaglandins. Constrict the ductus arteriosus & persistent

pulmonary hypertension & increase mortality All of them are category D in the third trimester.

Corticosteroid

Cleft palate Inhibit brain growth Indicated only for treatment of severe systemic

maternal illness (e.g. RA)

Sedative agents

Barbiturates Anxiolytic agents Inhalational sedative

Barbiturates

Cross the placental membrane Cleft palate-lip

Anxiolytic agents

Diazepam Cleft lip and palate Chronic diazepam user- tremors in infants Accumulate in the tissue of fetus

Inhalation sedatives

Increase the rate of spontanous abortion in chronic exposed persons

Vit-B12cofactor of foliate metabolism Foliate metabolism-thymidine formation (DNA base) N2Ooxidase Vit-B12

Dental Management of PregnantPatient

Elective treatment: it can be postponed easily for the pregnant patient after parturition.

However, emergency care should be taken into consideration.

The best method of treatment is to eliminate source of pain.

Thus for removal of caries, an infected pulp or tooth, surgical procedure should be done under small doses of local anesthetics to minimize use of systemic drugs.

Dental procedures are best performed in 2nd trimester for benefit of fetus and optimal comfort of pregnant women.

1st trimester: it is roughly 12–13 weeks. In this first 12 days from conception to implantation

known as ‘preimplantation period’, exposure to harmful drugs can kill the embryo.

From the 13th day, there is period of organogenesis and so the fetus is susceptible to insult and injury resulting in malformation.

2nd and 3rd trimester: after completion of organogenesis,

there is considerable growth and development of existing structures like teeth, bones, CNS, endocrine, genitals and immune system.

Malformation is less in II and III trimester but drug like streptomycin can still be harmful

causing retardation of physical and mental growth, premature labor or neonatal toxicity.

The adverse effect of drugs on the fetus is dependant on the drug and the phase of pregnancy in which the drug is administrated.

Preventive dental prophylaxis: preventive dental prophylaxis should be undertaken at the beginning of the 2nd and 3rd trimester.

Radiographs: radiographs are contraindicated in all but emergency situation, when taken lead shielding is mandatory.

Reduce chair time: prolonged chair time must be avoided to prevent supine hypotension.

Position: sitting up position is best for patient since low head position may cause pressure on vena cava and aorta in 2nd trimester

Fainting: in case of fainting, place patient on left side with legs and head elevated. Oxygen and lime juice with glucose could be given and vital sign monitored.

Guidelines for Prescribed Drugs inPregnancy

Don’t use drug unless it is absolute necessary— use drug in pregnant patient only when it is absolutely necessary.

Ruling out possibility of pregnancy— rule out possibility of pregnancy in every female of reproductive age group and restrict drug usage.

Risk and benefit ratio— prioritize drug usage in the situation and avoid drug usage if the non-usage can do i.e. risk Vs benefit ratio should be calculated.

Lower doses— use lower than usual doses of drug if necessary for short term.

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