drug use in pregnancy and lactation (2)

Drug Use inPregnancy and lactation (2)

ByM.H.Farjoo M.D. , Ph.D.

Shahid Beheshti University of Medical Science

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Drug Use in Pregnancy and lactation (2)

Fetal Effects of Therapeutic Drugs: Autonomic system Analgesics Antihypertensives Chemotherapeutics CNS Anticoagulants

Endocrine Antiemetics Antihistamines Digoxin Dyslipidemics “Azole” Drugs Anti Acne preparations

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Autonomic System: Adrenergics Several of adrenergics were teratogenic in animal

studies. They are in OTC decongestants, cold remedies, and

appetite suppressants. Some systemic adrenergics may retard labor; cause

hypokalemia and hypoglycemia in the mother; and hypoglycemia in the neonate.

These effects are unlikely with inhaled adrenergics. Oral albuterol and oral or IV terbutaline relax uterine

muscles and inhibit preterm labor.

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Autonomic System: Anticholinergics

Effects on the fetus depend on the maturity of its parasympathetic nervous system.

Atropine crosses the placenta rapidly with IV injection.

Scopolamine may cause respiratory depression in the neonate.

It may cause neonatal hemorrhage by reducing Vit. K dependent clotting factors in the neonate.

Atropine (oxygen at [1] is missing)Scopolamine (oxygen present).

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Analgesics: Opioids Maternal addiction and neonatal withdrawal

symptoms result from regular use of opioids. Use of codeine during the first trimester has

been associated with congenital defects. Opioids decrease uterine contractility in labor

and slow progress toward delivery.

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Analgesics: Opioids (Cont,d)

They may also cause respiratory depression in the neonate.

Meperidine (Pethidine) causes less neonatal respiratory depression than other opioids.

If respiratory depression occurs, it can be reversed by naloxone.

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Analgesics: NSAIDs NSAIDs should generally be avoided,

especially during the third trimester. All of them are category D in the third trimester. Near delivery, they cause delayed onset of labor

and risk of excessive bleeding. Diclofenac and aspirin are contraindicated in

pregnant women. The newer COX-2 inhibitors (celecoxib) have

not been studied in pregnant women.

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Analgesics: NSAIDs (Cont,d)

If taken in the third trimester, fetal side effects include: Prenatal constriction or postnatal nonclosure of the

ductus arteriosis Impaired function of the tricuspid valve in the

heart Pulmonary hypertension Degenerative changes in the myocardium Impaired platelet function with resultant bleeding

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Analgesics: NSAIDs (Cont,d)

Cont,d from previous slide: Intracranial bleeding Renal impairment or failure Oligohydramnios GI bleeding or perforation Increased risk of necrotizing enterocolitis, a

life-threatening disorder.

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Antihypertensives No teratogenic effects have been reported for

Methyldopa. Neonates of mothers receiving methyldopa

may have decreased blood pressure for 48 hr. Hydralazine is considered safe. The effects of Clonidine is not known and so

not recommended.

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Antihypertensives: ACE Inhibitors Adverse fetal effects apparently do not occur during

first trimester. With exposure during the second and third trimesters

they may cause: skull hypoplasia, renal failure, and death.

The drugs should be discontinued as soon as pregnancy is detected.

Infants exposed to the drugs in utero should be closely observed for hypotension, oliguria, and hyperkalemia.

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Antihypertensives: Beta Blockers

Teratogenicity has not been reported, but problems may occur during delivery.

These include neonatal bradycardia, apnea, hypoglycemia, low Apgar scores, and low birth weight.

Neonatal effects may last up to 72 hr.

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Antihypertensives: Ca2+ Blockers Teratogenic effects occurred in small animals

given large doses. Diltiazem caused fetal death, skeletal

abnormalities, and increased risk of stillbirths. Nifedipine caused developmental toxicity in

animals. There is a potential risk of inadequate blood

flow to the placenta and the fetus.

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Antihypertensives: Thiazide Diuretics

Thiazides decrease plasma volume and decrease blood flow to the placenta.

They cause: jaundice, thrombocytopenia, fluid and electrolyte imbalances, and impaired carbohydrate metabolism.

Thiazides are not indicated for treatment of dependent edema caused by uterine enlargement.

They also are not effective in prevention or treatment of preeclampsia.

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Antihypertensives: Loop Diuretics

Loop diuretics are not considered teratogenic, but animal studies indicated fetal death.

Loop diuretics may decrease plasma volume and blood flow to the placenta and fetus.

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Chemotherapeutics: Antibacterials

Penicillins and Cephalosporins cross the placenta but apparently are safe.

Trimethoprim, often in combination with sulfamethoxazole, is contraindicated during the first trimester.

It is a folate antagonist and interferes with folic acid metabolism in the fetus.

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Chemotherapeutics: Antibacterials (Cont,d)

Fetal serum levels of Aminoglycosides may reach 50% of maternal levels.

Ototoxicity may occur with gentamicin. Serious adverse effects on the fetus have not

been reported with other aminoglycosides. There is potential harm because the drugs are

nephrotoxic and ototoxic.

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Chemotherapeutics: Antibacterials (Cont,d)

Clindamycin should be used only when infection with Bacteroides fragilis is suspected.

Fluoroquinolones are contraindicated in pregnancy. No fetal abnormalities have been reported for

Erythromycin. In animal studies, adverse fetal effects were reported

with clarithromycin but not with azithromycin. Clarithromycin is contraindicated if a safer alternative

is available.

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Chemotherapeutics: Antibacterials (Cont,d)

Nitrofurantoin should not be used during late pregnancy because of possible hemolytic anemia in the neonate.

Sulfonamides should not be used during the last trimester because they cause kernicterus.

Tetracyclines are contraindicated and interfere with development of teeth and bone in the fetus.

Vancomycin is not recommended because fetal effects are unknown.

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Chemotherapeutics: Anti TB These drugs are recommended for treatment of active

tuberculosis. Use for prophylaxis can be delayed until after

delivery. Isoniazid, ethambutol, and rifampin were

embryocidal or teratogenic in animal studies. However they are used if necessary. Pregnant women taking INH should also take

pyridoxine supplementation.

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Chemotherapeutics: Anti TB (Cont,d)

Treatment of Latent Tuberculosis Infection (LTBI): INH is used for LTBI. For HIV-positive women with higher risks of

progression to active TB, treatment should not be delayed.

For those with lower risks, treatment can begin after delivery.

Pyrazinamide and streptomycin are contraindicated during pregnancy.

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Chemotherapeutics: Antivirals & Antifungals

Most systemic antivirals were teratogenic in animal studies.

No well-controlled studies support their use in pregnancy.

An exception is zidovudine and other anti HIV drugs to prevent transmission of HIV to the fetus.

Antifungals Systemic antifungals are generally contraindicated.

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CNS: Antianxiety These drugs should generally be avoided. If taken during the first trimester, they may

cause physical malformations. During labor, they cause tremor, respiratory

depression, hypotonia, and sucking difficulties in the neonate.

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CNS:Antidepressants & Antipsychotics

TCAs and SSRIs have been associated with teratogenicity when given in large doses.

MAO inhibitors, were associated with growth retardation in animal studies.

Studies indicate that Phenothiazines are not teratogenic.

Use near term may cause abnormal reflexes and jaundice in the neonate.

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CNS: Antimanic Lithium concentrations in fetus are similar to

those of the mother. Cardiac and other birth defects may occur. In the neonate, lithium causes bradycardia,

cyanosis, diabetes insipidus, hypotonia and hypothyroidism.

Most of these effects resolve within 1 to 2 wk.

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Anticoagulants Heparin does not cross the placenta and has not been

associated with congenital defects. It is the anticoagulant of choice during pregnancy. Warfarin causes fetal hemorrhage, spontaneous

abortion, stillbirth, and congenital anomalies. If pregnancy occurs during warfarin therapy, discuss

the possibility of terminating the pregnancy.

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Endocrine: Corticosteroids Animal studies indicate that large doses of cortisol

early in pregnancy produces cleft palate. Chronic maternal ingestion during the first trimester

has shown a 1% incidence of cleft palate in humans. Infants of women who received large amounts of

corticosteroids during pregnancy should be closely observed for adrenal insufficiency.

Inhaled corticosteroids are less likely to cause adverse effects.

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Endocrine: Thyroid Gland Levothyroxine does not cross the placenta and

seems safe in appropriate dosages. When given to hypothyroid women, the drug

should be continued through pregnancy. Radioactive iodide (and any other radioactive

drug) and iodine is contraindicated during pregnancy.

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Endocrine: Antidiabetics Insulin is the only antidiabetic drug

recommended for use during pregnancy. Sulfonylureas except glyburide are teratogenic

in animals. Acarbose, metformin, and miglitol are category

B.

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Antiemetics

None of the available antiemetic drugs has been proven safe.

If drug therapy is necessary some antihistamines (dimenhydrinate) are safer than others.

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Antihistamines H1 blockers should generally not be used

during the third trimester. H2 blocker agents, are considered acceptable

for treatment of gastroesophageal reflux.

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Digoxin Digoxin is apparently safe for use during

pregnancy. Fetal toxicity and neonatal death have

occurred with maternal overdose. Serum drug levels must be closely monitored

during pregnancy. Digoxin is given to the mother for treatment of

fetal tachycardia and heart failure.

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Dyslipidemics Cholestyramine and colestipol are considered

safe because they are not absorbed orally. HMG-CoA reductase inhibitors (statins) are

contraindicated during pregnancy (category X). They can be given to women of childbearing

age only if they are highly unlikely to become pregnant and are informed of hazards.

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“Azole” drugs All azoles (miconazole, ketoconazole, etc.) are

contraindicated because of teratogenicity and malformations.

Metronidazole is contraindicated during the first trimester.

Mebendazole and pyrantel are contraindicated during pregnancy.

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Anti Acne preparations Retinoids (etretinate and isotretinoin) are

contraindicated in women of childbearing potential. Isotretinoin (Accutane) is used in the treatment of

severe cystic acne that is recalcitrant to standard therapies.

Isotretinoin may act by inhibiting sebaceous gland size and function.

Teratogenicity is a significant risk in patients taking isotretinoin.

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Anti Acne preparations (Cont,d)

Women must use contraception for 1 month before, throughout therapy, and for one menstrual cycle after stopping the treatment.

A serum pregnancy test must be obtained within 2 weeks before therapy

Therapy should be initiated on the second or third day of the next menstrual period.

Thank youAny question?