2INTRODUCTIONThe safety of approximately 50 % of medications for the mother and fetus remains unknownPharmacokinetics are profoundly affected by pregnancy associated physiologic changes and dose adjustments are sometimes necessary for optimal clinical outcome
3TeratogensA substance, organism, physical agents or deficiency state capable of inducing abnormal structure or function such as:Gross structural abnormalitiesFunctional deficienciesIntrauterine growth restrictionBehavioral aberrationsDemise
4Current Categories for Drug Use in Pregnancy Category A : Adequate, well-controlled studies in pregnant women have not shown an increased risk of fetal abnormalities.Examples:Magnesium sulphateLevotyroxinevitamins
5Current Categories for Drug Use in Pregnancy Category B :Animal studies have revealed no evidence of harm to the fetus, however, there are no adequate and well- controlled studies in pregnant women. orAnimal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus
7Current Categories for Drug Use in Pregnancy Category C:Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women. or No animal studies have been conducted and there are no adequate and well-controlled studies in pregnant women
9Current Categories for Drug Use in Pregnancy Category D:Studies, adequate well-controlled or observational, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential harm
11Current Categories for Drug Use in Pregnancy Category X:Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant.
13DRUGS USED COMMONLY IN PREGNANCY ANTIBIOTICS:CephalosporinsFluoroquinolonesMacrolidesAminoglycosidesMiscellaneous
14CEPHALOSPORINS (Eg: Ceftriaxone, Cefixime, Cefotaxime) Category B in pregnancyCross the placenta during pregnancySome reports of increased anomalies with specific cephalosporins (cefaclor, cephalexin, cephradrine)Primarily cardiac and oral cleft defectsLactationExcreted into breastmilk in low concentrationsConsidered compatible with breastfeeding
15FLUOROQUINOLONES (Eg: Ciprofloxacin, Norfloxacin) Pregnancy Category CNot recommended in pregnancyCartilage damage in animalsSafer alternatives usually existLactationExcreted into breastmilkLimited human datacompatible with breastfeeding
16MACROLIDES (Eg: Azithromycin, Clarithromycin, Erythromycin) Pregnancy Categories B/C/BCross the placenta in low amountsLimited data with azithromycin and clarithromycinLactationErythromycin compatibleOthers probably compatible
17AMINOGLYCOSIDES (Gentamicin, Amikacin) Pregnancy Category CRapidly cross placentaEnter amniotic fluid through fetal circulationLactationCompatible with breastfeedingNot absorbed through GI tract
18Tetracyclines (doxycycline, minocycline, tetracycline) Pregnancy Category DCan cause problems with teeth and bone and other defects/effectsHave been linked to maternal liver toxicityLactationCompatible with breastfeedingSerum levels in infants undetectable
19MISCELLANEOUS ANTIBIOTICS ClindamycinPregnancy Category B, commonly usedLactation – CompatibleMetronidazolePregnancy Category B, carcinogenic in animals, avoid in 1st trimester if possibleLactation – hold feeds for 12-24hrs afterward
20MISCELLANEOUS ANTIBIOTICS VancomycinPregnancy Category B, compatibleLactation – likely compatible, not absorbedNitrofurantoinPregnancy Category B, possible hemolytic anemia with use at termLactation – Compatible, avoid with G-6-PD deficiency
21MISCELLANEOUS ANTIBIOTICS TrimethoprimPregnancy Category C, potentially problematic early in pregnancyLactation – Compatible as combination drug
22Antivirals (acyclovir, famciclovir, valacyclovir) Pregnancy Category BAcyclovir and valacyclovir readily cross the placentaCan be used for HSV treatment and suppressionLactationAcyclovir and valacyclovir are compatibleFamciclovir should be avoided
23Antiretrovirals/NRTI (abacavir, didanosine (ddI), emtricitabine (FTC)) Pregnancy Categories C/B/BMaternal benefit usually outweighs fetal riskCross the placentaLimited data with each do not show increased risk of anomaliesDidanosine has been associated with severe lactic acidosis w/ or w/o pancreatitis
24Antiretrovirals/NRTI (lamuvidine (3TC), stavudine (d4T)) Pregnancy Category CMaternal benefit usually outweighs fetal riskCross the placenta by simple diffusionData with lamivudine show no increased risk of anomaliesStavudine has been associated with severe lactic acidosis w/ or w/o pancreatitisAll NRTIs have been possibly linked to mitochondrial dysfunction postnatally
25Antifungals/Azoles (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole) Pregnancy Categories C/C/C/DLikely cross placentaFluconazole > 400mg/day seems to be associated with cranio-facial abnormalitiesItraconazole appears to have low riskKetoconazole can impair testosterone and cortisol synthesisNo data in humans is available for voriconazole, increased risk in animals
26Antifungals/Azoles (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole) LactationFluconazole is compatibleItraconazole could concentrate in milk and body tissues, not recommendedKetoconazole is compatibleNo data with voriconazole, not recommended
28Triptans (5-HT1 agonists) Pregnancy Category CLimited human data exists, sumatriptan has been associated with VSDs in several casesNo data available in humans for almotriptan, eletriptan, frovatriptan, or zolmitriptanLimited human data exists with naratriptan and rizatriptan, although animal data indicates moderate risksPregnancy registry available for exposures
29Triptans (5-HT1 agonists) LactationCross into breastmilk and may concentrateNo reports of human lactation with almotriptan, frovotriptan, naratriptan, rizatriptan, or zolmitriptanSumatriptan is compatibleEletriptan is likely compatible with low concentrations
30Ergots (Dihydroergotamine, ergotamine) Pregnancy Category XOxytocic properties could cause IUGR by vascular disruption or increased uterine toneEarly exposure appears safe, not teratogensChronic exposure is contraindicatedLactationContraindicated
31ANTICONVULSANTS HYDANTOIN AGENTS Category D Hydantoin agents (Phenytoin) are teratogens long recognised for constellation of congenital anomalies known as fetal hydantoin syndromeThe syndrome consists of craniofacial abnormalities , mental deficiency , hypoplasia of phalanges
32ANTICONVULSANTS CARBAMAZEPINE: Category D Was considered relatively safe for use during pregnancy but recent FDA reports suggest increased risk of neural tube defects with carbamazepine too and a pattern of malformations similar to phenytoinIncreases the risk facial dysmorphology, neural tube defects, cardiovascular defects, and urinary tract defects.
33ANTICONVULSANTS VALPROIC ACID: Category D It is commonly used for petit mal seizures1 to 2 % risk of neural tube defects with use in pregnancyatrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis.
34AntidepressantsRecent publications have implicated some of the SSRIs administered in the last trimester with postnatal neurobehavioral effects that are transient and whose long-term effects have not been determined. First- trimester exposures to some SSRIs have been reported to increase the risk of some congenital malformations, predominantly congenital heart disease. The results have not been consistent, but warnings have been issued.
35Antituberculous therapy Isoniazid and paraaminosalicylic acid have an increased risk for some CNS abnormalities.
36CorticosteroidsHigh exposures administered systemically have a low risk for cleft palate in some studies, but the epidemiologic studies are not consistent.
37MethimazoleAplasia cutis has been reported to be increased in mothers administered this drug during pregnancy*
38Warfarin and warfarin derivatives Early exposure during pregnancy can result in nasal hypoplasia, stippling of secondary epiphysis, intrauterine growth restriction. Central nervous system malformations can occur in late pregnancy exposure because of bleeding.
39NSAIDs and aspirinAspirin has been used for years in patients requiring NSAID therapy during pregnancy. Salicylates readily cross the placenta, but a meta-analysis did not find evidence of an overall increase in risk of congenital defects associated with first trimester use of aspirin .Although some case-control studies have reported associations between human congenital malformations and aspirin use early in gestation, no consistent adverse outcome attributable to drug use has been observed.The NSAIDs and salicylates are considered by the FDA as category C drugs in terms of the risks associated with their use during the first two trimesters .A number of the NSAIDs are labeled as category D drugs from week 30 onwards, and high-dose aspirin is considered a category D medication during the third trimester
40However, third trimester use of these agents may pose greater risk However, third trimester use of these agents may pose greater risk. The inhibition of prostaglandin synthesis by NSAIDs or by high-dose aspirin therapy in the third trimester has the potential for causing premature closure of the ductus arteriosus; indomethacin and ibuprofen appear to have much stronger ductal effects than aspirin .High-dose aspirin near delivery may increase the risk of fetal or neonatal bleeding or bruising although data are inconsistent
41PROSTAGLANDINS They are synthesised from essential fatty acids PGF2a promotes myometrial contractility , is produced mainly from deciduaPGE2 helps cervical maturation / ripening , is mainly produced from amnionThey also sensitise myometrium to oxytocinCommonly used for induction of labour
42PROSTAGLANDINS PGE1 – Misoprostol: (Category X) PGE1 promotes cervical ripening and myometrial contractility is increasedTransvaginally used for induction of labourFailure of induction is lessCan be used per rectally /orally alsoIncidence of tachysystole is high and thus should not be used in cases with previous ceasarean birth
43ANTIHYPERTENSIVES METHYL DOPA: Category B It is the drug of first choice in pregnancyHas central and peripheral anti adrenergic actionSafe for both mother and fetusPostural hypotension is a common side effectMay be given orally or i.vDoses start from 25o mg bd to 500 mg four times a day
44ANTIHYPERTENSIVES NIFEDIPINE: Cause direct arteriolar vasodilatation by inhibition of slow calcium channelsFlushing , hypotension , headache , tachycardia are side effects noted
45ANTIHYPERTENSIVES LABETALOL: Has combined alpha and beta adrenergic blocking actionsCan be used orally and as iv infusionEfficacy and safety appears to be equal to methyl dopaDose is 100 mg twice a day
46ANTIHYPERTENSIVES ACE INHIBITORS: Category C or D Not used in pregnancy as studies show increased risk of oligohydramnios , neonatal anuria , renal anomalies and nephrotoxicity when used in 2 nd and 3 rd trimestersThus considered human teratogens
47ANTIHYPERTENSIVES SODIUM NITROPRUSSIDE: It is used to treat serious , life threatening hypertensionAnimal studies have shown fetal cyanide toxicity but human studies have not proved the sameNonetheless , it is avoided in preganancy and is only used as last resort
48ANTIHYPERTENSIVES MAGNESIUM SULPHATE: Category A Mechanism of action : It decreases acetycholine release from nerve endings and reduces motor end plate sensitivity to acetylcholineIt blocks calcium channels and causes vasodilation
49Can be given by Pritchard regime or Zuspan regime 4 gm iv slowly followed by 5 gm in each buttock deep im -- loading dose5 gm deep im 4 hourly in alternate buttock
50Indications: Contraindications Dosage: In eclampsia , as an anticonvulsantAs a tocolyticContraindicationsIn patients with renal impairmentDosage:For I.V infusion , 50% solution must be diluted to 20 % before administration50% solution (undiluted) is given for intramuscular injections
51It is relatively safe . Muscular paresis , respiratory failure and renal effects on mother are known side effectsThus deep tendon reflexes, respiratory rate and urine output monitoring is essential in a patient receiving Magnesium SulpahateHas no harmful effects on fetus though neonatal respiratory depression may be seen
52BETAMIMETICS:( Terbutaline , Isoxsuprine) TOCOLYTICSBETAMIMETICS:( Terbutaline , Isoxsuprine)Category CMechanism of action:They activate intracellular enzymes and reduce intracellular free calcium which leads to reduced interaction of actin and myosin
53Dosage:Terbutaline can be subcutaneously 0.25 mg 6 hourly or orally 0.5 mg 6 hourlyIsoxsuprine is given either as intravenous infusion drip or intramuscularly(10mg 6 hourly) or orally (10 mg 6/8 hourly)
55Maternal side effects are headache , palpitations , pulmonary edema , hyperglycemia and hypotension Fetal tachycardia , heart failure may be seen
56INDOMETHACIN AND CALCIUM CHANNEL BLOCKERS : They are also used commonly for tocolysisIndomethacin may cause gastric disturbances in motherCalcium channel blockers may cause headache , flushingBoth cause no known fetal harm
57OXYTOCIN Mechanism of action: It acts through calcium channels to initiate myometrial contractionsAlso stimulate amniotic and decidual prostaglandin production
58OXYTOCIN Routes of administration: Can be given intramuscularly or by controlled intravenous infusionIt is also available as nasal solution , buccal tablets
59OXYTOCIN Indications: Induction of labour Augmentation of labour In active management of third stage, as an alternative to metherginTo control postpartum hemorrhage
60OXYTOCIN Contraindications: Obstructed labour Malpresentations Contracted pelvisHistory of previous Caesarean section/hysterotomy (relative contraindication)
61OXYTOCIN Maternal side effects: Uterine hyperstimulation (sometimes rupture)Water intoxication due to its antidiuretic effectHypotension
62OXYTOCIN Fetal side effects: Fetal distress , fetal hypoxia or even fetal death may occur due to hyperstimulation
63ERGOT DERIVATIVES METHERGIN: (Category X) Mechanism of action: Acts directly on myometrium and cause tetanic uterine contractionsRoute of administration:Parenterally – 0.2 mg ampoules availableOrally – 0.5 or 1 mg tablets available
64ERGOT DERIVATIVES Indications: Therapeutic: To stop atonic uterine bleeding following delivery or abortionProphylactic :Should be only used in second stage of labour after delivery of anterior shoulder or following delivery of baby
65ERGOT DERIVATIVES Contraindications: In cardiac diseases Rh negative pregnanciesSevere pre-eclampsia/eclampsia
66IRON DEXTRANIt is intramuscularly used iron preparation for treatment of iron deficiency anemia1 ml of iron dextran contains mg elemental ironOral iron to be stopped 24 hour before therapy to avoid reactions
67IRON DEXTRAN Mode of administration: Dose to be given is initially calculatedInitial test dose is givenThis is followed by daily or alternate day injections given deep im by Z technique
68IRON DEXTRAN Drawbacks: Injections are painful May cause staining of skinAllergic reactions , though rare , may occurAbscess formation over injection site may occur
69IRON DEXTRAN Indications: Iron deficiency anemia , when oral iron therapy is unsatisfactory or not toleratedContraindications:Anemia other than iron deficiencyHypersensitivity to the product
70Ionizing radiationRadiation Ionizing radiationRadiation exposure above a threshold of 20 rad (0.2 Gy) can increase the risk for some fetal effects such as microcephaly or growth retardation, but the threshold for mental retardation is higher.
72Some common teratogenic medications include: Retinoic acid is highly teratogenic in the first trimester of pregnancy, leading to spontaneous abortions and fetal malformations, including microcephaly and cardiac anomalies . At doses of only several times the RDA , many animal models as well as human studies have shown high incidence of birth defects in mothers who ingested therapeutic doses of retinoic acid for dermatological uses . A safe upper limit for vitamin A intake has been recognized at about 800 to 10,000 IU/day . Acitretin should not be used by women who want to become pregnant as conception is contraindicated for at least three years after discontinuation.
73Some common teratogenic medications include: Androgenic agents, such as testosterone or danazol, do not cause malformation, but can virilize a female fetus. Cocaine induced vasoconstriction of uterine vessels is one mechanism for fetal damage from this substance . Infants whose mothers consume alcohol during pregnancy can have fetal alcohol effects (FAE), alcohol- related birth defects (ARBD), fetal alcohol syndrome, or they may be normal.
74Some common teratogenic medications include: Folicacid antagonists(eg, trimethoprim, triamterene, car bamazepine, phenytoin, phenobarbital, primidone, met hotrexate) increase the risk of neural-tube defects and possibly cardiovascular defects, oral clefts, and urinary tract defects and placenta-mediated adverse pregnancy outcomes, including preeclampsia, placental abruption, fetal growth restriction, and fetal death .
75Specific information on the fetal and neonatal risks of maternal drug ingestion during pregnancy and lactation are available from several resources , including:subscription)file://depts.washington.edu/terisweb/teris/ (requires subscription)UpToDate drug information database
76Antibiotics in Pregnancy PenicillinsErythromycinCephalosporinsNitrofurantoinMetronidazoleTrimethoprimSulpha drugsChloramphenicolTetracyclineGentamicinAB2B3CD
77Anti-malarial drugs for Pregnancy ChloroquineQuininePaludrineMaloprim, DaroprimLariumFansidarDoxycyclineADB2B3
78HAART drugs for Pregnancy AZTLamivudineNevirapine3TCAbacavirB3
79Anti-emetics for Pregnancy PyridoxineDiphenhydramineMetoclopromideHyoscineOndansetronPromethazineProchlorperazineAB2B1C
80Antihypertensive drugs in Pregnancy AldometHydralazineBeta blockersCa channel blockersThiazidesACE InhibitorsACD↑risk of CNS & CHD defects 3- fold in 1st trimester, ?cause fetal death in 3rd trimester
81Analgesic Drugs for Pregnancy ParacetamolCodeineAspirinNarcoticsNSAIDsACHave the potential to cause in utero closure of the ductus arteriosus >34w