1. Drugs In Pregnancy

2. INTRODUCTION
The safety of approximately 50 % of medications for the mother and fetus remains unknown
Pharmacokinetics are profoundly affected by pregnancy associated physiologic changes and dose adjustments are sometimes necessary for optimal clinical outcome

3. Teratogens
A substance, organism, physical agents or deficiency state capable of inducing abnormal structure or function such as:
Gross structural abnormalities
Functional deficiencies
Intrauterine growth restriction
Behavioral aberrations
Demise

4. Current 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 sulphate
Levotyroxine
vitamins

5. Current 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. or
Animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus

6. Examples:
Amoxiciliin
Amoxicillin + Clavulanic acid
Cefotaxime
Methyl dopa
Metronidazole
Erythromycin

7. Current 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

8. Calcium channel blocker
Examples:
Diclofenac
Rifampicin
Fluoroquinolones
Aminoglycosides
Glyburide
Beta blocker
Calcium channel blocker

9. Current 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

10. Examples:
Tetracyclines
Phenytoin
Valproic acid
Carbamazepine
ACE inhibitors
Litium
azothioporine

11. Current 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.

12. Examples:
Thalidomide
Oral contraceptive pills
Misoprostol

13. DRUGS USED COMMONLY IN PREGNANCY
ANTIBIOTICS:
Cephalosporins
Fluoroquinolones
Macrolides
Aminoglycosides
Miscellaneous

14. CEPHALOSPORINS (Eg: Ceftriaxone, Cefixime, Cefotaxime)
Category B in pregnancy
Cross the placenta during pregnancy
Some reports of increased anomalies with specific cephalosporins (cefaclor, cephalexin, cephradrine)
Primarily cardiac and oral cleft defects
Lactation
Excreted into breastmilk in low concentrations
Considered compatible with breastfeeding

15. FLUOROQUINOLONES (Eg: Ciprofloxacin, Norfloxacin)
Pregnancy Category C
Not recommended in pregnancy
Cartilage damage in animals
Safer alternatives usually exist
Lactation
Excreted into breastmilk
Limited human data
compatible with breastfeeding

16. MACROLIDES (Eg: Azithromycin, Clarithromycin, Erythromycin)
Pregnancy Categories B/C/B
Cross the placenta in low amounts
Limited data with azithromycin and clarithromycin
Lactation
Erythromycin compatible
Others probably compatible

17. AMINOGLYCOSIDES (Gentamicin, Amikacin)
Pregnancy Category C
Rapidly cross placenta
Enter amniotic fluid through fetal circulation
Lactation
Compatible with breastfeeding
Not absorbed through GI tract

18. Tetracyclines (doxycycline, minocycline, tetracycline)
Pregnancy Category D
Can cause problems with teeth and bone and other defects/effects
Have been linked to maternal liver toxicity
Lactation
Compatible with breastfeeding
Serum levels in infants undetectable

19. MISCELLANEOUS ANTIBIOTICS
Clindamycin
Pregnancy Category B, commonly used
Lactation – Compatible
Metronidazole
Pregnancy Category B, carcinogenic in animals, avoid in 1st trimester if possible
Lactation – hold feeds for 12-24hrs afterward

20. MISCELLANEOUS ANTIBIOTICS
Vancomycin
Pregnancy Category B, compatible
Lactation – likely compatible, not absorbed
Nitrofurantoin
Pregnancy Category B, possible hemolytic anemia with use at term
Lactation – Compatible, avoid with G-6-PD deficiency

21. MISCELLANEOUS ANTIBIOTICS
Trimethoprim
Pregnancy Category C, potentially problematic early in pregnancy
Lactation – Compatible as combination drug

22. Antivirals (acyclovir, famciclovir, valacyclovir)
Pregnancy Category B
Acyclovir and valacyclovir readily cross the placenta
Can be used for HSV treatment and suppression
Lactation
Acyclovir and valacyclovir are compatible
Famciclovir should be avoided

23. Antiretrovirals/NRTI (abacavir, didanosine (ddI), emtricitabine (FTC))
Pregnancy Categories C/B/B
Maternal benefit usually outweighs fetal risk
Cross the placenta
Limited data with each do not show increased risk of anomalies
Didanosine has been associated with severe lactic acidosis w/ or w/o pancreatitis

24. Antiretrovirals/NRTI (lamuvidine (3TC), stavudine (d4T))
Pregnancy Category C
Maternal benefit usually outweighs fetal risk
Cross the placenta by simple diffusion
Data with lamivudine show no increased risk of anomalies
Stavudine has been associated with severe lactic acidosis w/ or w/o pancreatitis
All NRTIs have been possibly linked to mitochondrial dysfunction postnatally

25. Antifungals/Azoles (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)
Pregnancy Categories C/C/C/D
Likely cross placenta
Fluconazole > 400mg/day seems to be associated with cranio-facial abnormalities
Itraconazole appears to have low risk
Ketoconazole can impair testosterone and cortisol synthesis
No data in humans is available for voriconazole, increased risk in animals

26. Antifungals/Azoles (fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole)
Lactation
Fluconazole is compatible
Itraconazole could concentrate in milk and body tissues, not recommended
Ketoconazole is compatible
No data with voriconazole, not recommended

27. Migraine Headache Therapy
Triptans
Ergots
Caffeine

28. Triptans (5-HT1 agonists)
Pregnancy Category C
Limited human data exists, sumatriptan has been associated with VSDs in several cases
No data available in humans for almotriptan, eletriptan, frovatriptan, or zolmitriptan
Limited human data exists with naratriptan and rizatriptan, although animal data indicates moderate risks
Pregnancy registry available for exposures

29. Triptans (5-HT1 agonists)
Lactation
Cross into breastmilk and may concentrate
No reports of human lactation with almotriptan, frovotriptan, naratriptan, rizatriptan, or zolmitriptan
Sumatriptan is compatible
Eletriptan is likely compatible with low concentrations

30. Ergots (Dihydroergotamine, ergotamine)
Pregnancy Category X
Oxytocic properties could cause IUGR by vascular disruption or increased uterine tone
Early exposure appears safe, not teratogens
Chronic exposure is contraindicated
Lactation
Contraindicated

31. ANTICONVULSANTS HYDANTOIN AGENTS Category D
Hydantoin agents (Phenytoin) are teratogens long recognised for constellation of congenital anomalies known as fetal hydantoin syndrome
The syndrome consists of craniofacial abnormalities , mental deficiency , hypoplasia of phalanges

32. ANTICONVULSANTS 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 phenytoin
Increases the risk facial dysmorphology, neural tube defects, cardiovascular defects, and urinary tract defects.

33. ANTICONVULSANTS VALPROIC ACID: Category D
It is commonly used for petit mal seizures
1 to 2 % risk of neural tube defects with use in pregnancy
atrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis.

34. Antidepressants
Recent 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.

35. Antituberculous therapy
Isoniazid and paraaminosalicylic acid have an increased risk for some CNS abnormalities.

36. Corticosteroids
High exposures administered systemically have a low risk for cleft palate in some studies, but the epidemiologic studies are not consistent.

37. Methimazole
Aplasia cutis has been reported to be increased in mothers administered this drug during pregnancy*

38. Warfarin 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.

39. NSAIDs and aspirin
Aspirin 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  

40. However, 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 

41. PROSTAGLANDINS They are synthesised from essential fatty acids
PGF2a promotes myometrial contractility , is produced mainly from decidua
PGE2 helps cervical maturation / ripening , is mainly produced from amnion
They also sensitise myometrium to oxytocin
Commonly used for induction of labour

42. PROSTAGLANDINS PGE1 – Misoprostol: (Category X)
PGE1 promotes cervical ripening and myometrial contractility is increased
Transvaginally used for induction of labour
Failure of induction is less
Can be used per rectally /orally also
Incidence of tachysystole is high and thus should not be used in cases with previous ceasarean birth

43. ANTIHYPERTENSIVES METHYL DOPA: Category B
It is the drug of first choice in pregnancy
Has central and peripheral anti adrenergic action
Safe for both mother and fetus
Postural hypotension is a common side effect
May be given orally or i.v
Doses start from 25o mg bd to 500 mg four times a day

44. ANTIHYPERTENSIVES NIFEDIPINE:
Cause direct arteriolar vasodilatation by inhibition of slow calcium channels
Flushing , hypotension , headache , tachycardia are side effects noted

45. ANTIHYPERTENSIVES LABETALOL:
Has combined alpha and beta adrenergic blocking actions
Can be used orally and as iv infusion
Efficacy and safety appears to be equal to methyl dopa
Dose is 100 mg twice a day

46. ANTIHYPERTENSIVES 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 trimesters
Thus considered human teratogens

47. ANTIHYPERTENSIVES SODIUM NITROPRUSSIDE:
It is used to treat serious , life threatening hypertension
Animal studies have shown fetal cyanide toxicity but human studies have not proved the same
Nonetheless , it is avoided in preganancy and is only used as last resort

48. ANTIHYPERTENSIVES MAGNESIUM SULPHATE: Category A Mechanism of action :
It decreases acetycholine release from nerve endings and reduces motor end plate sensitivity to acetylcholine
It blocks calcium channels and causes vasodilation

49. Can be given by Pritchard regime or Zuspan regime
4 gm iv slowly followed by 5 gm in each buttock deep im -- loading dose
5 gm deep im 4 hourly in alternate buttock

50. Indications: Contraindications Dosage:
In eclampsia , as an anticonvulsant
As a tocolytic
Contraindications
In patients with renal impairment
Dosage:
For I.V infusion , 50% solution must be diluted to 20 % before administration
50% solution (undiluted) is given for intramuscular injections

51. It is relatively safe . Muscular paresis , respiratory failure and renal effects on mother are known side effects
Thus deep tendon reflexes, respiratory rate and urine output monitoring is essential in a patient receiving Magnesium Sulpahate
Has no harmful effects on fetus though neonatal respiratory depression may be seen

52. BETAMIMETICS:( Terbutaline , Isoxsuprine)
TOCOLYTICS
BETAMIMETICS:( Terbutaline , Isoxsuprine)
Category C
Mechanism of action:
They activate intracellular enzymes and reduce intracellular free calcium which leads to reduced interaction of actin and myosin

53. Dosage:
Terbutaline can be subcutaneously 0.25 mg 6 hourly or orally 0.5 mg 6 hourly
Isoxsuprine is given either as intravenous infusion drip or intramuscularly(10mg 6 hourly) or orally (10 mg 6/8 hourly)

54. Contraindications : Cardiac arrhythmias
Poorly controlled diabetes mellitus
Poorly controlled thyroid disorders

55. Maternal side effects are headache , palpitations , pulmonary edema , hyperglycemia and hypotension
Fetal tachycardia , heart failure may be seen

56. INDOMETHACIN AND CALCIUM CHANNEL BLOCKERS :
They are also used commonly for tocolysis
Indomethacin may cause gastric disturbances in mother
Calcium channel blockers may cause headache , flushing
Both cause no known fetal harm

57. OXYTOCIN Mechanism of action:
It acts through calcium channels to initiate myometrial contractions
Also stimulate amniotic and decidual prostaglandin production

58. OXYTOCIN Routes of administration:
Can be given intramuscularly or by controlled intravenous infusion
It is also available as nasal solution , buccal tablets

59. OXYTOCIN Indications: Induction of labour Augmentation of labour
In active management of third stage, as an alternative to methergin
To control postpartum hemorrhage

60. OXYTOCIN Contraindications: Obstructed labour Malpresentations
Contracted pelvis
History of previous Caesarean section/hysterotomy (relative contraindication)

61. OXYTOCIN Maternal side effects:
Uterine hyperstimulation (sometimes rupture)
Water intoxication due to its antidiuretic effect
Hypotension

62. OXYTOCIN Fetal side effects:
Fetal distress , fetal hypoxia or even fetal death may occur due to hyperstimulation

63. ERGOT DERIVATIVES METHERGIN: (Category X) Mechanism of action:
Acts directly on myometrium and cause tetanic uterine contractions
Route of administration:
Parenterally – 0.2 mg ampoules available
Orally – 0.5 or 1 mg tablets available

64. ERGOT DERIVATIVES Indications: Therapeutic:
To stop atonic uterine bleeding following delivery or abortion
Prophylactic :
Should be only used in second stage of labour after delivery of anterior shoulder or following delivery of baby

65. ERGOT DERIVATIVES Contraindications: In cardiac diseases
Rh negative pregnancies
Severe pre-eclampsia/eclampsia

66. IRON DEXTRAN
It is intramuscularly used iron preparation for treatment of iron deficiency anemia
1 ml of iron dextran contains mg elemental iron
Oral iron to be stopped 24 hour before therapy to avoid reactions

67. IRON DEXTRAN Mode of administration:
Dose to be given is initially calculated
Initial test dose is given
This is followed by daily or alternate day injections given deep im by Z technique

68. IRON DEXTRAN Drawbacks: Injections are painful
May cause staining of skin
Allergic reactions , though rare , may occur
Abscess formation over injection site may occur

69. IRON DEXTRAN Indications:
Iron deficiency anemia , when oral iron therapy is unsatisfactory or not tolerated
Contraindications:
Anemia other than iron deficiency
Hypersensitivity to the product

70. Ionizing 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.

71. Some common teratogenic medications include:
Angiotensin converting enzyme inhibitors.
Anticonvulsant agents
Antineoplastic agents
Thalidomide, retinoic acid, methylene blue, misoprostol, penicillamine, fluconazole, lit hium, isotretinoin, and acitretin 

72. Some 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.

73. Some 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.

74. Some 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 .

75. Specific 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

76. Antibiotics in Pregnancy
Penicillins
Erythromycin
Cephalosporins
Nitrofurantoin
Metronidazole
Trimethoprim
Sulpha drugs
Chloramphenicol
Tetracycline
Gentamicin A B2 B3 C D

77. Anti-malarial drugs for Pregnancy
Chloroquine
Quinine
Paludrine
Maloprim, Daroprim
Larium
Fansidar
Doxycycline A D B2 B3

78. HAART drugs for Pregnancy
AZT
Lamivudine
Nevirapine
3TC
Abacavir B3

79. Anti-emetics for Pregnancy
Pyridoxine
Diphenhydramine
Metoclopromide
Hyoscine
Ondansetron
Promethazine
Prochlorperazine A B2 B1 C

80. Antihypertensive drugs in Pregnancy
Aldomet
Hydralazine
Beta blockers
Ca channel blockers
Thiazides
ACE Inhibitors A C D
↑risk of CNS & CHD defects 3- fold in 1st trimester, ?cause fetal death in 3rd trimester

81. Analgesic Drugs for Pregnancy
Paracetamol
Codeine
Aspirin
Narcotics
NSAIDs A C
Have the potential to cause in utero closure of the ductus arteriosus >34w

82. THANK YOU