Drugs In Pregnancy

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Drugs In Pregnancy
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• Dr P K SHAH
• Professor and Unit incharge,
  Seth G.S.
  Medical college and KEM hospital, Parel, Mumbai.
• Secretary General, FOGSI

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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

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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

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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

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• Examples
• Amoxiciliin
• Amoxicillin Clavulanic acid
• Cefotaxime
• Methyl dopa
• Metronidazole
• Erythromycin

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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

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• Examples
• Diclofenac
• Rifampicin
• Fluoroquinolones
• Aminoglycosides
• Glyburide

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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

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• Examples
• Tetracyclines
• Phenytoin
• Valproic acid
• Carbamazepine
• ACE inhibitors

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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.

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• Examples
• Thalidomide
• Oral contraceptive pills
• Misoprostol

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DRUGS USED COMMONLY IN PREGNANCY

• ANTIBIOTICS
• Cephalosporins
• Fluoroquinolones
• Macrolides
• Aminoglycosides
• Miscellaneous

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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

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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
• AAP says compatible with breastfeeding

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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

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AMINOGLYCOSIDES(Gentamicin, Amikacin)

• Pregnancy Category C
• Rapidly cross placenta
• Enter amniotic fluid through fetal circulation
• Lactation
• Compatible with breastfeeding
• Not absorbed through GI tract

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MISCELLANEOUS ANTIBIOTICS

• Clindamycin
• Pregnancy Category B, commonly used
• Lactation Compatible per AAP
• Metronidazole
• Pregnancy Category B, carcinogenic in animals,
  avoid in 1st trimester if possible
• Lactation hold feeds for 12-24hrs afterward

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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

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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

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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

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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

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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

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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

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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

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ANTIHYPERTENSIVES

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

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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

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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

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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

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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

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• Can be given by Pritchard regime or
  Zuspan regime
• Pritchard 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

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• Indications
• 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

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• 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

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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

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• 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)

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• Contraindications
• Cardiac arrhythmias
• Poorly controlled diabetes mellitus
• Poorly controlled thyroid disorders

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

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• 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

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OXYTOCIN

• Mechanism of action
• It acts through calcium channels to initiate
  myometrial contractions
• Also stimulate amniotic and decidual
  prostaglandin production

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OXYTOCIN

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

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OXYTOCIN

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

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OXYTOCIN

• Contraindications
• Obstructed labour
• Malpresentations
• Contracted pelvis
• History of previous Caesarean section/hysterotomy
  (relative contraindication)

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OXYTOCIN

• Maternal side effects
• Uterine hyperstimulation (sometimes rupture)
• Water intoxication due to its antidiuretic effect
• Hypotension

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OXYTOCIN

• Fetal side effects
• Fetal distress , fetal hypoxia or even fetal
  death may occur due to hyperstimulation

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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

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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

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ERGOT DERIVATIVES

• Contraindications
• In cardiac diseases
• Rh negative pregnancies
• Severe pre-eclampsia/eclampsia

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IRON DEXTRAN

• It is intramuscularly used iron preparation for
  treatment of iron deficiency anemia
• 1 ml of iron dextran contains 50 mg elemental
  iron
• Oral iron to be stopped 24 hour before therapy to
  avoid reactions

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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

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IRON DEXTRAN

• Drawbacks
• Injections are painful
• May cause staining of skin
• Allergic reactions , though rare , may occur
• Abscess formation over injection site may occur

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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

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• THANK YOU