PHARMACOTHERAPEUTICS IN OBSTETRICS

OXYCTOCICS IN OBSTETRICS
 OXYTOCIN
 ERGOT DERIVATIVES
 PROSTAGLANDINS
OXYTOCIN
 It is synthesised in the supra-optic and para ventricular nuclei of the hypothalamus.
 a half life of 3-4 minutes and duration of action of approximately 20 minutes
 Mode of action receptor and voltage mediated calcium channels
 amniotic and prostaglandin decidual production
OXYTOCIN
 Preparations used
 Synthetic oxytocin
 Syntometrine
 Desamino oxytocin
 Oxytocin nasal solution
 Effectiveness
 In later months of pregnancy and during labour
INDICATIONS
 THERAPEUTIC:
 Pregnancy:
 Early:
 to accelerate abortion.
 To stop bleeding following evacuation of the uterus.
 Used as an adjunct of abortion along with other abortifacient agents.
 Late:
 To induce labour.
 To facilitate cervical ripening for effective induction.
 Augmentation of labour.
 Uterine intertia.
INDICATIONS
 Labour:
 In active management of third stage of labour.
 Following expulsion of placenta.
 Pueperium:
 To minimize the blood loss and to control the PPH.
 DIAGNOSTIC:
 Contraction stress test
 Principles:
 The test is based on the determination of respitratory function of the feto placental unit during induced
contractions
CST
 Candidates for CST:
 Intra uterine growth restriction.
 Postmaturity.
 Hypretensive disorders of pregnancy.
 Diabetes
 Contraindications:
 Compromised fetus.
 Previous history of caesarean section.
 Complications likely to produce preterm labour.
 APH.
INTERPRETATION :CST
  Positive: persistent late deceleration of FHR following 50 % or more uterine contrations.
 Negative: no late deceleration or significant variable deceleration.
 Suspicious: inconsistent but definite decelerations do not persist with more uterine contractions.
 Unsatisfactory: poor quality of recording or adequate uterine contraction is not achieved.
 Hyperstimultaion:
 Deceleration of FHR with uterine contraction lasting > 90 seconds or occurring more frequently than every 2
minutes.
OXYTOCIN STIMULATION TEST
 Procedure
 Inference
 Contraindications of oxytocin:
 Pregnancy:
 Grand multipara.
 Contracted pelvis.
 History of caesarean or hysterotomy.
 Malpresentation.
 Labour:
 All the contraindications in pregnancy.
 Obstructed labour.
 Inco-ordinate uterine action.
 Fetal distress.
 Any time:
 Hypovolemic state.
 Cardiac disease.
OXYTOCIN STIMULATION TEST
 Methods of administration:
 Controlled intravenous infusion
 For induction in labour
 Use in labour
 Intramuscular
 5-10 units after the birth of the baby as an alternative to ergometrine
ADVERSE EFFECTS MATERNAL
 Uterine hyperstimulation
 Uterine rupture
 Water intoxication
 Hypotension
 Anti-diuresis FETAL
 Fetal distress, fetal hypoxia and fetal death
NURSE’S RESPONSIBILITIES
 Assess
 Intake output ratio.
 Uterine contractions and FHR.
 Blood pressure, pulse and respiration.
 Administer
 By IV infusion. Monitor drop rate.
 Make crash cart available.
 Evaluate
 Length and duration of contractions.
 Notify physician of contractions lasting over 1 minute or absence of contrcations.
 Teach
 To report increased blood loss, abdominal cramps or increased temperature.
ERGOT DERIVATIVES
 Mode of action: Ergometrine acts directly on the myometrium
  Effectiveness It is highly effective in hemostasis
 Indications:
 Therapeutic: To stop the atonic uterine bleeding following delivery, abortion or expulsion of hydatidiform mole.
 Prophylactic: Against excessive haemorrhage following delivery.
ERGOT DERIVATIVES CONTRAINDICATIONS: Prophylactic:
 Suspected plural pregnancy.
 Organic cardiac diseases.
 Severe pre-eclampsia and eclampsia
 Rh- negative mother. Therapeutic:
 Heart disease or severe hypertensive disorders
ERGOT DERIVATIVES Preparations Ampoules tablet Ergometrine[ergon ovine] Methergin[methyl- ergonovine]
Syntometrine[Sand oz] 0.25 mg or 0.5 mg 0.2 mg 0.5 mg ergometrine + 5 units of syntometrine 0.5 mg 0.5-1 mg
Onset of action Routes Ergometrine Methergin IV IM Oral 45-60sec 6-7mt 10 mt 5.min 7 min 10 min
ERGOT DERIVATIVES Hazards:
 Common side effects are nausea and vomiting.
 Precipitate rise of blood pressure, myocardial infarction, stroke and bronchospasm because of vasoconstrictive
effect.
 Prolonged use may result in gangrene formation of the toes.
 Prolonged use in puerperium may interfere with lactation.
 ERGOT DERIVATIVES
 Cautions: Ergometrine should not be used during pregnancy, first stage of labour, second stage of labour,
second stage prior to crowning of the head and in breech delivery prior to crowning
ERGOT DERIVATIVES Nurse’s responsibilities: Assess Blood pressure, pulse and respiration.
 Watch for signs of haemorrhage. Administer
 Orally or IM in deep muscle mass.
 Have emergency cart readily available. Evaluate
 Therapeutic effect: decreased blood loss. Teach
 To report increased blood loss, abdominal cramps, headache, sweating, nausea, vomiting or dyspnoea.
PROSTAGLANDINS Source
 arachidonic acid Mechanism of action
 PGF2α promotes myometrial contractility
 PGE2 helps cervical maturation
 PROSTAGLANDINS Use in obstetrics
 Induction of abortion.
 Termination of molar pregnancy.
 Induction of labour.
 Cervical ripening prior to the induction of abortion or labour.
 Acceleration of labour.
 Management of atonic PPH.
 Medical management of tubal ectopic pregnancy.
 PROSTAGLANDINS Contraindications:
 Hypersensitivity to the compound.
 Uterine scar. Preparations
 Tablet.
 Vaginal suppository
 Vaginal pessry
 Prostin E2.
 Parentral
PROSTAGLANDINS Advantages:
 It has got a powerful oxytocic effect, irrespective of period of pregnancy. As such it can be used independently
specially in the induction of abortion with success.
 In later months it can be used for acceleration of labour.
 It has got no anti diuretic effect.
PROSTAGLANDINS Drawbacks:
 It is costly.
 Unpleasant side effects on systemic use are nausea, vomiting, diarrhoea, pyrexia or bronchospasm.
 When used as abortifacient, extensive lacerations may occur.
 Tachysystole.

ANTI-HYPERTENSIVE THERAPY
1. Symp athom imetics
Methyldo pa
Reserpin e
1. adrenergic Receptor blocking agent
Labetalol
Propanalol
1. vasodilat ors
Hydralazine
Prazocin
Sodium nitroprusside
1. calcium channe l blocke rs
Nifedipine
nicardia
1. ACEI Inhibit ors
Captopril
lisinopril

METHYLDOPA Mechanism of action

 -Drugs of first choice
 -Central and peripheral anti-adrenergic action
 -Effective and safe for both mother and fetus. Contraindications
 -hepatic disorders
 -psychic patients
 -CCF Dose
 -orally 250mg bid may be increased to 1 gm tid depending upon the response.
 -IV infusion 250-500mg
METHYLDOPA
Side effects -maternal:
 postural hypotension
 haemolytic anemia
 sodium retension
 excessive sedation
 coomb’s test may be positive. -fetal:
 intestinal ileus
LABETALOL Mechanism of action
 Combined alpha and beta adrenergic blocking agents. Contraindication
 hepatic disorders. Dose orally: 100mg tid. May be increased upto 800 mg daily.
 -IV infusion [hypertensive crisis] 1-2 mg/mt until desired effect Side effects Experience is less compared to
methyl dopa. efficacy and safety with short term use. Appear equal to methyl dopa.
PROPRANOLOL Mechanism of action
 Beta adrenergic receptor blocker Contraindication
 bronchial asthma.
 renal insufficiency.
 diabetes.
 Cardiac failure
  The drug is better avoided for long term therapy during pregnancy. Dose
 orally: 80-120 mg in divided doses
PROPRANOLOL Side effects maternal:
 severe hypotension
 sodium retension
 Bradycardia
 Bronchospasm
 CCF
 hypoglycaemia. fetal:
 bradycardia and impaired fetal responses to hypoxia, IUGR when began in I and II trimester. -neonatal:
hypoglycaemia
PRAZOCIN Mechanism of action
 -selective post synaptic blocker. Decrease plasma renin activity.
 -reduces cardiac preload and after load. Contraindication
 Low first dose, to avid hypotension and syncope. Dose
 Orally 1 mg bd may be increased upto 20 mg/day Side effects
 -hypotension
 -nasal congestion
 -fluid retension
HYDRALAZINE Mechanism of action
 Arteriolar vasodilator. Contraindication
 Because of the variable sodium retention, diuretics should be used. Dose
 orally: 100mg/day in 4 divided doses.
 -IV : 5mg bolus followed by 25g in 200 ml NS at a rate of 2.5 mg/hr to be doubled every 30 mts. Side effects
 -maternal: hypotension,tachycardia, arrhythmia, palpitation, lupus like syndrome.
 -fetal: reasonably safe.
 -neonatal: thrombocytopenia
NIFEDIPINE Mode of action:
 Direct arteriolar vasodilation. Dose:
 Orally 5-10 mg TID. Contraindications:
 Simultaneous use of magnesium sulphate could be hazardous due to synergic effect. Side effects:
 Flushing
 Hypotension
 Head ache
 Tachycardia
 Inhibition of labour.
SODIUM NITROPRUSSIDE Mechanism of action:
 Direct vasodilator. Dose:
 Orally 6.25 bid. Side effects:
 Maternal
 Nausea
 Vomiting
 Fetal
 Oligohydramnios
 IUGR
 Fetal and neonatal renal failure.
NITROGLYCERINE Mechanism of action
 Release mainly venous but also arteriolar smooth muscles. Dose:
 Given as IV infusion 5µg/min. to be increased at every 3-5 min. upto 100µg/min. Side effects:
 Tachycardia
 Headache
 Methaemoglobinaemia
DIURETICS
Diuretics are used in the following conditions during pregnancy.
 Pregnancy induced hypertension with massive edema.
 Eclampsia with pulmonary edema.
 Severe anemia in pregnancy with heart failure.
 Prior to blood transfusions in severe anemia.
 As as adjunct to certain antihypertensive drugs, such as hydralazine or dioxide
FUROSEMIDE Mechanism of action
 Acts o loop of the Henle by increasing excretion of sodium and chloride. Dose
 40 mg tab, daily following breakfast for 5 days a week. In acute conditions, parentrally 40-120 mg daily.
Contraindications:
 Hypersensitivity
FUROSEMIDE Maternal
 Weakness
 Fatigue
 muscle cramps
 hypokalemia
 hyponatremia
 hypokalemia
 hypochloremic alkalosis
 postural hypotension fetal
 fetal compromise due to decreased placental perfusion.
 Thrombocytopenia
 Hyponatremia
HYDROCLOROTHIAZIDE Mechanism of action:
 Acts on distal tubule by increasing excretion of water, sodium, chloride and potassium. It is used in edema and
hypertension.
Dose:
 PO 25-100 mg/day. Side effects:
 Polyuria, glycosuria, frequency.
 Nausea, vomiting, anorexia.
 Rash, urticarial, fever.
 Increased creatinine, decreased electrolytes.
TOCOLYTIC AGENTS
 Betamimetics
 prostaglandin synthetase inhibitors
 magnesium sulphate
 calcium channel blockers
 oxytocin receptor antagonists
 nitric oxide donors
 antibiotics.
BETAMIMETICS Commonly used drugs:
 Terbutaline
 Ritodrine
 Isoxurpine
Mechanism of action:
 Activation of the intracellular enzymes [adenylate cyclase, cAMP, protein kinase] reduces intracellular free
calcium [Ca++] and inhibits the activation of MLCK
BETAMIMETICS Dose:
 Ritodrine is given by IV infusion, 50µg/min. and increased by 50µg every 10 min. until contractions cease.
Maximum dose of 350µg/ min. may be given. Infusion is continued for about 12 hours after contraction cease.
 Terbutaline has longer half life and has fewer side effects. Subcutaneous injection of 0.25 mg every 3-4 hours is
given.
  Isoxurpine is given as IV drip 100 mg in 5D. Rate 0.2 µg/minute. To continue for at least 2 hours after
contraction ceases. Maintenance is by IM 10mg six hourly for 24 hours, tab 10 mg 6-8 hourly.
BETAMIMETICS Side effects: Maternal:
 Headache
 Palpitation
 Tachycardia
 Pulmonary edema
 Hypotension
 Cardiac failure
BETAMIMETICS
 Side effects
 Hyperglycemia
 ARDS
 Hyperinsulinemia
 Lactic academia
 Hypokalemia
 Even death Neonatal:
 Hypoglycaemia
 Intraventricular haemorrhage
INDOMETHACIN Mechanism of action:
 Reduces synthesis of PGs thereby reduces intracellular free Ca++, activation of MLCK and uterine contractions.
Dose:
 Loading dose , 50 mg P.O. or .P.R. followed by 25mg every 6 hrs for 48 hours. Side effects:
 Maternal
 Heart burn
 G.I. bleeding
 Asthma
 Thrombocytopenia
 Renal injury.
CALCIUM CHANNEL BLOCKERS
 Nifedipine
 Nicardipine Mechanism of action:
 Nifedipine blocks the entry of calcium inside the cell. Compared to β- mimetics, effects are less. It is equally
effective to MgSO4.
Dose:
 Oral 10-20 mg every 6-8 hours.
CALCIUM CHANNEL BLOCKERS Side effects:
 Maternal
 Hypotension
 Headache
 Flushing
 Nausea
MAGNESIUM SULPHATE Mechanism of action:
 inhibition to calcium ion Contraindications:
 Myasthenia gravis Impaired renal function Dose:
 Loading dose: 4-6 gm I.V. over 20-30 min. followed by an infusion of 1-2 gm/hr to continue tocolysis for 12
hours after contarctions have stopped.
MAGNESIUM SULPHATE Side effects:
 Maternal
 Flushing
 Perspiration
 Headache
 Muscle weakness
  Pulmonary edema rarely
 Neonatal
 Lethargy
 Hypotonia
 Respiratory depression rarely.
OXYTOCIN ANTAGONISTS:
 Atosiban Mechanism of action:
 It blocks myometrial oxytocin receptors. Dose:
 I.V.infusion 300µg/min. initial bolus may be needed. Side effects:
 Nausea
 Vomiting
 Chest pain
ANTICONVULSANTS
1. MAGNESIUM SULPHATE:
 Mode of action:
 It decreases the acetylcholine release from the nerve endings.
 Dose:
 IM – loading dose: 4 gm IV [20% solution] over 3-5 min. to follow 10 gm deep IM, 5gm in each buttocks.
Maintenance dose : 5gm deep IM on alternate buttocks every 4 hrs.
 IV- loading dose: 4-6 gm IV over 15-20 min. maintenance dose: 1-2 gm/hr. IV infusion.
MAGNESIUM SULPHATE Side effects:
 MgSO4 is relatively safe and is the drug of choice. Muscular paresis[ diminished knee jerks], respiratory failure.
Renal function to be monitored.
Antidote:
 Injection of calcium gluconate 10% 10 ml IV.
DIAZEPAM mode of action:
 central muscle relaxant and anticonvulsant.
Dose:
20-40 mg IV Side effects:
 Maternal:
 Hypotension
 Fetal
 Respiratory depression
 Hypotonia
 Thermoregulatory problem
PHENYTOIN Mode of action:
 Centrally acting anticonvulsant
Dose:
 10 mg/ kg IV at the rate not more than 50 mg/ min followed 2 hrs later by 5 mg/kg. In epilepsy 300- 400 mg
daily orally in divided doses.
Side effects:
 Maternal
 Hypotension Cardiac arrhythmias
 Phlebitis at injection site.
 Fetal
 Fetal hydantoin syndrome
ANTICOAGULANTS:
HEPARIN Mechanism of action:
 It inhibits action of thrombin Dose:
 5000-10000 I.U. to be administered parenterally [SC or IV].
 Low molecular weight heparin is 2500 IU Side effects:
 Maternal:
 Haemorrhage
  Urticarial
 Thrombocytopenia
 Osteopenia.
 Fetal
 It does not cross the placenta
WARFARIN Mechanism of action:
 Interferes with synthesis of vit K dependent factors. Dose:
 10 mg orally Side effects:
 Maternal
 Haemorrhage
 Fetal
 Contradi’s syndrome [skeletal and facial anomalies]
 Optic atropy
 Microcephaly
 Chondrodisplasia punctate.
ANALGESIA AND ANAESTHESIA IN OBSTETRICS
1. SEDATIVES AND ANALGESICS
 OPIOID ANALGESICS:
 PETHIDINE Mechanism of action:
 Inhibits ascending pain pathways in CNS , increase pain threshold and alters pain perception.
Indications:
 Moderate to severe pain in labour, postoperative pain, abruption placentae, pulmonary edema.
Dose:
 Injectable preparations contains 50mg/ml can be administered SC, IM,IV. Its dose is 50-100 mg IM combined
with promethazine.
PETHIDINE
Contraindications:
Should not be used IV within 2 hrs and IM within 3 hrs of expected time of delivery of the baby, for fear of birth
asphyxia. It should not be used in cases of preterm labour and when respiratory reserve of the mother is reduced
Side effects:
 Maternal
 Drowsiness
 Dizziness
 Confusion
 Headache
 Sedation
 Nausea
 Vomiting
 Fetal
 Respiratory depression
 Asphyxia
FENTANYL Mechanism of action:
 Inhbits ascending pathways in CNS, increases pain threshold and alters pain perception.
Indications:
 Moderate to severe pain in labour, post operative apin an dadjunct to general anaesthetic.
Dose:
 0.05 to 0.1 mg IM q1-2 hrs prn. Available in injectable form, 0.05 mg/ml.
 Side effects:
 Dizziness
 Delirium
 Euphoria
 Nausea
 Vomiting
  Muscle rigidity
 Blurred vision
PENTACOZIN
 dose of 30-40 mg
 Naloxone is an efficient and reliable antagonist. Adverse effects
 Neonate respiratory depression secondary tothe medication crossing the placenta and affecting the fetus.
 Unsteady ambulation of the client.
 Inhibition of the mother’s ability to cope with the pain of labor.
TRANQUILIZERS
 DIAZEPAM:Usual dose is 5-10 mg.
 MIDAZOLAM:Dose of 0.05 mg/kg is given intravenously
 COMBINATION OF NARCOTICS AND TRANQUILIZERS
 BUTORPHANOL and NALBUPHINE
INHALATIONAL METHODS
 Nitrous oxide and air
 Premixed nitrous oxide and oxygen
 Trichloroethylene
 Methoxyflurane, isoflurane, enflurane
EPIDURAL AND SPINAL REGIONAL ANALGESIA Adverse effects
 nausea and vomiting.
 Inhibition of bowel and bladder elimination sensations.
 Bradycardia or tachycardia.
 Hypotension.
 Respiratory depression.
 Allergic reaction and pruritus.
PUDENDAL BLOCK
 It consists of a local anesthetic such as lidocaine(Xylocaine) or bupivacaine (Marcaine) being administered
transvaginally into the space in front of the pudendal nerve.
EPIDURAL ANAESTHESIA
 Epidural block consists of a local anesthetic bupivacaine (Marcaine) along with an analgesic morphine
(Duramorph) or fentanyl (Sublimaze) injected into the epidural space at the level of the fourth of fifth vertebrae.
Adverse effects
 Maternal hypotension.
 Fetal bradycardia.
 Inability to feel the urge to void.
 Loss of the bearing down reflex.
SPINAL BLOCK
 Spinal block consists of a local anaesthetic injected into the subarachnoid space into the spinal fluid at the third,
fourth, or fifth lumbar interspace, alone or in combination with an analgesic such as fentanyl .
Adverse effects
 Maternal hypotension.
 Fetal bradycardia.
 Loss of the bearing down reflex.
PARACERVICAL BLOCK
 It consists of lidocaine (Xylocaine) being injected into the cervical mucosa early in labor during the first stage to
block the pain of uterine contractions.
 Adverse effects include fetal bradycardia. Improper technique can result in serious toxicity.
GENERAL ANAESTHESIA
 100% oxygen is administered by tight mask fit for more than 3 minutes. Induction of anaesthesia is done with
the injection of thiopentone sodium 200- 250 mg as a 2.5 % solution IV.,followed by refrigerated
suxamethonium 100 mg. the patient is intubated with cuffed ET tube. Anaesthesia is maintained with 50% NO2 ,
50% oxygen and a trace of halothane. Relaxation is maintained with non- depolarizing muscle relaxant [
vecuronium 4 mg or atracurium 25 mg].
FETAL HAZARDS ON MATERNAL MEDICATION DURING PREGNANCY
Mechanism of teratogenicity
 Folic acid deficiency.
 Epoxides or arena oxides
 Environmental and genes abnormalities.
 Maternal disease and drugs
 Homebox genes
Maternal-fetal drug transfer and the hazards:
 before D 31: Teratogen produces an all or none effect.
 D31-d71: It is the critical period for organ formation.
 After D 71: The development of other organs continues.
PLACENTAL TRANSFER OF DRUGS
The factors responsible for transfer are:
 Molecular weight [molecular wght more than 1000 Da do not cross the placenta].
 Concentration of free drug.
 Lipid solubility.
 Utero-placental blood flow.
 Placental solubility.
GUIDELINES
 If the benefit outweighs the potential risks, only then can the particular drugs be used with prior counselling.
 Only, well tested and reputed drugs are to be prescribed and that too using the minimum therapeutic dosage
for the shortest possible duration.

CATEGORY DESCRIPTION EXAMPLE

Adequate studies in pregnant woman
have failed to show a risk to the fetus in Thyroid
A
the first trimester of pregnancy; there is hormone
no evidence of risk in last trimester.
Animal studies have shown an adverse
effect on the fetus. But, there are no
B Insulin
adequate studies on humans. Pregnancy
risk is unknown.
Animal studies have shown an adverse
effect on the fetus, but there are no
Docusate-
C adequate studies on humans, or there are
sodium
no adequate studies in animals or
humans. Pregnancy risk is unknown.
There is evidence of risk to the human
fetus, but potential benefits of use in Lithium
D
pregnant woman may be acceptable acetate
despite potential risks.
Studies in animals or humans show fetal
abnormalities, or adverse reaction reports
isotretinoin
X indicate evidence of fetal risk. The risks
involved clearly outweigh potential
benefits
 DRUG TERATOGENIC EFFECT
Cytotoxic drugs -Diethyl Multiple fetal malformations and
stilbestrol abortion. vaginal adenosis, cervical
hoods, uterine hypoplasia of the
female offspring
androgenic steroids Masculinization of the female
offspring
lithium Cardiovascular anomalies, neonatal
goitre, hypotonia and cyanosis.
anticonvulsants Phenytoin Benefits of treatment outweigh the
risks to the fetus. Polytherapy should
be avoided.
Valproate Increase risk of neural tube defects,
neonatal bleeding
Aspirin High doses in the last few weeks cause
premature closure of ductus
arteriosus. Persistent pulmonary
hypertension and kernicterus in
newborn.
Paracetamol Amount too small to be harmful.

DRUG TERTOGENIC EFFECT

Antimalarials Chloroquine, quinine- no evidence of fetal toxicity in
therapeutic doses; benefits outweighs the risk. High
doses [>10 mg prednisolone daily] may produce fetal
and neonatal adrenal suppression.

-corticosteroids Auditory or vestibular damage.

-aminoglycosides Gray baby syndrome [peripheral vascular collapse].

-chloramphenicol Dental discolouration [yellowish] and deformity.

-tetracycline Inhibition of bony growth- should be avoided.

-quinolones Arthropathy in animal studies

-long acting sulphonamides Neonatal hemolysis, jaundice and kernicterus

-nitrofurantoin Hemolysis in newborn with G6 PD deficiency, if used

at term
Drugs Teratogenic effect
-metronidazole N evidence f fetal r ne natal t xicity, high d ses
regimens sh uld n t be used.

-ACE inhibitors IUGR, fetal and ne natal renal failure.

-vitamin K[large dose] Hyperbilirubinemia and kernicterus.

-all live viral vaccines P tentially danger us t the fetus.

-narcotics Depressi n f CNS-apn ea, bradycardia and hyp thermia.

-anaesthetic agents C nvulsi n, bradycardia, acid sis, hyp xia, and hypert nia.

-anticogulants [warfarin] Fetal bleeding and an malies.

-antidepressants [imipramine] cardi vascular abn rmalities.

-benzodiazapines Gr wth restricti n, CNS dysfuncti n.

MATERNAL DRUG INTAKE AND BREASTFEEDING

Transfer of drugs through breast milk depends on following factors:

 Chemical properties
 Molecular weight
 Degree of protein binding
 Ionic dissociation
 Lipid solubility
 Tissue pH.
 Drug concentration.
  Exposure time.
DRUGS IDENTIFIED AS HAVING EFFECT ON LACTATION AND THE NEONATE
 Bromide: Rash. Drowsiness, and poor feeding.
 Iodides: Neonatal hypothyroidism
 Chloramohenicol: Bone marrow toxicity
 Oral pill: Suppression of lactation.
 Bromocriptine: Suppression of lactation.
 Ergot: Suppression of lactation.
 Metronidazole: Anorexia, blood dyscrasias, irritability, weakness, neurotoxic disorders.
 Anticoagulants: Haemorrhagic tendency.
 Isoniazid: Anti-DNA activity and hepatotoxicity.
 Anti-thyroid drugs and radioactive iodine: Hypothyroidism and goitre, agranulocytosis.
 Diazepam, opiates, phenobarbitone: Sedation effect with poor sucking reflex.