2. Drug excretion in milk: Mechanisms of transfer from blood to milk : low molecular weight 1-Diffusion of water soluble low molecular weight substances (through small,water-filled pores). lipid soluble compounds 2- Diffusion of lipid soluble compounds (through lipid soluble membrane) 3-Carrier mediated, active transport. E.g. iodide

3. FACTORS INFLUENCING DRUG TRANSFER INTO BREAST MILK 1.Maternal Factors Clearance, dose & frequency, duration of therapy, route of administration, PPB 1.Infant Factors Age, drug absorption, metabolism, extent of breastfeeding (quantity, frequency, solid foods), timing of feeds 1.Drug factors (transfer) –Breast blood flow, breast metabolism pKa (ionization), lipid solubility, protein binding, MW, bioavailability, pH differences

4. 4 Factors affecting adverse effects of drugs in suckling infants: 1.Passage of the drug from the maternal blood into milk 2.Concentration of the drug in milk 3.Volume of the milk sucked 4.Pharmacokinetics of the drug in the infants; particularly its absorption and clearance 5.Inherent toxicity of the drug Drug therapy & breast feeding

5. 5  Most drugs reach in very low conc. In breast milk including nicotine and caffeine  Some drugs reach in significant amount affecting the fetus like: 1.Cancer chemotherapy… ►.cytotoxicity & neutropenia 2.Tetracyclines… ► …Bones & teeth 3.Sedatives and hypnotics ► lethargy, sedation, poor suckling 4.Opioids … ►.addiction 5.Codeine is safe but may be fetal? 2D6 6.Alcohol 7.Lithium (high milk to plasma ratio) psychoactive drugs 8.Radioactive substances… ►.carcinogenic 9.Laxatives… ►.diarrhea 10.Ergotamine… ►..Vomiting, diarrhea, convulsions Drug therapy & breast feeding

6. 6 11. Ciprofloxacin… ►..arthropathy 12. Chloramphenicol… ►.bone marrow suppression, GBS 13. Iodine- containing compounds… ►.thyroid effect 14. Amiodarone… ►.effect on thyroid 15. Androgens… ►..androgenization of the infant 16. Danazole… ► …antiandrogenic effects 17. Gold… ►..Rash, nephritis, hepatitis, hematological problems 18. Doxepin… ► ….respiratory depression 19. Sedatives/hypnotics 20. Isoniazid 21. Amphetamine, cocaine 22. Nicotine 23. Sulphonamides 24. Chloroquine…….retinal damage Drug therapy & breast feeding

7. 7 Some drugs to be avoided in breast feeding mothers High excretion or hypersensitivity AmiodaroneCo-trimoxazoleSulfonamides AmphetamineCiclosporinestetracyclines AndrogensDoxazocintrimethoprim AnticancerVitamin A analogue AntipsychoticsEthosuxamideVitamin D (High dosage) AntithyroidFluoxitineXanthines Aspirin (Reye’s S)Lithiumcontraceptives BarbituratesMetronidazoleEphedrine BenzodiazepinesNitrofurantoinTetracyclines bromocriptineOral contraceptives ChloramphenicolOral hypoglycemics CiprofloxacinPhenytoin ColchicineRadioactive iodine Corticosteroids (high dose) Statins

8. 8 Some drugs appear to be safe during breast feeding ACE inhibitorsClavulinic acidNifedipine AcetazolamideClomethiazoleNortryptyline ACTHCodieneNSAIDs Adrenaline (destroyed) DigoxinPyrizinamde Antiasthmatic drugs (inhalation) DisopyraminePyridostigmine AntihistaminesEthambutolRifampicin BaclofnFrusemideTerbutaline B. Blockers (But?)HeparinThyroid hormones CarbamazepineHydralazineTricyclic antidepressants except doxepin chloroquineInsulin (destroyed)Valproate PenicillinsMethydopaVerapamil CephalosporinesNeuroleptic drugs in moderate doses e.g. chlorpromazine Warfarin (very low)

9. Drugs safely used during breast feeding: 1. ACEIs 2. Antihistamines 3. β-lactam antibiotic 4. CCBs 5. NSAIDs 6. TCAds 7.Aminoglycosides. Why safe?

10. Drugs that affect milk production Drugs which inhibit milk production? 1.Bromocriptine 2.Cabergoline 3.Thiazide diuretics 4.Combined oral contraceptive pills 5.Ergotamine Drugs which stimulate Milk production??? 1.Metoclopramide 2.TRH 10

11. General principles of prescribing during lactation 1.Drugs licensed 1.Drugs licensed for use in children (neonatal period) can be safely given to the nursing mother serious toxic effects 2.Drugs known to have serious toxic effects in adults are avoided 3.Drugs known to affect lactation are avoided 4.Give drugs of short half –lives 5.Minimize the neonatal exposure by timing the feed to coincide with the trough blood concentrations in the mother, which is just before taking a dose 11