Drug excretion in milk:Mechanisms of transfer from blood to milk:

1-Diffusion of water soluble low molecular weightlow molecular weight substances (through small ,water-filled pores).

2- Diffusion of lipid soluble lipid soluble compoundscompounds (through lipid soluble membrane)

3-Carrier mediated , active transport. E.g. iodide

FACTORS INFLUENCING DRUG TRANSFER INTO BREAST MILK

1. Maternal FactorsClearance, dose & frequency, duration of

therapy, route of administration, PPB

1. Infant FactorsAge, 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

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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 milk3. Volume of the milk sucked4. Pharmacokinetics of the drug in the infants;

particularly its absorption and clearance5. Inherent toxicity of the drug

Drug therapy & breast feedingDrug therapy & breast feeding

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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 & neutropenia2. Tetracyclines…►…Bones & teeth3. Sedatives and hypnotics► lethargy, sedation, poor

suckling4. Opioids …►.addiction5. Codeine is safe but may be fetal? 2D66. Alcohol7. Lithium (high milk to plasma ratio) psychoactive drugs8. Radioactive substances…►.carcinogenic9. Laxatives…►.diarrhea10. Ergotamine…►..Vomiting, diarrhea, convulsions

Drug therapy & breast feedingDrug therapy & breast feeding

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11. Ciprofloxacin…►..arthropathy12. Chloramphenicol… ►.bone marrow suppression, GBS13. Iodine- containing compounds… ►.thyroid effect14. Amiodarone… ►.effect on thyroid15. Androgens… ►..androgenization of the infant16. Danazole… ► …antiandrogenic effects17. Gold… ►..Rash, nephritis, hepatitis, hematological problems18. Doxepin… ► ….respiratory depression19. Sedatives/hypnotics20. Isoniazid21. Amphetamine, cocaine22. Nicotine23. Sulphonamides24. Chloroquine…….retinal damage

Drug therapy & breast feedingDrug therapy & breast feeding

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Some drugs to Some drugs to be avoided be avoided in breast feeding mothersin breast feeding mothersHigh excretion or hypersensitivityHigh excretion or hypersensitivity

Amiodarone Co-trimoxazole Sulfonamides

Amphetamine Ciclosporines tetracyclines

Androgens Doxazocin trimethoprim

Anticancer Vitamin A analogue

Antipsychotics Ethosuxamide Vitamin D (High dosage)

Antithyroid Fluoxitine Xanthines

Aspirin (Reye’s S) Lithium contraceptives

Barbiturates Metronidazole Ephedrine

Benzodiazepines Nitrofurantoin Tetracyclines

bromocriptine Oral contraceptives

Chloramphenicol Oral hypoglycemics

Ciprofloxacin Phenytoin

Colchicine Radioactive iodine

Corticosteroids (high dose)

Statins

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Some drugs appear to be Some drugs appear to be safe safe during breast feedingduring breast feeding

ACE inhibitors Clavulinic acid Nifedipine

Acetazolamide Clomethiazole Nortryptyline

ACTH Codiene NSAIDs

Adrenaline (destroyed)

Digoxin Pyrizinamde

Antiasthmatic drugs (inhalation)

Disopyramine Pyridostigmine

Antihistamines Ethambutol Rifampicin

Baclofn Frusemide Terbutaline

B. Blockers (But?) Heparin Thyroid hormones

Carbamazepine Hydralazine Tricyclic antidepressants except doxepin

chloroquine Insulin (destroyed) Valproate

Penicillins Methydopa Verapamil

Cephalosporines Neuroleptic drugs in moderate doses e.g. chlorpromazine

Warfarin (very low)

Drugs safely used during breast feeding:

1. ACEIs

2. Antihistamines

3. β-lactam antibiotic

4. CCBs

5. NSAIDs

6. TCAds

7. Aminoglycosides. Why safe?

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

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General principles of prescribing during lactation

1.1. Drugs licensed Drugs licensed for use in children (neonatal period) can be safely given to the nursing mother

2. Drugs known to have serious toxic effects 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

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