DRUGS AND LACTATION

Factors Influencing the Transfer of Drugs from Mother to Infant in Breast Milk
Factors that affect the concentration of drug in the mother
Drug dose, frequency, route, and patient compliance Clearance rate Plasma protein binding

 Factors that affect transfer across the breast

Breast blood flow Metabolism of drug within the breast Molecular weight of the drug Degree of ionization of the drug Solubility of the drug in water and lipids Relative binding affinity to plasma and milk protein Difference between the pH of maternal plasma and milk

 Factors that affect drug concentration in the infant

Timing of feeds Frequency and duration of feeds Volume of milk consumed Ability of the infant to metabolize the drug

Prolactin
Therapeutic Uses / Preparations:

Causes of Hyperprolactinaemia Physiological (pregnancy & post-partum: oestrogen-stimulated) Hypothyroidism (causing TRH excess) (Macroprolactinaemia) Prolactinoma Hypothalamic dopamine deficiency Defective dopamine delivery Lactotroph cells insensitivity to dopamine Dopamine antagonists present

Treatment of Hyperprolactinaemia Correction of underlying cause Dopamine analogues

Drugs That Inhibit Milk Production

Bromocriptine Cabergoline Thiazide diuretics The combined oral contraceptive pill Ergotamine

Dopamine Analogues
Bromocriptine
Ergot peptide alkaloid Highly selective dopamine receptor agonist. Weak a-adrenergic and 5-HT agonist. Inhibits Gi-protein coupled adenylyl cyclase Inhibits prolactin release. Inhibits growth hormone release, especially in GH-secreting tumours which co-secrete prolactin.

Dosage once - three times daily. Safe in first 3-weeks of pregnancy Adverse Effects nausea (stimulation of medullary vomiting centre). Vasospasm at high dosage Pulmonary infiltrate in chronic use.

Dopamine Analogues
Cabergoline
very long half-life of prolactin suppression allows twiceweekly dosage. Less tendency than bromocriptine to cause nausea; probably better receptor selectivity. Newer; less experience in early pregnancy; no reason to believe a problem exists. Long-term adverse effects unknown

Drugs That Stimulating Milk Production

Remember the following commonly used drugs may cause Hyperprolactinaemia: Dopamine antagonist Anti-nausea agents: e.g. metoclopramide (e.g. Maxolon) prochlorperazine (Stemetil) domperidone (Motilium) Neuroleptics / Major tranquillisers e.g. chlorpromazine trazodone prochlorperazine thioridazine.

Some drugs contraindicated in lactation (breast-feeding)

Bromocriptine Cocaine Cyclophosphamide Cyclosporine Doxorubicin Lithium Methotrexate Phencyclidine

Phenindione
Radioactive iodine and other radiolabled elements

Some drugs contraindicated in lactation (breast-feeding)

Ciprofloxacin Chloramphenicol Doxepin Gold Cytotoxic drugs Iodine-containing compounds (including topical iodine) Amiodarone Androgens Danazol Ergotamine Laxatives