Learning Objectives: 1. Relation of Drugs and Lactation 2. Factors Modifying Passage of Drugs in Milk 3
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Learning Objectives: 1. Relation of drugs and lactation 2. Factors modifying passage of drugs in milk 3. Effects of drugs on milk production 4. Role of lactation on drugs excretion This lecture was done by: 5. Drug safety during lactation / use of Abdullah Saleh Bawazir safe drugs 6. Drugs contraindicated during lactation And reviewed by: Tuqa Alkaff Lactaon: • Breast feeding is very important because breast milk is the healthiest form of milk for babies. • It provides the baby with immunoglobulins (IgA, IgM) that are essenAal for protecAon against gastroenteriAs. Drugs & Lactaon: . Most drugs administered to breast feeding woman are detectable in milk. The concentraon of drugs achieved in breast milk is usually low (< 1 %). However, even small amounts of some drugs may be of significance for the suckling child. (all the execratory mechanisms are going down in babies) Pediatric populaon are classified into: • Newborn: less than one month old – Preterm neonates: born before 38 weeks of pregnancy (it's the harmful stage) – Full-term neonates: 38-42 weeks of gestaonal age • Infants (babies): 1 month – 12 months of age • Children: 1 -12 years of age – Toddler (young child): 1-5 years – Older child: 6-12 years • Adolescent: 13-18 years 2 Pharmacokine%cs in pediatric: • Higher gastric PH • Higher concentraon of free drug • Higher percenrage of body water • Neonate’s especially premature babies have limited capacity for metabolism and excreAon. • Neonates have very limited rate of metabolism due to immaturity of liver enzymes. • Renal clearance is less efficient: ( decrease Renal blood flow – decrease GFR). • The epithelium of the breast alveolar cells is most permeable to drugs during the 1st week postpartum, so drug transfer to milk may be greater during the 1st week of an infant’s life. Physiologic Differences between Neonates and Adults of Pharmacokine%c Importance (Hilligoss 1980) Neonate Adult Gastric acid output (mEq/10kg/hr) 0.15 ↓ 2 Gastric emptying me (min) 87 ↑ 65 Total body water 78 ↑ 60 (% of body weight) 12 ↓ Adipose %ssue (% of b.wt.) 12-25 3.7 ↓ Serum albumin (gm/dL) 4.5 Glomerular filtraon rate (ml/min/m2) 3 11 ↓ 70 Factors that affect passage of drugs into breast milk: Factors related to drugs Molecular weight: Lipid solubility of the drug: pH of drug: weight:Very small molecules (< 200 Daltons) such Lipid soluble drugs pass as alcohol, equilibrate rapidly between plasma more freely into .pH of milk is slightly more acidic than and breast milk via the aqueous channels the breast milk than water maternal blood. surrounding alveoli. soluble drugs.can easily .Weak basic drugs tend to concentrate Large molecules drugs (>800 Daltons) are less cross any membrane in breast milk and become trapped likely to be transferred to breast milk than low Degree of ionizaon: secondary to ionizaon. molecular weight. .Ionized form of drugs are Insulin: MW > 6,000 daltons less likely to be transferred .Weak acidic drugs don't enter the Heparin: MW 40,000 daltons into breast milk. milk to a significant extent and tend to Monoclonal anAbodies, pass very poorly into milk .e.g., heparins pass poorly be concentrated in plasma.maternal aer the first 1st week postpartum. into breast milk circulaon The epithelium of the breast alveolar cells is most permeable to drugs during the 1st week Plasma protein binding of postpartum, so drug transfer to milk may drugs be greater during the 1st week of an infants life. Drugs circulate in maternal Volume of distribuon Transfer of drug from circulaon in unbound (free) or bound forms to maternal blood to milk is low with drugs that have albumin. large volume of distribuAon (Vd)to prevent from Only unbound form gets staying from blood.let it stay in Assues. into maternal milk. Half life of drug DefiniAon of good protein binding > 90% Avoid the use of drugs with long half lives 4 e.g. warfarin also heparin short half life (t ½) are preferable. could be prescribed Oxazepam vs diazepam Factors that affect passage of drugs into breast milk: Factors related to mother Route of administra%on (to minimize exposure of drug) Health status Breaseeding is contraindicated .Route of administraon affect the concentraon of the in case of: drug in maternal blood. Mother HIV AcAve, untreated TB in mother .Maternal use of topical preparaons (creams, nasal sprays or inhalers) are expected to carry less risk to a Herpes on breast breasged infant than systemically administered drugs. Use of illegal drugs by mother Time of breaseeding Certain medicaons .The concentraon of the drug in the milk at the Ame of feeding. .Lactang mother should take medicaon just aer nursing and 3-4 hours before the next feeding.(injecAon-minutes) (to allow Ame for drug to be cleared from the mother’s blood – drug concentraon in milk will be low). 5 Factors that affect passage of drugs into breast milk: Factors related to neonates Age -Body weight(premature lower body weight than mature)- Health status The amount of a drug to which the baby is exposed as a result of breast feeding depends on: The amount of milk consumed. The amount of drug absorbed from GI. The ability of the baby to eliminate the drug. Age & Health status Special cauons are required in - Premature infants - Low birth weight(even those with full term-gestaon) - Infants with G6PD deficiency- Infants with impaired ability to metabolize /excrete drugs e.g. hyperbilirubinemia.(physiological jaundice) Pathological condions Neonatal hyperbilirubinemia Neonatal Methemoglobinemia Premature infants or infants with inherited Infants under 6 months of age are G6PD(found in RBC’s membrance(anoxidant) parAcularly deficiency are suscepAble to oxidizing drugs that can prone to develop methemoglobinemia upon cause → hemolysis of RBCS →↑ bilirubin exposure to some oxidizing drugs. (hyperbilirubinemia) →↑ Kernicterus(go BBB) Examples for oxidizing drugs: Methemoglobin is an oxidized form of An%bio%cs6 sulfonamides, trimethoprim hemoglobin that has a decreased affinity for An%malarials: Primaquine oxygen → ssue hypoxia. Drugs contraindicated during lactaon: An%cancer CNS acng Lithium (an Atenolol Radioaph Potassium drugs drugs manic Drug) armaceu iodide cals Risk of Growth Amphetamine, high concentraon of Risk of RadioacAve risk of retardaon heroin, cocaine , the drug will pass with Bradycradia and iodine Hypothyroidism Doxorubicin, BZDs , the milk and appear Hypoglycemia cyclophosphamid Bulbutarates & as skin rash on the e, methotrexate even Smoking baby Chloramphenic ol antibiotic Remember gray baby syndrome Drugs that can suppress lactaon: (does not produce harmful ac%ons) >> reduce prolac%n Levodopa Bromocripn Androgens Estrogen,combi Thiazide Ergot e ned oral diure%cs derivaves contracepves (dopamine precursor). (dopamine that contain high- anA Migraine Dopamine will Inhibit agonists ). dose of estrogen and Drugs ProlacAn leading to Same AcAon as a progesn.take mini Milk Suppression Dopamine pills or progestrins only 7 Also, Pyridoxine, and MAO inhibitors suppress lactaon Drugs to be avoided during lactaon: Barbiturates: Benzodiazepi An%thyroid Hormonal Analgesics : An%bio%cs: Phenobarbito nes: drugs: contracepv Aspirin Tetracyclines ne diazepam carbamizole es: estrogen only Note: These drugs are contraindicated also but they can be used under some restricons when there’s no other choice Dopamine antagonists: they sAmulate prolacAn secreAon (Hyper-ProlacAnemia) such as: like anA- Drugs that can augment lactaon: physicoAcs,have risk parkinsonism Metoclopramide Haloperidol Phenothiazin Methyl dopa Theophylline Domperidone (aneme%c) (anpsychoc) e (anhypertensive (used in (aneme%c) drug) asthma) *preferred in Has narrow pregnancy also therapuc index Note: Infant with G6PD deficiency may develop hemolysis and hyperbilirubinemia with sulphonamides8 and anmalarial drug primaquine Some anbiocs are contraindicated in lactang women e.g. chloramphenicol Antibiotics Penicillins No significant adverse effect Ampicillin allergic reacAons, diarrhea (!st prescribed) amoxacillin Cephalosporins If she’s allergic to penicllins or the baby has diarreah Macrolides erythromycin No significant adverse effect clarithromycin Alteraons to infant bowel flora hyperbilirubinemia -neonatal jaundice Should be avoided in premature Sulfonamides (co-trimoxazole) infants or infants with G6PD deficiency Quinolones TheoreAcal risk of arthropathies Should be avoided Chloramphenicol “Gray baby” syndrome avoid Tetracyclines AbsorpAon by the baby is probably prevented by chelaon with milk calcium. Avoid due to possible risk of teeth discoloraon.theoriAcally not proven hyperbilirubinemia -neonatal jaundice Should be avoided in premature Sulfonamides infants or infants with G6PD deficiency (co-trimoxazole) 9 Sedative/hypnotics Barbiturates Lethargy, sedaon, poor suck reflexes with prolonged (phenobarbitone) use.(addicAon to mom&baby) Benzodiazepines Single use of low doses is probably safe. Diazepam Lethargy, sedaon in infants with prolonged use. Lorazepam Oral contraceptives Non hormonal method should be used Avoid estrogens containing pills Estrogens ↓ milk quanAty ProgesAn only pills or minipills are preferred for birth control. 10 Antidiabetics Insulin safe Oral anAdiabeAcs compable Megormin avoid due to lacAc acidosis Analgesics Paracetamol safe Ibuoprofen compable Aspirin avoid due to theoreAcal risk of Reye's syndrome 11 AnAthyroid drugs Propylthiouracil May suppress thyroid funcAon in infants. Carbimazole Methimazole Propylthiouracil should be used rather potassium iodide than carbimazole or methimazole. AnAcoagulants Safe, not present in breast milk.