수유 중 약물 복용의 상담 원칙      안 현경
Advice on infant feeding•   Breast milk is the best form of nutrition for infants.•   Exclusive breastfeeding for the firs...
Medication and breastfeeding•   Breast-feeding has many benefits.•   Potential harm to the nursing infant from maternal dr...
Structure of the breast
A ductsB lobulesC dilated section of duct to hold milkD nippleE fatF pectoralis major muscleG chest wall/rib cageEnlargeme...
Methods of drug transfer into milk•   Passive diffusion•   Active transport against a concentration gradient•   Transcellu...
•   Diffusion     – Plasma levels in the mother     – Lipid solubility of the drug and fat content of milk     – Milk ph  ...
Transfer of dugs into Breast Milk•   Nearly all drugs transfer into breast milk to some extent.•   Notable exceptions are ...
The effect of drugs on the nursing infant depends on•   Transfer of drug into Breast Milk•   The amount of breast milk con...
Route of drugs from mother to baby via breastmilk                                   Drug          Oral bioavailability var...
Drug therapy during lactation                                    •   Drugs that passes minimally into milk:               ...
Factors affecting drug transfer•   The maternal serum drug concentration.•   Drugs:     – pKa of drug (fraction of drug th...
Factors determining drug concentration in milk•   Milk composition     – Milk at the end of a feed (hindmilk) contains con...
Estimating risk to infant•   Milk to plasma concentration (M/P) ratio:•   If M/P ratio of a drug is known•   Amount (dose)...
Calculation of infant exposure to drugs•   The infant dose (mg/kg)     – D infant (mg/kg/day)= C maternal (mg/L) x M/PAUC ...
How much of the medicine reaches the baby?Depends on:•   Blood level of medicine in the mother.•   Characteristics of the ...
Methods of decreasing toxicity in nursing infant•   Select safe drug•   Nurse immediately before taking drug.•   Take drug...
General advice•   Avoid unnecessary use of medicines.•   Assess risk / benefit for mother and baby.•   Higher risk for pre...
Essential questions to ask•   Has mum already taken the medicine(s) or is she wanting to take?•   Medicine(s), indication,...
WHO classification of drugs during breastfeeding (2002)•   1. Compatible with breastfeeding•   2. Compatible with breastfe...
Compatible with breastfeeding•   There are no known or theoretical contraindications for their use, and it is considered s...
Compatible with breastfeeding {Occasional mild side-effects}                 Monitor infant for side-effects•    If side-e...
Avoid if possible {significant side effects}     Monitor infant for side-effect
Avoid if possible {May inhibit lactation}•   However, if a mother has to take one of these drugs for a short period, she d...
Contraindicated {Dangerous side-effects}.•   If they are essential:•   stop breast feeding until treatment is completed.• ...
LACTATION RISK CATEGORY                       BY THOMAS W HALE• L1 safest• L2 safer• L3 moderately safe• L4 possibly hazar...
DRUG CLASSIFICATION BY AAP•   Cytotoxic drugs•   Drugs of abuse for which adverse effects on the infant•   Radioactive com...
AMERICAN ACADEMY OF  PEDIATRICS (2001)
Before prescribing drugs to lactating women•   Is drug really necessary? If drugs are required, consultation between the p...
Medication selection•   Choose medications with the shortest half-life and highest protein-binding ability.•   Choose medi...
Medication dosing•   Administer single daily-dose drugs just before the longest sleep interval for the infant, usually    ...
Common drugs excreted in breast milk•   Most antibiotics taken by nursing mothers can be detected in breast milk•   Tetrac...
•   Chloral hydrate can produce sedation if infant is fed at peak milk concentrations.•   Diazepam can have a sedative eff...
•   Breast-feeding should be avoided in mothers receiving cancer chemotherapy•   Opioids such as heroin, methadone, and mo...
상담 시 주지 사항 및 상담내용•   약을 꼭 복용해야 하는지 평가한다.•   젖을 빨리고 난 다음 약을 복용한다.•   약물을 단기간 사용 할 경우에는 수유를 잠시 멈춘다.•   정확한 정보가 있는 약으로 아이에게 영...
수유 중 약물 복용의 상담 원칙/안현경 교수
수유 중 약물 복용의 상담 원칙/안현경 교수
수유 중 약물 복용의 상담 원칙/안현경 교수
수유 중 약물 복용의 상담 원칙/안현경 교수
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수유 중 약물 복용의 상담 원칙/안현경 교수

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수유 중 약물 복용의 상담 원칙/안현경 교수

  1. 1. 수유 중 약물 복용의 상담 원칙 안 현경
  2. 2. Advice on infant feeding• Breast milk is the best form of nutrition for infants.• Exclusive breastfeeding for the first 6 months.• Breastfeeding (and/or formula milk) with appropriate solid food after 6 months, ideally for up to 1 year.
  3. 3. Medication and breastfeeding• Breast-feeding has many benefits.• Potential harm to the nursing infant from maternal drugs is a reason to discontinue breast- feeding.• Physicians receive little education about breast-feeding and even less training on the effects of maternal drugs on the nursing infant.
  4. 4. Structure of the breast
  5. 5. A ductsB lobulesC dilated section of duct to hold milkD nippleE fatF pectoralis major muscleG chest wall/rib cageEnlargement:A normal duct cellsB basement membraneC lumen (center of duct)
  6. 6. Methods of drug transfer into milk• Passive diffusion• Active transport against a concentration gradient• Transcellular diffusion
  7. 7. • Diffusion – Plasma levels in the mother – Lipid solubility of the drug and fat content of milk – Milk ph – Molecular size of the drug – Protein binding of the drug in mother’s plasma – Maternal half-life of the drug – Molecular weight of drug – Bioavailability of the medication to the infant
  8. 8. Transfer of dugs into Breast Milk• Nearly all drugs transfer into breast milk to some extent.• Notable exceptions are heparin and insulin {too large to cross biological membranes}.• Drug transfer from maternal plasma to milk is, with rare exceptions, by passive diffusion across biological membranes.• Almost all medication appears in small amounts, usually less than 1% of the maternal dose• Very few drugs are contraindicated for nursing mothers
  9. 9. The effect of drugs on the nursing infant depends on• Transfer of drug into Breast Milk• The amount of breast milk consumed by the infant.• The pharmacologic activity of the drug: absorption, distribution, metabolism and elimination by the infant.• Condition of the infant:• Greater precaution for infants – premature or – compromised or – in the first week of life than for older, healthy infants.
  10. 10. Route of drugs from mother to baby via breastmilk Drug Oral bioavailability varies High (>90%) Low (<50%) Acetaminopen Acyclovir Lorazepam Azithromycin Maternal gut and liver Metronidazole Budesonide Minoxidil Sulfasalazine Maternal plasma Dilution of all drugs leads to low concentrations in mother’s plasma Only drugs are not protein-bound can pass into milk Drug protein binding High Low Bepridil >99% Bisoprolol 30% Diazepam 99% Cyclophosphamide 13% Diclofenac >99% Ranitidine 15% Propranolol 90% Primidone <20%Oral bioavailiability varies Infant gut Usually very low levels (often undetectable) Infant plasma
  11. 11. Drug therapy during lactation • Drugs that passes minimally into milk: – Acid drug – Highly protein bound drug – E.g NSAID Blood Milk – Weekly basic drug with low plasma protein binding and highly lipophilicProtein 19% 2.5% will achieve higher concentration inLipid 1% 4.5% milk – E.g. sotalol.pH 7.4 7.2(6.8-7.6)
  12. 12. Factors affecting drug transfer• The maternal serum drug concentration.• Drugs: – pKa of drug (fraction of drug that is ionized at a given pH) • Basic drugs -> ionized at acidic pH(low pH) -> trapped in milk • Acidic drug ionized at higher pH -> trapped in maternal plasma – Protein binding (highly protein bound drug -> less transfer to milk) – Lipipophilicity: (high lipophilic drugs-> more drug in milk). – Molecular weight of drug: high MW -> less drug in milk (insulin, heparin do not enter breast milk)
  13. 13. Factors determining drug concentration in milk• Milk composition – Milk at the end of a feed (hindmilk) contains considerably more fat than foremilk and may concentrate fat-soluble drugs.• Age of infant: • In the early postpartum period, large gaps between the mammary alveolar cells allow many dugs to pass. These gaps close by the 2nd week of lactation. • Premature babies & infants less than 1 month have a different capacity to absorb and excrete drugs than older infants.• Nursing time of baby.• Milk to plasma concentration(M/P) ratio: for most drug M/P ratio is <1 (drugs with higher M/P ratio (e.g. 5) are unsafe)
  14. 14. Estimating risk to infant• Milk to plasma concentration (M/P) ratio:• If M/P ratio of a drug is known• Amount (dose) of drug ingested by infant can be calculated by• Dinfant = Cpmat x M/P x Vmax• Cpmat: average maternal plasma concentration• Vmax: volume of milk which is assumed to be 150ml• For most drug, an exposure <10% of weight adjusted maternal dose is acceptable.
  15. 15. Calculation of infant exposure to drugs• The infant dose (mg/kg) – D infant (mg/kg/day)= C maternal (mg/L) x M/PAUC x V infant (L/kg/day) Cmaternal= maternal plasma concentration M/PAUC ratio = milk to plasma concentration ratio area under curve. Vinfant= volume of milk ingested• As a percentage of the maternal dose (mg/kg). The volume of milk ingested by infants is commonly estimated as 0.15 L/kg/day. An arbitrary cut-off of 10% has been selected as a guide to the safe use of drugs during lactation.
  16. 16. How much of the medicine reaches the baby?Depends on:• Blood level of medicine in the mother.• Characteristics of the medicine.• Amount of medicine passed into breast milk.• Amount of milk taken by baby per feed (approx 150mL/kg).
  17. 17. Methods of decreasing toxicity in nursing infant• Select safe drug• Nurse immediately before taking drug.• Take drug 3-4 hours before next feeding• Avoid feeding when drug reaches peak concentration in milk and plasma• Use drug with short half life• Instruct patient to monitor ADRs
  18. 18. General advice• Avoid unnecessary use of medicines.• Assess risk / benefit for mother and baby.• Higher risk for premature babies.• Check if medicine licensed for babies.• Avoid long-acting medicines• Avoid new medicines.• Try to time feed to avoid when drug levels in milk are highest.• Monitor baby for adverse effects.
  19. 19. Essential questions to ask• Has mum already taken the medicine(s) or is she wanting to take?• Medicine(s), indication, dose, frequency, route & duration of exposure?• Has this been prescribed or self-treating?• Have any other medicines been considered or tried?• What age is the baby? Full term & healthy?• How often is baby feeding? – Totally breast fed or bottle too?
  20. 20. WHO classification of drugs during breastfeeding (2002)• 1. Compatible with breastfeeding• 2. Compatible with breastfeeding {occasional mild side effects} Monitor infant for side effects• 3. Avoid if possible. {significant side effects} Monitor infant for side-effects• 4. Avoid if possible. {May inhibit lactation}. Monitor for amount of milk• 5. Contraindicated {dangerous side effects}
  21. 21. Compatible with breastfeeding• There are no known or theoretical contraindications for their use, and it is considered safe for the mother to take the drug and continue to breastfeed.
  22. 22. Compatible with breastfeeding {Occasional mild side-effects} Monitor infant for side-effects• If side-effects: – stop the drug, and – find an alternative.• If the mother cannot stop the drug, she may need to stop breastfeeding and feed her baby artificially until her treatment is completed.
  23. 23. Avoid if possible {significant side effects} Monitor infant for side-effect
  24. 24. Avoid if possible {May inhibit lactation}• However, if a mother has to take one of these drugs for a short period, she does not need to give artificial milk to her baby. She can off set the possible decrease in milk production by encouraging her baby to suckle more frequently. – Estrogen – COC – Ergometrin – Thiazides
  25. 25. Contraindicated {Dangerous side-effects}.• If they are essential:• stop breast feeding until treatment is completed.• If treatment is prolonged, she may need to stop breastfeeding altogether.• There are very few drugs in this category apart from anticancer drugs and radioactive substances.
  26. 26. LACTATION RISK CATEGORY BY THOMAS W HALE• L1 safest• L2 safer• L3 moderately safe• L4 possibly hazardous• L5 contraindicated
  27. 27. DRUG CLASSIFICATION BY AAP• Cytotoxic drugs• Drugs of abuse for which adverse effects on the infant• Radioactive compounds that require temporary cessation of breastfeeding• Drugs for which the effect on nursing infants in unknown but may be concern• Drugs that have been associated with significant effects on some nursing infants and should be given to nursing mothers with caution• Maternal medication usually compatible with breastfeeding
  28. 28. AMERICAN ACADEMY OF PEDIATRICS (2001)
  29. 29. Before prescribing drugs to lactating women• Is drug really necessary? If drugs are required, consultation between the pediatrician and the mother’s physician can be most useful in determining what options to choose.• The safest drug should be chosen e.g. acetaminophen rather than aspirin for analgesia.• If there is a possibility that a drug may present a risk to the infant, consideration should be given to measurement of blood concentrations in the nursing infant.• Drug exposure to the nursing infant may be minimized
  30. 30. Medication selection• Choose medications with the shortest half-life and highest protein-binding ability.• Choose medications that are well-studied in infants.• Choose medications with the poorest oral absorption.• Choose medications with the lowest lipid solubility.• Use topical therapy when possible.• Drugs that are safe for the nursing infant’s age are generally safe for the breast- feeding mother.• Drugs that are safe in pregnancy are not always safe in breast-feeding mothers {nursing infant must independently metabolize and excrete the medication}.
  31. 31. Medication dosing• Administer single daily-dose drugs just before the longest sleep interval for the infant, usually after the bed-time feeding.• Breast-feed infant immediately before medication dose when multiple daily doses are needed
  32. 32. Common drugs excreted in breast milk• Most antibiotics taken by nursing mothers can be detected in breast milk• Tetracycline concentrations in breast milk is 70% of maternal serum concentrations and present a risk of permanent tooth staining in infant• Isonized rapidly reaches equilibrium between breast milk and maternal blood. So that signs of pyridoxine deficiency may occur in the infant if the mother is not given pyridoxine supplements.• Most sedatives and hypnotics enters breast milk sufficient to produce a pharmacologic effect in infants.• Barbiturates taken in hypnotic doses by mother can produce lethargy, sedation, and poor suck reflexes in infant.
  33. 33. • Chloral hydrate can produce sedation if infant is fed at peak milk concentrations.• Diazepam can have a sedative effect on the nursing infant• Lithium enters breast milk in concentrations equal to those in maternal serum• Radioiodine can cause thyroid suppression• Breast-feeding is contraindicated after large doses of radioiodine and should be withheld for days to weeks after small doses.
  34. 34. • Breast-feeding should be avoided in mothers receiving cancer chemotherapy• Opioids such as heroin, methadone, and morphine enter breast milk (neonatal narcotic dependence).• Very small amounts of caffeine are excreted in the breast milk of coffee-drinking mothers.
  35. 35. 상담 시 주지 사항 및 상담내용• 약을 꼭 복용해야 하는지 평가한다.• 젖을 빨리고 난 다음 약을 복용한다.• 약물을 단기간 사용 할 경우에는 수유를 잠시 멈춘다.• 정확한 정보가 있는 약으로 아이에게 영향이 적은 약을 선택하게 한다.• 전신적으로 작용하는 약보다는 국소적으로 작용하는 약을 선택하게 한다.
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