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수유 중 약물 복용의 상담 원칙2013


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수유 중 약물 복용의 상담 원칙2013

  1. 1. 수유 중 약물 복용의 상담 원칙 안 현경
  2. 2. 임신 중 모유수유 계획율
  3. 3. 99.7 68.9 59.0 36.4 14.1 10.2 6.5 12.7 37.4 46 0.0 20.0 40.0 60.0 80.0 100.0 1970 1982 1985 1988 1997 2000 2002 2005 2007 2009 모유수유율
  4. 4. Healthy People 2010 Goals • Increase to at least 75% the proportion of mothers breastfeeding upon discharge and 50% still breastfeeding when the infant is 6 months of age. 0 10 20 30 40 50 60 70 80 90 100 1970 1995 1998 2010 Goal Discharge 6 Months
  5. 5. 모유수유 중단요인 • 의료인의 권유 • 젖이 모자라서 • 함몰 유두 • 젖을 못 빨아서 • 물 젖이어서 • 유두가 아파서 • 기타 37.1% 18.8% 12.1% 10.5% 7.0% 6.1% 8.4% 이승주 등. 소아과 40: 1336
  6. 6. Obstacles to Initiating and Continuing Breastfeeding • Physician apathy and misinformation • Insufficient pre-natal breastfeeding education • Distribution and promotion of infant formula • Disruptive hospital policies • Inappropriate interruptions of breastfeeding • Early hospital discharge • Lack of social support
  7. 7. Role of the Physician • Establish positive attitudes in pregnancy • Address medical issues/ physical obstacles • Encourage nursing immediately after delivery • Provide post-partum support • Explain nutritional needs • Assess substance use • Discuss employment concerns
  8. 8. Establish Positive Attitudes • Endorse and encourage breastfeeding because it is best for mother and baby. • Ask about previous experience • Provide positive statements about breastfeeding • Offer confirmatory words from all office staff • Distribute appropriate education materials • Be supportive no matter what the woman plans
  9. 9. General Benefits of Breastfeeding • Maternal-infant bonding • Inexpensive • Convenient (no preparation) • Perfect temperature • Easily digested • Immunological protection • Allergy prophylaxis
  10. 10. Breastfeeding Advantages for Mothers • May delay return of ovulation. • Loss of pregnancy associated adipose tissue. • Reduction in postpartum blood loss due to increased oxytocin levels. • Reduction in pre-menopausal breast cancer and reduced risk of ovarian cancer. • Improved bone remineralization postpartum.
  11. 11. Immunological Contents of Breast Milk • Immunoglobulins – IgA, IgG, IgM, leukocytes, cytokines • Host resistance factors – Complement macrophages, lymphocytes, lactoferrin • Anti-inflammatory components – Enzymes: catalase, histaminase, lysozymes, lactoperoxidase – Antioxidants: acsorbic acid, alpha-tocopherol – Prostoglandins • Interleukin-6 – Stimulates an increase in mononuclear cells in breast milk.
  12. 12. Breastfeeding Advantages for Baby • Decreased incidence and/or severity of otitis media, diarrhea, lower respiratory infections, bacteremia, bacterial meningitis, botulism, urinary tract infections, and necrotizing enterocolitis. • Less hospitalization in first 6 months. • Possible protective effect against sudden infant death syndrome, type 1 diabetes, Crohn’s disease, ulcerative colitis, lymphoma, allergies, and chronic digestive diseases.
  13. 13. Drugs in Breastfeeding • Healthcare professionals should always encourage breastfeeding • Most drugs excreted into breast milk but usually in small amounts • Few drugs are absolutely contra-indicated • Some drugs may increase or decrease milk yield.
  14. 14. Background - Mothers • 90% of women are prescribed a medication in first week postpartum • Mothers worry about effect of medication on nursing infant • Leads to: non compliance, weaning, avoidance of breastfeeding • 50% of mothers more reluctant to take a medication while nursing than during pregnancy
  15. 15. Seven contraindications to breastfeeding (AAP 2 005) • Mother HIV + (in USA) • Use of illegal drugs by mother • Certain medications • Active, untreated TB in mother • Galactosemia in baby • Mother HTLV + • Herpes on breast
  16. 16. How to decide if a medication or drug is ok? • Pharmacokinetic factors • Factors which govern drug transfer across membranes into breast milk as well as the metabolism of the drug in mother and infant
  17. 17. Pharmacokinetic factors 1. Passive diffusion 2. Molecular weight 3. Protein binding 4. Lipid solubility 5. Half life 6. Oral bioavailability
  18. 18. Passive diffusion • Drugs move in and out of breast milk • High to low • With time direction may shift • Example: alcohol
  19. 19. Molecular weight • High molecular weight limits movement into breast milk • MW >500 daltons does not enter breast milk
  20. 20. Molecular weight: examples • Insulin: MW > 6,000 daltons • Heparin: MW 40,000 daltons • Ethanol: MW 200
  21. 21. Protein binding • Medications circulate in maternal circulation bound or unbound to albumin • Only unbound drug gets into maternal milk • Definition of good protein binding = > 90%
  22. 22. Protein binding High protein binding • Propranolol 90% L2 • Diazepam 99% L3 Low protein binding • Lithium 0% L3
  23. 23. Lipid solubility • Drugs that are very lipid soluble penetrate into breast milk in higher concentration • Drugs that are active in the CNS are drugs with high lipid solubility
  24. 24. Half life Short half life drugs • Alcohol 24 min • Keflex 50 min • Ibuprofen 120 min • General anesthesia Long half life drugs • Prozac 216 hours
  25. 25. Oral bioavailability • Amount of drug that is absorbed from the gut into the blood stream
  26. 26. Oral bioavailability Drug Maternal GI Tract Maternal Plasma Breast Milk Infant GI Tract Infant Plasma
  27. 27. Oral bioavailability • Low bioavailability may be due to – Reduced absorption in GI tract – Poor GI stability due to acidity – High first-pass uptake by liver
  28. 28. Poor oral bioavailability • Gentamycin – <1% oral bioavailability • Insulin (destroyed in gut) – 0% oral bioavailability • Heparin (destroyed in gut)
  29. 29. Drug Maternal gut and liver Maternal plasma Infant gut Infant plasma Oral bioavailability varies High (>90%) Low (<50%) Acetaminopen Acyclovir Lorazepam Azithromycin Metronidazole Budesonide Minoxidil Sulfasalazine 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 Usually very low levels (often undetectable) Route of drugs from mother to baby via breastmilk
  30. 30. In general, baby gets <1% of maternal dose of drug
  31. 31. Choice of Drug • Short acting • Highly protein bound • Low lipid solubility • High molecular weight • No active metabolites • Low oral bioavailability • Route of administration
  32. 32. Drugs in Lactation – Factors to consider • Avoid unnecessary drug use and limit use of OTC products • Assess the benefit/risk ratio for both mother and infant • Avoid use of drugs known to cause serious toxicity in adults or children • Drugs licensed for use in infants do not generally pose a hazard • Neonates (esp premature infants) are at greater risk from exposure to drugs via breast milk • Route of administration (minimum amount of drug to the infant) • Avoid long-acting preparations • Monitor Infants exposed to drugs via breast milk for unusual signs/symptoms • Avoid new drugs if possible
  33. 33. Drug transfer into the breast milk • Maternal factor – Dose and duration of therapy – Route of administration – Drug pharmacokinetics • Infant factor – Infant’s ability to absorb, metabolize, and excrete the drug – Gestational age of infant and its postnatal age
  34. 34. Way to minimize infant drug exposure • Avoid feeding the infant at the time of peak concentration of the drug in milk. • Withhold breastfeeding temporarily if the drug is only used for a short duration. • Choose drugs for the mother that have known and established information about their pharmacokinetics and toxicity and have low concentrations in breast milk and low relative infant dose • Choose drugs that can be locally rather than systemically administered • In case of long-acting drugs, time the drug administration to a once- a-day dose just before the infant’s longest sleep period to lessen exposure.
  35. 35. Evaluation of the infant • Infant age – Premature and newborn infants are at somewhat greater risk • Infant stability – Unstable infants with poor GI stability may increase the risk of using medications • Pediatric approved drugs – Generally are less hazardous if long-term history of safety is recognized • Dose – In a premature infant various doses may be more risky than in a 1 year old healthy infant • Drugs that alter milk production – May be much more risky during neonatal period than much later
  36. 36. Summary • Nearly all drugs pass into human milk • Almost all medication appears in small amounts, usually less than 1% of the maternal dose • Very few drugs are contraindicated for nursing mothers
  37. 37. LACTATION RISK CATEGORY BY THOMAS W HALE • L1 safest • L2 safer • L3 moderately safe • L4 possibly hazardous • L5 contraindicated
  38. 38. 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
  39. 39. 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.
  40. 40. Reasons for using the telephone line in breastfeeding women Hemorrhoid CV disease GI disease Contraception Hepatitis B Respiratory disease Others Psychotic disease Nutrition Breast problem Dental disease Pain Inflamation Dermatologic disease Thyroid disease 12.5% 11% 9.6% 7.4%
  41. 41. Antihistamine Regional agents Miscellaneous CV agents Nutritional agents Natural & Herbal pro Endocrine agents Respiratory agents Systemic antibiotics CNS agents & Analges GI drugs Drugs prescribed for breastfeeding women
  42. 42. Drugs to avoid in the newborn and in infants < 6months of age • Beta-blocking agents – Acebutolol – Atenolol – Labetalol – Propranolol – Sotalol • Salicylates • Lithium • Antineoplastic agents • Drugs of abuse
  43. 43. Cytotoxic drugs that may interfere with cellular metabolism of the nursing infant  Cyclophosphamide  Cycloserine  Doxorubicin  Methotrexate
  44. 44. Drugs of abuse for which adverse effects on the infant during breastfeeding have been reported Drug Reported effect or reasons for concern Amphetamine Irritability, poor sleeping pattern Cocain Cocaine intoxication: irritability, vomiting, diarrhea, tremulousness. seizure Heroin Tremous, restlessness, vomiting, poor feeding Marijuana Only 1 report in literature; no effect mentioned; very long half-life for some components Phencyclidine Potent hallucinogen
  45. 45. AAP Clssification Radioactive compounds that require temporary cessation of breastfeeding  Copper 64  Gallium 67  Indium 111  Iodine 123  Iodine 125  Iodine 131  Technetium 99  Radioactive sodium
  46. 46. Anti-anxiety antidepressants antipsychotic Others Alprazolam Diazepam Lorazepam Midazolam Perphenazine Prazepam Quazepam Temazepam Amitryptiline Amoxapine Bupropion Clomipramine Desipramine Dothepine Doxepine Fluoxetine Fluvoxamine Imipramine Nortriptyline Paroxetine Sertraline Trazodone Chloropromazine Chlorprothixene Clozapine Haloperidol Mesoridazine Trifluoperazine Amiodarone Chloramphenicol Clofazimine Lamotrigine metronidazole Metoclopramide Tinidazole Drugs for which the effect on nursing infants is unknown but may be of concern AAP Clssification
  47. 47. AAP Clssification Drug Reported effect Acebutolol Hypotension; bradycardia; tachycardia 5-aminosalicylic acid Diarrhea Atenolol Cyanosis; bradycardia Bromocriptin Suppresses lactation; may be hazardous to the mother Aspirin Metabolic acidosis Clemastine Drowsiness irritability, refusal to feed, high-pitched cry, neck stiffness Ergotamine Vomiting, diarrhea, convulsions Lithium One-third to one-half therapeutic blood concentration in infants Phenindione Anticoagulant; increased prothrombin and partial thromboplastin time in 1 infant; not used in united states Phenobarbital Sedation; infantile spasm after weaning from milk containing phenobarbital Primidone Sedation feeding problems Slfasalazine Bloody diarrhea Drugs that have been association with significant effects on some nursing infants and should be given to nursing mothers with caution
  48. 48. Acetaminophen Acetazolamide Acitretin Acyclovir Alcohol (Ethanol) Allopurinol Amoxicilline Antimony Atropine Azapropazone Aztreonam B1(Thiamin) B6(Pyridoxine) B12 Baclofen Barbiturate Bendroflumethiazide Dicumarol Bromide Butorphanol Caffeine Captopril Carbamazepine Carbetocin Carbimazole Cascara Cefadrxil Cefazolin Cefotaxime AAP Clssification Maternal medication usually compatible with breastfeeding
  49. 49. Cefoxetine Cefprozil Ceftazidime Ceftriaxone Chloral hydrate Chloroform Chloroquine Chlorothiazide Chlorothalidone Cimetidine Ciprofloxacin Cisapride Cisplatin Clindamycin Clogestone Codeine Colchicine Oral contraceptive pill with estr/proges Cycloserine D (vitamin) Danthron Dapson Dexbrompheniramine Diatrizoate Digoxin Diltiazem Dipyrone Disopyramide Domperidone Dyphylline Enalpril Erythromycin Estradiol Ethambutol Ethosuximide AAP Clssification Maternal medication usually compatible with breastfeeding
  50. 50. Fentanyl Fexofenadine Flecainide Fleroxacin Fluconazole Flufenamic acid Fluorescein Folic acid Gadopentatic Gentamicin Gold salts Halothane Hydralazine Hydrochlorothiazide Hydroxychloroquine Ibuprofen Indomethacin Iodides Iodine Iodine(Povidone-iodine) Iohexol Iopanoic acid Isoniazid Interferon Ivermectine K1(vitamin) Kanamycin Ketoconazole Labetalol Levonorgesterol Lidocaine Loperamide Loratadine Magnesium- sulfate AAP Clssification Maternal medication usually compatible with reastfeeding
  51. 51. Medroxypro- gesterone Mefenamic acid Meperidine Methadone Methimazole Methohexital Methyldopa Methyprylon Metoprolol Metrizamide Metrizoate Mexiletine Minoxidil Morphine Moxalactam Nadolol Nalidixic acid Naproxen Nefopam Nifedipine Nitrofurantoin Norethynodrel Norsteroids Noscapine Ofloxacin Oxprenolol Phenylbutazone Phenytoin Piroxicam Prednisolone Prednisone Procainamide Progesterone Propoxyphene Propranolol AAP Clssification Maternal medication usually compatible with breastfeeding
  52. 52. Propylthiouracil Pseudoephedrine Pyridostigmine Pyrimethamine Quinidine Quinine Riboflavin Rifampin Scopolamine Secobarbital Senna Sotalol Spironolactone Streptomycin Sulbactam Sulfapyridine Sulfisoxazole Sumatriptan Suprofen Terbutaline Terfenadine Tetracycline Theopylline Thiopental Thiouracil Ticarcillin Timolol Tolbutamide Tolmetin Trimethprim/ Sulfamethoxazol Triprolidine Valproic acid Verapamil Warfarin Zolpidem AAP Clssification Maternal medication usually compatible with breastfeeding
  53. 53. condition Recommended agents Use with caution Allegic rhinitis Beclomethasone Fluticasone, cromolyn Depression Sertraline, Paroxetine Fluoxetine, Diabets Insulin, Glyburide Tolbutamide Metformin Thiazolinediones Asthma Cromolyn, Nedocromil Pain Ibuprofen, Morphin acetaminophen Naproxen meperidine Contraception Barrier method Estrogen-containing contraceptives Epilepsy Phenytoin, Carbamazepine Phenobarbital Chaves RG 2004 Medications commonly prescribed for maternal ailments during breastfeeding