การใช้ยาในสตรีมีครรภ์

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การใช้ยาในสตรีมีครรภ์

  1. 1. 1 : F F F 1 F F F (Drug used in pregnancy and lactation) . . F F ˈ F (physiology) F F (pathology) F F F F F F F F F F F F F F F F (physiological change of pregnancy) F F F F F (absorption) (distribution) F (metabolism) F (excretion) F F F F F F F F F F F F F F F F F F 3-15 F F F F (heart burn) ˈ F F F F F F F (malformation) F F ˈ F ˈ F F F F F F F F F 1. (alteration in drug absorption) 1.1 F F pepsin F mucus F F F F F F F F (increase gastric emptying time) F F (metabolism) F F ˈ (absorption) F F F F (peak concentration) F F F 1.2 F F F F F F F F (tidal volume) F 39% F F F F halothane, F F F F F F F F F 1.3 F F F 6 2 F F F F F F F
  2. 2. 1 : F F F 2 2. (alteration in drug distribution) 2.1 F F F F 2 (increase plasma volume) F F F Vd F F F F F F ˈ (albumin) F ˈ F F F (pregnancy-related hypoalbuminemia) F F F plasma protein binding capacity F F (free from) (action) F 2.2 F ˈ F ˈ 25% F F Vd F 2.3 F F F F F stroke volume ˈ F F 1 (cardiac output) F F F F F 3. F (alteration in drug metabolism) F (metabolism) F ˈ F F oxidation, reduction, dealkylation ˈ F ˈ (metabolites) F F F F F F F F F F F F F F F F F F F progesterone F metabolizing enzyme (free from) F F F F 4. F (alteration in drug excretion) 4.1 F (excretion) (metabolites) F F ˈ F F glomerular filtration, tubular secretion tubular reabsorption F (renal plasma flow) F F glomerular filtration rate (GFR) F 50 F F ˆ F (increase renal clearance) F F F F F F F F F 4.2 F (unionized drug) F F F F F F F F F F F F F F F F F F F F F F F
  3. 3. 1 : F F F 3 1 F • Gastric emptying time • Intestinal motility • Pulmonary function • Cardiac output • Blood flow to the skin • Plasma volume • Total body water • Plasma proteins • Boday fats F • Hepatic metabolism • Extrahepatic metabolism • Plasma proteins • Renal blood flow • Glomerilar filtration rate • Pulmonary function • Plasma proteins + - + + + + + - + + + - + + + - + - 2. F (drug metabolism) F ˈ F F F F F F F F F F F F F 3. F (drug excretion) F F F F ˈ F F F F F F F (renal blood flow) F 3 (fetal cardiac output) F F F F F ˆ F F F F F F F F F F ˈ ˆ F F F F F F F F ˈ F F F F F F F F F F F F F F F F F F F F F F F F 1. (drug distribution) F F F F (total body water) F F F F F F F (free from) F
  4. 4. 1 : F F F 4 (Terminology) Teratogen Teratogen F Teras, Terat ˈ F F (monster) F Teratogen F F (critical period) F (usual pharmacologic dose) F F F F (embryo) F F F F (congenital malformation) (teratogenesis) F F (congenital anormalies) F terratogenesis F F F terratogen F F F F (dead fetus in utero), F F F (intrauterine growth restriction), F F (carconogenesis) F F (malformation) ˈ F Congenital malformation F F F F F F F (Physical well-being) Congenital anormalies F (congenital malformation) F (functional) F F F F (physical growth retardation) ˆ F (mental growth retardation) F F ˈ F Major congenital anormalies F F F F ˈ F ˈ F F F F F F F F (congenital heart disease) Minor congenital anormalies F F F F F F F ˈ F F (behavioral disorder) ˆ F (mental retardation) F F F F ˈ ˈ F F F F 2-3 F F ˆ F F F F F F F ˂ F F F ˁ ˀ F F F F F F F F ˈ F F ˆ F F F F
  5. 5. 1 : F F F 5 1. F F F ˈ 3 F 1.1 Pre-embryonic period F F 17 ˈ F F F terratogen ˈ All or None Effect F F F F F F F F F ˈ F F F terratogen F F F F F 2 F F F - F F 18-38 18-40 24-40 24-36 45-90 50-150 1.3 Fetal period F F 56 F F F F F F F F F F F F F F F F F F F ˈ F F F F 2. F F F F F metabolites F F F F F F F F F F F F F F F Thalidomide F F teratogen F F (cocaine) F F F F F F F F F F F F F ˆ F ˆ (mental retardation) F (fetal alcohol syndrome) F F F F (cognitive ability) Teratogenic agents threshold effect F F threshold F F F F F F threshold 1 3 F F 50% F F F F F F F F F 1.2 Embryonic period F 18 55 F F F ˈ (critical period) F F F F F F ˈ F F F (organogenesis) F F F F F F F F F ( 2)
  6. 6. 1 : F F F 6 F F F F F ˈ 3 2.1 F F F ( 3) F ˈ F F ˈ teratogen F F (teratogenic effect) F 3 F F F (drugs) (teratogenic effect) Alcohol Fetal alcohol sysdrome Angiotensin converting enzyme inhibitors Severe neonatal renal insufficiency, Decrease skull ossification Anticholinergic drugs Neonatal meconium ileus Androgenic drugs Musculinization of female fetus Diethyl stilbestrol Adenosis of the vagina of young women exposed in utero Iodine Fetal thyroid agenesis (when exposed in early gestation) Goiter, hypothyroidism (when exposed in late gestation) Isotretinoin Lithium Ebsteins anomaly of fetal heart, Fetal goiter, Fetal nephrogenic diabetes insipidus Misoprostol Mobieus sequence NSAIDs Consrtiction of ductus arteriosus, Necrotizing enterocolitis Psychoactive drugs (ie.Benzodiazepine, Barbiturate,Opioid) Neonatal withdrawal symptom Tetracycline (especially weeks 24-26) Teeth and bone anomalies Warfarin Skeletal defect (chondrodysplasia punctata) Central nervous system defect (mental retardation) 2.2 F F F ( 4) F F F 4 F F F (drugs) (teratogenic effect) Antineoplastic, Cytotoxics Multiple congenital anomalies, Intrauterine growth retardation, stillbirth, abortion Paramethadione Multiple congenital anomalies Sex hormone (ie. Androgen, Estrogen) Increase malformation, Vaginal adenosis, Hypotrophic testis, Eppididymal cyst Thalidomide Severe deformity of the limb, Blindness, Deafness, Phocomelia, Cleft palate, Malformed internal organs Trimathadione Multiple congenital anomalies
  7. 7. 1 : F F F 7 2.3 F F F F F ( 5) 5 F F F (drugs) (teratogenic effect) Aminoglycoside Ototoxicity Anticonvulsant Carbamazepine and Valproic acid Phenytoin Neural tube defect Central nervous system defect, Growth retardation Antithyroid drugs (PTU and Methimazole) Neonatal goitor and Hypothyroidism, Aplasia cutis Chloramphenicol Gray baby syndrome Corticosteriods Central nervous system defect Hypoglycemic drugs Neonatal hypoglycemia Methyldopa Neonatal meconium ileus, Reduced neonatal blood pressure Propanolol Neonatal hypoglycemia, Neonatal respiratory depression, Bradycardia Reserpine Nasal congestion, Lethargy Sulfonamides Hyperbilirubinemia, Hemolytic anaemia (in G-6-PD deficiency), Competition of albumin sites-neonatal kernicterus Thiazide diuretics Neonatal thrombocytopenia (rare) 3. F F F F F F F ˈ F F F 4. F teratogen F F F F F F F (valiability in gene expression) F Thalidomide F 25% F F ˈ F F Teratogen F ˈ F ˈ Teratogen F F F 1-3 F 1, 2 4 F F F F F F F 1. F F 2 F F 2. F F F (organogenesis) F 3. F F
  8. 8. 1 : F F F 8 4. F F (rare environment exposeure) F F F F F (rare defect) 5. F F ˈ teratogen F 6. ˈ teratogen F 7. F F F F 8. F F 9. F F F F F F 10. F F F F 11. F F F ˈ teratogen (anomaly) F F F F F F F F F F F ˈ teratogen 6 6 F F F ˈ Teratogen Aminopterin/Methotrexate Androgens (ie. Danazol) ACEIs Anticonvulsant Busulfan Carbamazepine Cocaine (abuse) Coumarin derivatives Cyclophosphamide Diethylstibestrol Ethanol (high dose) Etretinate Iodides Isotretionin Lithium Live vaccines Methotrexate Methyl mercury (organic) Paramethadione/ Trimethadione Phenytoin Polycholinates biphenyls (PCBs) Tetracycline (esp.weeks 24-26) Thalidomide Valproic acid Vitamin A (>18000 IU/day) 7 F F F F (drugs) F F ˆ Diazepam Oral cleft No increase in risk Oral contraceptive Birth defect Muculinizing effect of female fetus No association between first trimester exposure and malformation Spermicide Limbs defect, hypospadia No increase in risk Salicylates Congenital heart disease, Cleft palate No increase in risk F Thalidomide F F F F 1960 F (US FDA) F F F F F F F F F F ʾ . . 1979 F F F F F Teratogenity F F F ˈ 5 F F
  9. 9. 1 : F F F 9 Category A ˈ F F F F F ˈ F F F F F F F F F F F F F F F F (multivitamin) Category B F F F F F F F F F F F F F F F Category C F F F F F F F F F F F F F F F F F F Category D F F F F F F F F F ˈ F F F F F F F F F F F , F (tricyclic antidepressant) Category X F F F F F F Thalidomide, DES F F F F F F F F F F F F F F F F F F F F F F F F F ˈ F F F F F F F F F F ˈ Teratogen F Ethinyl estradiol F F Category X F F F F F F ˈ Teratogen F F ˈ F F F F F F F F F Teratogen F 1.Toxicologic studies ˈ teratogen F (in vitro) (embryo and organ culture) ˈ teratogen F ˈ teratogenesis F F F F F F F F F F F F ˂ (alert) F F F F 2.Case reports ˈ F F F ˈ teratogen F F (bias) F F F F (randomized trials) F F F F ˈ teratogen F F case report 3.Case-control studies ˈ F F ˈ F F F F F
  10. 10. 1 : F F F 10 F F F F F F F F (recall bias) 4.Prospective studies ˈ F 2 F F F F F F F F ˁ F F F F F F F F F F F F F ˁ F 5.Historical cohort studies F Prospective cohort studies F F F ( F F ) F F F F 6.Randomised controlled studies ˈ F F F F F F F F F F F F F F ˈ teratogen F F F F F F ˁ F F F F ˈ F F F F F F F F F ( 8) F F F ˈ 3 1. F F F F (heart burn) F F 2. F F F F ˆ F 3. F F F F ˈ F F 8 F (drug of choice) F F F F F F F Analgesics Acetaminophen Acetaminophen Anticoagulants Heparin, preferably LMWH Heparin, Warfarin Anticonvulsants Phenobarbital Carbemazepine, Ethosuximide or Valproic acid Antidiabetics Insulin Insulin, Tolbutamide Antihypertensives Methyldopa ACEI or CCB Anti-infectives Penicillin, cephalosporin Penicillin, cephalosporin Corticosteriods Prednisolone Prednisolone Decongestants Oxymetolazine drops/ spray Oxymetolazine drops/ spray GI protectants Magnesium hydroxide, Calcium carbonate, Aluminium hydroxide, Ranitidine, Sucralfate Sucralfate or Famotidine
  11. 11. 1 : F F F 11 Laxatives/Stool softeners Psyllium or docusate Psyllium or docusate
  12. 12. 1 : F F F 12 F (nausea, vomiting) F ˈ F F F ( 80%) F F F F 4 F F F F F F Morning sickness F F F ˈ F HCG (Human Chorionic Gonadotrophin) F F F F F F F (electrolyte imbalance), F F F F F F F F F F F ˈ F F F F F F F F F F F F F F F F F F F F ˈ F F F F F 83% F F F F F F Vitamin B6 (Pyridoxine) F 6 ˈ ˆ ˈ F F F 6 50-200 mg F F F F ˈ 6 F F F F F 2-3 ˈ F 6 F F F F 6 (plasma pyridoxal 5-phosphate, PLP) F F F F 6 F F F 6 F F F F (p=0.0008) F F F F F F 6 ˈ F F Promethazine 25 Cyclizine ˈ F F F F F F F F teratogenic F F F F F ˈ Meclizine ˈ F ˈ F F F F teratogenic F F Methoclopamide ˈ F F F F Extrapyramidal side effect F F F F Dimenhydrinate, Diphenhydramine ˈ F F F F F F F F F F ˈ
  13. 13. 1 : F F F 13 Ondansetron F F (heartburn) F F (indigestion) F F F 70% F F F F F (relaxation of lower esophageal sphincter) (increase pressure from the uterus onto the stomach) F F F F F F F F F F F (antacid) F F F F F F F F Sucralfate F F F F F F F F F F F F F F F F F (indigestion) F F F (flatulance) F Disfatyl, Simethicone F F (headache) F F F F 50 F F F F (pregnacy category B) F F (pregnacy category C D F 3 F) ˂ F intracranial hemorrhage bleeding F F F F F F prostaglandin F F F F (prolong labor) F F F F NSAIDs (pregnacy category B D F 3 F) F F F F F F F ˈ F F F (migraine) ˈ F F F F F F F F F NSAIDs F F Triptans (pregnacy category B) F F F Sumatriptan, Naratriptan, Zolmitriptan, Rizatriptan, Frovatriptan ˈ F F F F Ergotamine, Dihydroergotamine pregnacy category X F F F F ˂ F F F F F F F F F Beta-blocker Tricyclic antidepressant F F F F F F F Sodium valproate,
  14. 14. 1 : F F F 14 Phenobarbital, Phenytoin (pregnacy category D) F F F F F F F F F F (constipation) F F F F F F 4 F F (bleeding) F F F F F F (lower abdominal pain) F ˈ F ˈ F F F F (decrease peristalsis) ˈ F F F ˈ F progesterone F F F ˈ F F F ˆ F F F F F ˆ F F F F F F F F ˁ F F ( F 25-30 F ) F F F F F F F 10-12 F F ( F ˈ F) ˈ F F 20-30 F 3 F F F F F F 30 F ˈ F F F F F F F F F ˈ F F F ˈ F F F F F F F2 F F F F (bulk laxative) F psyllium, methyl cellulose F F F F F F F ˂ F F F F (stool softener) F dioctyl sodium sulfosuccinate lactulose F F F F F F F F F ˈ F F mineral oil F ano-rectal disorders F F F F bisacodyl, senna F F ˈ F F F (odd ratio 0.3, 95% CI 0.14-0.61) F
  15. 15. 1 : F F F 15 F F F F F F F ( F senna F F F F F) (leg cramps) F F F F F (nocturnal leg cramp) F F F F F F F F F F quinine ˈ F F F F quinine F F ˆ F magnesium citrate F F F magnesium citrate (equivalent to 300 mg magnesium salt) F (diarrhea) F (abdominal pain) F F ˈ F F (Vaginal irritation) F F Candida albicans Trichomonas vaginalis F F F F F F F F F, F (chorioamniotitis), F , F F F F ˈ F ˈ Candida albicans F imidazole F clotrimazole F F F fluconazole, itraconazole ˈ F F (pregnacy category C) F F F Trichomonas vaginalis ˈ F F F F F F F F ˈ F F F F F ˈ F F F T.vaginalis ˈ F F F metronidazole 200 mg 3 7 F F metronidazole ˈ F (carcinogenic) F F F ˈ F F (mutagenic) F F metronidazole F F F F F F F F F metronidazole F F F F F F F ˆ (urinary tract infection) F ˆ F F F ˆ (ureter) F F F ˆ ˆ F F F F F F F F ˆ ˈ • F F F F F F penicillin, cephalosporin nitrofuratoin • F F trimetroprim cotrimoxazole • F F F F F tetracyclines, quinolones
  16. 16. 1 : F F F 16 (common cold) F F F F F F F ˈ F ˈ teratogen F ˈ ˆ F (poly- pharmacy) F F F ˆ ˈ F F F ˈ ˂ F F F F F F F F ˈ F F F ˈ F F F F F ˁ F F F ˁ ˈ F F F F F (antihistamine) F F F F F chlorpheniramine tripolidine F F F brompheniramine F F (birth defect) F F F F F F F F F F F F F F F (retrolental fibroplasia) F F F F F F F F F F (second generation antihistamine) F acrivastine, astemizole, azelastine, cetirizine, ebastine, fexofenadine, loratadine terfenadine F pregnancy category B F F F F F F F ˈ F F F cetirizine ˈ active metabloite hydroxyzine F F F (teratogen risk) F terfenadine astemizole F F F F (cardiovascular effect) F (decongestants) F F F F F (clubfoot) (inguinal hernia) F F ˈ F F F F pseudoephedrine F F phenylpropranolamine F F (physical deformation) F F F F F F dextrometrophan, guifenesin F F F F F F F F F F F F F Fetal Alcohol Syndrome, FAS ( FAS F F F F (uterine growth restriction), (microencephaly), (micropthalmia), (abnormal CND development) F F F F ) (hemorrhoids) F ˈ F F F F F F F F F F F (increase veneous pressure) F ˂ F F
  17. 17. 1 : F F F 17 F F F F F ˈ F
  18. 18. 1 : F F F 18 (hypertension) F F(pregnancy-induced hypertension, PIH) F F ˈ F F F F F / ˆ F F F ˈ ˆ ˈ F F F F F F F F 16% F F F F F 40% F F F ˈ 2 1. Pre-eclampsia F 140/90 mmHg F 20 F F ˆ ( F ˆ (proteinuria) F 300 mg/ 24 ˆ F 100 mg/dL F ˆ 2 F 6 ) / F (pathologic edema) F F 2.3 / F 2. Eclampsia F ˁ pre-eclampsia F ˆ pre-eclampsia F F F ˈ ( F 85%), F , F (multiple gestation), pre-eclampsia , F ˈ , F ˈ (essential hypertension) F F F pre-eclampsia F F prostaglandins F (thromboxane A2 vs. prostacyclin) F F thromboxane A2 prostacyclin F F PIH prostacyclin F thromboxane A2 vasoconstriction ˂ pre-eclampsia F F F F Aspirin (60 mg/day) F thromboxane A2 F prostacyclin F F 24-28 F F ˂ pre-eclampsia F F F F F F F ˂ pre-eclampsia F ˁ , ˂ F F F F F F , ˆ 2 / F F ˆ (diureitcs) 48 5 F F F F F ˁ F F Pre-eclampsia F 160/110 F 6 / F F F F ˆ F 4 g/ 24 ˆ F 2+ F (dipstick) / F ,
  19. 19. 1 : F F F 19 F (visual disturbance), ˆ F F 400 . . 24 , F ˁ F F F magnesium sulfate, IV or IM 4 g loading dose F 1-3 g/hr continuous infusion ˂ F F F F ˁ F F F 4-7 mEq/L ( F F F 1g, calcium gluconate), F (patellar reflex), F 10 / ˆ (urine output) F 25 mL/hr F ˁ ( Systolic pressure F 160 mmHg Diastolic pressure F 110 mmHg) ˈ F F F (cerebrovascular accidents) F F Hydralazine, IV 5-10 mg F 5-10 mg 10-20 Diastolic pressure F 110 mmHg F ˁ F Hydralazine F F (tachycardia) F (flushing) (headache) (tremor, palpitation) F F F F propranolol F hydralazine F F F propranolol Diazoxide F F F F F F F , Latetalol (α- and β- adrenergic blocker) ˈ F hydralazine (Latetalol F F (tachycardia) F F F F F hydralazine) F 10-20 mg, IV F 10-30 F F 300 mg F F F ˁ F F pre-eclampsia F methyldopa 250 mg 2-3 F F F clonidine hydralazine F F F methyldopa F F β- blocker ˈ F F F F F F F F F F F F F F F F F F ( F F ) F F F F 24-72 Calcium channel blocker ˈ F F F F F F F F nifedipine F F F F F F F F hypoxia, acidosis (decrease uterine bloood flow) ACEI ˈ F F F F ˈ teratogen F (congenital hypocalvaria, renal anomalies, nephrotoxicity, neonatal anuria, oligohydramnios pulmonary hypoplasia) F F Diuretics F F F F F F F F F F F F F
  20. 20. 1 : F F F 20 F F thiazide F F F (neonatal hypoglycemia) F F (electrolytes imbalance) F (seizure disorder) F ˈ F F anticonvulsant F F 2-3 F F F F F F F F F F F F ˈ F F ˆ F F F F F F F F F F F F F F F F F F ˈ F F F 3% F F anticonvulsant F folic acid ˈ F neural tube F ˆ F F folic acid ˂ F F F folic acid 5-10 mg/day F epoxide ˈ intermediated metabolites F hydrolyse F epoxide hydrolase F F epoxide hydrolase F ( F ) F F F F Phenytoin ˈ F ˈ F Fetal Hydantoin Syndrome (FHS) F 7-11% F (mental retardation) F (congenital heart disease) F F F F F metabolism F F F (Hemorrhagic disease of New Born: HDN) ˈ F F Vitamin K1 (phytonadione) 0.5-1.0 mg ˂ F F F Phenytoin (nystagmus) (ataxia) (hirsutism) (gingival hyperplasia) (megaloblastic anaemia) F Carbamazepine F F (drowsiness) (ataxia) (leukopenia) ˈ F (mild hepatotoxicity) F F (facial dysmorphism) (neural tube defect) Phenobarbital F F (drowsiness) (ataxia) F (neonatal withdrawal) F
  21. 21. 1 : F F F 21 9 ˆ F F F F ˆ - F ˈ - F - F - (metabolism) ˆ - - pKa - - - F - ˆ - - pH F - GI flora - GI transient time - bile salts pancreatic enzymes - F F - F F Valproic acid F F (drowsiness) (ataxia) F (alopecia) ˈ F (hepatotoxicity) F F (facial dysmorphism) (neural tube defect) F F F ˈ F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F F , ˈ unionized from F lipid membrane F F F , ˈ - F ˈ F F F , (> 200-300) F F F ˈ F F F F F F F F F F F F F F F F F F F chloramphenicol F glucuronide conjugation F F F F F F F F F F AUC (Area Under the Curve) F F F F Dinfant (mg/kg/day) = Cmaternal (mg/L) x M/PAUC x Vinfant (L/kg/day) Dinfant (mg/kg/day) = F Cmaternal (mg/L) = F F
  22. 22. 1 : F F F 22 M/PAUC = F AUC F Vinfant (L/kg/day) = F ( 0.5 L/kg/day) F F F F F 10% F F F F ( 10) 10 F M/PAUC F F F Acetaminophen 0.8 2.9-7.9 F F Acyclovir ID 1.1 1.2 F F Amiodarone* ID 37 F F Amitriptyline 0.83 0.6 0.9 F F , F Amoxycillin ID 0.7 F F F F F F Amoxycillin/clavulonic acid Aspirin 0.06 3.2 F F Reyes syndrome F Carbamazepine 0.36-0.39 2.8-7.3 F F F F F F F Cephalosporin - Cefaclor - Cefalexin - Cefotaxime - Ceftriaxone ID 0.09 ID 0.04 0.7 0.5-1.2 0.3 0.7-4.7 F F F F 3rd generation cephalosporin F GI flora F F F Caffeine 0.5 - 0.8 0.6 21.0 F (80-100 ) Chlorpromazine ID 0.2 F , F F F F Cimetidine 1.7 - 5.8 5.4 6.7 F F F Ciprofloxacin 2.17 4.8 F F Fluoro quinolone F F arthropathies F F Clarithromycin 0.25 1.8 F F F F GI flora Codeine 2.16 6.8 F F Despiramine ID 0.5 1.0 F F
  23. 23. 1 : F F F 23 , F Digoxin 0.6 - 0.9 2.3 5.6 F F Domperidone ID 0.05 F F , F ID = Insufficient data * = F F F F
  24. 24. 1 : F F F 24 10 F ( F ) M/PAUC F F F Enalapril 0.02 < 0.1 F F Ethanol 0.9 3-4 ˈ F F ˆ Famotidine 1.5 1.6 F F Fluconazole 0.75 11 F F F Haloperidol ID 0.15 2.0 F F , F , F Ibuprofen 0 < 0.6 F F F Indomethacin 0.37 < 1.0 F F F 1 Lamotrigine ID 10 - 22 F F Loratadine 1.2 0.7 F F F F F F Mefenamic acid ID 0.3 F F Methadone 0.47 2.2 F F Metoclopamide ID 4.7 11.3 F , Metronidazole 0.9 1.1 0.1 -36.0 F F F F F F Minocycline ID 3.6 F F tetracycline F ˆ Morphine 2.46 0.4 F F Naproxen ID 1.1 F F Nitrofurantoin ID 0.6 6.0 F ˈ G-6-PD F F hemolysis Nortriptyline ID 0.53 F F F Nicotine* 2.92 ID F ID = Insufficient data * = F F F F
  25. 25. 1 : F F F 25 10 F ( F ) M/PAUC F F F Phenobarbital ID 23 - 156 F F F Phenytoin 0.13 - 0.18 3.0 - 7.2 F F F F F F F , methemoglobinemia 1 Piroxicam ID 5-10 F NSAIDs F F F F F Prednisone ID 0.26 F F F 20 mg/day Propranolol 0.32-0.76 0.2 0.9 F F Pseudoephedrine 2.5 4.0 F Quinapril 0.12 1.6 F F Ranitidine 2.8 5.0 7.8 F F F F ( F ) Verapamil 0.6 0.14 0.84 F F Sodium valproate 0.05 1.8 F F ( F F hepatitis) Sumatriptan 4.1 - 5.7 0.3 6.7 oral bioavaiability F F F F F F F F F F F F F 8 TMP/SMX 1.26/0.1 3.8-5.5/2-2.5 F G-6-PD hyperbilirubinemia Tetracycline 0.58 4.8 F tetracycline F ˆ Tripolidine 0.53 0.9 F F Vigabatin ID < 1 F F F Warfarin 0 <4.4 F prothrombin time,PTT F F F PTT F Zopicone 0.5 4.1 F
  26. 26. 1 : F F F 26 12 F F F F F Copper 64 Gallium 67 Indium 111 Iodine 123 Iodine 125 Iodine 131 Technetium 99 50 2 F 20 36 12 2-14 15 3 ID = Insufficient data * = F F F F F ˈ F F F F F F F F 1. F F ˈ F F F ( 11) 11 F F F F F Amiodarone Amphetamine* Bromocriptine* Cocaine* Cyclophosphamide* Cyclosporine* Doxorubicin* Ergotamine* Heroin* Isotretinoin Lithium* Marijuanna* Methotrexate* Nicotine (smoking)* Phencyclidine* Phenindione * American academy of pediatrics statement 2. F F F F F F 3. F F F F F F F F 4. F F F F ˈ 1 3 F F F F F F F F F F F F F (short half-life) F F (nonextended-relesed dosafe from) 5. F F F F F F F F 6. ˈ F F F cancer chemotherapy ( 12) F F F F 7. F F F radioactive compounds ( 12) F ˈ 4-5 F F ˈ F F F 98% 8. F F (long pediatric half life) F Barbiturate, Benzodiazepine F F F F F F F 9. F F F F F
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