OB_drugs_effects_pregnancy-1

OB_drugs_effects_pre - Benha University Hospital Email [email protected] Impact of the problem Egypt 86 takes drugs without prescription(Rizk

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Unformatted text preview: Benha University Hospital Email: [email protected] Impact of the problem Egypt: 86% takes drugs without prescription (Rizk et al, 1993) KSA: 60% takes drugs (Alkhawaja,1991) USA: 2%: Category A drugs 50%: Category B drugs 40%: Category C drugs 4%: Category D drugs 4%: Category X drugs (Andrade et al, 2004) Teratogens • Teratos= monster, in Greek • Any agent {drug, infection, physical condition or deficiency} that acts on embryo or fetus producing permanent alteration of morphology or function (Shepard, 1998). Causes of congenital malformation Unknown or multifactorial: 70% Genetic: 20% Environmental: 10% Drugs & chemicals: 5% Infection: 2% Maternal disorders: 2% Irradiation: 1% Factors affecting the teratogenic effect of the drug A. Fetal factors : I. Developmental stage : 1.Predifferentiation stage (0-7 days of gestation): Death or no effect. 2.Differentiation stage (7-57 days of gestation): Malformation 3.Post differentiation stage (after 57 days of gestation): Functional defects, Growth retardation II. Genetic susceptibility : 1. Species differences: Thalidomide is teratogenic in human & not in animals. 2. Individual differences: difference in maternal or fetal metabolism of the drug B. Drug factors: I. The route, dose & duration of administration II. Effect of other agents: Excess vit. A: cleft palate & exencephaly in rats. Excess vit A + Cortisone: Increased incidence Excess Vit A+ Vit B: No teratogenic effect III. Access to fetoplacental unit: Lipid solubility Molecular weight: > 600 not cross the placenta Protein binding Thickness of the placental membrane • Drugs not cross the placental membrane: Erythromycin, TSH, ACTH • Drugs negliably cross: Insulin, Heparin, Thyroxin S. choline, T. curarine, Guanthidine Furadandin, Chlorapromazine Appearance of teratogenic effect: • Immediate: Death & abortion • At birth: Malformation Functional defects (Streptomycin: nephrotoxic & ototoxic) • Delayed: Carcinogenesis: DES Mutagenesis: Food & Drug Administration classification (1980) • 5 categories RCT Animal Human • Varies according to gestational age • Updated 1.Category A: • Controlled studies in humans demonstrated no fetal risk. • E.g.: Prenatal vitamins, not megavits K CL, citrate & gluconate, Thyroxin 2. Category B: • Animal studies indicate no fetal risk & no controlled studies in humans. • E.g. Penicillins, terbutaline, Acetaminophen, cyclizine, antacids, Prednisone, insulin, ampicilln, Clindamycin, nitrofurantoin, Miconazole, spiramycin,. 3.Category C: • Animal studies indicate fetal risk & no human studies. • These drugs are administered only when their benefits outweighs the potential fetal harm. • E.g. Furosemide, Rifampicin, βblockers, Phenothiazine, methyl dopa, nifedipine, Heparin, aminophyllin, gentamycin, Chloroquin, acyclovir, cyclosporin,. 4.Category D: • There is evidence of fetal risk in humans but the benefits may outweigh the risk. • These drugs are given only in serious disease because no alternative. • E.g. Phenytoin, valporic acid, diazepam, Imipramine, captopril, thiazides, Spironolactone, coumarine, chlorpropamide Progestins, tetracyclin, streptomycin, Quinine, methotrexate, vinblastin, Azathioprine. 5. Category X: • There is clear human risk that outweigh the benefits. • These drugs are contraindicated. • E.g. Estrogen, androgens, Aminopterin, isotretinoin, Thalidomide Category Animal Category Animal risk risk Human Risk Administration A No risk No risk Yes B No risk No studies Yes C Risk No studies If benefits> Risk D Risk< Benefit If No alternative X Risk> Benefit Contraindicated Contraindicated T shaped uterus of DES Fetal alcohol syndrome IUGR Behavior disturbance Brain defects Cardiac defects Spinal defects Craniofacial anomalies )Phocomelia (limb reduction defects Bone defects Anomalies of ear, CVS www.perinatology.com I. CNS disorders 1. General anesthesia: Thiopental: No increase in malformation Nitrous oxide, Halothane: No increase of malformation in humans but increase in animals Ketamine {B} Analgesic. 2 B C D Acetaminophen Aspirin Ibuprofen, indomethacin, Ibuprofen, Codiene naproxin, pentazocine indomethacin, Mepridine, morphine, naproxin, Sulindac {premature closure of D. arteriosus pentazocine Asprin, Codien (if used at Mepridine, term) morphine Sulindac :Acetaminophen Antiprostaglandin effect is short, bleeding time is not prolonged in . contrast to aspirin .It is preferred over aspirin Indomethacin is contraindicated after 34 w 3. Narcotic antagonist: B D Naloxone Nalorphine, levallorphan, cyclazocine 4. Anticonvulsant B C D Mg sulphate Carbamazepine Phenytoin (Dilantin): Hydantoin syndrome Metharbital (tegretol): Phenobarbital, carbamazepin syndrome Valporic acid: Clonazepam valporic syndrome, (Clonopin) Trimethadione barbiturates Fetal anticonvulsant syndrome Craniofacial abnormalities Broad nasal bridge Epicanthal fold Limb defects Growth deficiency Mental Deficiency 5. Psychotropic B Selective serotonin reuptake inhibitors: fluoxetine, paroxetine, sertraline Antipsychotic: Clozapine Bupropion C Monoamine oxidase :inhibitors isocarboxazid, phenelzine, tranylcypromine Tricyclic antidepressants: desipramine, doxepin Antipsychotics: chlorpromazine, thioridazine, perphenazine Benzodiazipines: clonazepam, lorazepam, oxazepam D Tricyclic antidepressants: amitriptylin, amoxapine, imipramine clomipramine, nortriptyline Benzodiazipines: alprazolam, diazepam lithium :Chlorpromazine Negliably cross the placenta :Diazepam . 1st trimester: cleft lip Before delivery: hypotonia, .hypothermia, respiratory depression :Imipramine limb reduction defects :Lithium Cardiovascular anomalies II. Cardiovascular disorders 1. Antihypertensives C Methyldopa Hydralazine, ß blockers, Nifedipine (adalat) Clonidine (catapress), Prazosin (minipress) Diazoxide (hyperstat) D Angiotensin converting enzyme inhibitors: ((Captopril Nitroprusside Reserpine Captopril: oligohydramnios, pulmonary hypoplasia, IUGR ß blockers: propranolol (inderal), atenolol (tenormin), labetolol (trandate) 2. Anticoagulant B Heparine (low C D Heparine Warfarin mol wt 4000-6000 (conventional) (coumarin): Streptokinase hemorrhage & e.g. enoxaparin Urokinase warfarin syndrome Phenindione (dindivan) 3. Diuretics: B C Amiloride Furosemide Ethacrynic acid D Thiazide: thrmbocytopenia Spironolactone: antiandrogenic Acetazolamide: limb abnormalities 4. Heart: B C Lidocaine Digoxin, Quinidine, Procainamide III. Pulmonary disorders 1. Asthma B Cromolyn Terbutaline Ipratropium bromide Prednisone, Prednisolone C Albuterol, , Metaproterenol Betamethazone, Beclomethazone, Dexamethazone, Flunisolide, Theophylline, Aminophylline Epinephrine, ephidrine D Triamcinolone acetonide Prednisone & prednisolone are inactivated in the placenta 2. Antihistaminics B C Azatadin, clemastine, Brompheniramine, Cyclizine, Doxylamine Hydroxzine, pheniramine 3. Cold B Pseudoephydrine, Oxymetazoline Chlorpheniramine, Dextrome thorphan C D Phenylephrine Iodide Pyrilamine 4. Antitussive & expectorants B Amm. C D X Iodinated Potassium glycerol chloride Hydrocodon iodide, Sodium iodide Codeine, Guaifenesin IV. Gastrointestinal disorders 1. Antiemetics B C Cyclizine Chlorpromazine, promethazine, Meclizine prochlorperazine, trimethobenzomide 2. Antiulcer B Sucralfate (not absorbed) Antacids (poorly absorbed) Ranitidine Cemetidine (antiandrogenic) Famotidine, nizatidine C X Omeprazole Misoprostol (uterine contraction) 3. Gallstone solubilizing agents B Ursodiol X Chenodiol 4. Laxatives & purgatives B C Lactulose Casanthranol, Cascara sagrada, danthron, Mg sulphate docusate, mineral oil, phenolphthalein, senna 5. Antidiarrheals B Loperamide C D Kaolin, pectin, diphenoxylate Paregoric V. Endocrine disorders 1. Antidiabetics B Insulin Metformin Acarbose C Chlorpropamide, tolazamide, Tolbutamide, Acetahexamide, Glyburide, Glibpizide 2. Thyroid & parathyroid disorders A B C Thyroid, Calcitonin Protirelin thyrotropin levothyroxin Liothyronin Thyroglobulin iodothyrine, liotrix D P.thiouracil Methimazole Carbimazole Lithium carbonate Methimazole: scalp defects Iodides: goiter & hypothyroidism X Sod iodide I131 3. Adrenal B C Prednisolone, Betamethazone, prednisone Beclomethazone, Dexamethazone, Triamcinolone D Cortisone 4. Gynecologic disorders C Bromocriptin D X Progestagens: Progestagens: ethisterone, ethyndiol hydroxy progestrone Tamoxifen norethindrone, norethyndrel, norgestrel Estrogens, Clomiphene Androgens, Danazol, Mifipristone DES: •Female: Uterus: T shaped, Vagina: adenosis, Vagina & cervix: adenocarcinoma (at 20 yr) & abnormalities •Male: hypoplastic, un descended tsetse, epidedmal cysts VI. Skin disorders B Dithranol& tar Orphermine Metronidazole Lindane Sulphur in petroleum Piperonal butoxide C Topical corticosteroids D Podophyllin Tetracyclin Methotrexate & tretinoin Azathioprine Pyrilimine Chloroquine, Grisofulvin Acyclovir, zidovuidine X Vit A derivatives: isotretinoin (Accutane) etretinate ((Tegison Thalidomide VII. Infections 1. Antibacterial B Penicillin, Erythromycin, Ampicillin, augmentin. Cephalosporin, clindamycin, azithromycin spectinomycin, spiramycin Nitrofurantoin, nalidexic acid, S. amide. Metronidazole Polymyxin, Aztreonam C Trimethoprime Chloramphenicol Gentamycin, Neomycin, Amikacin, Vancomycin Quinolones D Tetracyclins S.amide Tobramycin Streptomycin Kanamycin :Tetracyclin After 4th month when calcium starts to deposit in bone: yellow or brown discoloration of deciduous teeth, hypoplasia of enamel & .delayed bone development :Chloramphenicol .Gray baby syndrome: cyanosis, collapse, death :Trimethoprime Folate antagonist :Sulphonamides in 3rd trimester: hyperblirubinaemia & neonatal jaundice 2. Antituberculosis C B Ethmbutol Rifampicin, INH, PAS, Ethionamide, Cycloserin, pyrazinamide 3. Antifungal B Miconazole, clotrimazole Amphotericin, Nystatin C Griseofulvin, fluconazole, itraconazole, ketoconazole, miconazole, teraconazole 5 flucytosine, gentian violet 3. Antimalarial B C D Proguanil Chloroquine, primaquine, Quinine , Pyrimethamine, Dapsone Quinacrine, quinidine 4. Antihelminthic B C Piperazine Mebendazole, thiabendazole Pyrantel, pyrvinium, quinacrine, Gentian violet 5. Amebicides B Metronidazole 6. Antiviral B Didanosine Famciclovir Ritonavir C Chloroquine, iodoquinol, paromomycin C Acyclovir, Ganciclovir, Zidovudine D Carbarsone X Ribavirin IX. Immunosupressive C Cyclosporin D Azathioprine VIII. Antineoplastic B Prednisone C D X Cytosine, Methotrexate, 5 Aminopterin arabinoside flurouracil, 6M.P Leuprolide Dactinomycin Doxorubicin, Interferon daunorubicin, alfa bleomycin Cyclophosphamide, melphalan, busulphan, Cisplatin, vincristin, vinblastin, Etopside IX. Vitamins A Vitamins, multiple Folic acid/C, Niacin/C, Niacinamide/C, Pantothenic acid/C, Pyridoxine/C, Riboflavin/C, Thiamin/C, Vitamin B12/C, Vitamin C/C, Vitamin E/C Calcefediol/D, calcitriol/D, Cholecalciferol/D, Dihydrotachysterol/D Vitamin D/D, Vitamin A/X C D X ßCarotene, Tretinoin Etretinate Leucovorin, systemic Isotretinoin Menadione/X, Phytonadione, Tretinoin topical Isotretinoin: •Craniofacial malformation Microtia or anotia, flat depressed nasal bridge Malformation of the heart, CNS, & thymus •Avoid pregnancy during treatment Long acting contraceptive method is required )Etretinate: (Psoriasis •Malformation has been described 13 months after discontinuation (Lammer, 1988) Contraception for at least 2 years after treatment )(Geier et al, 1994 Recommendation Before pregnancy: Familiar with teratogenic drugs Avoid pregnancy if teratogenic drug should be given Ask about the LMP :In 1st trimester Avoid drugs Exception folic acid & vit C If absolutely indicated for short time & minimal effective dose :2nd & 3rd trimester Beneficial & safe drugs if indicated for short time & minimal effective dose :Last week Avoid drugs that may affect neonates If needed stop 7-10 days before labor Teratogenic drugs ACE inhibitor Alchol Aminopterin Androgens Busulfan Carbamazepine Chlorbiphenyls Coumarins Cyclophosphamide DES Eteretinate Isotretinoin Lithium Methimazole Methotrexate Penicillamine Phenytoin Radioactive iodine Tetracycline Trimethadione Valporic acid Benha University Hospital E-mail: [email protected] ...
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This note was uploaded on 12/24/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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OB_drugs_effects_pre - Benha University Hospital Email [email protected] Impact of the problem Egypt 86 takes drugs without prescription(Rizk

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