ࡱ> {}zG Rbjbjَ "M/],,,,,,,@@@@8x4@ (r"'''''''$)s+f',' ,, :,,'@@,,,,' h 6&,,'Xt @@( 'Drugs in Pregnancy November 14, 2002 By: Joanne C.Y. Chan Introduction Limited # of drugs that can negatively affect a patients pregnancy 30% of pregnancies go on to have spontaneous abortions/miscarriages before women knows she is pregnant 15% go on to have miscarriages after women has missed a period 3% of all pregnancies have major congenital anomaly no matter what Material exposure to drugs or environmental chemicals are responsible to 4-6% of abnormalities of the 3% Teratogenic Drugs If any meds given after vulnerable period (after fetus is formed) wont cause structural abnormalities there is a fixed amount of time to be concerned about structural abnormalities due to a drug Hormonal Medications Oral Contraceptives no relationship with 1st trimester OCP use and congenital abnormalities ( can reassure the patient 100% that no harm will be done to baby Danazol/Androgenic Meds If taken during pregnancy, can cause clitoral enlargement in fetus if you take it < 13 weeks DES (Diethyl ?) associated with clear cell cancer of vagina and cervix Uterine abnormality in daughters whos mothers took DES while pregnant Abnormality in male children (cryptorchism problems with testes) Drugs that should NEVER be given to a Pregnant Women Warfarin In Canada this is NEVER used in pregnant women In Europe, they still use it b/c they think its safe 25% of fetuses develop a congenital abnormality if mom takes it in 1st trimester Critical time period = 6 9 weeks Fetal Warfarin Syndrome Symptoms Hypoplastic nose Epiphyseal stipling Optic atrophy Small head Intrauterine growth retardation Neurologic abnormality (mental retardation) Exam Hint: She said that the FWSS would be a good exam question Alternative to Warfarin If mom is on W b/c of a clotting abnormality, can switch to heparin or LMWH, which are both safe in pregnancy Anti-Convulsants Significant (ed risk of neural tube defects Carbomezipine1% risk above baseline riskValproic Acid2% risk above baseline riskPhenytoin10% risk of above baseline risk Carbomezipine is the DOC for a pregnant women at risk of seizures b/c it is associated with the lowest risk You would never use Phenytoin (high risk) Fetal Hydratoin Syndrome Cradle, facial and limb deformities Mental deficiencies Folic acid supplementation4 mg/day in pregnancyNeeded for all epileptics Needed to prevent neural tube defectsVitamin K supplementation20 mg/d for 2 weeks before estimated delivery dateNeeded for patients on Carbomezipine, otherwise Fetal Coagulopathy Aside Benzodiazepines are safe In pregnancy, you always have to consider that there are 2 patients ( must consider BOTH the mothers and the fetuss well-being Often need to weigh risk/benefit ratio of both of Lithium 0.5% risk of Ebsteins anomaly (serious cardiac anomaly) if you take it in late pregnancy, can get: transient lithium toxicity in fetus Isotretinioin Retinoids Vitamin A No (ed risk associated with it OK to use Tretinoin Most potent drug that we know about 35-50% exposed (taken anytime in pregnancy) will have abnormalities including: (ed risk of marriage risk of heart disease deafness cleft lip/palate small ears and eyes if a female is trying to get pregnant, dont take it Topical tretinoin is safe in pregnancy In general, most drugs will cause a problem early on in pregnancy, therefore, the first 12 weeks of pregnancy is CRUCIAL time NOT to take these medications Thalidomide If the fetus is exposed to this, there is a 20-25% risk of the following: Severe limb abnormalities General heart disease Kidney problems Stomach problems (e.g duodenal atresia) Hearing problems Hernias Once exposed, the risk of limb defects is 80% NEVER take it anytime during pregnancy Misoprostol (Cytotec ) 1 2 % above baseline risk of Moebius seqius (sp?) congenital cardiac abnormalitiy and facial abnormalities - very rare defect used as an abortefacient (e.g. used to abort fetus in 1st trimester if fetus has a genetic abnormality or if personal has had a miscarriage) has prostaglandin ( makes uterus contract, induces labor Varying doses (400-800 ug) ( can give vaginally or P.O. 800 ug PV give 12 hours apart for 2 doses very effective In Canada, trials underway about inducing labor term Used for cervical softening before procedures such as: D & C, hystroscopy Softens it up by making uterus contract Decreases risk of perforating Giving it vaginally Experiments underway for using this in post-partum hemorrhage Makes uterus contract Term studies use lower doses (50 ug) Giving Misoprostol after Miscarriage except pain/cramps (putting them in labor) Rx Tylenol #3 (analgesia) after taking Misoprostol, the following occurs: development of menstrual cramps (get more intense) short period with extreme bleeding abnormal dead fetus is passed If this occurs < 10 wks cant tell that it is a baby, as it appears like grayish tissue among a blood clot a women will continue to bleed after passing the dead fetus, but her bleeding and cramps will ( If she still has a heavy period (heavy = you have to change your pad every hour) send them to ER Variable time effect a few hours, some have to repeat dose to get effect if pass fetus and bleeding stops dont need to take the 2nd dose Alcohol Fetal Alcohol Syndrome Microencephaly Heart defects Facial abnormalities Mental retardation You need to intake > 3 oz/day of alcohol every day of your pregnancy to get this (you have to be a severe alcoholic) In pregnancy, you can take most things in moderation, and it will be ok. 1 glass of wine is safe Tobacco Tobacco is now illegal to sell in the pharmacy, you can only buy them in the grocery store Associated with: Miscarriage Low birth weight Placenta abruption (placenta separates from the uterus prematurely and cuts off circulation to the baby) If a women stops smoking in the last 4 months of her pregnancy, the risk of having a low birth weight baby is the same as people who have been non-smokers for life Can smoke up to 20 weeks with no problem Marijuana Has been shown to be teratogenic in animals only, no human studies Other Drugs to Avoid ACE-Inhibitors cause fetal damage Tetracycline can cause bone abnormalities and yellow teeth NSAIDS can cause: premature closure of the ductus arteriosis (doesnt allow oxygenated blood to the fetus) fetal kidney problems care with long term NSAID use safe to take 1 2 tablets, but better options available, that are safe: Tylenol (100% safe) Codeine In general, there are often better options available Sulfonamides avoid when near term Methotrexate avoid at all costs MTX is used to abort pregnancy For Etopic Pregnancy for patients that are stable and dont want surgery, they use MTX to kill etopi Some people are experimenting with this for abortion rather than surgical abortion They use MTX first, and then use Misoprostol Infections that are Dangerous in Pregnancy Varicella (Chicken Pox) < 13th week of pregnancy, there is a 1% risk of congenital varicella if exposed > 13th week of pregnancy, this increases to a 2% risk if exposed this is very severe syndrome, as it can cause: mental retardation limb and eye abnormalities no documented cases of congenital varciella syndrome with herpes zoster Cases If women is exposed to chicken pox and.. 1) HAD it before = shes ok, dont need to do anything 2) NEVER had it before: She needs to go see MD/walk-in clinic and get tests to see if she is sero-positive (+) or sero-negative (-) If sero-positive (+) = she is ok, she is not at risk If sero-negative (-) = give immunoglobin BC? Rubella Part of the routine prenatal screening is for rubella Screening is performed in the form of a blood test Want to know if you are immune to it, if not, need to get vaccinated If this is transmitted in: First 10 weeks of pregnancy100% that baby Is infected can get heart defect, deafness, mental retardation13 16th weeks of pregnancyonly deafness has been reported> 20th week of pregnancyno abnormalities Exam hint = she mentioned this would be a good exam question Uterus Size Changes in Pregnancy different weeks in pregnancy correspond with different uterus sizes Normal UterusAbout the size of a fist, or a small plumAt 10-12 weeksUterus comes out of the pelvis, can feel it abdominally About the size of an orangeAt 20 weeksUterus is felt at the belly buttonAt 36 weeksUterus is up to the rib cage Right after delivery, the uterus goes back to the belly button, and after 10 days, should be back at the pelvis and you shouldnt be able to feel it. Pre-Natal Vitamins can use ANY pre-natal vitamin, doesnt have to be Materna these do NOT replace a well-balanced diet still need a well-balanced, Canada Food Guide diet eating for 2 is a myth you are only eating for ONE Iron (Fe) need 30 mg elemental Fe/day in pregnancy nausea/vomiting in first 3-4 months in pregnancy which is aggravated by Fe Option 1 = It is ok to NOT take Fe during the first 12 weeks Option 2 = take Fe at BEDTIME (so nausea occurs while you sleep) Vitamin C need 20% increase during pregnancy use 70 mg/d Folic Acid ( neural tube defects Spina epifida = failure to close neural tube at 26-28 days of gestation occurs very early on, therefore it is important to take this BEFORE you get pregnant often found in multi-vitamin it is very important to take this medication right before due date should recommend to anyone in child-bearing age who may want to get pregnant For general population0.4 mg/d X 1 month prior to conceptionFor high risk (i.e. previous infant w/ spina epifida, or mother has epilepsy)4 mg/d X 3 months prior to conception Random Questions Lower C-section (go transversely in the lower part of the uterus) CAN potentially have vaginal delivery afterwards (not dangerous) 2% risk of rupturing uterus (mom and baby can die from this) if you had a lower C section Classically C-section (go up and down uterus) or previous surgery involving cavity (removal of fibroid) Not eligible for a eligible for a vaginal delivery Dont want to belabor that scar b/c the risk of rupture increases a lot (4-8%) Cold C-Section Had a C-section b/c you had breached baby, twins, patient wasnt allowed to go into labor Chances to have a successful vaginal delivery is the same as someone who has NEVER had a C-section If you had a C-section b/c you previous tried labor (e.g. for 18 hours), wouldnt recommend you do vaginal delivery. 75% of V-backs (vaginal birth after C-section) will have vaginal delivery How long do you bleed? It is variable, could be 5-7 days you have heavy bright red bleeding, then similar to a regular period, then brownish, old blood, then a yellow discharge ends in 6 weeks heavy bleeding stops in a 1-2 weeks Intercourse safe in pregnancy? perfectly safe to have sex during pregnancy (encourage right before pregnancy) Detecting twins at regular MD visits, they should be measuring the size of the abdomen, which should correlate to the number of weeks into pregnancy So between 20-36 weeks, size of abdomen should ( 1 cm/week (e.g. at 23 wk, should measure roughly 23 cm) E.g. at 31 weeks, if you measure 39 cm, may be indicative of twins Usually ultrasound is used Weight gain Usually patients gain 25-35 lbs during pregnancy Obese patients gain less weight, thinner patients tend to gain more weight Dont try to lose weight during pregnancy Generally lose around 11 lbs after pregnancy, and you have to lose the right of the weight by exercise Metabolic changes that occur during pregnancy Those who arent breastfeeding takes a lot longer to lose weight Common Complaints in Pregnancy Nausea/Vomiting most serious between 6-13 weeks (majority will get better after this time) 1st line treatment: a) Adjust diet smaller more frequent meals, dry bland foods separate solids from liquids if this method doesnt work by itself, go to b) b) Gravol safe, very effective, can take P.O. or rectally no RCTs, but long term evidence that show there are no contraindications. Safe all the way through pregnancy, but we dont give it all the way through b/c it makes them feel tired. Good for needed it the odd time c) Dicleptin longer term Txs, can be used for entire pregnancy give according to patient Sx max 4/day typical dosing regimen 1 @ AM, 1 @ Noon, 2 @ Bedtime can stop at 14 weeks and see how they feel Constipation During pregnancy, you get a lot of smooth muscle relaxation uterus grows and compresses bowels exacerbated by Fe and vitamins taken during pregnancy Options: 1) ( Fiber 2) Metamucil/Protium or Stool softeners (want stools soft, to prevent hemorrhoids) Hemorrhoids uterus obstructs venous return in all veins including rectal vein thus you get hemorrhoids b/c of the increased pressure they get worse as pregnancy progresses Options 1) Stool softeners can give any 2) For Sx relief - use Anusol HC or Anusol Cream safe in pregnancy generally, hemorrhoids improve after pregnancy (go away spontaneously) Cortisone and steroids are safe in pregnancy (e.g. inhaled steroids, oral steroids, often used for rash) Heartburn uterus pushes up the stomach and esophagus and compresses it smooth muscle relaxation causes lower esophageal sphincter to not close properly Options 1) Change diet avoid spicy foods or things that aggravate it, avoid lying down after eating. This doesnt work very well 2) Antacid (Maalox, Zantac, or Tums (has Ca+)) for patients with bad heartburn, liquid formulation may be more effective than tablet dont recommend Pepto-Bismol b/c better options are available Yeast Infection 30-40% occurrence in pregnant women no danger to fetus when you have yeast infection toward end of term (week 35) avoid putting creams/tablets inside the vagina, but put it around on the outside (worry that if you rupture membrane, you would have the cream/tablets lingering around) before end of term, can use cream/tablet inside vagina cant use Diflucan, is contraindicated Option only use topical azoles 1 day Tx dont use this as patients will relapse recommend 3 or 7 day Tx Headaches Options DOC = Tylenol safe in pregnancy Codeine safe in pregnancy Morphine/demoral for severe pain safe Dont give close to delivery b/c it may ( fetus respiration AVOID ASA/NSAIDS b/c they can cause: Premature closure of ductus arteriosis Kidney problems Bleeding problems at end of pregnancy Exceptions 1) Sometimes women on 81 mg/d ASA b/c of hypercoagulable state (thrombophila) that may predispose them to clotting, but never had documented clot so not on heparin 2) Infertility patients on low dose ASA to prevent miscarriage or pre-term labor advise patients to STOP low-dose ASA @ 36 weeks Cough and Cold OTC meds are generally safe AFTER 1st trimester (12 weeks) Tell patients to use drowsy formulations b/c there are more studies done on them Try to avoid preps with ASA and NSAID in them Options Vicks vapor rub Lozenges Pseudoephedrine avoid if you can, probably ok after 1st trimester B2-agonist and steroids - use if you have prolonged cough or refractory asthma can use If unsure about anything call Mother Risk have lots of EP info Antibiotics most are safe stay away from tetracycline, sulfa, quinolones (avoid in breastfeeding) quinolones = controversial topic, animal studies showed grey matter problems, therefore dont use 1st line Choice of Antibiotic UTI asymptomatic bacteruria (2-7% occurrence in pregnant women) 25% of patients with asymptomatic bacteruria go on to develop symptoms big concern of UTI is that it puts you at risk of preterm labor 1st line Nitrofurantoin Amoxicillin-Clavulin Macrobid 30% will fail on any Tx regimen Duration = 5-7 days (as opposed to 3-days) Cardiac Prophylaxis American Heart Association - Tx all intermediate - high risk groups during high risk procedures (i.e. labor delivery) ACOG said to use prophylaxis all women with any cardiac problems E.g. Patients with mitral valve prolapse with NO regurgitation considered LOW RISK Prophylaxis is given only during labor delivery (ampilcillin and gentamicin) High risk = any women with cardiac problems Prevents 90% of infections Mostly for vaginal deliveries (infection during passage through vagina) Prophylaxis given only during labor Group B Streptococcus 15-20% of women carry this vagina or rectum part of your normal flora Guidelines regarding Tx are always changing 1) Base Tx on risk factors Risk factors: preterm labor before 37 completed weeks of pregnancy ruptured membranes over 18 hours (break water but dont go into labor) a previous infant who has been affect by Group B Strep temperature therefore, Tx if ANY RF are present 2) Screen everyone by obtaining a culture If culture is (-) ruptured X 24 hours ( Dont Tx If culture is (+) Treat Give Penicillin G + Ampicillin IV Use clindamycin if allergic Risk is to newborn, not to mother Two types of infection 1) Early onset disease immediately after birth, usually 6-12 hours 25% mortality rate 2) Late onset disease occurs > 1 wk after birth usually manifests as meningitis Drugs during Induction of Labor before labor, want to ripen their cervix (gets cervix ready for labor and delivery) typically, your cervix is usually 3-4 cm long and hard as a rock you need it to be shortened, and dilated PGE2 various formulations gel that you put in vagina (1-2 mg) gel that you put in cervix (0.5 mg) New insert called Servedil -10 mg that is CR (0.3 mg/hr) It has a long string attached to it for easy removal if big long uterus contraction is cutting off circulation to the baby. Side Effect uterine hyperstimulation (5%) remove as much of PG as possible (try to flush out gel not easy or effective), or can give Salbutomol or Terbutaline (stops contraction) Oxytocin uterine response to this depends on gestational age (( myometrial receptors as you age) t = 5 minutes, response within 3-5 minutes Goal is to have 3-5 contractions every 10 minutes, and you dont want them to last more than 1 minute Dosing Usually 10-20 U of oxytocin in a liter of normal saline Start at 1-2 milli units/ minute, and increase by 1-2 milli units every 20-30 minutes until good contractions SE = uterine hyperstimulation seen as: > 5 contractions in 10 minutes, or contractions < 2 minutes apart or contractions that last for > 1 minute Risk of this is Fetal Distress - uterus squeezes down and the baby is not getting O2 At higher doses (45 milliunits/minute) can get Anti-diuretic effect and water intoxification Hypertension in Pregnancy Pre- Eclampsia = transient pregnancy-induced hypertension These are patients who have never had high BP before 20 weeks of pregnancy, and they develop it after 20 weeks and it is not associated with other Sx associated with proteinuria Essential or Chronic Hypertension = developed it > 20 weeks can get pre-eclampsia superimposed onto chronic HTN very common that people with underlying HTN will develop Sx consistent with pre-clampsia such as proteinuria, headache, visual disturbances and gastric pain. Treatment Doesnt affect maternal outcome Benefits fetus Low dose ASA low dose prevents preeclapmsia DOC = methyldopa Labetolol (blocks ( and (), recent RCT shows that it may be better than methyldopa, Hydralazine 5 mg IV for emergency use (relaxes smooth muscle) MgSO4 give IV, bolus 4g, then run 1-2 g/hr Give to ( seizure threshold Pre-eclampsia can go onto eclampsia, which is a full-blown seizure In emergency situation = dont want to ( blood flow too quickly, b/c the first place it will cut circulation is the placenta Avoid: Calcium Channel Blockers in 1st trimester (only animal study shown teratogenic) 2nd /3rd line Diuretics ACE-inhibitors (contra-indicated) Post Partum Depression Up to 15% occurrence very big concern refer to see psychiatrist can use almost any anti-depressant during pregnancy and breastfeeding (SSRI) OBGYN Nov 14, 2002 PAGE  PAGE 1 '<=J)*l x C T ` a    , 6 ^ x STUcm{|6>*CJOJQJ5CJOJQJ jCJOJQJ6CJOJQJ>*CJOJQJ jCJOJQJCJH*OJQJ CJOJQJ CJOJQJOJQJE'<=J4wZkl)qh & F  & F & F & F$'<=J4wZkl)q" Y  ! , L |sja                                                                %" Y  ! , L x ? @ A B C T $$h & F & F & FL x ? @ A B C T    o   7 ] ^ x 0TUcmƽ                                                  2    o   7 ] άά$ & F & F$$0$$l t0!] ^ x 0TUcmxDh & F & F & F$$$;$$l tFh#@ mx 5KTeyst 2CKyǾǾ~ulf`ZT              =   N   v                    l   }                       x 5KTeyst 2CKy & Fh & F & F & F !tCQpr)Y)6eli+/1OJQJ>*CJOJQJ6CJH*OJQJ jCJOJQJ jCJOJQJCJH*OJQJ5CJOJQJ CJOJQJ6CJOJQJ jCJOJQJ CJOJQJA9:fu:N5eH & Fh & F & F & F9:fu:N5eHYż{tke_YSM   .      -   ,   +        z       *   )   (     '   p       &   %       $   #   "   !Yw=NZkyh & F & F & Fw=NZky()6delwztnhaXR   :       9      8      7    6      5   4          3   2      1   0   /           ()6delwMaig & Fh & F & FMaig+{ a g K!!!!{tkd]T   _            F   E       D   C   B      A     @   ?   >      =      <       ; +{ a g K!!!!!! 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