Drugs in pregnancy

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drugs safety in pregnancy medications medication in pregnancy treatment during pregnancy healthy pregnancy teratogen teratogenecity teratogenic drugs in pregnancy drugs and congenital malformation

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Drugs in pregnancy

  1. 1. ‫بسم‬‫هللا‬‫الرحمن‬‫الرحيم‬ Drugs in pregnancy Ahmad abdul kareem
  2. 2.  Drugs in pregnancy  Assess risk/benefit ratio for the mother-fetus pair.  Avoid non-essential drugs.  Where drug treatment is clinically indicated, select an effective agent with the best safety profile.  Use the lowest effective dose for the shortest possible time.  Provide timely and accurate counselling to help avoid unfounded maternal fears about drug safety that may otherwise result in non-adherence with drug therapy or unnecessary pregnancy termination.  Use the statement ‘avoid all drugs in the first trimester where possible’ cautiously as drug exposure in the second and third trimesters may still result in fetal harm.  Remember that the harmful effects of a drug on the fetus may differ depending on the trimester of exposure. Key points
  3. 3.  Normal physiologic changes that occur during pregnancy may alter medication effects, resulting in the need to monitor and, sometimes, adjust therapy. 1. maternal plasma volume, cardiac output, and glomerular filtration increase by 30% to 50%. 2. As body fat increases during pregnancy. 3. Plasma albumin concentration decreases. MATERNAL PHARMACOKINETIC CHANGES IN PREGNANCY
  4. 4. 4. Nausea and vomiting, as well as delayed gastric emptying, may alter the absorption of drugs. 5. Likewise, a pregnancy-induced increase in gastric pH may affect the absorption of weak acids and bases. 6. Higher levels of estrogen and progesterone alter liver enzyme activity and increase the elimination of some drugs but result in accumulation of others. continued
  5. 5.  A teratogen is defined as any agent that results in structural or functional abnormalities in the fetus, or in the child after birth, as a consequence of maternal exposure during pregnancy.  The teratogenic mechanism for most drugs remains unclear(idiosyncratic), but may be due to the direct effects of the drug on the fetus and/or as a consequence of indirect physiological changes in the mother or fetus. Teratogen
  6. 6.  Teratogenic risk is determined largely by timing of drug expo- sure :  Establishment of full implantation of the fertilized egg takes 1 to 2 weeks. Teratogenic exposure during this stage elicit an ‘all-or-nothing’ response, leading either to death of the embryo or completely normal development of the fetus. Pathophysiology
  7. 7. continued • Embryonic stage (weeks 3-8 post-conception) The critical time for organogenesis is during the first 8 weeks of pregnancy. Organogenesis occurs predominantly during the embryonic stage and, with the exception of the central nervous system, eyes, teeth, external genitalia and ears, is complete by the end of the 10th week of pregnancy. Exposure to drugs during this critical period therefore represents the greatest risk of major birth defects.
  8. 8.  For this reason, women are often advised to avoid or minimize all drug use in the first trimester whenever possible.  After 8 weeks, most teratogenic effects are related to fetal growth restriction or functional deficits such as mental retardation. continued
  9. 9. Drugs during pregnancy can be categorized as:  A : Fetal risk not revealed in controlled studies in humans  B : Animal studies have revealed no evidence of harm to the fetus, while, there are no adequate studies in pregnant women, or animal studies have shown an adverse effect, but studies in pregnant women have failed to demonstrate a risk to the fetus.  C : Animal studies have shown an adverse effect and there are no adequate and well-controlled studies in pregnant women. So
  10. 10.  D : Studies, adequate well-controlled, in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy may outweigh the potential risk.  X : Studies, adequate well-controlled or observational, in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. The use of the product is contraindicated in women who are or may become pregnant. continued
  11. 11.  Six Principles of Teratology which are still applied today : 1. Susceptibility to teratogenesis depends on the genotype of the conceptus and the manner in which this interacts with adverse environmental factors. 2. Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence. 3. Teratogenic agents act in specific ways on developing cells and tissues to initiate sequences of abnormal developmental events. Wilson's 6 principles
  12. 12. 4. The access of adverse influences to developing tissues depends on the nature of the influence. Several factors affect the ability of a teratogen to contact a developing conceptus, such as the nature of the agent itself, route and degree of maternal exposure, rate of placental transfer and systemic absorption, and composition of the maternal and embryonic/fetal genotypes. 5. There are four manifestations of deviant development (Death, Malformation, Growth Retardation and Functional Defect). 6. Manifestations of deviant development increase in frequency and degree as dosage increases from the No Observable Adverse Effect Level (NOAEL) to a dose producing 100% Lethality (LD100). continued
  13. 13.  Although once thought to be a barrier to drug transfer  the placenta is fundamentally the organ of exchange for a number of substances, including drugs, between the mother and fetus. Most drugs move from the maternal circulation to the fetal circulation by diffusion. Certain chemical properties, such as lipid solubility, electrical charge, molecular weight, and degree of protein binding of medications, may influence the rate of transfer across the placenta also. TRANSPLACENTAL DRUG TRANSFER
  14. 14.  Drugs with molecular weights less than 500 Da readily cross the placenta, whereas larger molecules (600–1,000 Da) cross more slowly.  Lipophilic drugs, such as opiates and antibiotics, cross the placenta more easily than do water-soluble drugs.  fetal albumin increases during the course of pregnancy  Fetal pH is slightly more acidic than maternal pH, permitting weak bases to more easily cross the placenta. Once in the fetal circulation, however, the molecule becomes more ionized and less likely to diffuse back into the maternal circulation. continued
  15. 15.  Although some drugs have the potential to cause teratogenic effects, most medications required by pregnant women can be used safely.  There are many misconceptions about the association of medications and birth defects.  The overall incidence of congenital malformations is approximately 3% to 5%.  medication exposure accounts for less than 1% of all birth defects.  Genetic causes are responsible for 15% to 25%.  other environmental issues (e.g., maternal conditions and infections) account for 10%, and the remaining 65% to 75% of congenital malformations result from unknown causes. Myths v.s Facts
  16. 16. PREGNANCY-INFLUENCED ISSUES ACUTE CARE ISSUES IN PREGNANCY CHRONIC ILLNESSES IN PREGNANCY LABOR AND DELIVERY Therapy needed in pregnancy due to
  17. 17. Constipation : occurs commonly in pregnancy.  use of stool softener is appropriate.  Lactulose, sorbitol, and bisacodyl are acceptable treatments but should be reserved for occasional rather than routine use.  Senna can be used occasionally. Cat C  Castor oil and mineral oil should be avoided. Cat X can induce labor and can cause vomiting and dehydration PREGNANCY-INFLUENCED ISSUES
  18. 18. Gastroesophageal reflux disease  Drug therapy can be initiated with aluminum, calcium, or magnesium antacid preparations  Sucralfate is another option  and evidence supports the use of ranitidine and cimetidine.  Literature on the use of famotidine and nizatidine is limited  metoclopramide, lansoprazole,omeprazole, are viable options.  sodium bicarbonate risky cat C PREGNANCY-INFLUENCED ISSUES
  19. 19. Hemorrhoids : Therapy is generally conservative; high intake of dietary fiber, adequate oral fluid intake, and use of sitz baths are helpful.  Topical anesthetics, skin protectants, and astringents can be used. Other options for refractory hemorrhoids include rubber band ligation, sclerotherapy, and surgery. PREGNANCY-INFLUENCED ISSUES
  20. 20.  Nausea ,vomitting &hyperemesis gravidarum:  Vitamins:B6 ,B12(cyanocobalamine)  Antihistamines (meclizin,cyclizine,dimenhydrate,  doxylamine) have not proved to be toxic except amobarbital.  Phenothiazines (chlorpromazine)& metoclobromide  Ondanstron (limited studies)  Steroids(dexamethazone,prednisolone)effective +increase risk of cleft lip(in 1st trimester).  Ginger has shown efficacy for hyperemesis. PREGNANCY-INFLUENCED ISSUES
  21. 21.  GESTATIONAL DIABETES :  Mx = diet control(decrease calory for obese) +/- drug therapy. Exercise(as possible).  Drug of choice =insulin, if insulin can’t be used (for one reason or another):  Glyburide :oral sulphonylurea does not cross the placenta or metformin (inadequately studied) PREGNANCY-INFLUENCED ISSUES
  22. 22.  HYPERTENSION(preeclampsia):  Mx =diet control+/- drug therapy.  Preventive measures : 1g/day Ca++ supplements,,  Low dose aspirin(<325mg/day)for high risk women.  Drugsfor severe hypertension:  Maintanence : methyldopa,,nifedipine  ACE inhibitors : risky(oligohydramnia,fetal anurea renal agenesis)  Acute settings: labetalol , hydralazine.  Avoid : nimodipine, Mg sulphate (except for eclampsia prophylaxis) & high-dose diazoxide. PREGNANCY-INFLUENCED ISSUES
  23. 23.  THROMBOEMBOLISM:  Warfarin : avoid whenever possible(goup D,X); it can cause CNS anomalies, deformed nose & stippled epiphysis(early in pregnancy) ,fetal & neonatal bleeding(later in pregnancy).  Acute thromboembolism: LMWH or unfractioned heparin(during pregnancy &6 wks postpartum)  Antiphospholipid syndrome: LMWH, unfractioned heparin &/or aspirin.  Women with prosthetic valves:LMWH, unfractioned heparin PREGNANCY-INFLUENCED ISSUES
  24. 24. Side effect of warfarin
  25. 25. PREGNANCY-INFLUENCED ISSUES Alternative regimen: Beginning of pregnancy Heparin product 13 wks change to warfarin Middle of 3rd trimester return to 6 wks post partum High-risk women with prosthetic heart valves may also receive aspirin therapy in doses of 75 to 162 mg/day
  26. 26. URINARY TRACT INFECTIONs : Asymptomatic bacteruria, cystitis and pyelonephritis Antibiotic selection should be based on urine culture sensitivities, if known. Often, therapy must be initiated on an empirical basis, before culture results are available. This requires clinical knowledge of the most common organisms and their practice-specific or hospital-specific sensitivities to medications. ACUTE CARE ISSUES IN PREGNANCY
  27. 27.  Oral antibiotics are the treatment of choice for asymptomatic bacteriuria and cystitis. Appropriate oral regimens include the following:  Cephalexin 500 mg 4 times daily  Ampicillin 500 mg 4 times daily  Nitrofurantoin 100 mg twice daily  Sulfisoxazole 1 g 4 times daily ACUTE CARE ISSUES IN PREGNANCY DCIM
  28. 28. Pyelonephritis :  Current regimens are :  First-line therapy  Nitrofurantoin monohydrate/macrocrystals 100 mg orally twice daily for 5-7 days or  Amoxicillin 500 mg orally twice daily for 5-7 days or  Amoxicillin-clavulanate 500/125 mg orally twice daily for 3-7 days or  Cephalexin 500 mg orally twice daily for 3-7 days or  Cefuroxime 250 mg orally twice daily for 3-7 days  Second-line therapy  Fosfomycin 3 g orally as single dose with 3-4 oz. of water  Macrolides are safe but not first-line agents for UTI in pregnancy. ACUTE CARE ISSUES IN PREGNANCY
  29. 29.  The most common m.o is E.coli which has resistence to many drugs: Ampicillin(28-29%),co-trimoxazole(31%),1st generation cephalosporins (9-19%).  Risks with use of antibiotics :  Tetracyclines:fetal teeth &bones abnormalities& congenital defect.  Trimethoprim(in 1st trimester):facial defect &cardiac defects.  Cloramphenicol:gray baby syndrome.  Sulphonamides in 3rd trimester: jaundice &kernicterus, in the mother, H. anemia if she has G6PD deficiency. ACUTE CARE ISSUES IN PREGNANCY
  30. 30.  Fluoroquinolones are contraindicated in pregnancy myelomeningocele, hydrocephaly, hypospadias, maldescended testes, inguinal hernia, bilateral hip dysplasia, and atrial septal defects.  Nitrofurantoin is safe &effective(&can be used once daily as prophylaxis) but with poor tissue penetration &so it has limited use in treatment of pylonephritis.  It’s not used in last several wks of pregnancy(due to hemolytic effects on fetal/neonatal blood because of glutathione instability in their immature RBCs.
  31. 31.  SEXUALLY TRANSMITTED DISEASES(STD) :  STDs in pregnant women range from : A. infections that may be transmitted across the placenta and infect the infant prenatally (e.g., syphilis). B. to organisms that may be transmitted during birth and cause neonatal infection (e.g., Chlamydia trachomatis, Neisseria gonorrhoeae, or herpes simplex virus) C. to infections that pose a threat for preterm labor (e.g., bacterial vaginosis). ACUTE CARE ISSUES IN PREGNANCY
  32. 32.  Always treat both partners. Neisseria gonorrhoeae  The treatment of choice is ceftriaxone 125 mg i.m as a single dose or cefixime 400 mg orally in a single dose.  For women unable to use a cephalosporin, spectinomycin 2 g i.m as a single dose is appropriate.  Quinolones or tetracyclines should not be used. ACUTE CARE ISSUES IN PREGNANCY
  33. 33. Chlamydia trachomatis:  The recommended treatment of C. trachomatis cervicitis is azithromycin 1 g orally as a single dose or  amoxicillin 500 mg three times daily for 7 days.  Erythromycin base or ethylsuccinate regimens can be considered as alternatives.  Erythromycin estolate should be avoided because of an increased risk for hepatitis ACUTE CARE ISSUES IN PREGNANCY
  34. 34. Syphilis:  the drug of choice is penicillin (it prevents transmission to the fetus and in treating the fetus, if already infected).  The dose and route of administration are determined by the stage of syphilis and are the same for pregnant women as for other patients.  No alternatives for penicillin are acceptable for pregnant women allergic to penicillin; therefore, penicillin skin testing and desensitization are required.  There is a risk of premature labour &/or fetal distress for women taking the drug in the 2nd half of pregnancy(due to jarish-herixhimer reaction. ACUTE CARE ISSUES IN PREGNANCY
  35. 35.  Genital Herpes :  Neonatal herpes often occurs in infants born of women lacking clinical evidence of genital herpes.  Primary infection near the time of delivery carries 30-50% risk of transmission.  In recurrent herpes infections at term or an initial episode during the first half of the pregnancy, the risk of transmission is less than 1%.  However, because recurrent herpes is more common than initial episodes during pregnancy, it remains the cause for most cases of neonatal transmission. ACUTE CARE ISSUES IN PREGNANCY
  36. 36.  The usefulness of antiviral agents for preventing transmission of genital herpes to pregnant women has not been studied.  Acyclovir , valacyclovir and famciclovir  Acyclovir use during late pregnancy has been associated with a reduced frequency of cesarean section because of fewer recurrences.  No data suggest benefit of treatment for women who are seropositive for herpes simplex virus but have not experienced a clinical episode. ACUTE CARE ISSUES IN PREGNANCY
  37. 37. Bacterial Vaginosis  Although not a STD, bacterial vaginosis is a risk factor for premature PROM, preterm labor, spontaneous abortion, and postpartum endometritis.  Treatment is the same as in nonpregnant patients:  Metronidazole at 250-500 mg orally twice per day for 7 days  or clindamycin 300 mg orally twice per day for 7 days are recommended.  clindamycin cream should be avoided during the second half of pregnancy because it can increase the risk of premature birth.  Oral therapy is preferred for pregnant women because of the possibility of subclinical upper genital tract infection. ACUTE CARE ISSUES IN PREGNANCY
  38. 38. Antifungal: topical, vaginal:  Topical : the following agents can be used safely:  Clotrimazole, Naftifine , Nystatin, Amphotericin B Ciclopirox Haloprogin Oxiconazole Terbinafine. The other topical agents considerd cat C  Vaginal agents :  Nystatin cat A  Clotrimazole cat B  Miconazole Butoconazole Terconazole Tioconazole : Cat C ACUTE CARE ISSUES IN PREGNANCY
  39. 39. Systemic antifungal :  Systemic antifungal agents have traditionally been regarded as toxic medications, and their use in pregnancy has been limited to life-threatening fungal infections.  Fluconazole : should be avoided multiple congenital anomaly  Itraconazole :used only in life threatining situation.  Ketoconazole, Posaconazole :use if risk outweighs benefit.  Amphotericin B : not known to be harmful but manufacturer advice to avoid .some resources says it is cat B ACUTE CARE ISSUES IN PREGNANCY
  40. 40. Antiparasitic agents: all of them are cat C except nitazoxanide wich is cat D. Anthelminthic agents: praziquantel cat B Albendazole, mebendazole , ivermectin cat C Diethylcarbamazine cat X ACUTE CARE ISSUES IN PREGNANCY
  41. 41. HEADACHE Headaches in pregnant women can be classified as primary (tension, migraine) or secondary (trauma, infection) .  Acetaminophen (with or without codeine), codeine, or other narcotic analgesics(Meperidine, morphine) can be used to treat headaches. ACUTE CARE ISSUES IN PREGNANCY
  42. 42.  NSAIDs are considered safe (Ibuprofen Naproxen) during the first trimester but are generally contraindicated in late pregnancy.  sumatriptan : controversal but it is cat C and may be used.  Dihydroergotamine, Ergotamine are contraindicated in pregnancy ACUTE CARE ISSUES IN PREGNANCY
  43. 43.  ALLERGIC RHINITIS AND ASTHMA:  Rx of asthma is considered safer than risks to the fetus from untreated asthma.  A short-acting β2- agonist should be available to use for quick relief of symtoms.  Mild intermittent asthma: require only a short-acting, inhaled β2-agonist(albuterol is the preferred agent) CHRONIC ILLNESSES IN PREGNANCY
  44. 44.  Mild persistent asthma: Low-dose inhaled corticosteroids are Rx of choice (budesonide is the preferred agent).  alternatives to steroids:cromolyn(less efficacy),leukotrines receptor antagonists (less experience with their use) or theophylline (more potential toxicity than inhaled steroids).  Mg sulphate is safe in pregnancy (dilate airway by smooth muscle relaxation).  Severe asthma exacerbation :epinephrine(with risk of cong. malformations,fetal tachycardia & vasoconstriction of uteroplacental circulation). CHRONIC ILLNESSES IN PREGNANCY
  45. 45.  For moderate persistent asthma; either:  low- dose inhaled corticosteroids + a long-acting β2- agonist(Formoterol,salbutamol)  or an increase in the dose of the inhaled corticosteroids.  For severe persistent asthma, the inhaled corticosteroid dose should be increased to the high-dose range.  Addition of systemic corticosteroids may be warranted if symptoms continue. CHRONIC ILLNESSES IN PREGNANCY
  46. 46. Allergic rhinitis : Beclomethasone and budesonide are most widely studied. nasal cromolyn &1st generation antihistamines: (chlorpheniramine,tripelennamine &hydroxyzine)are also considered 1st line choice. 2nd generation (loratidine &cetirizine) do not appear to increase risk to the fetus. Oral decongestants (pseudoephedrine) may be associated with an increased risk for gastroschisis. Use of an external nasal dilator, short-term topical oxymetazoline, or inhaled corticosteroids may be preferable to use of oral decongestants CHRONIC ILLNESSES IN PREGNANCY
  47. 47. DERMATOLOGIC CONDITIONS :  topical agents with minimal pregnancy risk:  bacitracin, benzoyl peroxide(for acne), ciclopirox(antifungal) , mupirocin (antibacterial), permethrin (for lice/scabies), and terbinafine (antifungal).  Systemic agents considered safe include : cyproheptadine, dicloxacillin, nystatin.  Lidocaine and lidocaine + epinephrine can be used topically during pregnancy  acitretin, fluorouracil, isotretinoin, methotrexate, and thalidomide are contraindicated CHRONIC ILLNESSES IN PREGNANCY
  48. 48. EPILEPSY: antiepileptic drugs(AED):  Major malformations occur in 4% to 6% of offspring of epileptic women taking benzodiazepines, carbamazepine, phenobarbital, phenytoin, or valproic acid.  Lamotrigine has been associated with an incidence of oral cleft palate and/or lip of one case per 113 exposed.  Combination regimens of antiepileptic drugs are associated with higher malformation rates. CHRONIC ILLNESSES IN PREGNANCY
  49. 49.  Use antiepileptic drug monotherapy, if possible, and optimize any drug therapy prior to conception.  Medication change exclusively to minimize teratogenic risk & prior recommendation to switch from other antiepileptic drugs, is no longer recommended.  Drug withdrawal, if planned, should be attempted at least 6 months before conception is attempted
  50. 50.  the mother should receive supplementation with 10 mg oral vitamin K1 daily during the last month of gestation.  In addition, all women with epilepsy should take folic acid supplementation of 0.4 to 5 mg daily. CHRONIC ILLNESSES IN PREGNANCY
  51. 51. Cardiovascular diseases HYPERTENSION  ARBs, ACE inhibitors are cat(C/D).  renal dysgenesis or death (if used in 2nd & 3rd trimesters)  increased risk of cardiovascular and CNS malformations when used in the first trimester.  Diuretics avoided in pregnancy, as they prevent the physiologic volume expansion. They may be used in states of volume- dependent hypertension, such as renal or cardiac disease. CHRONIC ILLNESSES IN PREGNANCY
  52. 52. Three treatment options are available in cases of mild chronic hypertension in pregnancy:  Antihypertensive drug may be discontinued, with subsequent close observation of blood pressure.  If a woman is on unacceptable agent in pregnancy, she may be switched to an alternative antihypertensive agent preferred for use in pregnancy.  If a woman is on pharmacologic treatment with an agent acceptable in pregnancy, she may continue her current antihypertensive therapy. CHRONIC ILLNESSES IN PREGNANCY
  53. 53. Valvular heart diseases:  hydralazine, digoxin, adenosine, and procainamide can be safely used in pregnancy.  amiodarone, and nitroprusside are contraindicated during pregnancy regardless of the indication.  Most other medications carry a potential risk to the fetus and should only be used when the maternal benefit outweighs the fetal risk. CHRONIC ILLNESSES IN PREGNANCY
  54. 54. Coronary Artery Disease  Low-dose aspirin is safe but prolonged use of 100 mg aspirin can cause increased maternal bleeding complications and low birth weight.  Beta-blockers are the drug of choice in pregnancy(safe).  Nitrates and calcium channel blockers should be used with caution to avoid maternal hypotension.  Thrombolytic therapy has limited data in pregnancy. No reports of teratogenic effects exist, but an increased risk of maternal hemorrhage exists CHRONIC ILLNESSES IN PREGNANCY
  55. 55. Beta-blockers : Atenolol cat D Metoprolol cat C (D at term or prolonged use) Nadolol cat C (D at term or prolonged use) Propranolol cat C (D at term or prolonged use) Timolol cat C (D at term or prolonged use)  Coronary reperfusion by percutaneous transluminal coronary angioplasty or coronary bypass graft surgery has been reported with favorable outcomes. CHRONIC ILLNESSES IN PREGNANCY
  56. 56. Respiratory system  ipratropium bromide can be used safely  Common antibiotics used for respiratory infections:  penicillin, cephalosporins, and erythromycin.  Antibiotics that have relative contraindications include: sulfonamides(kernicturus) , trimethoprim (folate deficiency) , aminoglycosides (fetal ototoxicity) , nitrofurantoin (g6pdd), tetracyclines (discoloration of teeth), and quinolones (cartilage damage), chloramphenicol(not adivsed because of gray baby syndrom) ,  Vancomycin ,teicoplanin , daptomycin and linezolids are adviced only if risk outweighs benefit. CHRONIC ILLNESSES IN PREGNANCY
  57. 57. Tuberculosis:  Pregnant women with active TB should be treated, even in the first stage of pregnancy.  Isoniazid, rifampin, ethambutol and pyrazinamide may be used.  Streptomycin should not be used, because it has been shown to have harmful effects on the fetus (has the heighest risk of ototoxicity). CHRONIC ILLNESSES IN PREGNANCY
  58. 58. MENTAL HEALTH CONDITIONS  An estimated 500,000 pregnancies each year involve women with psychiatric illnesses (either newly or previously diagnosed) .  Anxiety disorders, including panic disorder, obsessive compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder, social anxiety disorder, and phobias, are the most commonly occurring psychiatric illnesses.  Depression, Schizophrenia eating disorder are less common than anxiety disorders. CHRONIC ILLNESSES IN PREGNANCY
  59. 59.  All TCA are cat C  except nortriptyline , imipramin cat D  Use only when risk outweigh benefit  The SSRI are the drugs of first choice in the general population and are widely used by pregnant women.  About one to two babies per 1,000 develop persistent pulmonary hypertension when used after week 20 of pregnancy. CHRONIC ILLNESSES IN PREGNANCY
  60. 60.  Another risk associated with use of SSRIs late in pregnancy is a withdrawal reaction in the infant consisting of irritability and difficulty with feeding and breathing.  Finally, an epidemiologic study suggests that 1st trimester use of paroxetine may be associated with an increased risk for cardiac defects in the infant. CHRONIC ILLNESSES IN PREGNANCY
  61. 61.  Benzodiazepines : category - D or X &  increases risk for oral clefts.  Benzodiazepine use in the third trimester can be associated with infant sedation and withdrawal symptoms.  “floppy baby syndrome,” consisting of low Apgar scores, hypothermia, poor muscle tone, and poor temperature adaptation.  Chlordiazepoxide seem to be safe in pregnancy.  flurazepam, temazepam, and triazolam (category X).  Avoidance of alprazolam during pregnancy seems prudent. CHRONIC ILLNESSES IN PREGNANCY
  62. 62.  Lithium : avoid if possible in first trimester (Ebstein anomaly ).  needs dose adjustment in 2nd and 3rd trimesters.  Other reported side effects in the newborn include “loppy baby syndrome,” nephrogenic diabetes insipidus, hypoglfycemia, cardiac arrhythmias, thyroid dysfunction, polyhydramnios, and premature delivery  Chlorpromazine, haloperidol, and perphenazine have long histories of use during pregnancy . CHRONIC ILLNESSES IN PREGNANCY
  63. 63. Atypical antipsychotics : use of them in pregnant women is controversial.  olanzapine and clozapine have been associated with weight gain and an increased incidence of glucose intolerance, which have implications for poorer obstetric outcomes.  Other agents, such as quetiapine, risperidone, aripiprazole, and ziprasidone, have been used less in pregnancy, so only limited information is available. At present, atypical antipsychotics do not appear to be safer than the typical agents. CHRONIC ILLNESSES IN PREGNANCY
  64. 64. THYROID DISORDERS  levothyroxine if hypothyroidism is diagnosed can be used safely with doses more than non-pregnant woman.  thioamides (e.g., propylthiouracil, methimazole)  thioamides can crosses placenta.  Radioactive Iodine-131 is contraindicated because of the risk of thyroid damage in the fetus.  The best time to do surgery for thyroid disorders is during the 2nd trimester. CHRONIC ILLNESSES IN PREGNANCY
  65. 65.  Anti-neoplastic : all of them are teratogen and should be avoided unless risk outweigh benefit. CHRONIC ILLNESSES IN PREGNANCY
  66. 66. Tocolytic Therapy  β-agonists, magnesium, Ca channel blockers, NSAIDs have similar effectiveness in prolonging pregnancy from 48 hrs to 1 week.  The β-agonists(terbutaline and ritodrine) have been used as tocolytics.(only ritodrine had FDA approval for this use but has been withdrawn from the market).  Mg sulphate: Maternal side effects are rare but can include pulmonary edema.  At toxic levels, hypotension, muscle paralysis, tetany, cardiac arrest, and respiratory depression may occur LABOR AND DELIVERY
  67. 67.  Nifedipine is associated with fewer side effects than magnesium or β-agonist therapy.One concern with the use of nifedipine is the potential negative effect on blood flow between the placenta and the uterus.  NSAIDs (such as indomethacin) have been used for tocolysis with increased rate of premature constriction of the ductus arteriosus. LABOR AND DELIVERY
  68. 68. Corticosteroids  betamethasone 12 mg intramuscularly every 24 hours for two doses or  dexamethasone 6 mg intramuscularly every 12 hours for four doses to pregnant women between 26 and 34 weeks’ gestation who are at risk for preterm delivery within the next 7 days. LABOR AND DELIVERY
  69. 69. CERVICAL RIPENING AND LABOR INDUCTION  Dinoprostone Prostaglandin E2 analogs [Prepidil gel , Cervidil insert].  Misoprostol : prostaglandin E1 analog.  Mifepristone :is an antiprogesterone agent.  Oxytocin is the most commonly used agent for labor induction after cervical ripening. Misoprostol : it is cat X and causes mobius syndrom. LABOR AND DELIVERY
  70. 70. Mobius syndrome
  71. 71. Pharmacologic Approaches to Labor Pain Management :  parenteral opioids and epidural analgesia.  parenteral Meperidine, morphine, and fentanyl are the most commonly used agents  Epidural analgesia involves introducing a catheter into the epidural space and administering an opioid and/ or an anesthetic (e.g., fentanyl and/or bupivacaine) LABOR AND DELIVERY
  72. 72.  Another method is a combined spinal– epidural, which consists of injection of a single bolus of an opioid into the subarachnoid space, providing instant pain relief, and placement of an epidural catheter with a local anesthetic.  In comparison with epidural analgesia, parenteral opioids have lower rates of oxytocin augmentation, result in shorter stages of labor, and require fewer instrumental deliveries. LABOR AND DELIVERY
  73. 73.  What are the implications of the disease itself for which the drug is to be given regarding risk of anomaly?  What are available sources of information about its use in pregnancy and its effects on the fetus? Certain questions need to be answered---
  74. 74. After looking for answers to these questions proceed by giving the following information to the woman:- medication exposure accounts for less than 1% of all birth defects. Genetic causes are responsible for 15% to 25%. other environmental issues (e.g., maternal conditions and infections) account for 10%, and the remaining 65% to 75% of congenital malformations result from unknown causes. How to proceed with counseling
  75. 75. Wisdom and knowledge are the key to good counseling and prescribing in pregnancy! fewer than 1% are due to prescribed drugs !
  76. 76. Thank you

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