drugs in pregnancy
DESCRIPTION
drugs safety in pregnancy medications medication in pregnancy treatment during pregnancy healthy pregnancy teratogen teratogenecity teratogenic drugs in pregnancy drugs and congenital malformationTRANSCRIPT
الرحيم الرحمن الله بسمDrugs in pregnancy
Ahmad abdul kareem
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
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. 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
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
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
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.
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
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
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
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
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
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
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
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
PREGNANCY-INFLUENCED ISSUES
ACUTE CARE ISSUES IN PREGNANCY
CHRONIC ILLNESSES IN PREGNANCY
LABOR AND DELIVERY
Therapy needed in pregnancy due to
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
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
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
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
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
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
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
Side effect of warfarin
PREGNANCY-INFLUENCED ISSUES
Alternative regimen:
Beginning of pregnancy
Heparin product
13 wks change to
warfarinMiddle of 3rd trimester return to
Heparin product6 wks post
partum
High-risk women with prosthetic heart valves may also receive aspirin therapy in
doses of 75 to 162 mg/day
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
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
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
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
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.
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
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
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
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
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
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
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
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
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
Antiparasitic agents: all of them are cat C except nitazoxanide wich is cat D.Anthelminthic agents: praziquantel cat BAlbendazole, mebendazole , ivermectin cat CDiethylcarbamazine cat X
ACUTE CARE ISSUES IN PREGNANCY
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
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
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
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
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
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
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
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
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
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
Cardiovascular diseasesHYPERTENSION 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
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
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
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
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
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
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
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
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
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
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
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
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
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
Anti-neoplastic : all of them are teratogen and should be avoided unless risk outweigh benefit.
CHRONIC ILLNESSES IN PREGNANCY
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
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
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
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
Mobius syndrome
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
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
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---
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
Wisdom and knowledge are the key to good counseling
and prescribing in pregnancy!
fewer than 1% are due to prescribed drugs !
Thank you