Use of Drugs in pregnancy ppt. .

Introduction
Pregnancy is a critical period for both maternal and fetal health. The use of drugs during this time poses significant risks, potentially leading to severe complications for the unborn child. Understanding the implications of drug use, recognizing the types of substances that are particularly harmful, and exploring prevention and support strategies are crucial for ensuring a healthy pregnancy.

Impact of Drug Use on Fetal Development
1. Teratogenic Effects
Drugs that are teratogenic can cause birth defects. Teratogens are substances that interfere with the normal development of the fetus, leading to structural abnormalities. For example, certain prescription medications, recreational drugs, and even over-the-counter drugs can disrupt the formation of organs and tissues, resulting in congenital anomalies. Common examples include:

Antiepileptic Drugs (AEDs): Medications used to control seizures, such as valproic acid, can cause neural tube defects and cognitive impairments.
Isotretinoin: Used for severe acne, this drug is known to cause severe birth defects, including heart abnormalities and limb malformations.
2. Preterm Birth and Low Birth Weight
Drug use can increase the likelihood of preterm birth and low birth weight. These conditions are associated with a range of complications, including respiratory problems, developmental delays, and higher mortality rates. For instance:

Cocaine: Cocaine use during pregnancy is linked to preterm labor and placental abruption, leading to premature delivery and low birth weight.
Opioids: Opioid use can lead to neonatal abstinence syndrome (NAS), where the baby experiences withdrawal symptoms after birth.
3. Long-Term Developmental Issues
Beyond immediate physical effects, drug use can impact a child's long-term development. Research indicates that children exposed to drugs in utero may face developmental delays, learning disabilities, and behavioral issues. For example:

Alcohol: Fetal alcohol spectrum disorders (FASDs) can result in lifelong cognitive and behavioral challenges.
Methamphetamines: Exposure can lead to problems with attention, motor skills, and emotional regulation.
Types of Drugs and Their Effects
1. Prescription Medications
Some prescription drugs are safe during pregnancy, but others can be harmful. The FDA categorizes drugs into pregnancy categories based on their safety profiles:

Category A: No risk to the fetus in any trimester.
Category B: No adverse effects in animal studies, but no well-controlled studies in humans.
Category C: Risk cannot be ruled out; animal studies have shown an adverse effect.
Category D: Positive evidence of human fetal risk, but the benefits may outweigh the risks in certain situations.
Category X: Contraindicated in pregnancy; the risks clearly outweigh any potential benefits.
Examples of potentially harmful prescription drugs include:

Certain Antidepressants: Some may increase the risk of birth defects or cause withdrawal symptoms in newborns.

1. USE OF DRUGS IN PREGNANCY Dr. BK SHORAISHAM (JR 2) DEPT. OF PHARMACOLOGY GSVMMC

2. GSAHDHJ HGUGI DRUG EPIDEMIOLOGY Pregnant women and prescription/ otc drugs Birth defects General consideration

3. GSAHDHJ HGUGI DRUG DISPOSITION IN THE MATERNAL FETAL UNIT

4. GSAHDHJ HGUGI MATERNAL PHARMACOKINETICS Body fluid volume CVS parameters Pulmonary function Gastric activity Serum binding protein conc. Kidney function alterations

5. GSAHDHJ HGUGI FETAL PHARMACOKINETICS Plasma blinding proteins First pass metabolism Liver metabolising enzyme Fetal kidney

6. GSAHDHJ HGUGI PLACENTAL PHARMACOKINETICS Blood flow through placenta Transfer of flow limited drugs Compounds that alter blood flow Placental metabolism Surface area of placenta

7. GSAHDHJ HGUGI DRUG TRANSFER Molecular weight < 1000 daltons Mothers blood concentration Lipid solubility & protein binding Ionization and pH Placental blood flow and surface area

8. GSAHDHJ HGUGI DRUG TRANSFER Before the 20 th day after fertilization—All or nothing effect During organogenesis After organogenesis

9. GSAHDHJ HGUGI TIMING OF DEVELOPMENT OF MAJOR BODY STRUCTURES IN EMBRYO AND FETUS

10. GSAHDHJ HGUGI TYPES OF EFFECT Teratogenicity Long term latency—DES Predisposition to metabolic disease Impaired intellectual or social development

11. GSAHDHJ HGUGI

12. GSAHDHJ HGUGI TERATOGENESIS Structural and functional dysgenesis of the fetal organs Congenital malformations with varying severity IUGR, Carcinogenesis Fetal demise Critical time—First trimestar

13. GSAHDHJ HGUGI MALFORMATIONS Overall incidence Major—2 to 3% Minor—9% 25% are—Genetic or chromosomal abnormalities 10% are—Environmental causes including drugs 65% are—Unknown aetiology The part played by drugs is probably small

14. GSAHDHJ HGUGI ORGANOGENESIS Critical time for drug induced malformation About 20 to 55 days after conception About 34to 69 (5-10 weeks) after first day of LMP If drug given after this—not major defect but more of a functional one

15. GSAHDHJ HGUGI

16. GSAHDHJ HGUGI ANTIBIOTICS Category B Penicillin Cephalosporins Macrolides, Nitrofurantoin Metronidazole—not recommended for lactation Vancomycin (oral)—possible fetal ototoxic

17. GSAHDHJ HGUGI ANTIBIOTICS Category C Aminoglycosides (neomycin-tobramycin) Quinolones (ciprofloxacin-levofloxacin)- C/I except for when no other safe alternative antibiotic exist Trimethoprim—affect folate metabolism, C/I specially in 1 st tri Chloramphenicol—Gray baby syndrome

18. GSAHDHJ HGUGI ANTIBIOTICS Category D Aminoglycosides (streptomycin-gentamicin)— hearing deficit and 8 th CN damage Tetracycline—Permanent teeth discolouration and enamel hypoplasia

19. GSAHDHJ HGUGI ANTIVIRALS Acyclovir [B] treatment of Varicella, especially in 2 nd and 3 rd tri Amantadine [C] CHD; TOF/ Single ventricle with pulmonary atresia Anti- retro viral agents [B]— Didanosine , Etravirine, Ritonavir, Enfuviritide , Maraviroc [C]—Lamivudine, Delaviridine , Indinavir

20. GSAHDHJ HGUGI ANTIFUNGALS CATEGORY B Amphotericin B—remains the DOC for systemic fungal infections in pregnancy despite renal toxicity Terbinafine—approved for onychomycosis

21. GSAHDHJ HGUGI ANTIFUNGALS CATEGORY C Ketoconazole—inhibits placental microsomal aromatase & Cyt P-450 Fluconazole—depends on dose & duration CATEGORY X Griseofulvin—C/I, pregnancy must be avoided for 1 month after treatment

22. GSAHDHJ HGUGI ANTIMALARIAL CHLOROQUINE—DOC for prophylaxis and treatment of sensitive malaria species during pregnancy

23. GSAHDHJ HGUGI THALIDOMIDE Potent teratogen |X|-- was used for morning sickness Meromelia CHD Eye abnormalities Facial Palsy

24. GSAHDHJ HGUGI CYTOTOXIC DRUGS Methotrexate |X|; Potent teratogen, major congenital anomalies Cyclophosphamide—Chlorambucil |D| Teratogenic Growth restriction Ear and facial abnormalities Absence of digits, Hypoplastic limbs

25. GSAHDHJ HGUGI CYTOTOXIC DRUGS Azathioprine |D|; can cause birth defects Cyclosporine |C|; does not appear to be a teratogen but could cause complications like Pre eclampsia Eclampsia Oligohydramnios

26. GSAHDHJ HGUGI ANTI-INFLAMMATORY NSAIDs: Aspirin |D| in 3 rd trimester Ibuprofen |D| diclofenac, celecoxib |D| > 30 weeks Could cause Premature closure of DA

27. GSAHDHJ HGUGI ANTICONVULSANTS Phenytoin, Carbamazepine |D|; potent teratogen Fetal Hydantoin syndrome (5 to 10%) IUGR Cranio facial anomalies Developmental delay Mental retardation

28. GSAHDHJ HGUGI ANTICONVULSANTS Valproic acid |D| NTD Cognitive impairment Dysmorphic features Risk of autism

29. GSAHDHJ HGUGI DIETHYLSTILBESTROL Human teratogen |X| Vaginal adenosis Cervical erosions Transverse vaginal ridges Vaginal adenocarcinoma

30. GSAHDHJ HGUGI VITAMIN A ANALOGUES Isotretinoin |X|; potent teratogenic Severe birth defects Neuropsychiatric impairment Spontaneous abortion Premature birth Fetal death

31. GSAHDHJ HGUGI ANTICOAGULANTS Warfarin |X/D| for women with mechanical heart valve who are at risk of thromboembolism 1 st tri— fetal warfarin syndrome 2 nd / 3 rd tri—optic atrophy, cataracts microcephally , microphthalmia intellectual disability, fetal and maternal hemorrhage

32. GSAHDHJ HGUGI ANTICOAGULANTS Heparin—Low mol.wt |B| unfractionated |C| For venous thromboembolism in preg Do not cross placenta

33. GSAHDHJ HGUGI CARDIOVASCULAR DRUGS ACE inhibitors, ARBs—C/I , |C| in 1 st tri, |D| in 2 nd and 3 rd Prenatal exposure in 2 nd /3 rd tri— fetal BP↓ Renal failure Oligohydramnios– fetal growth restriction joint contractures, pulmonary hypoplasia stillbirth or neonatal death

34. GSAHDHJ HGUGI CARDIOVASCULAR DRUGS Beta blockers |C| Fetal bradycardia Hypoglycaemia Possibly fetal growth restriction

35. GSAHDHJ HGUGI CARDIOVASCULAR DRUGS Amiodarone—cat |D|; given when there are no alternatives and benefit outweighs risk CCB—cat |C|; 1 st tri—pharyngeal deformities 2 nd and 3 rd tri— fetal growth restriction Methyldopa—Cat |B|

36. GSAHDHJ HGUGI CARDIOVASCULAR DRUGS Thiazide diuretics Cat |D| Neonatal hyponatremia, hypokalaemia, thrombocytopenia Statins—Cat |X| Must be avoided Congenital anomalies reported

37. GSAHDHJ HGUGI INSULIN AND HYPOGLYCEMIC DRUGS Insulin is the DOC for diabetes in pregnancy Neonates born to mothers taking OHA during pregnancy may have hypoglycemia Metformin is FDA cat |B|

38. GSAHDHJ HGUGI PROGESTERONE Danazol, synthetic progestin (not the low dose used in OCP) when given during 1 st 14 weeks—masculinization of female fetus genitals. Cat |X| Progestin exposure—increased prevalence CVS abnormalities Combined OCPs in early stages of unrecognised preg —Believed to be Teratogenic agents

39. GSAHDHJ HGUGI ANTITHYROID DRUGS Carbimazole, propylthiouracil (PTU) Both cross placenta, may cause fetal hypothyroidism in high doses PTU is preffered for new cases as less transfer across placenta occurs

40. GSAHDHJ HGUGI CORTICOSTEROIDS Cat |B| 1 st trimester—orofacial clefts possible Hydrocortisone and prednisolone— metabolized (90%) by placental dehydrogenase Betamethasone and dexamethasone—are not, DOC when fetus is the aim of therapy, fetal lung maturation

41. GSAHDHJ HGUGI GI DRUGS Omeprazole—does not seem teratogenic, less known about other PPIs during pregnancy Ranitidine—crosses placenta, manufacturer advises to avoid during pregnancy, epidemiological studies revels no increased adverse fetal outcome, Rodent teratogenicity Metoclopramide—cat |B|

42. GSAHDHJ HGUGI BENZODIAZEPINES Cat |D| BZD with long t ½ in late pregnancy—neonatal respiratory depression, poor temp. regulation, poor feeding, hypotonicity Neonatal withdrawal symptom & craniofacial anomalies Avoid regular uses unless there is clear indication like seizure control

43. GSAHDHJ HGUGI LITHIUM FDA cat |D| Neonatal lethargy, hypotonia, poor feeding, hypothyroidism, goiter , nephrogenic DI In early preg — Ebstein’s anomaly DERMATOLOGICAL AGENTS Based on large population based studies, topical corticosteroids-safe in any stage of preg

44. GSAHDHJ HGUGI SSRI Fluoxetine—cat |C|; lowest risk in preg Paroxetine—cat |D| SSRI in early preg —increased risk of CHD Third tri—neonatal withdrawal syndrome, persistant pul HTN in the newborn SSRI must not be indicated unless potential benefit outweigh risk

45. GSAHDHJ HGUGI TCA Amitryptyline , imipramine, nortrptyline —lower risk than other newer antidepressants OPIOIDS Cat |C| In neonates of opioid addicted women, withdrawal symptoms occurs possibly 6h to 8hrs after birth High dose before delivery—neonatal CNS depression, Brady

46. GSAHDHJ HGUGI RESPIRATORY DRUGS No convincing evidence that any of the drugs commonly used for respiratory disorder cause particular problems during preg Pseudoephidrine —risk of gastroschisis, |C| Loratadine—Possible risk of hypospadias, |B|

47. GSAHDHJ HGUGI VACCINES Killed, toxoid, recombinant vaccines given Live attenuated vaccines (varicella, measles, mumps, polio and rubella) should be given 3 months before preg or post partum Live vaccines are C/I secondary to potential fetal infection risk Covid19 vaccine

48. GSAHDHJ HGUGI SMOKING Carbon monoxide and nicotine in cigarettes causes hypoxia and vasoconstriction, increasing risk of spontaneous abortion, fetal growth restriction, abruptio placenta, placenta previa, PROM, preterm delivery, chorioamnionitis, stillbirth

49. GSAHDHJ HGUGI SMOKING Neonates whose mothers smoke are also more likely to have anencephaly, CHD orofacial clefts, SIDS, deficiencies in growth and intelligence, behavioural problems Smoking during preg — linked to childhood asthama

50. GSAHDHJ HGUGI ALCOHOL Increased risk of spontaneous abortion ↓ birth wt. by 1 to 1.3 kg if regular drinking Binge drinking— fetal alcohol syndrome fetal growth restriction, facial and CVS defects, neurological dysfunction, vision or hearing problems, behavioural and intellectual disabilities Neonatal death due to failure to thrive

51. GSAHDHJ HGUGI ASPARTAME (artificial sweetner ) Most common metabolite, phenylalanine, is concentrated in the fetus by active placental transport Its toxic level may cause intellectual disability If in usual range (no more than 1 litre of diet soda/day) appears to pose little risk of fetal toxicity

52. GSAHDHJ HGUGI THANK YOU