25. DRUG USE IN OBSTETRICSsssssss 2.pptx

DRUG USE IN OBSTETRICSsssssss 2.

1. Adegboyega A Fawole MBBS(Ilorin). FWACS Professor of Obstetrics & Gynaecology SPECIAL ASPECTS OF OBSTETRICS PHARMACOLOGY

2. Presentation Layout Introduction Pharmacokinetics Teratogens Medications, Alcohol, Illicit drugs Summary

3. Why is it important?

4. More than 90% of pregnant women take drugs, use social drugs, illicit drugs or traditional drugs in pregnancy. Very few drugs have proven safety in preg. About 2-3% of all congenital birth defects are drugs induced(other than alcohol).

5. But, drugs are very essential sometimes for the health of the mother and the fetus Prescribing drugs in preg involves balancing the benefit to the mother and harm to fetus. as such prescribe only well known and tested drugs at the smallest possible doses only when benefit outweighs the risk.

6. AND………….. Chronic conditions require ongoing therapy Benefits outweigh risk

7. Development of the fetus

8. Pharmacokinetics in pregnancy Absorption Decreased gastric emptying Decreased intestinal motility Affects the rate and extent of drug absorption Distribution Increased plasma volume and extracellular fluid Increased body fat distribution Decrease in albumin

9. Metabolism Liver metabolism is altered Increased drug elimination Renal Excretion Renal plasma flow increases Increased renal elimination

10. Placental Transfer Diffusion from high to low concentration Rate of transfer: A - concentration gradient B - thickness & surface area of the membrane C - diffusion constant = K

11. The rate of drug crossing is also dependent on The chemical properties of the drug - protein binding, lipid solubility, molecular weight, pH difference etc Increased placenta surface as pregnancy advances, highest in the 3rd trimester

12. A-The dose absorbed by the mother B-The period of gestation The effect of a drug on the fetus:

13. Classification of Drugs/Medication

14. Drugs commonly used in pregnancy Asthma Most medications are safe during pregnancy Inhalers, systemic steroids, theophyllin NSAIDs Non teratogenic but may effect renal function in the offspring and persistent fetal circulation Antiemetics Benedectin, metoclopramide, piperazine, prochlorperazine.

15. Drugs commonly used in pregnancy Antibacterial agents Category B Category C Category D Azithromycin Cephalosporins Erythromycin Nitrofurantoin Penicillins Sulfonomides Aminoglycloside Chloroquine Fluoroquinolones Imipenem Quinolones Trimethoprim Vancomycin Aminoglycloside Tetracyclines

16. Drugs commonly used in pregnancy Antivirals/Antiprotozoals/Antifungals Category B Category C Category D Didanosine (ddl) Lindane Amphoterisine Nystatin Acyclovir Ganciclovir Zidovidine Stavudine (d4T) Mebendazole Pyrantel Fluconazole Miconazole Quinine

17. Antimalarials. Chloroquine and quinine are safe in all trimesters. Artemesinin drugs, safety in 1 st trimester is doubtful. Sulphadoxine –pyrimethamine shld be avoided in the 1 st trimester.

18. Drugs commonly used in pregnancy Cardiovascular drugs Category B Category C Category D Low molecular weight heparin Local anaesthetic antiarrhytmics Urokinase Adenosine ß blockers Calcium antagonists Digoxin Furosemide Heparin Methyldopa Streptokinase ACE inhibitors Amioderone Warfarin Thiazides

19. Drugs commonly used in pregnancy Psychiatric drugs Category B Category C Category D SSRI’s Clozapine Clomipramine MAO Chlorpromazine Haloperidol Perphenazine Thioridazine Clonazepam Lorazepam Oxazepam Amitriptyline Imipramine Alprazolam Midazolam

20. Teratogens Word root: “ terato- ” = monster “ -gen ” = to make

21. Teratogens Any substance that acts during embryonic or fetal development to produce a permanent alteration of form or function is known as a teratogen Permanent alteration of form or function Defect must be completely characterized

22. Thalidomide ONE OF THE BIGGEST MEDICAL TRAGEDIES OF MODERN TIME

23. Thalidomide Hypnotic/sedative used in leprosy and TB treatment and also to treat nausea in 1 st trimester Teratogenic effect day 27 – 42 Phocomelia: absence of long bones, external ear and nose abnormalities and heart defects

24. Retinoids (Vit A, isotretinoin) Essential nutrient Acne/ Psoriasis treatment - roaccutane Microtia, anotia, micrognathia, cleft palate, heart defects, eye abn, hydrocephalus, thymic agenesis, limb reduction defects

25. Exposure in 6 th -9 th week results in nasal hypoplasia and stippled vertebral and femoral epiphysis Agenesis of corpus callosum, Dandy Walker, cerebellar atrophy, microopthalmia, optic atrophy, blindness, mental retardation Haemorrhage Warfarin Embryopathy Exposure in 2 nd and 3 rd trimester: dysharmonic growth and deformation from scarring

26. Warfarin Embryopathy

27. Anticonvulsants Valproic acid, Phenytoin, Carbamazepine Most frequent abnormalities include orofacial clefts and congenital heart defects Major malformations Minor malformations Congenital heart defects Mental subnormality Oral facial clefts Hypertelorism Neural tube defects Palmar creases Microcephaly Digital hypoplasia

28. Known teratogens(cont) Tetracycline Cosmetic and transient Yellow- brown discoloration of deciduous teeth Hypoplasia of enamel  dental caries ACE inhibitors Enalapril in particular Oligohydramnios, renal anomalies, neonatal renal failure, pulmonary hypoplasia, hypocalvaria and growth restriction

29. Known teratogens(cont) Lithium Associated with severe cardiovascular anomalies Ebstein’s anomaly Penicillamine Used in rheumatoid arthritis Associated with connective tissue disorders in the offspring

30. Other teratogens Antineoplastics Most are teratogenic Methotrexate and Aminopterine (folate antagonists) Cyclophosphamide (alkylating agent) Associated with cranio facial abnormalities: Hydrocephalus, hypertelorism, micrognathia, cleft palate, craniosynostosis

31. Known teratogens (cont)

32. Testosterone/anabolic steroids/ androgenic progestins/ danazol Masculinization of female fetus: labioscrotal fushion phallic enlargement At puberty: female maturation surgery to correct genitalia Androgens

33. Diethylstilbestrol(DES) – 1940-1971 given to “support” high risk pregnancies Female offspring Male offspring Clear cell carcinoma of vagina/cervix Epididymal cyst Vaginal adenosis Hypoplastic testis T-shaped uterus Cryptorchidism Uterine hypoplasia Paraovarian cysts Incompetent cervix Estrogens

34. Immunisation during pregnancy Vaccines : a suspension of dead or attenuated live micro-organisms or fractions thereof (esp viruses) Toxoids : modified bacterial toxins rendered non toxic but still able to stimulate antibody formation and activity Immunoglobulins : antibody containing derivatives of pooled human serum Antitoxins : antibody containing preparations form pooled serum of animals immunised with specific antigens

35. Dangers of immunisations Local reaction Hypersensitivity Transport of live virus to the fetus

36. Vaccines during pregnancy Live vaccines In general contraindicated Virusses : Rubella, Measles, Mumps, Varicella Zoster Bacteria : Typhoid, Polio, Yellow fever Inactivated & activated vaccines Same as for non pregnant: Rabies, Hepatitis A & B, Pneumococcal, Meningococcal, Hemophilus

37. Vaccines in pregnancy Toxoids DPT: inadequately immunised or no booster in last 10 years or non immune Hyperimmune globulins Post exposure prophylaxis : Hepatitis B, rabies, tetanus, varicella Pooled immune serum globulins Post exposure prophylaxis : Hepatitis A, Measles

38. Vaccines. Live vaccines e.g rubella, varicella are not given in pregnancy. Vaccines like TT, Cholera, Diptheria, Hepatitis A and B, Rabies can be given if there is substantial risk of developing the infection.

39. Illicit Drug Use in Pregnancy

40. Substance abuse Multiple drugs, incl. alcohol and tobacco Poor antenatal care Poor pre-pregnancy health Inadequate nutrition Impurity of street drugs

41. Alcohol Chronic large volume drinkers as well as binge drinkers Exposure dose not been established Associated with fetal alcohol syndrome

42. Effects of Alcohol in pregnancy Brain defects Cardiac defects Spinal defects Growth restriction Behavioural problems

43. Fetal Alcohol Syndrome

44. Range of substances used Extensively used: Alcohol, Dagga, Dagga-Mandrax mixture (white pipe), Over-the-counter preparations – benzodiazepines, slimming tablets Moderately used: Crack cocaine, cocaine, heroin, speed, LSD, Ecstasy Less frequently used: Opium, rohypnol

45. Substances in pregnancy Tobacco No real teratogenic effect. Some association with cleft palate Increase in infertility, first trimester miscarriage, abruptio placenta, preterm labour, IUGR, SIDS and ADHD Marijuana No associated anomalies Low birth weight and developmental problems

46. Substances in pregnancy Amphetamines Cleft palate, exencephaly and eye defects in rats Congenital heart disease, biliary atresia and limb reduction defects in humans Methamphetamines Symmetrical growth restriction Developmental problems

47. Substances in pregnancy Cocaine Effects due to vasoconstriction Skull defects, cutis aplasia, porencephaly, ileal atresia, cardiac anomalies, viceral infarcts, limb reduction defects, prune belly syndrome, SB, withdrawal Heroin Growth restriction and developmental problems Withdrawal

48. CAFFIENE: Is not clear weather it has any effects with a cup / day. Taking of >7cups/day there is increase risk of IUFD, preterm labor, LBW and miscarriage. It may cross placenta, stimulate the fetus and causes tachycardia. May lead to reduced placenta blood flow.