TERATOGENICITY AND DRUGS AFFECTING THE FETUS (Part four)

6 - NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)

- Various studies have shown that they do not have teratogenic effects but only show some side effects during their use in pregnancy.

- Indomethacin is used for the treatment of rheumatoid arthritis, ankylosing spondylitis, and osteoarthritis.

- It reversibly inhibits the activity of the enzyme cyclo-oxygenase necessary for the synthesis of prostaglandins, prostacyclins, and thromboxane, unlike aspirin which inhibits the enzyme irreversibly.

- This drug in therapeutic doses does not cause teratogenic effect in the first trimester of pregnancy.

- At high doses above 100 times the therapeutic dose, the following have been observed: fusion of ribs and other skeletal anomalies, incomplete virilization of the male genital organs, hypospadias, ovarian hyperstimulation syndrome.

- Use in the third trimester of pregnancy (after week 32) increases the risk for various complications including closure of the ductus arteriosus, tricuspid regurgitation, cardiac insufficiency, hydrops, pulmonary hypertension, renal dysfunction, necrotizing enterocolitis, interstitial perforation, intracranial hemorrhage, cystic lesions in the brain.

- Maternal side effects include: gastrointestinal bleeding and perforation, acute reversible renal failure, interference in renal excretion of water, sodium, potassium, interstitial nephritis, nephrotic syndrome, interference in diuretic and antihypertensive therapy, interference in platelet function and masking the signs of an occult chorioamnionitis.

7 - ANTIMICROBIALS

- Many antimicrobial agents are capable of crossing the placental barrier and causing various problems.

- The problems caused depend on the time of exposure.

- The preconception period is important for both men and women. The use of medications in the first 7 days of conception leads to an all-or-nothing effect on the fertilized egg, resulting in the death of the embryo or in its complete regeneration and normal development.

- After implantation, 14 days later, the differentiation of the embryo begins. During this period, the use of unnecessary medications should be avoided as it is the most critical period for congenital anomalies.

- The second and third trimesters of pregnancy have a low risk for structural anomalies and a high risk for metabolic disorders.

- During the breastfeeding period, many medications pass into breast milk but do not have side effects on the fetus in therapeutic doses. They cause problems in high doses and in a premature fetus.

A-Aminoglycosides

- There is limited and uncertain data regarding transplacental passage and the safety doses of aminoglycosides use.
- The medications included in this group are: gentamicin, streptomycin, amikacin, tobramycin, kanamycin.
- Only gentamicin is included in category C, the others are included in category D of medications.
- These medications should be avoided during pregnancy due to the risk of ototoxicity and nephrotoxicity.

B-Tetracycline

- Included in category D of medications.
- It easily crosses the placental barrier and is deposited in growing bones and disrupts their longitudinal development, causing hypoplasia and yellow discoloration of bones and teeth.
- When taken in high doses, it causes liver degeneration and pancreatitis in the pregnant woman.

C-Fluoroquinolones

- Included in category C of medications.
- Should not be used during pregnancy, especially in the first trimester of pregnancy.
- Causes various effects on the musculoskeletal system.

D-Chloramphenicol

- Included in category C of medications.
- During pregnancy, it causes serious side effects in blood (up to aplastic anemia) and gray baby syndrome (vasomotor collapse, hypothermia, cyanosis, fetal gray discoloration).