11 Jun Let’s explore the mysterious connection between pre-eclampsia, teratogenicity, and pharmacology for your medical licensing exams, such as USMLE Step 1, USMLE Step 2CK, USMLE Step 3, MCCQE-1, or any other medical licensing exams!
Here we go …
A female patient, aged 21 and in her 20th week of gestation, presented with hypertension and proteinuria. She has a medical history of pre-eclampsia in her first pregnancy. Her mother was diagnosed with hypertension in her fourth decade, while her father and five siblings, including a twin sister, were healthy. The patient has no history of smoking or alcohol consumption and is not taking any regular medications, health products, or herbs. Baseline laboratory investigations revealed normal renal and liver function with normal serum urate concentration. Random glucose was 3.8 mmol/l. Urine protein indicated mild proteinuria with a protein:creatinine ratio of 40.6 mg/mmol (normal range <30 mg/mmol in pregnancy). Considering the clinical scenario presented, which medication would be a viable option to manage hypertension in this patient?
A. Hydralazine
B. Atenolol
C. Lisinopril
D. Losartan
E. Enalapril
F. Captopril
Take a few moments to contemplate the question and select the appropriate answer…
Pause for a moment to mull over the puzzle. Sort through your thoughts, ditch the crazy ideas, and focus on what clicks. Trust your instincts, make a savvy move, and voilà! You’ve got this in the bag!
Consistent practice and a curious mind are the keys to mastering any topic.
Here we go.
Let’s verify if we have the correct answer …
“Correct answer: Hydralazine”
Hydralazine is a medication that is now considered the first line of therapy for treating acute severe hypertension in pregnancy. This medication functions as a direct arteriole vasodilator, although its precise mechanism of action is not yet fully understood. Researchers have theorized that it is linked to intracellular calcium homeostasis. Specifically, hydralazine inhibits inositol trisphosphate (IP3)-induced calcium release from the sarcoplasmic reticulum of smooth muscle cells. It inhibits myosin phosphorylation in arterial smooth muscle, leading to a reduction in peripheral vascular resistance. This, in turn, triggers a baroreceptor-mediated release of epinephrine and norepinephrine, resulting in increased venous return and cardiac output. The liver metabolizes Hydralazine and undergoes polymorphic acetylation. While it is an effective medication, it can also cause a range of side effects, such as headaches, nausea, flushing, hypotension, palpitations, tachycardia, dizziness, and angina. It may also lead to more severe adverse reactions such as drug-induced lupus erythematosus (DILE), serum sickness, hemolytic anemia, vasculitis, and glomerulonephritis. Hydralazine-related DILE is generally seen with exposure greater than six months, and the syndrome typically manifests with arthralgias, myalgias, serositis, and fevers.
Feedback:
– Atenolol should never be considered a drug for hypertension in pregnancy since it may cause low birth weight. It also causes neonatal bradycardia.
– Lisinopril: the use of angiotensin-converting enzyme (ACE) inhibitors during pregnancy has been linked to unfavorable neonatal outcomes, potentially resulting in fetal renal dysfunction. The underlying pathophysiology of this renal dysfunction is believed to be associated with fetal hypotension and the prolonged reduction in glomerular filtration.
– Losartan is a teratogenic drug. There have been several reports indicating that its use during pregnancy can lead to fetal pulmonary hypoplasia, oligohydramnios (reduced amniotic fluid), fetal hypoplastic skull bones, and subsequent fetal death. These fetal toxic effects are similar to the ones caused by exposure to angiotensin-converting-enzyme (ACE) inhibitors during pregnancy.
– Enalapril and Captopril are drugs that have teratogenic properties. In a study conducted on baboons, it was observed that the group treated with enalapril experienced a significant increase in fetal death or fetal growth restriction as compared to the placebo group. Similarly, the use of captopril in maternal sheep during late pregnancy resulted in low fetal blood pressure and substantially elevated the risk of stillbirth. Therefore, it is contraindicated to use these drugs during pregnancy to ensure the safety of the fetus.
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