PhD defence Y.H. Tran

Adverse drug reactions in the view of clinical pharmacology: a focus on the female population

The thalidomide tragedy drew significant attention to the gap between drug development and patients’ safety, notably in women. First, the pharmaco-epidemiological research of Hao Tran showed that among pregnant women, drug utilization increased with age. Those over 35 years and a history of chronic drug use were at a clear increased risk of polypharmacy and exposure to potentially harmful medications. This highlights the need to individualize preconception drug counseling for prospective mothers. Second, she examined outcomes following drug use during pregnancy, including birth defects and preeclampsia. In these studies, vascular disrupting drugs were associated with an increased risk of malformations in the exposed offspring. Prevalence rates of exposure and malformations were low and research with big data is therefore warranted. Regarding reactive-intermediate inducing drugs, increased risks to the nervous system were observed. Risks were both structural and functional, especially when the exposure occurred in critical pregnancy periods of brain development and prolonged. In addition, differential risks of antidepressants according to targeted transporters/receptors for preeclampsia were found for tricyclic antidepressants and antidepressants with 5-HT2A antagonism. This was most noticeable when these drugs were continued beyond week 20 of gestation.

Finally, Tran studied differential risks according to sex where type 2 diabetes was more frequently seen in patients treated with antidepressants. For drugs that antagonize M3 receptors, the risk of type 2 diabetes increased significantly for female users, but not in males. The findings suggest that drugs can pose differential risks in females regarding their therapeutic and adverse effects and, this needs to be addressed more in larger pharmacovigilance studies.

Promotores Prof.dr. E. Hak en Dr. H. Groen