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Cardiovascular Drugs during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Coumarin derivatives, including warfarin, are contraindicated for use during pregnancy. The fetal warfarin syndrome is comprised of skeletal and brain defects. Use after the first trimester includes brain and eye defects, and other anomalies associated with vascular disruption. Among 169 infants who received warfarin during the first trimester, six infants had severe birth defects (cleft lip/palate, aortic anomaly, hydrocephaly, VSD, musculoskeletal malformation) (Kallen, 2019). The frequency of ‘fetal warfarin syndrome’ was increased among 8 of 27 infants whose mothers used coumarin during the first trimester (Iturbe-Alesio et al., 1986). Among 58 infants whose mothers took warfarin during “early pregnancy,” three infants had major birth defects, and two were diagnosed with warfarin embryopathy (Vitale et al., 1999). The rate of warfarin embryopathy was estimated to be 7 percent (Hoyer et al., 2010).
Plant Source Foods
Published in Chuong Pham-Huy, Bruno Pham Huy, Food and Lifestyle in Health and Disease, 2022
Chuong Pham-Huy, Bruno Pham Huy
Due to its exotic flavor and hot taste, cinnamon is used as a culinary spice and also a traditional medicine since antiquity. In traditional medicine, cinnamon is used in the treatment of respiratory and digestive ailments, as a stimulant, and as an anointment since antiquity (246). Recently, many experimental and clinical trials have explored its antimicrobial, anti-inflammatory, antidiabetic, antioxidant, antilipemic, and cognition enhancer effects for the treatment of infection, diabetes, depression, hypercholesterolemia, and Parkinson’s disease (246–248). However, Cassia cinnamon (Chinese cinnamon) contains high levels of coumarins, about ten times more than Ceylon cinnamon. Coumarin is toxic to the liver in high doses. Therefore, its addition into food products is prohibited. Due to a lack of awareness regarding the standard limits of cinnamon in these products, it is advisable for patients of hepatic disorders to avoid cinnamon (246). In addition, a daily intake of coumarin more than 0.1 mg/kg body weight can lead to conspicuous effect on the blood coagulation profile if the patient is simultaneously on drugs such as warfarin. However, these results are still contradictory (246). So, it is recommended not to take a lot of pure cinnamon product or supplement. High intake of cinnamon can cause liver damage, mouth sore, cancer, hemorrhage, and breathing problems.
Venous Thromboembolism and Anticoagulation
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
In a review, VKAs throughout pregnancy was the regimen associated with the lowest risk of valve thrombosis/systemic embolism (3.9%); using UFH only between 6 weeks and 12 weeks’ gestation was associated with an increased risk of valve thrombosis (9.2%) [110]. This analysis suggests that VKAs are more efficacious than UFH for thromboembolic prophylaxis of women with mechanical heart valves in pregnancy; however, coumarins increase the risk of embryopathy. In the first trimester coumarin is associated with a 10–15% teratogenic risk (nasal hypoplasia, optic atrophy, digital anomalies, mental impairment). European experts have recommended warfarin therapy throughout pregnancy in view of the reports of poor maternal outcomes with heparin and their impression that the risk of embryopathy with coumarin derivatives has been overstated [111]. If coumarin is used, the dose should be adjusted to attain a target INR of 3.0 (range 2.5–3.5).
Intestinal epithelial damage due to herbal compounds – an in vitro study
Published in Drug and Chemical Toxicology, 2023
Susan M. Britza, Ian F. Musgrave, Rachael Farrington, Roger W. Byard
Coumarin is an aromatic organic compound found in hundreds of plant species and herbal products, most commonly in Apiaceae, Asteraceae, Clusiaceae, Lamiaceae, Oleaceae, Rutaceae and Thymelaeaceae families. Of particular note are common traditional and modern herbal medicines which contain high concentrations of coumarin compounds including Uncaria tomentosa (Willd.) DC (Cat’s Claw), Lawsonia inermis L. (Henna), Aeasculus hippocastanum L. (Horse-chestnut), and controversial Hypericum perforatum L. (Saint John’s Wort) (Matos et al.2015). Due to an abundance of coumarin compounds in nature and a high likelihood of dietary exposure, extensive research has been carried out into its toxicological properties (Fentem et al.1992, Loprinzi et al.1997, Lacy and O’Kennedy 2004, Tanaka et al.2016), and though human toxicity is rare, clinical presentations are often associated with hepatotoxic effects (Cox et al.1989, Egan et al.1990). This is largely due to the coumarin toxic metabolite o-hydroxyphenylacetaldehyde (o-HPA). Metabolism of coumarin is predominantly through cytochrome P450 enzymes, particularly CYP2A6 and CYP3A4, to form nontoxic 7-hydroxycoumarin and 3-hydroycoumarin respectively, and CYP2E1 and CYP1A1–2 forming non-reactive 3, 4-epoxide; o-HPA is formed from the intermediate metabolite, 3, 4-epoxide (Born et al.2000). Hence, the metabolism of coumarin is key to associated cases of toxicity.
Research progress of coumarins and their derivatives in the treatment of diabetes
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Yinbo Pan, Teng Liu, Xiaojing Wang, Jie Sun
At present, the hypoglycaemic agents in clinical use include incretin4–10 and insulin sensitizers11–14. In addition, there are other types of substances used to lower blood glucose, such as AMP-activated protein kinase AMPK15, α-glucosidase inhibitors16, amylases, and insulin analogues17. However, among the many marketed drugs, there are more or less some side effects while lowering blood glucose (Figure 1). Therefore, there is an urgent need to discover new drugs to compensate for or replace the shortcomings of current drugs. In recent years, more and more attention has been paid to the study of natural products. Coumarin compounds stand out in the process of drug research and development because of their advantages of multiple targets and less toxic side effects.
Implications for herbal polypharmacy: coumarin-induced hepatotoxicity increased through common herbal phytochemicals astragaloside IV and atractylenolide I
Published in Toxicology Mechanisms and Methods, 2022
Susan M. Britza, Ian F. Musgrave, Roger W. Byard
Coumarin-induced hepatotoxicity has been investigated previously in animal models and humans (Fetner et al. 1992; Loprinzi et al. 1997; Tanaka et al. 2016). Of note are several papers indicating that coumarin cytotoxic effects are metabolism dependent (Vassallo et al. 2004; Tanaka et al. 2016). In 2000, an in vitro study investigating the formation of o-hydroxyphenylacetaldehyde (o-HPA), it was shown that coumarin is metabolized by CYP enzymes, specifically CYP3A4 and CYP2E1/1A1-2, to produce toxicologically reactive metabolites 3-hydroxycoumarin and o-HPA, respectively, which are detoxified through glutathione conjugation. Nevertheless, substantial quantities of coumarin are required for toxic levels and it was suggested that toxicity would be rare in humans (Born et al. 2000). However, coumarins are common in many dietary and herbal supplements but are also found abundantly in many fruits, vegetables, nuts, seeds, wine, coffee, and teas (Stefanachi et al. 2018). Hence, more recent reviews of hepatotoxicity in patients treated with coumarin and hepatotoxicity from dietary intake suggested a reasonable level of risk and resulted in the definition of a lower tolerable dose of coumarin (0.1 mg/kg) (EFSA 2008).