Cefotiam, Cefuzonam, Cefamandole, Cefonicid, and Ceforanide
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Cefamandole can cause hypoprothrombinemia and bleeding. Parenteral vitamin K therapy rapidly reverses the abnormality, suggesting that cefamandole interferes with its synthesis or action. This is probably not due to antibiotic-induced killing of intestinal bacteria, because in humans the production of vitamin K by these bacteria does not play any role in the synthesis of clotting factors (Smith and Lipsky, 1983). Data from animal studies do not suggest that these antibiotics act directly on vitamin K–dependent enzymes (Uotila and Suttie, 1983). Cefamandole contains an N-methylthiotetrazole side chain. This side chain, released by In vivo degradation of the drugs, inhibits gamma-carboxylation of glutamic acid, which is necessary for the synthesis of prothrombin. Patients with renal failure may be at more risk of bleeding because in renal failure this side chain accumulates to a greater degree than cefamandole itself (Aronoff et al., 1986). Other factors are also involved in production of hypoprothrombinemia. Most reported cases of cefamandole-induced hypoprothrombinemia have occurred in elderly, debilitated, and/or malnourished patients. This suggests that preexisting vitamin K deficiency, or some other factor, must be present for cefamandole to produce this effect. It has been advised to give prophylactic parenteral vitamin K when cefamandole is used in such patients (Bailey, 1983; Smith and Lipsky, 1983).
Therapeutic Use of Carbonic Anhydrase Inhibitors and Their Multiple Drug Interactions
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
Indisulam (E7070) is another small molecule as anticancer agent that is currently being evaluated in phase II clinical studies (Haddad et al., 2004). The precise mechanism of action has not been determined, since it showed multiple mechanisms of action such as inhibitor of hCA IX and XII (Supuran, 2003) and multiple cell-cycle checkpoints (Ozawa et al., 2012) Also for this compound there are few reports regarding the interactions of these agents with other drugs. A phase I clinical trial reported the excessive hematological toxicity with relatively high exposure to carboplatin (Dittrich et al., 2007). In addition, the plasma protein binding of acenocoumarol was reduced at higher concentrations of E7070. This is caused by potential inhibition of cytochrome CYP2C9 that is the major enzyme involved in the metabolism of acenocoumarol. This could be lead to hypoprothrombinemia (van den Bongard et al., 2004).
Patty
Walter J. Hendelman, Peter Humphreys, Christopher R. Skinner in The Integrated Nervous System, 2017
The diagnosis of hepatic encephalopathy is made on clinical grounds, with the support of simple laboratory tests. Our patient’s story is characteristic: a long history of chronic alcoholism and documented liver disease; a period of increasing confusion and intermittent agitation followed by coma, evidence of portal-systemic shunting (periumbilical venous tortuosity, splenomegaly, GI bleeding, spider nevi, palmar erythema) and evidence of hepatocellular dysfunction (jaundice, peripheral edema). As will be seen in the next section, she also demonstrated a typical collection of biochemical abnormalities including hyperammonemia, low blood urea concentration, hyperbilirubinemia and hypoalbuminemia. Many patients also have hypoprothrombinemia, another hepatocellular synthetic defect, and may have pathological bruising.
Helicobacter pylori antibiotic eradication coupled with a chemically defined diet in INS-GAS mice triggers dysbiosis and vitamin K deficiency resulting in gastric hemorrhage
Published in Gut Microbes, 2020
Lisa Quinn, Alexander Sheh, Jessie L Ellis, Donald E Smith, Sarah L Booth, Xueyan Fu, Sureshkumar Muthupalani, Zhongming Ge, Dylan A Puglisi, Timothy C Wang, Tamas A Gonda, Hilda Holcombe, James G Fox
MKn composition was markedly different in antibiotic-treated groups where there was a 13.8% decrease in MK6 abundance and a 12.1% increase in MK11 abundance (Figure 4(c–f)). As an increase of similar magnitude in MK11 was observed in healthy mice on chow diet (Figure 4(f)), we focused on the large decrease in MK6 in antibiotic-treated mice on AAD diets. While bacterially derived MKn alone may not be sufficient to improve all blood coagulation metrics,51 Akiyama et al. were able to show differences in liver absorption and coagulation activity based on the number of prenyl units of MKn in a rat model of hypoprothrombinemia.49 In this model, hypoprothrombinemia was induced via a vitamin K-deficient diet and warfarin, leading to undetectable MKn levels in both plasma and liver. MK1-14, as well as MD, was administered orally or intravenously to hypoprothrombinemic rats. MK4, MK5, and MK6 increased hepatic MKn levels and markedly improved hypoprothrombinemia. MK7 and MK8 slightly improved coagulation activity, but the remaining MKn, including MK11, provided no improvement in coagulation activity.49
Congenital prothrombin defects: they are not only associated with bleeding but also with thrombosis: a new classification is needed
Published in Hematology, 2018
Antonio Girolami, Silvia Ferrari, Elisabetta Cosi, Bruno Girolami, Anna Maria Lombardi
Prothrombin deficiency is one of the rarest coagulation disorders with a prevalence of about 1:1.500.000 [1–3]. The defect is usually classified in Type I in which there is a concomitant decrease of prothrombin activity and antigen and in Type II in which prothrombin activity is low, whereas antigen is normal or near normal. The first type is also known as ‘True’ deficiency or hypoprothrombinemia, whereas the latter is known as dysprothrombinemia. Association of hypoprothrombinemia with dysprothrombinemia (hypo-dysforms) has also been described. The same is true for the combination between two dysprothrombinemias (dys-dysforms) [1–3].
Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study
Published in Expert Opinion on Drug Safety, 2020
Wen Wang, Yanmei Liu, Chuan Yu, Jing Tan, Weiyi Xiong, Duo Dong, Sheyu Li, Rui Zhang, Jijie Li, Yu Wu, Zhiyong Zong, Na Su, Kang Zou, Guizhi Wu, Xin Sun
The proportion of PT prolongation among patients treated with antibiotics containing cefoperazone varied between studies (range: 4–68%). Strom et al. revealed PT prolongation by 5 s in 12.3% of patients, which is higher than the proportion observed in our results [11]. The probable explanation for this inconsistency may be due to different definitions of hypoprothrombinemia, and the heterogeneity of patients across studies. Sattler et al. reported that 64% and 24.4% of patients with renal failure [6] and cancer [26], respectively, developed hypoprothrombinemia.