ABSTRACT
beta-blockers have been conclusively proven to increase survival and improve symptoms of heart failure, yet there is underutilization of these agents most commonly because of misunderstandings of the relative contraindications and adverse events during treatment. In this manuscript, we discuss the potential contraindications to beta-blockers in heart failure and compare the true risks against the significant benefits.
Subject(s)
Adrenergic beta-Antagonists , Adrenergic beta-Antagonists/adverse effects , Age Factors , Contraindications , Female , Heart Failure/drug therapy , Heart Failure/epidemiology , Humans , Male , Risk Assessment , Sex FactorsABSTRACT
The anti-tumor effect of 3-amino-N-substituted pyrrolidine-2,5-dione-N-mustard hydrochloride (PNM.HCl) against Ehrlich (ascites) carcinoma (EAC) was studied. A substantial increase in the survival of mice bearing EAC tumor was achieved following daily administration of PNM.HCl at subtoxic dosages. The therapeutic efficacy of PNM.HCl was maintained with changes in dosages and the schedules of administration. The effect of PNM.HCl when administered with conventional anti-cancer drugs at different time schedules against EAC was also studied. The results demonstrated an augmentation of anti-tumor activity in the case of certain anti-cancer drugs against EAC tumor, thereby suggesting a potential usefulness of PNM.HCl in multi-drug therapy.
Subject(s)
Antineoplastic Agents/pharmacology , Nitrogen Mustard Compounds/pharmacology , Pyrrolidinones/pharmacology , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Ehrlich Tumor/drug therapy , Carcinoma, Ehrlich Tumor/pathology , Mice , Neoplasm Transplantation , Nitrogen Mustard Compounds/administration & dosage , Pyrrolidinones/administration & dosageABSTRACT
alpha-[N,N-[bis(2-hydroxyethyl)]-amino]-N- (o-methoxyphenyl)pyrrolidin-2,5-dione (I), an intermediate in the synthesis of pyrrolidinedione-N-mustards, did not exhibit antitumour activity against P388 lymphocytic leukemia, Sarcoma 180 (ascites) and Ehrlich (ascites) carcinoma tumours. The effect of co-administration of (I) with established anticancer drugs was studied against these murine tumours. The activity of 5-fluorouracil against Sarcoma 180 (ascites) and Ehrlich (ascites) carcinoma was significantly enhanced by co-administration with (I). Other anticancer drugs, when co-administered with (I), did not show any enhancing effect.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Ehrlich Tumor/drug therapy , Leukemia P388/drug therapy , Leukemia, Experimental/drug therapy , Nitrogen Mustard Compounds/pharmacology , Pyrrolidinones/pharmacology , Sarcoma 180/drug therapy , Animals , Drug Synergism , Female , Fluorouracil/pharmacology , Male , MiceABSTRACT
(R,S)3-(N,N-[bis-(2-chloroethyl)]-amino)-1-(2'-methoxyphenyl)- pyrrolidine-2,5-dione hydrochloride (I) has shown antitumor activity against P388 and L1210 leukaemias and Sarcoma 180 (ascites). The effect of (I), when co-administered with anticancer drugs, was studied in these murine tumours. Although co-administration of (I) with methotrexate showed a significant increase of the activity against P388 and L1210 leukaemias and Sarcoma 180 (ascites), co-administration of (I) with 5-fluorouracil, mitomycin C, adriamycin or vincristine did not exhibit any enhancing, synergistic or additive effect in the activity of these drugs.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms, Experimental/drug therapy , Nitrogen Mustard Compounds/administration & dosage , Pyrrolidinones/administration & dosage , Animals , Drug Synergism , Female , Male , Mice , Mice, Inbred StrainsABSTRACT
A 2,5-pyrrolidinedione linked nitrogen mustard derivative, (R,S)3-[N,N-bis(2-chloroethyl)]-amino-1-(2'-methoxyphenyl)pyrrolidine- 2,5-dione hydrochloride (I) showed a marked antiproliferative effect on mouse Sarcoma 180. Since (I) is also active against L1210 and P388 leukaemias, its toxicity in mice was evaluated. A study of acute toxicity revealed focal liver cell necrosis. Another derivative, (R,S)3-[N,N-bis-(2-chloroethyl)]amino-1-(4'-n-butoxyphenyl)pyrrolidine- 2,5-dione dihydrate (II), which also possessed significant anticancer effect on P388 and L1210 leukaemias, was inactive against Sarcoma 180.
Subject(s)
Nitrogen Mustard Compounds/therapeutic use , Pyrrolidinones/therapeutic use , Sarcoma 180/drug therapy , Animals , Chemical and Drug Induced Liver Injury , Mice , Necrosis/pathology , Nitrogen Mustard Compounds/toxicity , Pyrrolidinones/toxicityABSTRACT
(R,S)alpha-[N,N-[bis (2-chloroethyl)]-amino]-N-(o-methoxyphenyl)-pyrrolidin-2,5-dione hydrochloride (I), a new nitrogen mustard incorporated into a 2,5-pyrrolidinedione ring system, was found to be active against P388 lymphocytic leukaemia when administered by i.p., s.c. and p.o. routes. The anti-tumour activity, exhibited by compound (I), against intracerebrally grafted P388 tumour is of interest. However, (R,S)alpha-[N,N-[bis (2-chloroethyl)]-amino]-N-(p-n-butoxyphenyl)-pyrrolidin-2,5-dione dihydrate (II), was found to be active against the P388 tumour following i.p. administration only.
Subject(s)
Antineoplastic Agents/administration & dosage , Leukemia P388/drug therapy , Leukemia, Experimental/drug therapy , Nitrogen Mustard Compounds/administration & dosage , Pyrrolidinones/administration & dosage , Animals , Antineoplastic Agents/metabolism , Blood-Brain Barrier , Brain Neoplasms/drug therapy , Cyclophosphamide/administration & dosage , Mice , Nitrogen Mustard Compounds/metabolism , Structure-Activity RelationshipABSTRACT
A precise colorimetric procedure is proposed for estimation of ethambutol hydrochloride, based on reaction of the drug with 2,4-dinitro-1-fluorobenzene under stipulated conditions. The yellow chromophore is quantitated spectrophotometrically at 376 +/- 1 nm. The relationship between absorbance and drug concentration was linear within a range of 5-40 micrograms/mL. The method is suitable for the analytical control of ethambutol HCl and its formulations.
