Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Jun 2006
Comparative StudyCisatracurium: myographical and electrophysiological studies in the isolated rat muscle.
Myographical and electrophysiological studies of cisatracurium were performed, in vitro, in the isolated sciatic nerve-extensor digitorum longus muscle preparation of the rat. Indirect twitches were generated at 0.1 Hz and tetanic contractions at 50 Hz. endplate potentials (epps) were generated in trains of 50 Hz. The electrophysiological variables used in the analysis of the epps were: amplitude of the first epp in the train, average amplitude of the 30 degrees to the 59 degrees epp in the train (epps-plateau), tetanic rundown (percent loss in amplitude of epps-plateau relative to the first epp in the train), quantal size and quantal content. ⋯ In cisatracurium 0.13 microm (a concentration which affects only tetanic contractions, inducing their fade, while leaving the twitch unaffected) there was a decrease in the quantal content of the first epp and of epps-plateau in the train. In cisatracurium (0.38 microm), a concentration, which affects the twitch, there was a decrease of the quantal size and of quantal content of epps-plateau, but not of the quantal content of the first epp in the train. The results indicate that the fade of the tetanic contraction induced by cisatracurium at the concentration of 0.13 microm is entirely because of a pre-synaptic blocking effect while the decrease in the twitch induced by cisatracurium at the concentration of 0.38 microm is due to a post-synaptic blocking effect.
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Fundam Clin Pharmacol · Feb 2006
Comparative StudyEarly pharmacological preconditioning by erythropoietin mediated by inducible NOS and mitochondrial ATP-dependent potassium channels in the rat heart.
Administration of recombinant human erythropoietin (rhEPO) is known to induce protection against cardiac ischaemia injury improving functional recovery and reducing apoptosis. But the underlying mechanisms are not elucidated. We determined the role of nitric oxide synthases (NOS) as well as ATP-dependent (K(ATP)) and calcium-activated (K(Ca)) potassium channels in the early cardioprotection induced by rhEPO. ⋯ We observed the same significant effect on its derivative (dP/dt). The rhEPO-induced improvement in ventricular function was abolished by perfusion prior to ischaemia with either N-nitro-l-arginine methyl ester (l-NAME, a nonspecific NOS inhibitor) or N-(3-(aminomethyl)benzyl)acetamidine (1,400W, a specific inducible NOS inhibitor) or 5-hydroxydecanoic acid (5HD, a mitochondrial K(ATP) channel blocker) but not with paxilline (a K(Ca) channel inhibitor). Thus, in vivo rhEPO administration provides early preconditioning against ischaemic injury in the isolated perfused rat heart that is dependent on iNOS and mitochondrial K(ATP) channels.
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Fundam Clin Pharmacol · Dec 2005
Randomized Controlled Trial Comparative StudyComparative trial of tramadol/paracetamol and codeine/paracetamol combination tablets on the vigilance of healthy volunteers.
Combination of tramadol 37.5 mg/paracetamol 325 mg (a), or codeine 30 mg/paracetamol 500 mg (b) or 300 mg have similar pain efficacy but a difference has been suggested concerning their adverse events on vigilance. In clinical practice, combinations are usually given at the above-mentioned dosage three to four times a day. ⋯ This observation is important and proves that even a single dosage of these largely used drugs may have a significant effect. This finding should be further investigated in elderly subjects who consume largely these drugs for chronic pain alleviation and who are more prone to this kind of adverse event.
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Herbal medicine has become a popular form of healthcare. Even though several differences exist between herbal and conventional pharmacological treatments, herbal medicine can be tested for efficacy using conventional trial methodology. ⋯ Ultimately, we need to know which herbal remedies do more harm than good for which condition. Because of the current popularity of herbal medicine, research in this area should be intensified.
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Fundam Clin Pharmacol · Jun 2005
ReviewThe pharmacology, toxicology, and medical treatment of sulphur mustard poisoning.
Sulphur mustard (SM) is regarded as one of the most important agents of chemical warfare because of its simple and cheap chemical synthesis that makes it readily available for both terrorist and military use. SM acts as an alkylating agent that induces disruption of nucleic acids and proteins, impairing cell homeostasis and eventually causing cell death. ⋯ In light of the possible threat of SM use against military and civilian populations, physicians should be aware of its grave effects and knowledgeable how to care for its victims. The pattern of immediate and long-term toxic effects following exposure to SM is reviewed in this article with special references to the recent data available from over 100,000 chemical casualties incurred during the Iran-Iraq conflict.