摘要:

The introduction of the new long acting local anaesthetics, bupivacaine and etidocaine, has stimulated an expansion of interest in regional anaesthesia, particularly for obstetrical applications and pain therapy.Systemic toxicity following injection of local anaesthetics occurs albeit infrequently, and tentative correlations have been made between the onset of CNS and cardiovascular effects and circulating drug concentrations in both adults and neonates. Amongst other factors, interpretation of these relationships depends upon blood distribution and plasma binding of the agents, sampling sites and acid-base balance.The disposition kinetics and placental transfer of the amide type agents have been well characterised. In adults their clearance is almost entirely hepatic but in neonates an increase in the renal component is, in part, a reflection of the immaturity of some of the enzymes responsible for their metabolism. Ester type agents are rapidly hydrolysed by plasma pseudocholinesterase and this has led to a preference for chloroprocaine in some obstetric procedures.Major determinants of the systemic absorption of the agents after perineural administration include their physicochemical and vasoactive properties, perfusion and tissue binding at the site of injection and whether or not adrenaline has been added. In respect of blood drug concentrations achieved after various regional anaesthetic procedures, the margin of systemic safety appears to favour bupivacaine and etidocaine compared to shorter acting analogues such as lignocaine and mepivacaine. The time course of local anaesthetic remaining at the site of injection has been calculated following intravenous regional anaesthesia and peridural block. This has allowed prediction of the local and systemic accumulation of the drugs following continued dosage.Blood concentrations of local anaesthetics after perineural injection are not closely related to age, weight or pregnancy but may be influenced by diseases associated with haemodynamic changes and by other drugs given at or around the time of regional blockade.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

Frusemide is an anthranilic acid derivative that is pharmacologically more potent than organomercurial agents in producing natriuresis and is effective when taken orally even in acid-base disorders or advanced renal failure. The bioavailability of commercially prepared tablets is comparable to an aqueous solution of frusemide. In healthy subjects the range of oral absorption is 60 to 69%. In patients with end-stage renal disease (ESRD), absorption is reduced to values between 43 and 46%. Food decreases the rate of absorption but does not affect bioavailability. Chronic phenytoin therapy, however, does reduce bioavailability to about the level of ESRD.Plasma protein binding in healthy subjects has been demonstrated to be between 91 and 99%. Frusemide is almost exclusively bound to albumin and it competes for binding sites with other acidic drugs. In patients with reduced plasma albumin concentration or azotaemia, frusemide binding is reduced.The mean apparent volume of distribution in the steady-state ranges from 0.07 to 0.18L/kg body weight in healthy adults. It may be modestly increased in adults with cardiac failure, but is very large in neonates with fluid overload. After intravenous injection, intact frusemide is the major urinary product in the first 4 hours. After this time, frusemide glucuronide and the free amine metabolite are also found. In healthy subjects, between 6 and 18% of an intravenous dose is found in the faeces. However, in renal failure, this is increased to 60% of the injected dose.Although apparently secreted by proximal portions of the nephron, frusemide has its principal action on the luminal surface of the ascending limb of Henle's loop. In this segment it exerts an inhibitory action on active chloride, thus producing a saluresis of both sodium and chloride. Probenecid substantially reduces the renal secretion of frusemide and the plasma clearance, and prolongs the half-life of the drug without impairing its natriuretic effect.Frusemide plasma clearance is greater than the creatinine clearance except in ESRD where it tends to be about 50% of the measured value. Elimination half-lives of 19 to 100 minutes are reported in healthy subjects but may be 8 to 15 hours in ESRD. In patients with both hepatic and renal insufficiency, reported half-lives were 11 to 20 hours. In neonates elimination half-lives of 7 to 8 hours have been reported apparently due to very large distribution volumes as well as low renal and hepatic clearance.Although the natriuretic effect of frusemide is variable and apparently dependent on the state of sodium reabsorption at the site of drug action, it appears that the saluretic response is more closely correlated with the urinary concentration of frusemide than with the plasma level. If the salt and water balance is maintained, a sigmoid-shaped dose-response curve is observed. From a therapeutic viewpoint, the maximum response with the least amount of drug would occur if the urinary excretion of frusemide were on the ‘steep’ portion of the curve. This concept has been applied in several clinical studies and probably explains the greater natriuresis seen when a divided oral dose regimen is given or small continuous infusions have been used.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be representative for pregnancy as such. Marked changes in most organ systems, particularly in renal function, but in composition and amounts of body fluids as well, make it likely that several pharmacokinetic parameters change, possibly gradually as pregnancy progresses.Accumulated data for several &bgr;-lactam antibiotics, and also for aminoglycosides indicate that antibiotics eliminated mainly by renal excretion will produce lower levels in serum or plasma in pregnant women than in other individuals. Also, the half-life of certain antibiotics in serum is shorter during pregnancy. Transplacental passage occurs for all antibiotics according to the physicochemical properties of the drug. Bolus injections to a pregnant woman are more efficient than continuous infusion in producing high levels of antibiotic in fetal serum and amniotic fluid. Fetal tissue levels are higher following multiple doses than after a single dose. Lower serum levels of antibiotics in pregnant women than in other individuals following the same dosage will be unsatisfactory as micro-organisms are less likely to be affected.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

摘要:

The pharmacokinetics of N1-acetylsulphamethoxazole and N4-acetylsulphamethoxazole in man are described. N1-Acetylsulphamethoxazole is deacetylated to sulphamethoxazole and acetylated to N4-acetylsulphamethoxazole. N4-Acetylsulphamethoxazole is excreted almost unchanged in the urine. The renal excretion rate is independent of the urine flow and urinary pH. N4-Acetylsulphonamides are less lipid soluble and more acidic than their corresponding parent sulphonamides.

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS

ISSN:0312-5963    

出版商:ADIS    

年代:1979

数据来源: ADIS