Pharmacokinetics of the local anesthetic ropivacaine after transversus abdominis plane block in healthy volunteers.

Purpose: The transversus abdominis plane (TAP) block is a regional anesthetic technique used for pain control following abdominal surgical procedures. While a minimum of systemic side effects is usually expected after local anesthesia, it is unknown to which extent systemic absorption and redistribution to the abdominal wall contributes to the effects of anesthetics. The aim of this study was to determine concentration-time profiles of ropivacaine after the injection of 150 mg of ropivacaine into the lateral abdominal wall in various compartments.

Ultrasound versus landmark-based technique for ilioinguinal-iliohypogastric nerve blockade in children: the implications on plasma levels of ropivacaine.

Background: Ilioinguinal-iliohypogastric nerve blockade (INB) is associated with high plasma concentrations of local anesthetics (LAs) in children. Ultrasonographic guidance enables exact anatomical administration of LA, which may alter plasma levels. Accordingly, we compared plasma levels of ropivacaine after ultrasonographic versus landmark-based INB.

Pharmacokinetic dosage guidelines for elderly subjects.

Ageing is associated with a decline in drug elimination; hence, using the same doses as in younger adults may result in higher plasma drug concentrations and toxicity. Two approaches are available for dose correction to account for decreased drug elimination. One procedure is based on the extrarenal elimination fraction (Q(0)) and the age-dependent changes in creatinine clearance; the other uses the decline in total drug clearance (CL).

Class I antiarrhythmics inhibit Na+ absorption and Cl- secretion in rabbit descending colon epithelium.

To clarify the mechanism of the diarrhea associated with the clinical use of antiarrhythmic drugs we assessed the effects of these agents on transepithelial Na+ absorption and Cl- secretion, on basolateral K+ conductance, and on the properties of single basolateral K+ channels of rabbit colon epithelium. Quinidine and propafenone, both at 10 microM, inhibited Na+ absorption by 27 and 38% respectively, compared with 50% with 5 mM Ba2+. The other tested class I antiarrhythmics disopyramide, mexiletine, lidocaine, and flecainide decreased Na+ current by 9-13%.

Drug therapy in the elderly.

Drug dosage in the elderly requires an understanding of the age-dependent changes in drug disposition and sensitivity. The most important pharmacokinetic alteration is a decline in renal function, the elderly should therefore be treated as renally insufficient patients. Metabolic clearance is primarily reduced with drugs that display high hepatic extraction, whereas the metabolism of drugs with low hepatic extraction usually is not diminished.

[Drug interactions with antiepileptic agents].

Drug interactions with antiepileptic agents are based in large part on pharmacokinetic mechanisms. Most prominent are induction or inhibition of enzymes of the cytochrome P450 (CYP) system, which is of central importance for metabolic elimination of lipophilic xenobiotics. Potent inductors of CYP isoenzymes are carbamazepine, phenobarbital, phenytoin, and primidone, thereby decreasing not only their own plasma levels and efficacy but also that of other antiepileptics and other drugs.

When drug therapy gets old: pharmacokinetics and pharmacodynamics in the elderly.

The age-related changes in the functions and composition of the human body require adjustments of drug selection and dosage for old individuals. Drug excretion via the kidneys declines with age, the elderly should therefore be treated as renally insufficient patients. The metabolic clearance is primarily reduced with drugs that display high hepatic extraction ('blood flow-limited metabolism'), whereas the metabolism of drugs with low hepatic extraction ('capacity-limited metabolism') usually is not diminished.

Simultaneous isocratic HPLC determination of vigabatrin and gabapentin in human plasma by dansyl derivatization.

A rapid and low-cost assay for simultaneous vigabatrin (VGA) and gabapentin (GBP) determination is described that can be performed with simple HPLC instrumentation. The method involves derivatization of the primary amine group of VGA and GBP with dansyl chloride followed by isocratic separation (column: microBondapak C-18, 10 microm, 300 x 3.9 mm; mobile phase: 50 mmol/L NaH(2)PO(4) in 40% acetonitrile) at 50 degrees C and fluorometric detection (excitation and emission wavelength: 318 and 510 nm, respectively) of the fluorescent product, which is stable for at least 7 days.

[Alternative and natural science therapy forms: incompatible contrast].

In spite of the accomplishments of science-oriented medicine, we are still confronted with a multitude of "alternative" or "complementary" therapies which claim to heal "holistically" without adverse effects. Common to alternative treatment methods, which are several or many centuries old, is the notion that a special force ("vis vitalis", "entelechy", "spiritual bioforce", etc.) is responsible for life that, ultimately, cannot be investigated.

Basolateral potassium channels of rabbit colon epithelium: role in sodium absorption and chloride secretion.

In order to assess the role of different classes of K(+) channels in recirculation of K(+) across the basolateral membrane of rabbit distal colon epithelium, the effects of various K(+) channel inhibitors were tested on the activity of single K(+) channels from the basolateral membrane, on macroscopic basolateral K(+) conductance, and on the rate of Na(+) absorption and Cl(-) secretion. In single-channel measurements using the lipid bilayer reconstitution system, high-conductance (236 pS), Ca(2+)-activated K(+) (BK(Ca)) channels were most frequently detected; the second most abundant channel was a low-conductance K(+) channel (31 pS) that exhibited channel rundown. In addition to Ba(2+) and charybdotoxin (ChTX), the BK(Ca) channels were inhibited by quinidine, verapamil and tetraethylammonium (TEA), the latter only when present on the side of the channel from which K(+) flow originates.

Alkalinization increases penetration of lidocaine across the human cornea.

Purpose: To test the hypothesis that corneal permeability of lidocaine complies with the principle of nonionic diffusion.

Setting: Department of Ophthalmology and Institute of Pharmacology, Vienna, Austria.

Methods: Human corneas, mounted in an in vitro perfusion system under short-circuit conditions, were exposed on the epithelial (tear) side to lidocaine 4% in a buffered solution of pH 5 or pH 7.

[Coxibs: cyclooxygenase-2 inhibitors].

The oxygenating enzyme cyclooxygenase (COX) catalysis the conversion of arachidonic acid to proinflammatory prostaglandins. For many years it was thought that COX is a single enzyme that is present constitutively in most tissues. But in the late 80ies COX activity was found to be increased in inflammatory states with cytokines and bacterial lipopolysaccharides as inducing agents.

Analgesic effects of caudal and intramuscular S(+)-ketamine in children.

Background: Previous studies suggest that caudal administration of ketamine cause effective analgesia. The purpose of the current study was to compare the clinical effectiveness and plasma concentrations of S(+)-ketamine after caudal or intramuscular administration in children to distinguish between local and systemic analgesia.

Methods: After induction of general anesthesia, 42 patients, aged 1 to 7 yr, scheduled to undergo inguinal hernia repair randomly received a caudal (caudal group) or intramuscular (intramuscular group) injection of 1 mg/kg S(+)-ketamine.

[Adverse effects of psychotropic drugs in the elderly].

As in other organs, homeostatic mechanisms become insufficient in the aging brain, in part because of reduced activity of various neurotransmitter systems. Counter-regulatory processes are therefore reduced and reactions to drugs may be increased. Aside from these pharmacodynamic mechanisms, the increased toxicity of psychotropic agents in the elderly may be a result of pharmacokinetic changes.

Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects.

Aims: The prevalence of hyperuricaemia and gout increases with age as does the incidence of adverse effects to allopurinol, the major uric acid lowering drug. The present study was performed to compare the disposition and effects of allopurinol and its active metabolite oxipurinol in elderly and young subjects without major health problems.

Methods: Ten elderly (age range 71-93 years) and nine young subjects (24-35 years) received an oral dose of 200 mg allopurinol in an open, single dose, cross sectional design.

Membrane phospholipid composition affects function of potassium channels from rabbit colon epithelium.

We tested the effects of membrane phospholipids on the function of high-conductance, Ca(2+)-activated K(+) channels from the basolateral cell membrane of rabbit distal colon epithelium by reconstituting these channels into planar bilayers consisting of different 1:1 mixtures of phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), and phosphatidylinositol (PI). At low ambient K(+) concentrations single-channel conductance is higher in PE/PS and PE/PI bilayers than in PE/PC bilayers. At high K(+) concentrations this difference in channel conductance is abolished.

Drug dosage in the elderly. Is it rational?

Pharmacotherapy in the elderly requires an understanding of the age-dependent changes in function and composition of the body. Aging is characterised by a progressive loss of functional capacities of most if not all organs, a reduction in response to receptor stimulation and homeostatic mechanisms, and a loss of water content and an increase of fat content in the body. The most important pharmacokinetic change in old age is a decrease in the excretory capacity of the kidney; in this regard, the elderly should be considered as renally insufficient patients.

Topical anesthesia with pH-adjusted versus standard lidocaine 4% for clear corneal cataract surgery.

Purpose: To evaluate and compare the efficacy of a sodium-bicarbonate-adjusted preparation of lidocaine 4% (pH = 7.2) and standard lidocaine (pH = 5.2) for topical anesthesia in clear corneal cataract surgery.

Inhibition of high-conductance, calcium-activated potassium channels of rabbit colon epithelium by magnesium.

High-conductance, Ca(2+)-activated K+ channels from the basolateral membrane of rabbit distal colon epithelial cells were reconstituted into planar phospholipid bilayers to examine the effect of Mg2+ on the single-channel properties. Mg2+ decreases channel current and conductance in a concentration-dependent manner from both the cytoplasmic and the extracellular side of the channel. In contrast to other K+ channels, Mg2+ does not cause rectification of current through colonic Ca(2+)-activated K+ channels.

[Incidence of ovarian hyperstimulation syndrome in in-vitro-fertilization treatment over a period of 11 years].

A total of 2915 cycles of controlled ovarian hyperstimulation (COH) were performed from 1981 to 1992 in an in-vitro fertilization--embryo transfer (IVFET) programme at our institute. In 325 (11.2%) cycles an ovarian hyperstimulation syndrome (OHSS) developed.

Pharmacokinetics and pharmacodynamics of the diuretic bumetanide in the elderly.

In a cross-sectional study of the pharmacokinetics and pharmacodynamics of peroral and intravenous bumetanide (0.5 mg, single dose), total and renal clearance of the diuretic was significantly lower in elderly persons than in young adults, resulting in higher bumetanide plasma levels in the aged. Nonrenal clearance, bioavailability, and the volume of distribution were not significantly changed.

[Geriatric pharmacology. Pharmacokinetics and pharmacodynamics in the elderly. Problems with geriatric and nootropic drugs].

The reasons for the increased frequency of adverse drug reactions in the elderly are a decrease in drug elimination, primarily via the kidneys, on the one hand and a decrease in adaptive counterregulatory mechanisms on the other hand that attenuate drug effects in younger subjects. Because of the decreased functional reserve in the aged drugs may adversely affect preexisting chronic diseases. Generally, the possibility that clinical symptoms in the elderly are drug-related has to be considered.

Neurogenic chloride secretion induced by scorpion venom and veratrine in rabbit colon.

In earlier reconstitution experiments the venom of the scorpion Leiurus quinquestriatus, LQV, was shown to block Ca(2+)-activated high-conductance K+ channels from the basolateral cell membrane of rabbit colonocytes (Turnheim K, Costantin J, Chan S, Schultz SG (1989) J Membrane Biol 112:247-254). These LQV-sensitive K+ channels do not seem to be involved in active Na+ transport across rabbit colon, as absorptive Na+ fluxes were not significantly affected by serosal addition of LQV to isolated epithelia of rabbit descending colon. While Na+ absorption was not changed, LQV and veratrine caused electrogenic Cl- secretion in this tissue by a neural (tetrodotoxin sensitive) mechanism.

Epithelial sodium transport: basic autoregulatory mechanisms.

The epithelial cell is equipped with autoregulatory mechanisms that coordinate the rates of apical Na+ entry and basolateral Na+ extrusion, so that intracellular Na+ activity is maintained relatively constant when the rate of active Na+ transport changes. The increase of basolateral Na+ extrusion via the ouabain-inhibitable Na+,K(+)-ATPase during Na+ transport stimulation appears to be a result of both an increase in the number of operative Na+,K(+)-ATPase units in the basolateral cell membrane and in the Na+ turnover per Na+,K(+)-ATPase unit. Further, it is possible that the number of epithelial cells, which are involved in active Na+ transport, changes when the rate of Na+ transport is altered.