Drugs in the physician's bag for emergency conditions

The list of drugs for the physician's bag depends on several factors, including practice location, conditions most likely to be found, costs and availability of drugs, organization of the emergency medicine in the region, shelf life and climatic vulnerability of certain drugs, population age, and size and design of the bag. Most of the drugs carried should be in an injectable form. However, the non-injectable drugs with relatively rapid systemic onset may be also included. Separation of drugs in the bag according to their usage may help in providing an organized treatment. For example, one could separate drugs for treatment of the following emergencies: cardiovascular, altered mental status, respiratory, gastrointestinal, bleeding, infections, and toxicological emergencies. The list of drugs needed for medical emergencies when physician makes house-calls is presented with short notes on their usage. Oncologic, toxicologic and pediatric emergencies are commented.     

The microcirculation and survival of experimental flow-through venous flaps

We assessed the effects of chronic (21 day) administration of antipsychotic drugs on the density of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor in rat brain. We used two typical antipsychotic drugs, haloperidol and pimozide, and two atypical antipsychotic drugs, risperidone and clozapine. Antipsychotic drugs as a group significantly elevated the density of the AMPA receptor measured with an AMPA receptor agonist ([3H]AMPA), but not with an AMPA receptor antagonist, 6-cyano-7-nitro-quinoxaline-2,3-dione ([3H]CNQX). In all regions studied, the magnitude of the increase seen with chronic typical antipsychotic drugs was significantly greater than that seen with chronic atypical antipsychotic drugs. In frontal cortex and striatum, typical antipsychotics but not atypical antipsychotics elevated AMPA receptor binding over control. These findings suggest that antipsychotic drugs alter the agonist affinity of the AMPA receptor without altering the number of AMPA receptors. Typical antipsychotic drugs may be more potent in this effect than atypical antipsychotic drugs, especially in critical corticostriatal circuits.     

Placental transfer of drugs administered to the mother

Drugs administered to mothers have the potential to cross the placenta and reach the fetus. Under particular circumstances, the comparison of the drug concentration in the maternal and fetal plasma may give an idea of the exposure of the fetus to the maternally administered drugs. In this review drugs are classified according to their type of transfer across the placenta. Several drugs rapidly cross the placenta and pharmacologically significant concentrations equilibrate in maternal and fetal plasma. Their transfer is termed 'complete'. Other drugs cross the placenta incompletely, and their concentrations are lower in the fetal than in maternal plasma. The majority of drugs fit into 1 of these 2 groups. A limited number of drugs reach greater concentrations in fetal than maternal plasma. It is said that these drugs have an 'exceeding' transfer. The impression prevails that suxamethonium chloride (succinylcholine chloride) and doxorubicin do not cross the placenta. However, a careful analysis of the literature suggests that this impression is wrong and that all drugs cross the placenta, although the extent transfer varies considerably. The following parameters were considered as possible factors determining the extent of placental transfer: (i) the molecular weight of the drug; (ii) the pKa (pH at which the drug is 50% ionised); and (iii) the extent of drug binding to the plasma protein. Drugs with molecular weights greater than 500D have an incomplete transfer across the human placenta. Strongly dissociated acid drug molecules should have an incomplete transfer, but this does not seem to be an absolute rule. For example, ampicillin and methicillin transfer completely and they are strongly dissociated at physiological pH. The extent of drug binding to plasma protein does not influence the type of drug transfer across the human placenta.     

Current opinion of muco-active drug research: strategies and problems

In general, mucoactive drugs are classified into several groups. However, since many drugs have overlapping effects, it is difficult to classify the drugs into groups based on their major actions. It has been reported that many mucoactive drugs have antioxidant effects. It is reasonable to suggest that an anti-inflammatory property is crucial to demonstrate effectiveness in a clinical context. From this point of view, we have evaluated several mucoactive drugs over two decades. Of these, we will consider the following drugs with anti-inflammatory properties: sodium aceneuramate; glucocorticoids; traditional Chinese medicines; and new cysteine derivatives. On the basis of these findings, we believe that the efforts to seek for compatible actions between glucocorticoids and oriental medicines may provide new opportunities for development of ideal mucoactive drugs with specified actions, i.e. suppression of gene expression.     

Modeling and implementing a database on drugs into a hospital intranet

Our objective was to develop a drug information service, implementing a database on drugs in our university hospitals information system. Thériaque is a database, maintained by a group of pharmacists and physicians, on all the drugs available in France. Before its implementation we modeled its content (chemical classes, active components, excipients, indications, contra-indications, side effects, and so on) according to an object-oriented method. Then we designed HTML pages whose appearance translates the structure of classes of objects of the model. Fields in pages are dynamically fulfilled by the results of queries to a relational database in which information on drugs is stored. This allowed a fast implementation and did not imply to port a client application on the thousands of workstations over the network. The interface provides end-users with an easy-to-use and natural way to access information related to drugs in an internet environment.     

Role of glycosoaminoglycans in venous disease. Mode of action of some flavonoid drugs

Varicose vein walls differ from normal venous walls by an important loss of their collagen content and an increase of their glycosaminoglycan content, essentially of hyaluronan. The decrease in fibrous protein content can be attributed to increased proteolytic (collagenolytic) activity as well as to free radicals. Glycosaminoglycan increase reflects a disregulation of the normal program of matrix biosynthesis by the cells of varicose vein wall, essentially smooth muscle cells. Some flavonoid drugs are capable of correcting these deviations by decreasing proteolytic attack on fibrous proteins and the accumulation of proteoglycans and hyaluronan. These effects, due to interactions between flavonoid drugs and the cells and fibrous proteins of the venous wall differ according to the nature of such drugs. A hypothesis is proposed to explain these differences in the intensity of action of flavonoid drugs with apparently closely related structures, based on the conformation of these drugs and their interaction with the triple helical structure of collagen fibers as well as with the cell membranes.     

Drug use during lactation

Breast-feeding is an essential physiologic process that provides ideal nutrition to the infant as well as protection against disease. All drugs are excreted into breast milk and are bioavailable to the infant. However, most medications do not pose significant risk to the nursing infant, and breast-feeding should be continued despite medication use in most cases. These decisions should be made using a stepwise approach Pharmacists should be aware of which drugs are contraindicated and which drugs should be used cautiously, in addition to which drugs should be recommended if necessary during lactation information on use of specific drugs is presented in this article. With knowledge of the principles of drug passage into breast milk, the goal of the pharmacist should be to minimize the infant's exposure to drugs while supporting the mother's desire to continue breast-feeding.     

Generation of a novel poliovirus with a requirement of hepatitis C virus protease NS3 activity

Hepatitis C virus (HCV) is the major etiologic agent of non-A, non-B hepatitis. One of the difficulties in developing anti-HCV drugs is the lack of an efficient HCV cultivation system. We have generated an artificial surrogate virus suitable for testing the antiviral effects of drugs affecting HCV protease NS3, an enzyme believed to be essential for HCV proliferation. The surrogate virus genome is composed of most of the poliovirus genome and HCV protease NS3 and an NS3-specific cleavage site. The activity of HCV protease NS3 is required for proliferation of this chimeric virus. The antiviral efficacy of HCV protease inhibitors can, therefore, be evaluated by examining the effects of the drugs on the surrogate virus proliferation.     

Causal assessment of drug-induced acute colitis. A prospective study of 58 consecutive cases

AIMS: The causal effect of drugs is underestimated in patients with inflammatory bowel disease. The aim of this study was to assess the causal implication of drugs in acute colitis. METHODS: A prospective study was conducted in 58 consecutive patients with an acute inflammation of the colonic mucosa. Recent drug intake was recorded and possible causal effects were analyzed exhaustively with respect to both intrinsic and bibliographic criteria. RESULTS: Causal assessment scores were high for 57 drugs and 41 patients. Drug-induced acute colitis was diagnosed in 35 cases. In 7 patients, physician practice had not taken into account drug use despite probable drug involvement. The main drugs implicated were antibiotics (n = 42) and non steroidal anti-inflammatory drugs (n = 10). CONCLUSION: Acute colitis is mainly induced by drugs.     

Modulation of platinum-induced toxicities and therapeutic index: mechanistic insights and first- and second-generation protecting agents

Platinum-type drugs have proven to be valuable in the treatment of a variety of solid tumors, beginning with the commercial approval of cisplatin 18 years ago. There are several clinically important toxicities commonly associated with the administration of these drugs. Despite the extensive use of cisplatin and carboplatin, the fundamental chemical transformations and mechanisms that underlie their antitumor and toxic effects have not been fully characterized. Several first-generation protective thiols have been clinically studied in an attempt to reduce the toxicity of platinum-type drugs; while some of these agents appear to protect against certain toxicities, nearly all platinum-protecting drugs have their own intrinsic toxicities, which can be additive to the toxicity of platinum-type drugs. Tumor protection by platinum-protecting drugs is an additional untoward effect that is associated with certain types of agents and must be addressed with care. Recent advances in theoretical and laboratory methods and the use of supercomputers have extended our understanding of the possible major mechanisms underlying platinum drug antitumor activity and toxicity; we present strong evidence that there are two classes of chemical species of platinum drug. One class appears to predominantly account for the antitumor activity, and the other class of chemical species produces many of the toxic effects of platinum drugs. We have discovered a new nontoxic, second-generation platinum-protecting agent, known as BNP7787, which appears to selectively inactivate and eliminate toxic platinum species. BNP7787 has recently entered phase I clinical testing in cancer patients.     

Isocratic, simultaneous reversed-phase high-performance liquid chromatographic estimation of six drugs for combined hypertension therapy

We report an isocratic, HPLC procedure for assay of the orally administered hypertension drugs [atenolol, amlodipine, nifedipine, nitrendipine, nimodipine and felodipine given in retention order] of which atenolol, an aryloxypropanolamine beta-blocker is administered with anyone of the other five dihydropyridine calcium channel blockers in combined hypertension therapy. The drugs were dissolved in methanol and 20 microliters of a mix of the drugs was injected onto a reverse phase JASCO-metaphase ODS (250 x 4.0 mm) 5 mu column. Any one of the six drugs could be used as the internal standard. The drugs were resolved by elution with a pH 4.5 equivolume mobile phase of acetonitrile-0.01 M KH2PO4, with pH adjustments done with H3PO4 (flow-rate 1.5 ml min-1). The column effluent was monitored at 250 nm. The detector response (peak height ratio) was linear in the dynamic range of 25-3200 ng ml-1 of these drugs, with the detection limits at approximately 15 ng ml-1. Full statistical evaluation of the data including linear regression (least-square fit) analysis was performed. The suggested procedure has the advantage that all the five dihydropyridine derivatives can be quantified alone or in formulation with atenolol.     

Frusemide inhibits angiotensin II-induced contraction on human vascular smooth muscle

OBJECTIVE: To provide an overview of the use of psychotropic drugs in preschoolers. METHOD: Literature review. RESULTS: Although controversy persists, the evidence suggests that preschool children are being given an increasing number of psychotropic drugs, especially by general practitioners and pediatricians. CONCLUSION: There is an urgent need to formally evaluate the efficacy of psychotropic medication for young children.     

Antiretroviral uptake in Australia: medical, attitudinal and cultural correlates

The objective of this study was to describe the medical, attitudinal and cultural correlates of antiretroviral uptake amongst people living with HIV/AIDS (PLWHA) in Australia. Stratified purposive sampling produced a sample of 925 PLWHA, which represents 8.3% of the current population of PLWHA in Australia. Respondents completed a self-administered questionnaire which revealed that 78% of respondents were using antiretroviral drugs for HIV/AIDS. Logistic regression revealed that PLWHA were more likely to use antiretroviral drugs if they had more favourable attitudes toward antiretroviral drugs, if they had been diagnosed with an AIDS-defining illness, and if they had ever had a CD4/T-cell count below 400 copies/ml blood. Women were less likely than men to use antiretroviral drugs, and logistic regression revealed different predictors of antiretroviral drug use amongst men and women. Given the importance of attitudes toward antiretroviral drugs, it is likely that if the current confidence in antiretroviral drugs were to change, this would be reflected in an equally rapid cessation of treatment amongst many PLWHA.     

Nonsteroidal antiinflammatory drugs interact with horseradish peroxidase in an in vitro assay system for hydrogen peroxide scavenging

The established horseradish peroxidase/guaiacol in an in vitro assay system was used for investigation of the reactivity of nonsteroidal antiinflammatory drugs with hydrogen peroxide. Although the drugs rapidly seemed to react in the selected conditions, difficulties were encountered in attempts to quantify the reaction and an interaction with horseradish peroxidase was suspected. A more specific assay system based on the absolute specificity of the enzyme glutathione peroxidase for glutathione was subsequently used which demonstrated that none of the investigated nonsteroidal antiinflammatory drugs was able to scavenge hydrogen peroxide. An original procedure to further evidence the interaction was developed thereafter, based on the reaction of 5-aminosalicylic acid with similar hemoproteins. This led to the demonstration that nonsteroidal antiinflammatory drugs were substrates for horseradish peroxidase and explained their reactivity in the horseradish peroxidase/guaiacol assay system. The compound 5-aminosalicylic acid showed an unusual behaviour that was attributed to its ability to both scavenge hydrogen peroxide and interact with horseradish peroxidase. It was concluded that the lack of specificity of horseradish peroxidase for its donor substrate may lead to erroneous results in assays for hydrogen peroxide scavenging of some drugs. An alternative method is however available and a simple spectroscopic assay can evidence the interaction with horseradish peroxidase.     

Drugs inducing or aggravating parkinsonism: a review

Drug-induced parkinsonism (DIP) is frequent. The list of drugs able to induce parkinsonism is long and probably incomplete, because new drugs, with previously unknown antidopaminergic activity, are constantly being added. Not all the drugs have the same potency for inducing parkinsonism. We classify these drugs in three groups: (1) drugs with obvious antidopaminergic activity which regularly induce parkinsonism; (2) drugs able to induce parkinsonism in particular individuals and (3) drugs which may aggravate Parkinson's disease treated with levodopa. The reports of isolated cases of parkinsonism induced by widely-used drugs (drugs in group 2) may be the result of either an idiosyncratic side effect or a misdiagnosis of parkinsonism. The antidopaminergic activity of the drugs of this group is weak and not sufficiently demonstrated. Maybe, in these cases, the blockage of other neurotransmitters different from dopamine plays a role in the induction of parkinsonism. Probably, the number of patients with DIP is higher than reported or detected, because many patients suffer from weak symptoms that quickly disappear after drug withdrawal. One of the main points of interest is knowing the list, because all these drugs, specially those of group 1, should be avoided or used with caution in the treatment of some common symptomatic problems in patients with Parkinson's disease, such as depression, arterial hypertension, diabetes mellitus and cardiac disorders. The precautions should extent to other populations especially susceptible to suffer from DIP, such as the elderly or patients with other neurodegenerative disorders, such as Alzheimer's disease.     

Molecular stereopharmacology and the search for stereoselective drugs

Analyzing modern trends in stereopharmacology shows that its theoretical aspects are mainly associated with the studies of the steric parameters of active centers of drug receptors and enzymes by using compounds having a well-established stereostructure. Applied stereopharmacology underlines the vital necessity of selective production and use of drug eutomers and active modifications of polymorphic drugs. The creation of an information computer database of stereostructural parameters of drugs is considered to be basic for further design of new selective drugs.     

Application of pharmacokinetically guided dose escalation with respect to cell cycle phase specificity

BACKGROUND: In 1986, the concept of pharmacokinetically guided dose escalation (PGDE) was proposed to predict the maximum tolerated dose (MTD) of an antitumor drug in humans from animal data. We have previously shown that antitumor drugs can be classified into two types, depending on their cytotoxic mechanisms: type 1 drugs, which are cell cycle phase-nonspecific agents, i.e., area under the curve for drug concentration in the plasma versus time (AUC)-dependent drugs; and type 2 drugs, which are cell cycle phase-specific agents, i.e., those that are time dependent. PURPOSE: The validity of the assumption that the AUC at the dose lethal for 10% of mice administered drug (LD10) is equal to the AUC at MTD for humans, the premise on which PGDE is based, was examined for type 1 and 2 drugs. METHODS: Findings in the literature, including those of Collins and co-workers, were retrospectively analyzed. The human/mouse ratios for the AUC were compared with each other and with the human/mouse dose ratios, based on milligram per meter square of body surface area, the measurement currently used in clinical trials of antitumor drugs. For six of the type 1 drugs, the human/mouse ratio for the AUC of total drug (AUC) and that of unbound drug (AUCu), which has been considered a determinant of pharmacologic and toxicologic effects, were also compared. RESULTS: There was an excellent correlation between log AUC at LD10 for mice and log AUC at MTD for humans for type 1 drugs (r = .898), but not for type 2 drugs (r = .677). For type 1 drugs, the correlation between mouse AUC at LD10 and human AUC at MTD was better for unbound drug (r = .961) than for total drug (r = .892). CONCLUSIONS: PGDE is useful for type 1 drugs; differences in protein binding between species should, however, be considered when using this method.