ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04660.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The euphoric effects of coca leaves have been known to mankind for thousands of years. Yet the first epidemic of cocaine use in America occurred during the late 19th century. Initially, there were no laws restricting the consumption or sale of cocaine. In fact, cocaine was freely available in drug stores, saloons, from mail‐order vendors, and even in grocery stores, it is reported that one drug manufacturer, in 1885, was selling cocaine in 15 different forms, including cigarettes, cheroots, inhalants, cordials, crystals, and solutions. Many famous imported wines, such as “Vin Mariani,” contained a mixture of wine and coca. For consumers on budgets, the wonder drug was available as Coca‐Cola and dozens of other soda pops and pick‐me‐up drinks. One of them even had a simple and direct name, Dope. Soon enough, the ill effects of cocaine became apparent, and by the 1920s cocaine was the most feared of all illicit drugs. Most states began enacting laws against cocaine use. President William Taft proclaimed cocaine as Public Enemy No. 1, and in 1914 the Congress passed the Harrison act, which tightly regulated the distribution and sale of cocaine. By the late 1950s, cocaine use in the United States was simply considered a problem in the past. Unfortunately, the people who were aware of the nation's first cocaine epidemic gradually passed away, and America once again was ready for its fling with cocaine in the 1960s. Today, it is estimated that upwards of 50 million Americans, that is one in four, have used cocaine. In addition, another fifty thousand people use this substance for the first time each day. More than 6 million Americans use cocaine on a regular basis. Little wonder, then, that America as well as the other countries have declared a “War on Drugs.” In this review, pharmacology of cocaine, major complications arising from its use, and efforts to curb its abus

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04661.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04662.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Adverse drug reactions are common and troublesome complications of contemporary pharmacotherapy. Adverse drug reactions are frequently, and often incorrectly, referred to as “allergy.” Although there are multiple mechanisms for adverse drug reactions, adverse drug reactions mediated by the immune system account for a disproportionate number of fatal and serious adverse reactions, and constitute a major clinical problem for patients and physicians. The immune system has evolved in multicellular organisms as a defence against infection, interactions between drugs and the immune system occur as inadvertent consequences of the protective function of the immune system, with drug molecules or drug‐carrier haptens being recognized as “non‐self” by the immune system. The classical mechanisms for drug hypersensitivity described by Gell and Coombs (Types 1 to 4) include IgE‐mediated, cytotoxic, immune complex‐mediated and delayed mechanism. These mechanisms provide elegant models for drug‐immune interactions that can provide mechanistic explanations for events such as urticaria associated with penicillins. However, these mechanisms do not account for many of the immunologically mediated adverse reactions commonly encountered in clinical practice. Over the last two decades, there has been an increasing awareness of the importance of reactive drug metabolites and drug‐protein interactions in the initiation of immunologic events mediating adverse drug reactions. Reactive drug metabolites may produce direct and profound effects on various functions of the immune system. Although some adverse reactions mediated by the immune system occur with equal frequency among adults and children, some of these reactions appear to be markedly more common among children than adults. There are a number of confounding factors that make the evaluation of immunologically mediated adverse reactions among children difficult, including differences in the formulations commonly used among children. There are considerable gaps in our understanding of the role and importance of the immune system in producing adverse reactions to drugs and chemicals. Laboratory assessment has a limited role in the investigation of adverse drug reactions believed to be mediated by the immune system. Clinical examination remains the cornerstone for the evaluation of adv

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04663.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

To study if an H2‐receptor antagonist, nizatidine, and its metabolites [N‐2‐monodesmethylnizatidine (N‐2‐MDMN) and nizatidine sulfoxide (nizatidine S‐Ox)] would be removed by an arteriovenous hemofiltration, the authors measured their plasma concentrations and amounts recovered in ultrafiltrate during 11 sessions of an intermittent hemofiltration performed in seven patients with renal failure who were given an oral administration of nizatidine (150 mg). The concentrations of the parent drug and its metabolites in plasma and ultrafiltrate were determined with a high‐performance liquid chromatography with ultraviolet absorbance detection. The mean (± standard deviation [SD]) amounts of nizatidine removed by the procedure performed at the mean ultrafiltration rate of 18 (range, 11–25) mL/min over the mean duration of 179 (60 to 300) minutes accounted for 1.9 ± 1.4% of the dose administered. The corresponding values for N‐2‐MDMN and nizatidine S‐Ox were 0.3 ± 0.2% and 0.2 ± 0.2% of the molar dose of nizatidine, respectively. There was a significant correlation between the filtration rate and the hemofiltration clearance of nizatidine (r = .94, P<.001) or its active metabolite, N‐2‐MDMN (r = 0.83, P<.01), indicating that the sieving coefficient (Sc), an index of filtration efficiency, for these compounds is largely constant (0.59 and 0.67 for nizatidine and N‐2‐MDMN, respectively) under the current hemofiltration conditions. Assuming that the respective Sc values for the compounds observed in the current study could be extrapolated into a 24‐hour continuous arteriovenous hemofiltration performed at a commonly used filtration rate (i.e., 6–12 mL/min), the 24‐hour hemofiltration clearances of both nizatidine and N‐2‐MDMN would be less than 10 mL/minute. The hemofiltration clearance value for nizatidine corresponded to, at most, 5% of the mean plasma clearance reported from patients with renal failure (about 140 mL/min). Based on the current data coupled with the above‐described theoretical extrapolation, the authors recommend that no supplemental doses of nizatidine be required for patients with renal failure during or after such an intermittent hem

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04664.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The effects of concurrent administration of either cimetidine 800 mg once daily or ranitidine 300 mg once daily on the single‐dose pharmacokinetics of ritanserin 10 mg were investigated in an open, randomized three‐way cross‐over, controlled investigation in 9 healthy volunteers. Concurrent administration of cimetidine had no significant effect on the area under the plasma concentration‐time curve of ritanserin compared with control experiments. The maximum plasma concentration of ritanserin was decreased significantly (105.0 ± 9.2 versus 125.0 ± 13.8 ng/mL; P = .0039), whereas time to reach maximal concentration (tmax) of ritanserin was only slightly but not significantly increased, if the subjects were pretreated with cimetidine. After concurrent ingestion of ranitidine, only a trend to a decrease in the maximum plasma concentration of ritanserin was observed. Time to achieve the maximum plasma concentration, terminal half‐life of elimination, and the total area under the plasma concentration‐time curve of ritanserin were not altered in comparison with control experiments. The results of the study show that concurrent treatment with cimetidine 800 mg once daily or ranitidine 300 mg once daily has no apparent effect on the systemically available amount of ritanserin after a single oral dose of 10 mg. Both H2‐antagonists cause a significant (cimetidine) or borderline significant (ranitidine} decrease of the maximum plasma concentration of ritanserin and a slight but not significant increase in tmax (cimetidine). These effects are of minor clinical importance and seem most likely be due to a decrease of the rate of absorption of ritanserin during concurrent administration of cimeti

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04665.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

A number of studies have shown an antihypertensive effect for high‐calcium diets, but others have found no effect or, even a prohypertensive effect. Because of these disparate results, studies were conducted in spontaneously hypertensive rats (SHR) fed either a normal calcium diet (1.0% calcium) or a high‐calcium diet (4.0% calcium) with or without verapamil HCl (50 mg/kg body weight) from ages 5 to 12 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured by indirect tail cuff method. During the analysis of the electrolytes and vasoactive hormones monitored in this study, it was found that rats fed high‐calcium diet had significantly elevated serum ionized and total calcium and calcium excretion. Systolic blood pressure for the verapamil‐normal calcium diet (week 5, 148 ± 4 mm Hg; week 7, 162 ± 4 mm Hg) did not differ significantly from that of normal calcium diet (week 5, 152 ± 2 mm Hg; week 7, 160 ± 1 mm Hg). The high‐calcium diet potentiated the development of hypertension, i.e, SBP was (157 ± 2 mm Hg) on the 5th week and (174 ± 4 mm Hg) on the 7th week. Conversely, verapamil high‐calcium diet prevented the development of hypertension (week 5, SBP was 139 ± 4 mm Hg; week 7, SBP was 146 ± 3 mm Hg). The authors conclude: (1) dietary calcium supplementation is prohypertensive in SHR; (2) dietary calcium must influence blood pressure in SHR by action at the verapamil calcium channel; (3) the antihypertensive efficacy of verapamil in SHR is not blocked by high‐calcium diet; (4) there may be a synergism between elevation of ionized serum calcium and verapamil with regard to antihypertensiv

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04666.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Chronic subcutaneous administration of heparin consistently lowers blood pressure in hypertensive rats. This antihypertensive effect is related at least in part to a concomitant decrease in hematocrit. Groups of spontaneously hypertensive (SHR) and normotensive Wistar (NWR) rats were treated with subcutaneous heparin (700 U/d) for 6 weeks. Weekly determinations of systolic blood pressure (tail‐cuff) and hematocrit were done. Peripheral plasma renin activity, plasma aldosterone, plasma prostaglandins (PGs) (PGF2alpha, PGI2), thromboxane A2, and urinary kallikrein were measured. Blood pressure responses of acute and chronic heparin treatment to vasoconstrictor substances, including angiotensin I, angiotensin II, and norepinephrine, were determined. As before, heparin produced a significant (P<.01) decrease in hematocrit in both SHRs and NWRs, but a parallel decrease in blood pressure was noted only in SHRs. A significant (P<.001) increase in plasma renin activity was found in heparin‐treated SHRs and NWRs; however, a corresponding elevation of plasma aldosterone level was noted only in heparin‐treated NWR. Plasma aldosterone level significantly (P<.01) decreased in heparin‐treated SHRs. Plasma PGs and urinary kallikrein levels were not different among the groups. The blood pressure responses to vasoconstrictor substances were essentially similar among the heparin‐treated and control groups. These findings suggest that PGs or kallikrein have a slight or no role in determining the antihypertensive effect of heparin. Conversely, the results suggest that a reduced aldosterone level contributes to the antihypertensive mechanism o

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04667.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Sixteen essential hypertensive patients were entered into a protocol assessing the effect of Spirapril, an angiotensin‐converting enzyme (ACE) inhibitor, on blood pressure, the renin‐aldosterone system, and renal function. Specifically monitored before, during 6 weeks, and 6 months of Spirapril therapy were plasma renin activity, plasma aldosterone, serum ACE, the renal clearances of creatinine, inulin, and para‐aminohippurate, and urinary albumin excretion. Blood pressure was well controlled. Spirapril stimulated plasma renin activity and suppressed ACE throughout the entire protocol. Renal clearances were unchanged. Renal vascular resistance was decreased. Urinary albumin excretion was decreased. The authors conclude that the ACE inhibitor, Spirapril, when used as an effective antihypertensive agent, preserves renal function, lowers renal vascular resistance, and decreases urinary albumin excr

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04668.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

This study characterized the pharmacokinetics of clentiazem (CLZ) after a single intravenous bolus (IV) and oral (PO) dose in humans. Twenty‐four healthy male subjects (28.5 ± 5.2 years; 77 ± 8.2 kg) received IV (20 mg) and PO (80 mg) doses of CLZ as part of a four‐way, randomized, complete crossover study. Serial blood samples were drawn up to 48 hours after administration of the drug. Plasma samples were analyzed for CLZ and three metabolites by a high‐pressure liquid chromatography method. The values (mean [CV,%])/or systemic clearance, volume of distribution at steady‐state, and half‐life of CLZ were 63.6 L/hour (23.5), 756.1 L (19.1), and 10.6 hours (33.1), respectively, after IV administration. The peak plasma CLZ concentration (Cmax) and time to Cmax were 37.0 ng/mL (38.7) and 3.7 hours (22.9), respectively, with a lag time after PO administration. The absolute bioavailability of PO CLZ was 45% (30.7). The ratio of area under the curve of N‐desmethyl CLZ to that of CLZ increased from 0.15 (57.0) after IV to 0.60 (21.4) after PO administration, suggesting a significant first‐pass effect. The mean residence time and mean absorption time of CLZ were 12.3 hours (24.3) and 3.1 hours (88.1), respectively. The plasma concentration‐time data of CLZ can be described by either a one‐ or two‐compartment

ISSN:0091-2700    

DOI:10.1002/j.1552-4604.1993.tb04669.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY