Drug education practice: results of an observational study.

Understanding normative practice in drug education is a key to identifying means of improving preventive intervention outcomes. In this paper, we report findings of an observational study in which drug education in multiple periods of 146 middle school classes was categorized minute-by-minute according to the type of instruction provided to students. Results indicate that nearly half of all drug education focused on providing students with knowledge. Alternative methods, particularly those that have shown programmatic effectiveness, and those that address risk and protective factors known to be highly predictive of drug use onset, were relatively ignored. Further, teachers showed relatively low consistency in understanding concepts other than knowledge based on comparisons of their ratings of intended instructions with those of trained observers. Nonetheless, there is evidence that some teachers systematically attempted to address drug prevention from either a social influence or an affective education perspective. These findings suggest that if improvements in the effectiveness of drug education are to be seen in the future, a relatively radical transformation of approaches to teaching will be needed.

How D.A.R.E. works: an examination of program effects on mediating variables.

The D.A.R.E. (Drug Abuse Resistance Education) program has relied on a curriculum that addresses a variety of psychosocial processes thought to be related to substance use and potentially modifiable through programmatic intervention. This study examines 12 postulated mediators of substance use prevention programs to determine the degree to which D.A.R.E. has an effect on mediators and the degree to which those effects account for behavioral outcomes of the program. Results indicate that the primary effect of D.A.R.E. is a change in commitment to not use substances. This change significantly mediates behavioral effects. However, the magnitude of D.A.R.E.'s effect on the mediator is relatively small. Other mediators that offer strong potential paths for intervention effectiveness are not affected by the program. These results suggest that in order to achieve prevention effectiveness, the curriculum used in the D.A.R.E. program needs to be replaced with one that targets and meaningfully changes appropriate mediating variables.

Hemodynamic effects of adenosine agonists in the conscious spontaneously hypertensive rat.

The present studies examined the underlying hemodynamic mechanisms contributing to the reduction in blood pressure observed in conscious spontaneously hypertensive rats after systemic administration of adenosine agonists. The effects produced by i.v. and i.a. injections of 2-phenylaminoadenosine [CV-1808, adenosine (A2) selective agonist], 5'-N-ethylcarboxamide adenosine (NECA, nonselective agonist), 2-chloroadenosine (2-CADO, A1 selective agonist) and cyclopentyladenosine (CPA, A1 selective agonist) were evaluated and compared to those of hydralazine. All agents produced hypotensive effects after bolus i.v. injection. Although CPA, NECA and 2-CADO elicited dose-dependent bradycardia, CV-1808 and hydralazine increased heart rate. These effects, with the exception of the hydralazine-evoked responses, were attenuated by prior treatment with 8-(p-sulfophenyl)theophylline (2 mg/kg/min), whereas both CV-1808 and hydralazine produced regional vasodilation, significant increases in blood flow occurred only after CV-1808 (3-30 micrograms/kg). The regional hemodynamic responses to NECA were more complex; low doses (0.1-1 microgram/kg) produced consistent reductions in regional vascular resistance, whereas at the highest dose renal vasoconstriction occurred. Although regional vasodilation occurred after 2-CADO, mesenteric vasoconstriction was observed subsequent to CPA administration. Whereas a significant increase in renin release was evident in animals treated with CV-1808 and hydralazine, no change occurred in response to the NECA-, 2-CADO- or CPA-induced hypotension. We conclude that the predominant hemodynamic response after selective activation of A2 receptors is one of regional vasodilation and hypotension leading to a reflex increase in heart rate and renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Degradation of atrial natriuretic peptide: pharmacologic effects of protease EC 24.11 inhibition.

Several processes participate in the clearance of atrial natriuretic peptide (ANP) from the circulation, one of which is enzymatic degradation. Endoprotease EC 3.4.24.11 (NEP 24.11), present within the kidney in high concentration, has been shown in vitro to degrade ANP. Phosphoramidon and thiorphan, two potent NEP 24.11 inhibitors, have been shown to prevent the enzymatic degradation of ANP. The purpose of the present study was to determine if phosphoramidon or thiorphan would alter the in vivo time course of the pharmacologic effects of ANP. The magnitude and duration of the ANP-induced increase in urine output and sodium and cyclic GMP excretion were examined with and without either thiorphan or phosphoramidon. Six separate groups of anesthetized rats received either a low, medium, or high infusion rate of thiorphan or phosphoramidon. Renal responses to ANP were potentiated and prolonged during the low phosphoramidon infusion (3 Ki) and the medium thiorphan infusion (150 Ki). At high inhibitor infusion rates in the anesthetized rat, ANP elicited a marked depressor response. In the conscious spontaneously hypertensive rat (SHR), a 15-min intravenous (i.v.) infusion of ANP (1 microgram/kg/min) lowered mean arterial pressure (MAP 23 +/- 6 mm Hg), with an approximately 35-min duration of action. A simultaneous i.v. infusion of phosphoramidon (high dose) produced both a potentiation (33 +/- 3 mm Hg) and a prolongation (greater than 65 min to return to baseline) of the depressor response. These data lend support to the hypothesis that enzymatic breakdown of ANP may play an important role in regulating the actions of atrial natriuretic peptide.