Problemas relacionados a medicamentos; reações adversas a medicamentos e erros de medicação: a necessidade de uma padronização nas definições e classificações / Drug Related Problems; Adverse Drug Reaction, Medication Errors: The requirement of an uniform definition and classification

Problemas Relacionados a Medicamentos (PRMs) é um termo freqüentemente utilizado na Atenção Farmacêutica e na Farmácia Clínica. Os PRMs podem estar relacionados a Reações Adversas a Medicamentos (RAMs), consideradas não evitáveis e que sempre produzem dano ao paciente, ou Erros de Medicação (EM), considerados evitáveis e que podem ou não causar danos ao paciente. Os EM classificam-se em erros de prescrição, dispensação e administração. Uma proposta de classificação adaptada da PCNE (Pharmaceutical Care Network Europe) é descrita neste artigo.

Drug Related Problems (DRPs) is a term often used in pharmaceutical care and in the clinical pharmacy. Drug Related Problems can be related to Adverse Drug Reactions (ADRs) that are considered unavoidable and always induce harm and Medication Errors (MEs), considered avoidable and may or not induce harm. Medication Errors are classified in prescribing, dispensing and administration errors. A proposal for classification adapted from the Pharmaceutical Care Network Europe (PCNE) is described in this article.

Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

Circadian time-dependent effects of fencamfamine on inhibition of dopamine uptake and release in rat striatal slices

Fencamfamine (FCF) is a central stimulant that facilitates central dopaminergic transmission through inhibition of dopamine uptake and enhanced release of the transmitter. We evaluated the changes in the inhibition of uptake and the release of striatal [3H]-dopamine at 9:00 and 21:00 h, times corresponding to maximal and minimal behavioral responses to FCF, respectively. Adult male Wistar rats (200-250 g) maintained on a 12-h light/12-h dark cycle (lights on at 7:00 h) were used. In the behavioral experiments the rats (N = 8 for each group) received FCF (3.5 mg/kg, ip) or saline at 9:00 or 21:00 h. Fifteen minutes after treatment the duration of activity (sniffing, rearing and locomotion) was recorded for 120 min. The basal motor activity was higher (28.6 + 4.2 vs 8.4 + 3.5 s) after saline administration at 21:00 h than at 9:00 h. FCF at a sigle dose significantly enhanced the basal motor activity (38.3 + 4.5 vs 8.4 + 3.5 s) and increased the duration of exploratory activity (38.3 + 4.5 vs 32.1 + 4.6 s) during the light, but not the dark phase. Two other groups of rats (N = 6 for each group) were decapitated at 9:00 and 21:00 h and striata were dissected for dopamine uptake and release assays. The inhibition of uptake and release of [3H]-dopamine were higher at 9:00 than at 21:00 h, suggesting that uptake inhibition and the release properties of FCF undergo daily variation. These data suggest that the circadian time-dependent effects of FCF might be related to a higher susceptibility of dopamine presynaptic terminals to the action of FCF during the light phase which corresponds to the rats' resting period.

Effect of apomorphine on rat motor activity induced by fencamfamine and other indirect psychostimulant drugs

We evaluated the effects of low doses of apomorphine on the stimulant behavioral effects induced by amphetamine (2.5 mg/Kg), fencamfamine (6.0 mg/Kg) and cocaine (15,0 mg/Kg). Rats received 0.02 mg/Kg of apomorphine (sc) and 30 min later were injected with one of the stimulants.Motor activity including locomotion, rearing and sniffing was quantified in the animals home cages for 60 min at 15-min intervals. All stimulant drugs induced hyperactivity. When apomorphine was administered before cocaine, but not when administered before fencmfamine or amphetamine, distinctive changes occurred. The behavioral pattern resulting from high stimulation was replaced by that related to low stimulation, suggesting that apomorphine induces a transfer in the predominant behvior in cocaine-, and partially in fencamfamine-, but not in amphetamine-treated animals, by decreasing the intensity of the stereotyped effect. While no changes occured when apomorphine was administered before amphetamine, the fencamfamine group showed intermediate alterations (nonsignificant changes in sniffing but a significant increase in rearing behavior). These results are discussed in terms of the different mechanisms of presynaptic action of the drugs studied

The behavioral sensitization induced by fencamfamine is not related to plasma drug levels

Fencamfamine (FCF) is a CNS stimulant that facilitates central dopaminergic transmission primarily though blockade of dopamine uptake. In the present study we evaluated the relationship between plasma FCF concentration and behavioral sensitization effect. Adult male Wistar rats (250-300 g) received FCF (10 mg/Kg, ip) or saline oince or daily for 10 consecutive days (N = 10 for each group). Blood samples were collected 30 min after injections and plasma FCF was measured by gas chromatography using an electron capture detector. FCF treatment enhanced sniffing duration (16.8 ñ 0.8 vs 26.6 ñ 0.9s) and decreased rearing behavior (8.2 ñ 0.8 vs 3.7 ñ 0.6s) when days 1 and 10 of drug administration were compared. Comparison of pair of means by the Student t-test did not show significant differences in plasma FCF concentration (390 ñ 40 vs 420 ñ 11 ng/ml) when blood samples were collected 30 min after acute FCF administration or after daily administration of 10 mg/Kg for 10 days. In conclusion, the behavioral sensitization to FCF could not be correlated with plasma drug levels, and changes in the activity of dopaminergic systems should be considered to explain the sensitization to the effect of FCF

Daily variation in plasma concentration of fencamfamine and striatal dopamine receptors in rats

Fencamfamine (FCF) is a psychostimulant drug classified as an indirect dopamine agonist. In the present study we evaluated the daily variation in plasma FCF concentration and in striatal dopamine receptors. Adult male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark cycle (lights on at 07:00 h) were used. Rats received FCF (10.0 mg/kg, ip) at 09:00, 15:00, 21:00 or 03:00 h and blood samples were collected 30 (N = 6) or 60 (N = 6) min after the injections. Plasma FCF was measured by gas chromatography using an electron capture detector. Two-way ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest value was obtained following injection at 21:00 h. Moreover, at 15:00, 21:00 and 03:00 h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of rats (N = 6) were decapitated at 09:00 or 21:00 h and the striata were dissected for the binding assays. The Bmax for [3H]-spiroperidol binding to striatal membranes was higher at 21:00 h, without changes in affinity constant (Kd). In conclusion, plasma FCF levels and dopamine receptors undergo daily variation, a phenomenon that should be considered to explain the circadian time-dependent effects of FCF

Effect of fencamfamine on avoidance performances of rats

The effects of fencamfamine (1.0 and 5.0 mg/kg, ip single dose) on an inhibitory task were studied in rats (N=15 per group).Post-training treatment with fencamfamine (1.0 mg/kg) significantly increased avoidance latency from 23 ñ 3 to 146 ñ 28 and 170 ñ 33 s for training day 1 and day 7, respectively, indicating an enhacement of retention.However, retention was significantly reduced with a high dose of fencamfamine (5.0 mg/kg). These results demonstrate that fencamfamine caused a reproducible dose-related increase and reduction in avoidance latency

On the mechanism which mediates the effects of long-term administration of fencamfamine in rats

This study analyzes the changes in the sensitivity of striatal dopaminergic (DA) receptors to apomorphine following withdrawal from long-term treatment with fencamfamine (10 mg/kg, for 40 days). Fencamfamine treatment decreased (34.8 + or - 3.2 vs 25.8 + or - 2.8,P<0.05) the stereotyped behavior induced by apomorfhine (2.0 mg/kg, sc), but potentiated the effect of apomorphine (0.02 mg/kg, sc) in reducing the striatal levels of homovanillic acid (HVA) (0.41 + or - 0.02 micron g/g vs 0.31 + or - 0.03 microng/g, P<0.01) and dihydroxyphenylacetic acid (DOPAC) (0.45 + or - 0.04 microng/g vs 0.34 + or - 0.03 microng/g, P<0.01). These results suggest that changes in pre- or postsynaptic DA receptors may underlie the tolerance and sensitization to the effects of fencamfamine