Tadalafil entfaltet seine Wirkung über eine selektive Hemmung der PDE5, wodurch die Konzentration von cGMP im glatten Muskelgewebe stabil bleibt. Diese biochemische Modulation resultiert in einer langanhaltenden Relaxation der Gefäßwände. Der Wirkstoff wird nach oraler Einnahme effizient resorbiert, mit einer Bioverfügbarkeit von rund 80 %. Seine Halbwertszeit von bis zu 36 Stunden ist innerhalb dieser Substanzklasse außergewöhnlich. Abgebaut wird er in der Leber, hauptsächlich durch CYP3A4, mit anschließender biliärer Exkretion. Typische unerwünschte Wirkungen entstehen durch eine verstärkte Vasodilatation, etwa Kopfschmerzen oder Flush. Pharmakologisch wird cialis generika vor allem durch die verlängerte Wirkungsdauer charakterisiert.

Treatment of heroin addiction in the netherlands: history, results and developments

Treatment of heroin addiction in the Netherlands: history, results and developments
Wim van den Brink
Professor of Psychiatry and Addiction
Academic Medical Center University of Amsterdam


Methadone treatment was introduced in the Netherlands as early as 1968. During the first
few years, methadone was prescribed to morphine dependent patients. Following the
introduction of heroin in the Netherlands in 1972, treatments with methadone were primarily
directed towards achieving abstinence from heroin addiction. Generally, these methadone
reduction programs suffered from high drop-out rates, and there was a serious threat that
they would loose contact with many addicts. Paralleling the rapid increase in the number of
heroin addicts during the mid 1970s, and the introduction of HIV/AIDS in the mid 1980s,
the aim of oral methadone prescription in the Netherlands shifted from abstinence towards
stabilization and harm reduction. Most of the programs developed into low-threshold
programs with low dosages of methadone (30-50 mg/day), extensive take-home regimens,
no mandatory psychosocial treatments and no sanctions on illegal drug use. Currently about
50-60% of all heroin addicts in the Netherlands are in methadone maintenance treatment. Of
these, approximately 40% is well functioning without illegal drug use and without any
criminal involvements. In contrast, approximately 25% is still using illicit drugs and is
involved in frequent (acquisitive) crimes.
In order to improve the outcomes for these non-responding patients, two studies were
performed: one study on the effect of higher dosages of methadone and the other on the
effectiveness of the medical prescription of heroin to chronic treatment-resistant methadone
patients. Higher dosages of methadone in low-threshold methadone maintenance treatments
are feasible and acceptable and result in better outcomes (Driessen et al. submitted). In
addition, heroin assisted treatment in chronic methadone-resistant heroin dependent patients
is feasible, safe, effective and cost-effective (Van den Brink et al., 2003; Dijkgraaf et al.,
2005). Together with an analysis of the historical development of the treatment situation in
the Netherlands, these results can provide the basis of a more comprehensive and more
effective treatment system.
However, some serious problems remain to be solved. First, most of the heroin addicts are
also dependent on cocaine and many of them also are heavy alcohol users. New experiments
and new studies are needed to investigate the best ways to tackle these complex problems
using new medications (e.g. modafinil, rimonabant) or new psychosocial interventions (e.g.
contingency management) in combination with methadone, buprenorphine or even heroin
maintenance programs. Other problems refer to the simultaneous presence of depression,
ADHD and schizophrenia. Again, new integrated treatments need to be developed and
tested using existing knowledge on the treatment of co-morbid depression (SSRIs), ADHD
(methylphenidate, dexamphetamine) and schizophrenia (clozapine) as an important starting
point. Finally, more and continuous attention should be paid to the treatment of co-occurring
physical ailments such as hepatitis B and C, HIV and AIDS.

Source: http://www.cran.qc.ca/sites/default/files/client/Activite_II_Pays-Bas_Abstract.pdf