Anand wrote a review article addressing the problems of drug dependence and withdrawal in the PICU. In his article he discussed the mechanisms, pharmacology and presentation of opioid withdrawal. He also discussed prevention of opioid withdrawal including such therapies as the concomitant infusion of opioid agonists and low dose Naloxone. Tobias also wrote a review article describing the consequences of the prolonged use of sedative and analgesic agents in the Pediatric ICU. Among the problems of note are tolerance, dependence and withdrawal in the Pediatric ICU. He discussed several possible therapies for the treatment and prevention of opioid withdrawal. Among these was the concomitant infusion of opioid agonist and low dose Naloxone, an opioid agonist. Naloxone selectively blocks those opioid receptors that are coupled with stimulatory G proteins, thus blocking mechanisms for super-activation of the cAMP pathway. This improves the efficacy of analgesia and prevents the development of acute tolerance.