Current drug targets
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Delirium is a global impairment of upper brain functions caused by an organic substrate. It is frequently observed in the postoperative period, particularly in elderly people. Vascular and orthopedic surgery and long-duration surgery are associated with a higher incidence of postoperative delirium. ⋯ Atypical neuroleptics, like risperidone, have not yet been studied in postoperative delirium, although some case reports in which they were successfully used have been published. Physiostigmine is effective in delirium caused by anticholinergic syndrome; vitamins may be useful in alcoholics; melatonin use has been suggested in order to prevent and treat delirium by normalizing sleep-wake cycle alterations. Environmental interventions are often costless and may be very useful to prevent and treat postoperative delirium in patients at risk.
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Critically ill patients, particularly those under mechanical ventilation, require analgo-sedation to control noxious stimuli and enhance comfort. Despite their harmful side effects, such as respiratory depression, physical dependence and difficult arousal, opioids are effective in providing a good level of analgesia and comfort. Traditional opioids (morphine and fentanyl) have been shown effective in providing analgesia; however, the respiratory adverse effects and their pharmacokinetics, with an high risk of accumulation, limits their use, especially for a long-term sedation. In the last decade, new synthetic opioids with limited side effects and favourable pharmacokinetics profile, such as Sufentanil and Remifentanil, have been investigated to evaluate their efficacy in mitigating pain and enhancing comfort in critically ill patients.
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In critically ill patients, adequate sedation increases comfort, minimizes stress response and facilitates diagnostic and therapeutic procedures. Propofol (2-, 6-diisopropylphenol) is an intravenous sedative-hypnotic agent popular for sedation in the Intensive Care Unit. The favorable propofol pharmacokinetic, characterized by a three compartment linear model, allows rapid onset and short duration of action. ⋯ Hypertriglyceridemia and pancreatitis are uncommon complications. A large number of trials have compared the use of propofol with midazolam. Sedation with propofol is associated with adequate sedation in ICU patients, shorter weaning time and earlier tracheal extubation compared to midazolam, but not before ICU discharge.
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Ketamine is a non-competitive antagonist to the phencyclidine site of N-methyl-d-aspartate (NMDA) receptor for glutamate, though its effects are mediated by interaction with many others receptors. It has been introduced in clinical use since 1960's but today it is not largely employed as a general anaesthetic for its undesired psychic effects (emergence reactions) occurring in approximately 12% of patients. ⋯ At present, non-definitive conclusion can be drawn. More data are needed to define the possible long term effects and the clinical goal of ketamine use.
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Epidural analgesia is widely used for postoperative pain in a variety of surgical operations and it is recognised to provide superior quality of analgesia when compared with systemic opioids. The combination of low doses of local anaesthetics and opioids appears to provide optimal analgesia with minimal motor blockade. However, side effects have been reported with epidural analgesia such as postoperative nausea and vomiting (PONV), respiratory depression and arterial hypotension. ⋯ Epidural failure due to technical failure or malposition of the catheter represents potential problems having direct consequence on the quality of analgesia provided. All epidural catheters have to be checked and the quality of analgesia assessed before patients are discharging from PACU to the surgical wards. With advances in pain pharmacology, multimodal interventions and adjuvants can be used safely with the intent of providing better analgesia and decreasing the side effects associated with one technique.