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This chapter focuses on the pharmacology of the drugs commonly used to provide moderate and deep sedation and their available reversal agents. Intravenous sedative and analgesic drugs should be given in small, incremental doses titrated to desired end points of sedation and analgesia, with adequate time allowed between doses to achieve those effects. Preemptive analgesia is a treatment that is initiated before surgical procedure to reduce sensitization of pain pathways. Potential drug interactions require the clinician providing sedation to be cognizant of potential drug-drug effects, which can lead to morbidity and mortality. Opioids in combination with benzodiazepines provide adequate moderate and/or deep sedation and analgesia for many potentially painful procedures. Other drugs used for deep sedation include propofol, ketamine, dexmedetomidine, and etomidate. Local anesthetics (LA) have the potential to produce deleterious side effects. The choice of a local anesthetic and care in its use are the primary determinants of toxicity.