Buprenorphine and Fentanyl transdermal patches are used for the management of chronic intractable pain in both malignant and nonmalignant patients. Both Buprenorphine and fentanyl are potent opioids, but they have different pharmacology and toxicology properties. It is important to understand the difference in these properties as this information is useful for clinicians and pharmacists to guide them to use the opioid patches effectively for the management of pain, and to monitor the side effects to ensure safe and efficacy of drug use. Opioid analgesics mimic endogenous opioid peptides by causing a prolonged activation of opioid receptors (usually μ receptor). This receptor medicate analgesia, respiratory depression, euphoria and sedation. Fentanyl is potent, highly lipid soluble, rapidly acting μ-opioid receptor full agonist. Buprenorphine is a highly lipophilic semisynthetic opioid. It has complex pharmacology which is different from Fentanyl. Buprenorphine is a partial μ-opioid receptor agonist. A partial agonist is a drug that binds to and activates a receptor but has only partial efficacy compared to a full agonist. This means that it may have ceiling effect and demonstrate both agonist and antagonist effects. In human studies using clinical effective analgesia doses, buprenorphine does not have a ceiling effect to analgesia. However, Buprenorphine does have a ceiling effect for respiratory depression. Buprenorphine is a partial agonist. Higher doses can be given with fewer respiratory depression side effect compared with higher doses of Fentanyl. Dose response studies showed that doses many times greater than normal buprenorphine therapeutic doses appear to be well-tolerated in most individuals, and rarely result in clinically-significant respiratory depression. Buprenorphine is safer in high doses than Fentanyl. The primary side effects of buprenorphine are similar to other μ-opioid agonists (eg, nausea, vomiting, and constipation), but the intensity of these side effects is reduced significantly compared to full agonist, Fentanyl. The most severe and serious adverse reaction associated with opioid use in general is respiratory depression, the B ISBN: 978-81-932966-1-5 GSPSC – 2017 January 30th-February 1st, 2017 Volume I, Issue VI Page | 23 GSPSC – 2017 www.bioleagues.com mechanism is behind fatal overdose. Buprenorphine behaves differently than other opioids in this respect, as it shows a ceiling effect for respiratory depression. Typically, 1%–11% of patients on opioid therapy suffer from respiratory depression. In one study using rats, much higher safety window (13.5- fold) is reported for buprenorphine than for fentanyl (1.2-fold) when comparing analgesia and respiratory distress doses. Buprenorphine has slow off rate (half-life of association/dissociation is 2–5 hours). The slow dissociation from μ-receptor accounts for its prolonged therapeutic effect for treatment of pain. Respiratory depression is rare with buprenorphine, but If occurs, it can be reversed by Naloxone, often larger doses are required than Fentanyl because buprenorphine dissociates slowly from the receptors. The maximal opioid effects of Buprenorphine are less than that of full agonist, Fentanyl. Buprenorphine has high affinity for but low intrinsic activity at μ-opioid. Comparing to Fentanyl, it has a higher affinity for μ opioid receptors. In conclusions, the pharmacology profile of buprenorphine is complex but unique, and contributes to its distinct safety and efficacy when it is used under appropriate clinical indications.