**4. Pharmacotherapy in pain management in palliative setting**

In normal conditions, the primary analgesic management in palliative care starts with *oral administration of the medicines.* The WHO in 1986, for nociception pain, proposed a "step by step" approach which understands escalation of the drugs from non-opioid to opioid analgesics [34].

Primarily the ladder approach was used for cancer pain, but today it is widely used for any kind of pain. In 2010, Vargas-Schaffer G. suggested a re-adapted four steps ladder [35] (**Figure 1**), which in 2012 was revised by Leung, who advised pain treatment in a tridimensional multimodal platform [36], and at list, in 2019 Cuomo introduced the trolley model for multimodal tailored therapy [37].

The administration of drugs in palliative care is recommended to be less invasive. When possible, the most appropriate method is oral administration. Also, among less invasive methods well accepted by the patients are rectal or transdermal (patches) application. When it is necessary to apply the invasive parenteral routes, intra venous (IV), intramuscular (IM), subcutaneous (SC), can be considered. Dosing is different and varies depending on the type of the pain from around-the-clock dosing, "asneeded dosing" to "patient-controlled analgesia (PCA)".
