In 1986 WHO proposed a three step analgesic ladder. Non-opioids (step 1) are administered in case of mild pain. If this is not enough, weak opioids (step 2) are being added. They may be exchanged by strong opioids (step 3). The analgesics from the ladder frequently need to be co-administered with other drugs aiming either reduction of adverse effects (e.g. laxatives) of increase of activity and widening the spectrum of analgesic activity (e.g. tricyclic antidepressants).