Long-Term Effects of Painkillers. There are a number of unpleasant side effects associated with painkiller abuse. Mild side effects include nausea, vomiting, and diarrhea, usually caused by the way the drug interacts with opioid receptors along the digestive tract. painkiller can be any one of a number of drugs, from over-the-counter (OTC) medications like ibuprofen, naproxen and aspirin to prescribed drugs like tramadol, morphine, Opana and hydrocodone. All painkillers carry risks — even OTC ones — but it's the narcotic painkillers that carry the highest risk of addiction.