Dihydrocodeine is an opioid analgesic used as an alternative or adjunct to codeine to treat moderate to severe pain, severe dyspnea, and cough. It is semi-synthetic, and was developed in Germany in 1908 during an international search to find a more effective antitussive agent to help reduce the spread of airborne infectious diseases such as tuburculosis. It was marketed in 1911. Dihydrocodeine is metabolized to dihydromorphine -- a highly active metabolite with a high affinity for mu opioid receptors. Dihydrocodeine is used for the treatment of moderate to severe pain, including post-operative and dental pain. It can also be used to treat chronic pain, breathlessness and coughing. In heroin addicts, dihydrocodeine has been used as a substitute drug, in doses up to 2500mg/day to treat addiction.

Acetaminophen, also known as paracetamol, is commonly used for its analgesic and antipyretic effects. Its therapeutic effects are similar to salicylates, but it lacks anti-inflammatory, antiplatelet, and gastric ulcerative effects. Acetaminophen (USAN) or Paracetamol (INN) is a widely used analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is extremely safe in standard doses, but because of its wide availability, deliberate or accidental overdoses are not uncommon. Acetaminophen, unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties or effects on platelet function, and it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. At therapeutic doses, acetaminophen does not irritate the lining of the stomach nor affect blood coagulation, kidney function, or the fetal ductus arteriosus (as NSAIDs can). Acetaminophen is thought to act primarily in the CNS, increasing the pain threshold by inhibiting both isoforms of cyclooxygenase, COX-1, COX-2, and COX-3 enzymes involved in prostaglandin (PG) synthesis. Unlike NSAIDs, acetaminophen does not inhibit cyclooxygenase in peripheral tissues and, thus, has no peripheral anti-inflammatory affects. Acetaminophen indirectly blocks COX, and that this blockade is ineffective in the presence of peroxides. This might explain why acetaminophen is effective in the central nervous system and in endothelial cells but not in platelets and immune cells, which have high levels of peroxides. Studies also report data suggesting that acetaminophen selectively blocks a variant of the COX enzyme that is different from the known variants COX-1 and COX-2. This enzyme is now referred to as COX-3. Its exact mechanism of action is still poorly understood, but future research may provide further insight into how it works. The antipyretic properties of acetaminophen are likely due to direct effects on the heat-regulating centers of the hypothalamus resulting in peripheral vasodilation, sweating and hence heat dissipation.

Aspirin is a nonsteroidal anti-inflammatory drug. Aspirin is unique in this class of drugs because it irreversibly inhibits both COX-1 and COX-2 activity by acetylating a serine residue (Ser529 and Ser516, respectively) positioned in the arachidonic acid-binding channel, thus inhibiting the synthesis of prostaglandins and reducing the inflammatory response. The drug is used either alone or in combination with other compounds for the treatment of pain, headache, as well as for reducing the risk of stroke and heart attacks in patients with brain ischemia and cardiovascular diseases.