Codeine is one of the first developed opioids for mild pain and cough relief in 1832 by Pierre Jean Robiquet. Codeine is a pro-drug which is O-demethylated by the liver forming morphine. Codeine is a precursor for hydrocodone (1920). Both codeine and hydrocodone are frequently prepared in combination with anti-inflammatory, non-opioids analgesics like aspirin or acetaminophen. They are also often combined with antihistamines and decongestants to treat coughs and colds. Most codeine formulations are for human use but there is published support for veterinary use.
Tramadol is a pro-drug of the benzenoid chemical class that forms an O-desmethyl metabolite at the liver (M1). The M1 metabolite has activity at the mu receptor. Additionally, tramadol acts as a reuptake inhibitor of norepinephrine and serotonin causing sedation and questionable analgesia. It is typically administered orally but the inter-animal, inter-species variability in the conversion of tramadol to M1 makes it a clinically unpredictable analgesic drug for dogs and cats. Tramadol is clinically applied by some veterinary professionals as a post-operative analgesic, often in combination with NSAIDs.