Hydrocodone/paracetamol - Pharmacodynamics

Pharmacodynamics

Besides the activity of hydrocodone and acetaminophen by themselves, there is observed a factor of analgesia related to the two substances in tandem that is not altogether understood, but this independent synergy has been observed to be related to the inhibition of prostaglandins. The pharmacodynamics of a mixed drug such as Vicodin depends on the kinetics of the drugs that comprise it.

Hydrocodone: Acts at μ-opioid receptors. Hydrocodone is metabolized to hydromorphone by the activity of cytochrome P450 2D6. Cytochrome 3A4 forms the substrate norhydrocodone. Note that this conversion is only somewhat responsible for the effects of hydrocodone. Hydrocodone passes through the blood–brain barrier (BBB) because of its modifications. The brain is typically where the analgesic effects are being carried out. Many of the side-effects of this drug are caused by the fact that it so readily crosses the blood–brain barrier. The half-life of hydrocodone is approximately 3.8 hrs.

Paracetamol: The major active metabolites are sulphates and glucuronide conjugates. Its main mode of action is to inhibit the activity of the enzyme cyclooxygenase (COX). COX enzymes are necessary for the production of prostaglandins. Prostaglandins are a form of hormone (although rarely classified as such) that are indicated to be mediators of pain, fever, and inflammation. The half-life of paracetamol may be measured either by salivary or by plasma counts. Both measurements give a varying half-life between 1 and 4 hours. Peak levels are reached 40–60 minutes after ingestion. It has been proposed that paracetamol aids in the reduction of pain by increasing serotonergic neurotransmissions. Paracetamol is a peripherally acting drug, and hence does not cross the BBB as readily as hydrocodone.