You may think that this whole ionization and pKa stuff is of little relevance to you as a clinician working in ED, Anesthesiology or ICU, but you are mistaken. The pH of blood (whether or not the [H+] exceeds the [OH-] has major impact on the pharmacokinetics of certain drugs. Moreover, some drugs rely on a differential between extracellular and intracellular pH to be effective.

This tutorial looks at the pharmacology of three types of drugs impacted by pH. These drugs are local anesthetics, opioids and the benzodiazepine – midazolam. All of these agents are weak bases whose degree of ionization varies with pH.

1. Speed of onset is related to the pKa – the lower the pKa of weak bases the more rapid the onset of action
2. Duration of action is related to protein binding – particularly albumin (there are other proteins). Albumin depletion is common in critical illness, leading to higher bioavailability and shorter duration of action.
3. Potency is related to lipid solubility. Fentanyl is highly potent because of this.

This tutorial is supplementary to the acid base course. The material is ESSENTIAL for trainees and practitioners in Anesthesiology and Dentistry. @ccmtutorials http://www.ccmtutorials.org