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.
This tutorial is supplementary to the acid base course. The material is ESSENTIAL for trainees and practitioners in Anesthesiology and Dentistry.
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Contents:
00:14 Intro
01:30 pKa Versus Degree of Dissociation of Acids and Bases (this is essential knowledge)
04:37 Contents of This Tutorial
05:00 Clinical Scenario Callum, Diabetic Foot, Ankle Block, Failed.
05:50 Local Anesthetics Are Weak Bases - Basic Pharmacology
06:50 pKa of Alkali
07:00 Local Anesthetics Are Prepared As Hydrochloric Acid Salts
07:38 Why the pH of Bupivicaine In the Amp is 6.0 and Why It Is Important
11:30 The Sodium Channel
12:25 The Local Anesthetic Inside the Cell
12:29 Speed of Onset is Related to pKa
14:20 Duration of Action is Related to Protein (Albumin and Globulin) Binding.
15:00 Potency of Local Anesthetics is Related to Lipid Solubility
15:53 Different Local Anesthetics in Clinical Practice
17:30 Adding Epinephrine (Adrenaline)
18:04 Mixing Long and Short Acting Local Anesthetics
19:00 Why Did Callum's Block Fail
21:00 Sodium Bicarbonate - Reduces Sting, Increases Onset of Action - Win Win
22:20 Intravenous Lidocaine
23:15 Freebasing Cocaine
24:15 Opioids
24:57 Opioids Are Weak Bases
25:30 Basic Pharmacokinetics of Opioids
26:54 pKa And Onset Of Action of Opioids
27:00 Remifentanil
27:37 Alfentanil
28:30 Oxycodone
29:05 Morphine
29:43 Long Acting Opioids (particularly Hydromorphone) in ICU
31:00 Fentanyl
31:55 Fentanyl During Caesarean Section (under GA) - Controversial but Risk is Overrated
33:15 Midazolam and It's Magic Ring
35:55 Review and Preview