Workbook:

Pharmacokinetics

Copyright 2016 APEX Anesthesia Review

Volume of Distribution

What does Vd assume?

Low Vd drugs tend to:

Examples:

High Vd drugs tend to:

Examples:
Clearance CL is Directly Proportional To: CL is Inversely Proportional To:

Define clearance.

What are the major clearing organs?

Define steady state.

How many half-times must elapse to achieve steady state?

Multi-Compartment Models
Alpha phase:

Beta phase:

Rate constants:
Use the 3 compartment model to create a story about how drugs move through the
body. Begin with IV injection and end with clearance.
Elimination half-life = Half-Time Amount of Drug Amount of Drug
Eliminated % Remaining %
0
Elimination half-time =

1
What is the problem with half-times?
2

Context sensitive half-time =

Discuss the context sensitive half-times of the commonly used opioids.

pKa, pH & Ionization
What is the difference between a weak acid and a weak base? When pKa and pH are the same,
_____% of the drug will be _______________ and
_____% of the drug will be _______________.

Define ionization. What happens when we put weak acids/bases in solution?

Ionized Unionized
Solubility

Pharmacologic Effect

Hepatic Biotransformation

Renal Elimination

Diffused Across Lipid

Bilayer:

Blood-brain barrier
GI tract
Placenta
Discuss ion trapping.

Apply the concept of ion trapping to the fetus.

 Increased Decreased
Plasma Protein Binding
Albumin
Detail the relevance of the 3 major plasma proteins.

Alpha 1-acid
glycoprotein

Beta-globulin

Discuss changes in plasma protein binding.

Zero Order Kinetics ( ) →

First Order Kinetics ( ) →

What are the most common sites of drug metabolism?

How does metabolism facilitate drug elimination?

Phase I Reactions Phase II Reactions

 Low Hepatic ER Intermediate ER High Hepatic ER
Hepatic Clearance
Extraction Ratio =

Flow Limited Elimination (ER > )

Capacity Limited Elimination ( ER < )

P450 Isoenzymes
P450 Enzyme Substrate Inducers Inhibitors
CYP 3A4

CYP 2D6

CYP 1A2
Renal Elimination

Getting Drug into the Urine

Urine pH
What are the 3 main metabolic pathways in the plasma?

Pseudocholinesterase Nonspecific Esterases Alkaline Phosphatase