Anesthesia Student Survival Guide.pdf - Index of

PhArmAcoloGy PrinciPles ● 31
● Volume of distribution (V ): d The volume of distribution is defined as the
total dose of drug given divided by the plasma concentration of drug. Drugs
which are highly hydrophilic or protein-bound and stay in the plasma have
a V close to the plasma volume. Those that are highly lipid-soluble will
d
redistribute from the plasma to adipose tissue, leading to a low plasma concentration
and a high apparent volume of distribution.
● Redistribution: This phenomenon describes a rapid fluctuation of drug concentration
in highly perfused tissues that is most commonly seen with very
lipid-soluble drugs (e.g., thiopental). It consists of the following stages:
● After injection, the free fraction of the drug rapidly enters highly perfused
tissues such as the brain and the heart, and more slowly enters into
less perfused tissues such as adipose tissue.
● As plasma drug levels drop because of continued entry of the drug into
adipose tissue, the drug distributes back from the highly perfused tissues
into the plasma. This typically terminates its therapeutic effect.
● The drug then continues to distribute into adipose tissue, where it is stored.
● Storage: If doses of highly lipid soluble drugs such as thiopental are given
repeatedly, the storage sites in adipose tissue may become saturated. The termination
of the drug’s therapeutic effect then becomes dependent on metabolism
and excretion, which are typically much slower than redistribution.
Metabolism and Excretion
Drug effects are terminated by metabolism and excretion. Factors affecting this
process include:
● Mechanisms of metabolism: Most anesthetic drug metabolism and excretion
occurs at the liver, kidneys, and lungs. The major mechanisms can be
summarized as below:
● Hepatic: The liver eliminates drugs primarily by metabolizing them to
inactive or less active compounds. The end products of hepatic metabolism
are typically polar, water-soluble compounds that are suitable for
renal excretion. Some excretion of drugs and drug metabolites into the
biliary system also occurs.
● Renal: The kidneys primarily eliminate drugs by excretion of water-soluble
drugs or drug metabolites into the urine. Some direct drug metabolism
also occurs in the kidneys.
● Pulmonary: The lungs are the primary site of elimination of inhalational
anesthetics, which are absorbed from the plasma and exhaled.