Study Set Content:
begins with the lipophilic drug or substrate
and converts it into a more hydrophilic metabolite, the reason for
this is to facilitate its elimination.
Drug metabolism
wide variety of foreign compounds
Xenobiotics
Food additives, poisons, toxins, certain drugs, chemicals,
environmental pollutants, pesticides, and other foreign
substances.
Xenobiotics
substances absorbed across the lungs or skin or, more
commonly, ingested either unintentionally as compounds
present in food and drink or deliberately as drugs for
therapeutic or “recreational” purposes.
Xenobiotics
Exposure to environmental xenobiotics may be
inadvertent and (blank) or—when they are present as
components of air, water, and food—(blank)
accidental, inescapable
Some xenobiotics are(blank), (harmless) but many can
provoke biologic responses.
innocuous
The mammalian drug biotransformation systems are thought to
have first evolved from the need to (blank)plant and
bacterial bioproducts and toxins, which later extended to drugs and
other environmental xenobiotics.
detoxify and eliminate
plays a pivotal role in terminating the biologic
activity of some drugs, particularly those that have small molecular
volumes or possess polar characteristics, such as functional groups
that are fully ionized at physiologic pH. However, many drugs do
not possess such physicochemical properties.
Renal excretion
Pharmacologically active organic molecules tend to be
lipophilic
Pharmacologically active organic molecules tend to be lipophilic and
remain
unionized or only partially ionized at physiologic pH;
Pharmacologically active organic molecules tend to be lipophilic and
remain unionized or only partially ionized at physiologic pH; these
are readily reabsorbed from the glomerular filtrate in the
nephron
Certain lipophilic compounds are often strongly bound to plasma
proteins and may not be readily filtered at the
glomerolus
Most drugs would have a prolonged duration of action if
termination of their action depended solely on
renal excretion
An alternative process that can lead to the termination or
alteration of biologic activity is
metabolism
In general, lipophilic xenobiotics are transformed to more
(blank)and hence more readily excreted products.
polar
The role that metabolism plays in the inactivation of lipid-
soluble drugs can be quite dramatic.
The role that metabolism plays in the inactivation of lipid-
soluble drugs can be quite dramatic.
For example, lipophilic barbiturates such as (blank) would have extremely long half-lives if it
were not for their metabolic conversion to more water-
soluble compounds.
thiopental and
pentobarbital
Metabolic products are often less pharmacodynamically
active than the parent drug and may even be
inactive
However, some biotransformation products have
enhanced activity or
toxic properties
synthesis of endogenous substrates such as steroid
hormones, cholesterol, active vitamin D congeners, and
bile acids involves many pathways catalyzed by enzymes
associated with the metabolism of
xenobiotics.
