Study Set Content:
Inherited as an autosomal recessive trait, the slow
acetylator phenotype occurs in about 50% of
blacks and
whites
Inherited as an autosomal recessive trait, the slow
acetylator phenotype occurs in about 50% of blacks and
whites in the USA, more frequently in (blank)
Europeans living in
high northern latitudes,
Inherited as an autosomal recessive trait, the slow
acetylator phenotype occurs in about 50% of blacks and
whites in the USA, more frequently in Europeans living in
high northern latitudes, and much less commonly in
Asians
and Inuits (Eskimos).
The (blank) is also associated with a higher
incidence of isoniazid induced peripheral neuritis, drug-induced
autoimmune disorders, and bicyclic aromatic amine-induced
bladder cancer.
slow acetylator phenotype
Genetic polymorphisms in the expression of other phase II
enzymes (UGTs and GSTs) also
occur
Thus, UGT polymorphisms (UGT1A1*28) are associated with
(blank) as well as
toxic effects due to impaired drug conjugation and/or
elimination (eg, the anti-cancer drug irinotecan).
hyperbilirubinemic diseases (Gilbert’s syndrome)
Genetic polymorphisms (GSTM1) in GST (mu1 isoform)
expression can lead to significant adverse effects and toxicities
of drugs dependent on its (blank) for elimination.
GSH conjugation
are known to
contribute to 100,000 annual US deaths, about 7% of all
hospital admissions, and an increased average length of
hospital stay.
Severe ADRs (adverse drug reactions)
could greatly enhance safe and
efficacious clinical therapy through dose adjustment or
alternative drug therapy, thereby curbing much of the
rising ADR incidence and its associated costs.
Genotype information
increasingly recognized that the human gut microbiome
can also significantly influence drug responses. It thus
serves as another relevant source of therapeutic
misadventures and adverse drug-drug interactions.
Commensal Gut Microbiota
More than (blank) species of intestinal microorganisms have
been identified, including obligate anaerobic bacteria and
various yeasts that coexist in a dynamic, often symbiotic,
ecological equilibrium.
1000
Their biotransformation repertoire is non-oxidative albeit
highly versatile, extending from predominantly reductive
and hydrolytic reactions to
decarboxylation,
dehydroxylation, dealkylation, dehalogenation, and
deamination.
contribute to individual
variations in drug metabolism.
Diet & Environmental Factors
foods and cruciferous vegetables are
known to induce CYP1A enzymes, whereas (blank)
is known to inhibit the CYP3A metabolism of co-
administered drug substrates
Charcoal-broiled foods, grapefruit juice
metabolize some drugs more rapidly
than nonsmokers because of enzyme induction.
Cigarette smokers
exposed to some pesticides
metabolize certain drugs more rapidly than unexposed
individuals.
Industrial workers
Such differences make it difficult to determine
effective and safe doses of drugs that have
narrow therapeutic indices.
Increased susceptibility to the pharmacologic or toxic
activity of drugs has been reported in very young and very
old patients compared with
young adults
Although this may reflect differences in absorption,
distribution, and elimination, differences in (blank)also play a role.
drug
metabolism
could be due to reduced activity of
metabolic enzymes or reduced availability of essential
endogenous cofactors.
Slower metabolism
