Clinical Manual for Management of the HIV-Infected ... - myCME.com

Recreational Drugs and Antiretroviral Therapy
Background
Very few data are available on interactions between
antiretroviral (ARV) medications and recreational
drugs. No controlled trials have investigated this issue
because of the legal and ethical issues regarding the
use of illicit agents. Most available information on
interactions between ARVs and recreational drugs has
been derived from pharmacokinetic studies and from
case reports. In addition, projections about ARV-drug
interactions have been based on what is known about
interactions between ARVs and similar agents.
Most phenomena related to drug-drug interactions arise
from the pharmacokinetic properties of each interacting
agent, specifically their metabolism and excretion.
One relevant issue is enzyme induction or inhibition,
explained as follows:
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Different agents have different effects on the liver
enzyme systems, specifically cytochrome p450
enzymes, used to metabolize the active form of
many agents.
Inducers are agents that increase the activity of these
enzymes, resulting in increased metabolism and
decreased serum concentration of the active drug
form. This lower drug concentration could cause a
loss of therapeutic efficacy of the interacting drug.
Inhibitors are agents that decrease the activity of
these enzymes, resulting in decreased metabolism
and increased serum concentration of the active drug
form. This higher drug concentration could lead to
increased drug toxicity.
Some agents have both inhibiting and inducing
activity, making assessment of drug interactions
more complicated.
Section 4—Complications of Antiretroviral Therapy | 4–27
Some agents exert most of their pharmacologic
activity through their active metabolites, in which
case inhibition and induction could affect the parent
compound and the active metabolite in different
or even opposite ways. For example, an agent that
inhibits the metabolism of a parent drug would
increase levels of the parent drug but decrease the
concentration of active metabolites. If the parent
compound has little pharmacologic effect compared
with the active metabolite, the net effect could be
decreased pharmacologic activity. This consideration
further complicates drug-drug interactions and the
understanding of their clinical significance. Further
considerations include the following:
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Some agents are not metabolized by the liver, but
instead are cleared by the kidneys and excreted in
the urine.
In the presence of hepatic or renal impairment, the
metabolism and excretion of certain agents may
be impaired, thus possibly increasing the amount
of drug in the body or the amount of its toxic
metabolites. Hepatic or renal dysfunction also may
worsen drug-drug interactions.
Street drugs are often impure, and sometimes are
not what they are thought to be. They are frequently
cut with substances that may themselves interact
with ARVs or other drugs, and their potency can
vary widely, even within the same batch.
Table 1 lists potential and documented drug
interactions associated with commonly used recreational
drugs. Pharmacokinetic properties and the interacting
agents are discussed briefly.