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

4–30 | Clinical Manual for Management of the HIV-Infected Adult/2006
Ecstasy (X, MDMA) and GHB (gamma hydroxybutyrate)
Ecstasy is an
amphetamine-like
compound that has
similar metabolism
as amphetamine
compounds, with
the major portion
metabolized by CYP2D6.
GHB is also thought to be
metabolized through the
CYP2D6 isoenzyme.
Inhibition of CYP2D6 is likely to impair
detoxification of ecstasy and GHB
because of large increases in serum
levels.
Such inhibitors include:
• Ritonavir (increases ecstasy levels
by 5- to 10-fold)
• Delavirdine
• SSRIs
Heroin, Morphine, Hydromorphone, and Codeine
Morphine and
hydromorphone
are extensively
metabolized to
glucuronides, mediated
by glucuronosyltransferases.
Codeine is mainly
metabolized by
glucuronidation, but
minor pathways include
a process mediated by
CYP2D6.
Heroin is converted
to morphine in the
blood rapidly and is
metabolized similarly.
Ketamine (Special K)
Undergoes extensive
demethylation and
hydroxylation in the liver,
possibly via CYP3A4, and
is excreted in the urine.
Ketamine is structurally
similar to phencyclidine
and may undergo similar
metabolism.
Plasma concentrations of all these
agents may be decreased by
agents that increase the activity
of glucuronosyltransferases (eg,
ritonavir). In the presence of ritonavir,
heroin serum concentrations
are reduced by as much as 50%.
Administration of codeine with
a CYP 2D6 inhibitor may inhibit
the bioactivation of codeine into
morphine.
CYP 3A4 inhibitors could inhibit the
metabolism of ketamine, resulting in
elevated serum concentrations of the
compound.
A wide range of CYP3A4 inhibitors can
play a significant role in interactions
with ketamine, including:
•
•
•
Protease inhibitors
Macrolide antibiotics
Delavirdine
At least 2 deaths from the
combination of ritonavir and ecstasy
have been reported.
Ritonavir can increase the risk of
life-threatening adverse effects
from ecstasy (eg, heatstroke and
dehydration) and GHB (eg, seizures,
bradycardia, respiratory depression,
loss of consciousness).
Dehydration effects of these
medications could increase the risk
of renal stones in patients taking
indinavir.
Decreased levels of all these agents
may result in loss of therapeutic effect
when administered with ritonavir.
Patients abusing these agents who
add ritonavir may develop withdrawal
symptoms, including lacrimation,
rhinorrhea, irritability, tachycardia,
elevated blood pressure, chills,
flushing, sweating, seizures, myalgias,
and arthralgias.
There is also potential for an increase
in a glucuronide metabolite, which is
45 times more potent than the parent
compound. This increase in active
metabolite could offset the abovedescribed
decreases in parent opiates.
Ketamine has a reported wide
margin of safety; however, elevated
serum concentrations could result in
increased heart rate, increased blood
pressure, or respiratory depression.
Chronic use of ketamine in the
presence of ritonavir may increase
ketamine concentrations and the
potential for hepatotoxicity and druginduced
hepatitis.
Strongly recommend avoiding the
combination of ecstasy or GHB with
ritonavir or other potent CYP2D6
inhibitors.
Recent research has shown that ecstasy
affects serotonin levels and can increase
the potential for depression and anxiety
disorders in individuals at risk.
At least 68 deaths have been attributed
to the combination of ecstasy and
alcohol.
Patients taking these agents with
ritonavir or a CYP2D6 inhibitor (of
codeine) should be monitored either for
loss of therapeutic effect (in the case of
prescribed opiates) or for withdrawal
symptoms.
Caution should be exercised with
concomitant use of ketamine and
agents that are CYP3A4 inhibitors.
Two cases of drug-induced hepatitis
have been reported in patients
concomitantly using ketamine and
ritonavir.
Ketamine is often added to other illegal
psychoactive substances such as ecstasy,
marijuana, and others.