Tolerance
may be acquired to the effects of many drugs, especially the opioids,
barbiturates, and other CNS (central nervous system) depressants. When this
occurs, cross-tolerance may develop to the effects of pharmacologically
related drugs. Tolerance to a pain medication will be manifested as an increase
in pain after the frequent use of the analgesic (pain medication). Tolerance
has been described to develop in as short as 10 days. Although this process may
take as long as a year in some patients, it is safe to assume that it will
occur to everybody who takes this type of medication on chronic basis. In our
practice, we try to assess the patient's narcotic requirements in as short of a
time period as possible. As soon as the patient admits to be comfortable on a
certain dose, we call such a dose "the patient's requirement".
Thereafter, any increases in the pain, within an otherwise stable condition, is
considered to be due to the development of tolerance. A common complaint of
patients is that, "the medications don't seem to work as well as they use
to." Tolerance also occurs to the use of medications directly injected
into the spine, as it is the case with Baclofen or Morphine Pumps. Interestingly,
this seems to occur approximately 8 month after the beginning of the therapy.
It is currently thought that there is an interesting phenomenon, unique to
pumps, where after a patient undergoes the first ìDrug Holidayî, the
development of tolerance seems to either slow down, or even not reoccur.
It is a
common misconception that changing from one narcotic to another prevents
the development of tolerance. Switching from one narcotic to another does
not help with tolerance, because of cross-tolerance. In fact, it
complicates the management of the patient's condition since it introduces more
variables. Essentially, what happens is that the substituting narcotic is
probably been given at a higher, non-equivalent dose, which gives the patient
and the unsuspecting physician the illusion that it is working, when in fact
the only thing that has been accomplished is an increased in the opioid dose.
It is a well known fact that tolerance is a problem that originates at the
level of the opiod receptors in the human body. Since most narcotics (opiods)
work at the same receptor, it is easy to understand why switching the medicine
would not solve the problem.
Most of the
tolerance seen with opioids is due to adaptation of cells in the nervous system
to the drug's action. The use of increased amounts may in turn enhance the risk
of toxic effects or produce other problems if the drug is expensive or obtained
illicitly. Although the lethal doses greatly altered in tolerant individuals, a
dose always exist that is capable of producing death from respiratory
depression. Tolerance to opioids largely disappears when withdrawals have been
completed, and many addicts have taken fatal overdoses by returning to their
previous dosage immediately after undergoing withdrawal.
Contrary to
alcohol or benzodiazepines withdrawals, narcotic withdrawals are, for the most
part, not lethal. In the case of short acting narcotics, such as morphine,
withdrawals can occur 12 to 14 hours after the last dose, reaching their peak
at 48 to 72 hours, and disappearing in 7 to 10 days. With longer acting
narcotics, such as methadone, withdrawals can begin 24 to 48 hours after the
last dose, reaching a peak at the 3rd day, and may not begin to
decrease until the 3rd week. They usually consist of: lacrimation,
runny nose, yawning, sweating, dilated pupils, loss of appetite, goosebumps,
restlessness, irritability, tremors, insomnia, sneezing, weakness, depression,
nausea, vomiting, diarrhea, abdominal cramps, chills, bone and muscle pains,
increased in respiratory rate, heart rate and blood pressure, muscle spasms,
cold and hot flashes, and increase in body temperature. For the most part,
withdrawals are more severe for the short-acting narcotics than for the long-acting.
This is the
name given to the period during which the medications are stopped. Drug
Holidays should always be tailored to the pharmacokinetics of the medication
for which it is intended. (e.i. in the above mentioned example for morphine,
they should be 7 to 10 days in duration while in the case of methadone, they
should be 3 weeks in duration.) During the Drug Holidays, clonidine can be
administered in the form of a 0.1 mg patch x one week, to help with the
hyperactivity of the sympathetic autonomic nervous system. During the Drug
Holidays, because of cross-tolerance, patients should not be allowed to
switch to another opioid. When returning to the opioid, at the end of the Drug
Holiday, the patient should always be started at a lower dose than the dose
prior to the Drug Holiday. They should be repeated as often as necessary to
allow the patient to control his/her medication intake, rather than allowing
the medication to control the patient. In the case of intrathecal pumps, the
narcotic can be substituted for another type of medicine, such as Baclofen (an
anti-spasmodic), Bupivacaine (a local anesthetic), or clonidine (a blood
pressure medicine with the ability to cause sedation and decrease the
sympathetic response to withdrawals). Your physician will discuss with you what
the best alternative may be.