Page 55 Guide to Pain Management in Low-Resource Settings

Opioids in Pain Medicine 43

Oxycodone with methadone doses that are 10% of the calculated
equianalgesic doses of conventional opioids. Excretion
Oxycodone is a strong oral μ-opioid agonist belonging occurs almost entirely in the feces, which makes it a
to step 3 of the WHO ladder, with 1.5 times the anal- good candidate for patients with renal failure. Metha-
gesic potency of morphine. Oxycodone has a high oral done has a much lower propensity for euphoric eff ects
bioavailability of 60–80%. It is metabolized in multiple and is therefore used in maintenance programs for
steps to diff erent metabolites, of which oxymorphone drug addicts. In addition, there is incomplete cross-
is the most active and 8 times more potent than mor- tolerance to other opioids. Unfortunately, methadone
phine. Oxycodone has a similar therapeutic profi le to has the potential to initiate Torsades de Pointes, a po-
morphine; however, it is only available as an oral ex- tentially fatal arrhythmia caused by a lengthening of
tended-release formulation (10–80 mg tablets). Since the QT interval in the ECG.
these tablets have a relatively high dose, they can be pul-
verized and made into an aqueous solution, which has
Tramadol
been misused for its euphoric eff ects by addicts.
Tramadol, a weak opioid, belongs to step 2 of the
Hydromorphone WHO ladder. Tramadol itself binds to norepinephrine
and serotonin reuptake inhibitors, which increases lo-
Hydromorphone is a μ-opioid agonist belonging to step cal concentrations of norepinephrine and serotonin,
3 of the WHO ladder (strong opioids) with 4–5 times leading to subsequent pain inhibition. In addition, one
the analgesic potency of morphine. After oral applica- of its metabolites (M1) binds to the μ-opioid receptor,
tion (single dose 4 mg), the onset of analgesia occurs af- which elicits additional analgesia. Tramadol has a high
ter 30 min and lasts up to 4–6 hours. Because of its high bioavailability of 60% and 0.2 times the analgesic po-
water solubility, it is available as both an oral and par- tency of morphine. Since the opioid component is de-
enteral formulation (2 mg/1 amp.) that can be adminis- pendent on hepatic metabolism to the M1 compound,
tered i.v., i.m., or s.c. Hydromorphone is extensively me- genetic variations may diff erentiate poor from exten-
tabolized in the liver, with metabolism of approximately sive metabolizers, and hence the respective diff erences
60% of the oral dose. Th e metabolite hydromorphone- in analgesic eff ects. Tramadol exists as an oral (50–
3-glucuronide can cause neurotoxic eff ects (excitation 100–150–200 mg tablets) and parenteral formulation
syndrome: hyperalgesia, myoclonus, epilepsy), similar to (50–100 mg). As with all opioids, hepatic and renal
morphine-3-glucuronide. impairment may lead to accumulation of the drug with
an increased risk of respiratory depression. Because of
Methadone potential interactions, tramadol should not be given
together with monoamine oxidase inhibitors, since the
Methadone is a μ-opioid receptor agonist with 0.3 combination may produce severe respiratory depres-
times the analgesic potency of morphine. In addition sion, hyperpyrexia, central nervous system excitation,
to its opioid receptor activity, it is also an antagonist delirium, and seizures.
of the N-methyl-D-aspartate (NMDA) receptor, which
might be advantageous in chronic pain states such as Meperidine
neuropathic pain in which the NMDA receptor seems
to be responsible for the persistent pain hypersensi- Meperidine, a weak μ-opioid agonist, belongs to step 2
tivity. Methadone is a lipophilic drug with good CNS of the WHO ladder with 0.13 times the analgesic po-
penetrability and high bioavailability (40–80%). It ex- tency of morphine and signifi cant anticholinergic and
ists as an oral (5–40 mg tablets) and parenteral for- local anesthetic properties. Meperidine is most often
mulation (levomethadone: 5 mg/mL). Methadone is used postoperatively, since in addition to its analgesic
metabolized with no active metabolites by multiple eff ects, it has anti-shivering properties. Meperidine ex-
diff erent enzymes of the liver in a highly variable ists as an oral (50 mg/mL solution) and parenteral for-
manner, which explains its broad variation of half-life mulation (50–100 mg/2 mL). It is metabolized in the
(up to 150 h) and makes regular dosing quite diffi cult liver to normeperidine with a half-life of 15–30 hours,
for patients. In general, pain relief is better obtained and has signifi cant neurotoxic properties. Meperidine