Enkephalinomimetic drugs - Morphinomimetic analgesics
They are synthetic derivatives whose pharmacological properties are very close to those of morphine.
Meperidine and other phenylpiperidine derivatives
Meperidine, also called pethidine, is approximately 10 times less analgesic than morphine, but the dose of meperidine used is approximately 10 times higher than that of morphine. Its duration of action by intramuscular route, approximately 2 to 3 hours, is shorter than that of morphine. T he respiratory depression induced by meperidine is equal or lower than that of morphine. It causes is less spasmogenic effect, induces less constipation and less miosis than morphine because it has an atropinic effect.
Fentanyl, alfentanil, sufentanil and remifentanil are other phenylpiperidine derivatives and are extremely powerful analgesics
Used in anesthesia by injection, systemic or epidural, their action is rapid and of short duration, approximately 30 minutes. They have, moreover, cholinomimetic effects such as bradycardia or lowering of arterial pressure, which can be prevented by atropine administration. Naloxone (see further) reverses their analgesic effect.
Transdermal devices for sustained-release of fentanyl to renew every 72 hours can be used for the treatment of chronic pain, particularly in patients with cancer. These devices are designed to release a constant quantity of fentanyl per hour under normal conditions.
Fentanyl is also presented in the form of tablets intended for the treatment of paroxystic access of pains occurring in cancer patients already taking a basal analgesic treatment.
Transdermal or oral administration does not exempt precautions for use nor risk of respiratory depression. Even administered by transdermal route, fentanyl causes constipation which is generally less than that induced by morphine. Fentanyl can induce various neuropsychiatric disturbances.
Dextromoramide, methadone and propoxyphene
Dextromoramide, methadone and propoxyphene are derivatives of diphenylpropylamine.
Dextromoramide is an analgesic which has properties similar to those of morphine over which it does not have any particular advantage. To the adverse effects of morphine, the possibility of states of indifference or excitation with delusion as well as intracranial hypertension may be added.
Methadone is primarily used as a substitute for morphine in patients dependant on morphine analogues.
The effects of methadone are similar to those of morphine, but it has different pharmacokinetic features: good bioavailability by oral route, long duration of action because of its long plasma half-life, about 35 hours, tissue redistribution and formation of active metabolites.
This long duration of action, with gradually attenuating effects, decreases the intensity of the withdrawal syndrome which exists however. Several drug interactions with methadone were described such as rifampicin, which accelerates methadone catabolism (by enzyme induction) with increased risk of withdrawal syndrome.
Dextropropoxyphene, structurally related to methadone, has analgesic activity in the range of that of codeine. Its adverse effects are gastralgia, nausea, constipation, drowsiness. In the event of overdose, one can observe hallucinations, confusions, seizures, consciousness disorders, respiratory depression and even death. The antagonist of propoxyphene is naloxone.
In many pharmaceutical preparations dextropropoxyphene is combined with acetaminophen.
Tramadol is an analgesic active by oral route, whose efficacy approaches that of codeine and propoxyphene. It is transformed in the body into an active metabolite, O-desmethyltramadol .In addition to its agonist effect on mu opioid receptors it inhibits serotonin and norepinephrine reuptake. Its most frequent adverse effect is dizziness but, in overdose, symptoms corresponding to sympathetic stimulation, tachycardia, hypertension, are possible. It can cause seizures.