Opioids

Collective term for synthetic or semi-synthetic substances which have a morphine-like effect (an effect corresponding to that of natural opium; morphine is the most important constituent of opium, accounting for 10% of its content). Morphine and all other substances with a morphine-like effect occurring naturally in opium (codeine, noscapine) are grouped together under the term opiates. Classification according to:

• endogenous opioids (so-called opioid peptides)
• exogenous opioids (administered to the body with therapeutic or abusive intent).

An important group of exogenous opioids are the opioid analgesics. These are opioid receptor antagonists.

The best known semisynthetic opioid is heroin, which is produced from morphine by a chemical process (acetylation). Other fully synthetic opioids include fentanyl and methadone. Opioid peptides, like endorphins (composed of "endogenous and morphine"), are so-called "endogenous opiods". They are the natural ligands of the opioid receptors.

According to their action at the opioid receptor, opioids are divided into:

Opiod (receptor) agonists

• Morphine
• Fentanyl
• Oxycodone
• Methadone
• Pethidine

Partial agonists

• Buprenorphine
• Codeine
• Tilidine
• Tramadol
• Dihydrocodeine

Mixed opioid (receptor) agonists/opioid (receptor) antagonists

• Buprenorphine

Opioid (receptor) agonists lead to activation, whereas opioid (receptor) antagonists lead to blockade of opioid receptors. Mixed agonist-antagonists simultaneously activate and inhibit different receptors. The only representative in this group is buprenorphine, which acts as an aprtial agonist at the µ-receptor and as an agonist at the kappa-receptor.

The opioid (receptor) agonists can be further subdivided into:

• strong opioid agonists (have no ceiling effect; these include: morphine, piritamide, fentanyl, burenorphine, oxycodone, methadone)

• weak opioid agonists (have a ceiling effect, including partial agonists such as codeine, dihydrocodeine, tilidine, tramadol)

according to their intrinsic potency at the receptor (Schäfer M 2009).

The effects of opiods are due to their binding to and activation of endogenous opioid receptors found in the brain, spinal cord, and peripheral nervous system, among others. These include the μ(Mü), δ(Delta), and κ(Kappa) opioid receptors. The individual opiod representatives have different affinities for the various receptors.

Analgesic action: Opioids, like the opiates, have a primary analgesic and analgesic-distancing action (see pain below). They are effective for severe and most severe pain. Unlike other analgesics such as the non-steroidal anti-inflammatory drugs, opioids have neither anti-inflammatory nor antipyretic properties.

Psychotropic effects: Opioids have sedative (depressant), psychotropic (euphoric), sedative effects. For the euphoric effect, higher opioid plasma levels are necessary than for the analgesic effect. They are due to activation of the mesolimbic dopaminergic praise pathways. Dopamine release in the n. accumbens is the neurochemical correlate of euphoria.

Dysphoric effects are due to activation of κ-receptors, leading to inhibition of the mesolimbic reward system (no longer plays a role with current opioids).

Respiratory depressant effects: excitation of µ-receptors in the medula oblongata decreases the sensitivity of the respiratory centre to the stimulatory effects of_CO2.

Cardiovascular effect: Opioids increase vagotonus leading to bradycardia . Furthermore, they cause hypotension.

Miotic effect: The constriction of the pupils is caused by the activation of the µ and kappa receptors. The pin-sized pupil is pathognomic of morphine or heroin intoxication.

Nausea, constipation, drowsiness, pupil constriction, pulmonary oedema, danger of addiction. Acute itching (<6 weeks) after taking opiod analgesics can often occur.

The opioids include:

• alfentanil
• buprenorphine
• codeine
• decocin
• dihydrocodeine
• fentanyl
• heroin
• hydromorphone
• levomethadone
• meptazinol
• methadone
• Methylnaltrexone
• morphine
• nalbuphine
• naloxone
• naltrexone
• oxycodone
• Pentazocine (withdrawn from the market)
• pethidine
• piritramide
• Remifentanil
• Sufentanil
• Tapentadol
• tilidine
• tramadol.

1. Graefe KH et al. Nociceptoves System. In: Graefe KH et al. (Eds) Pharmacology and Toxicology. Georg Thieme Verlag Stuttgart p.223-229

2. Schäfer M (2009) Mechanisms of opioid actions. In: Anesthetic pharmacology: physiologic principles and clinical practice, 2nd edition. Churchill LivingstoneGoogle Scholar