Background
Opioids have been used as painkillers for thousands of years. Initially in the form of opium, the dried milky sap of the opium poppy L. (Papaveraceae). In the early 19th century, the pure opium alkaloid morphine was isolated for the first time and later administered with the newly invented hypodermic needle. In the 20th century, numerous derivatives and synthetic opioids were developed and became subject to narcotics laws. Among them are some active ingredients that are no longer derived from the natural alkaloids. For example, pethidine, fentanyl and methadone are derived from the tropane alkaloid atropine from nightshade plants. Opioids is the collective name for all active ingredients; natural ingredients such as morphine and codeine are referred to as opiates. Opioid peptides such as the endorphins and enkephalins are the natural ligands of opioid receptors.
Effects
Opioids (ATC N02A) are primarily analgesic and analgesic-distancing. Unlike other analgesics such as nonsteroidal anti-inflammatory drugs, they have neither anti-inflammatory nor antipyretic properties. Opioids are additionally sedating (depressant), psychotropic (affecting the psyche), sedative, and cough-irritant, among others. The effects are due to binding to 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. Agents have different affinities for the different receptors.
Indications
Indications for the use of opioids include:
- Acute and chronic pain of various causes according to the WHO staging scheme, e.g., back pain, osteoarthritis, colic, labor pain, tumor pain, breakthrough pain, and myocardial infarction.
- For symptomatic treatment of irritable cough.
- For symptomatic treatment of diarrhea.
- Use in anesthesia.
- For substitution-assisted treatment, see, for example, under methadone substitution.
Abuse
Opioids have two faces – on the one hand, they are essential and highly effective drugs for pain management. On the other hand, they are abused as intoxicants due to their psychotropic, euphoric and sedative properties. Typical examples are heroin, morphine, codeine and oxycodone – but in principle all opioids can be used as drugs. Because of the high potential for dependence and the life-threatening and destructive adverse effects, abuse is strongly discouraged. Opioids can also be used as doping agents.
Active Substances
- Alfentanil (Rapifen)
- Benzhydrocodone (Apadaz)
- Buprenorphine (e.g., Temgesic, Transtec).
- Carfentanil (veterinary drugs).
- Codeine (numerous medicinal products)
- Dermorphin
- Desomorphine (narcotic)
- Dextromoramide (Palfivet)
- Dextropropoxyphene (out of trade).
- Dihydrocodeine (e.g., Codicontin, Paracodin).
- Ethyl morphine (Phol-Tux)
- Fentanyl (e.g., Durogesic, generic).
- Heroin (Diaphin, narcotic).
- Hydrocodone (Hydrocodone Streuli, out of commerce).
- Hydromorphone (e.g. Palladon)
- Levomethadone (L-polamidone)
- Levorphanol (not commercially available in many countries).
- Methadone (e.g., ketalgine, magistral prescriptions).
- Metopon (not on the market)
- Morphine (eg, MST Continus, morphine drops).
- Nalbuphine (Nalbuphine OrPha)
- Nicomorphine (Vilan, out of commerce).
- Opium (magistral formulations)
- Opium tincture (Dropizol)
- Oripavine (precursor)
- Oxycodone and naloxone (Targine).
- Oxycodone (Oxycontin, Oxynorm).
- Oxymorphone (Opana, generic).
- Pentazocine (Fortalgesic, off label).
- Pethidine (various manufacturers)
- Piritramide (Dipidolor)
- Remifentanil (Ultiva, generic).
- Sufentanil (Sufenta, generics)
- Tapentadol (Palexia)
- Tilidine (Valoron)
- Tramadol (Tramal, generics)
Opioid antagonists are antagonists at opioid receptors and cancel the effects of opioids. They are used in cases of poisoning, detoxification, alcohol dependence, constipation and to stop the effects of opioids, among others.
Contraindications
Numerous precautions must be observed during use. Full details can be found in the drug label.Contraindications include hypersensitivity, concurrent therapy with MAO inhibitors, respiratory failure, respiratory depression, intestinal obstruction, delayed gastric emptying, liver disease, increased intracranial pressure, traumatic brain injury, and severe obstructive pulmonary disease.
Interactions
- Some opioids are biotransformed by CYP450 isozymes and are susceptible to drug-drug interactions with CYP inhibitors and CYP inducers.
- Centrally depressant drugs may increase side effects and respiratory depression. These include other opioids, sedatives, sleeping pills, neuroleptics, muscle relaxants, antihistamines, and alcohol. A combination may be life-threatening.
- Combination with MAO inhibitors is not indicated because serious adverse effects are possible.
- Anticholinergic agents may increase anticholinergic side effects.
- Opioid antagonists cancel the effects of opioids.
Adverse effects
Opioids are potent agents and must be administered with caution. An overdose is life-threatening and manifests as respiratory paralysis, low blood pressure, low pulse, circulatory failure, and coma. Particularly feared is the possible respiratory depression. Possible side effects, which also occur with therapeutic doses, include:
- Constipation, nausea, vomiting, dry mouth, loss of appetite.
- Central and psychiatric disorders such as dizziness, headache, fatigue, drowsiness, confusion, anxiety, euphoria, dysphoria.
- Small pupils (miosis)
- Respiratory depression
- Itching, rash, redness of the skin, sweating.
- Urinary retention
- Hyperalgesia: Paradoxically increased sensitivity to pain.
- Cardiovascular disturbances such as low blood pressure, slow heartbeat.
- Development of tolerance, dependence and addiction, withdrawal syndrome after discontinuation.
Of advantage is that opioids do not cause organ damage like other painkillers.
