Opioids

Introduction

Opioids, a diverse group of substances, are typified by morphine. They include a number of prescription and illicit drugs and are often prescribed for both acute and chronic pain. They can be short- or long-acting and can be administered by many different routes, including oral, intravenous, subcutaneous, buccal, inhaled and transcutaneous. Opioids are among the commonest causes of drug-related deaths in Australia. The rate of accidental opioid deaths has more than doubled among Australians aged 35 to 44 since 2007, with greater than two-thirds of these deaths due to pharmaceutical opioids rather than heroin. Death from opioids is usually due to severe respiratory depression resulting in hypoxia. Death may occur many hours after ingestion, particularly from long-acting preparations, if patients are not carefully monitored. Furthermore, it is important to note than many opioid agents can have other toxic effects ( Table 25.23.1 ).

Pharmacology

Opioid drugs act both in the central and peripheral nervous systems. They act as agonists on various types of opioid receptors, but it is the mu opioid receptor that is responsible for the preponderance of clinical effects. These receptors are widespread and are found not only within the nervous system but also in other tissues, including the gastrointestinal tract, cardiovascular and immune systems. Some opioids act on non-opioid receptors, which can produce other toxic effects in overdose; for example, tramadol also inhibits both serotonin and noradrenaline reuptake, whereas methadone inhibits the hERG potassium channel.

The pharmacokinetics of opioids differ between agents. For example, there is varying bioavailability within the group, from low (10% oral bioavailability with buprenorphine) to high (70% with oxycodone) (see Table 25.23.1 ). The onset of toxicity is dependent on the route of administration. Opioids are in general rapidly absorbed, with peak concentrations within minutes of intravenous injection, 1 hour of intramuscular administration and 2 hours of oral ingestion. The metabolism of opioids occurs mainly in the liver via the cytochrome P450 system and conjugating enzymes. Metabolism can result in inactive and active metabolites. Duration of action varies between agents and formulations. Oral controlled-release formulations of morphine and oxycodone and topical preparations of fentanyl can have prolonged absorption with toxicity lasting for many hours. Table 25.23.1 gives an overview of the commonly prescribed and abused opioids and their pharmacokinetic properties.

Clinical effects

The main presenting features of opioid toxicity include miosis, central nervous system (CNS) and respiratory depression. The CNS effects can range from mild drowsiness to profound coma. Other common clinical effects are nausea and vomiting. It is important to note that many opioid agents can have other non-opioid effects specific to that particular agent (see Table 25.23.1 ). For example, tramadol in overdose commonly causes seizures, methadone results in a dose related-QT prolongation and dextropropoxyphene has sodium channel–blocking effects that can result in cardiac arrhythmias.

Opioid toxicity can also result in various complications secondary to a drug’s sedative and respiratory depressive effects. These can commonly include aspiration, non-cardiogenic pulmonary oedema, rhabdomyolysis (long lie), compartment syndrome, acute renal injury and hypoxic brain injury.