The opioids include natural opiates and semisynthetic alkaloids derived from the opium poppy, pharmacologically similar synthetic surrogates, and endogenous peptides. On the basis of their interaction with opioid receptors, the drugs are classified as agonists, mixed agonist-antagonists, and antagonists.
Opioid peptides released from nerve endings modulate transmission in the brain and spinal cord and in primary afferents via their interaction with specific receptors. Many of the pharmacologic actions of opiates and synthetic opioid drugs are effected via their interactions with endogenous opioid peptide receptors.
|Opiate||A drug derived from alkaloids of the opium poppy|
|Opioid||The class of drugs that includes opiates, opiopeptins, and all synthetic and semisynthetic drugs that mimic the actions of the opiates|
|Opioid peptides||Endogenous peptides that act on opioid receptors|
|Opioid agonist||A drug that activates some or all opioid receptor subtypes and does not block any|
|Partial agonist||A drug that can activate an opioid receptor to effect a submaximal response|
|Opioid antagonist||A drug that blocks some or all opioid receptor subtypes|
|Mixed agonist-antagonist||A drug that activates some opioid receptor subtypes and blocks other opioid receptor subtypes|
The opioid analgesics and related drugs are derived from several chemical subgroups and may be classified in several ways.
Spectrum of Clinical Uses
Opioid drugs can be subdivided on the basis of their major therapeutic uses (eg, analgesics, antitussives, and antidiarrheal drugs).
On the basis of their relative abilities to relieve pain, the analgesic opioids may be classified as strong, moderate, and weak agonists. Partial agonists are opioids that exert less analgesia than morphine, the prototype of a strong analgesic, or full agonist.
Ratio of Agonist to Antagonist Effects
Opioid drugs may be classified as agonists (receptor activators [full or partial]), antagonists (receptor blockers) or mixed agonist-antagonists, which are capable of activating one opioid receptor subtype and blocking another subtype.
Absorption and Distribution
Most drugs in this class are well absorbed when taken orally, but morphine, hydromorphone, and oxymorphone undergo extensive first-pass metabolism. In most cases, opioids can be given parenterally, and sustained-release forms of some drugs are now available, including morphine and oxycodone. Opioid drugs are widely distributed to body tissues. They cross the placental barrier and exert effects on the fetus that can result in both respiratory depression and, with continuous exposure, physical dependence in neonates.
With few exceptions, the opioids are metabolized by hepatic enzymes, usually to inactive glucuronide conjugates, before their elimination by the kidney. However, morphine-6-glucuronide has analgesic activity equivalent to that of morphine, and morphine-3-glucuronide (the primary metabolite) is neuroexcitatory. Codeine, oxycodone, and hydrocodone are metabolized by cytochrome CYP2D6, an isozyme exhibiting ...