オピオイドとその作用機序、薬物動態、薬理作用、薬物相互作用、およびオピオイド受容体に関する詳細な情報を提供しています。以下は、テキストの要約です。
オピオイドは神経細胞の過分極を引き起こし、神経伝達系を抑制することで鎮痛作用を発揮します。モルヒネ、フェンタニル、およびレミフェンタニルなどの代表的なオピオイドの薬物動態や特性が比較されています。それぞれのオピオイドは異なる特性を持ち、使用時の注意が必要です。
鎮痛作用のメカニズムには、脊髄後角で神経伝達物質の放出を抑制することが含まれます。オピオイドは中脳水道周囲灰白質にも作用し、下行抑制系を活性化することで脊髄後角での鎮痛作用を示します。また、末梢神経における鎮痛作用も報告されています。
オピオイドの使用には注意が必要であり、呼吸抑制や依存性などの副作用があることが指摘されています。特に、ベンゾジアゼピン系の薬物との併用は呼吸抑制が増強され、死亡事故が生じる可能性があるため注意が必要です。
オピオイド受容体はμ、κ、δ、σ、εの5つがあり、それぞれ異なる作用を示します。これらの受容体の作用によって、鎮痛、鎮静、呼吸抑制、徐脈などが引き起こされます。
最後に、医療大麻との併用に関する情報も提供されています。医療大麻は低用量でオピオイドの鎮痛効果を増強し、過剰摂取による死亡者数の低下が報告されています。
This text provides detailed information on opioids, including their mechanism of action, pharmacokinetics, pharmacological effects, drug interactions, and opioid receptors. Here is a summary of the key points:
Opioids are believed to induce hyperpolarization of nerve cells through the binding of opioids to opioid receptors, leading to the inhibition of the neurotransmission system via G-proteins. However, many aspects of the neural circuits involved are still unclear.
The pharmacokinetics and characteristics of opioids such as morphine, fentanyl, and remifentanil are compared, highlighting differences in pKa, ionization rates, lipid solubility, plasma protein binding, distribution volume, and clearance.
The mechanism of analgesic action involves the inhibition of neurotransmitter release from primary afferent nerve terminals in the spinal cord, suppressing the excitability of nociceptive neurons. Opioids also activate the descending inhibitory pathways in the central nervous system, providing analgesic effects at the spinal cord level and higher brain regions. Different opioids vary in potency, and the analgesic effect does not always parallel respiratory depression or sedation.
Opioids have central effects, including sedation, and can decrease the minimum alveolar concentration (MAC) of inhalation anesthetics. Prolonged use of opioids can lead to tolerance, dependence, and habituation. Opioids may induce pruritus as a side effect, and the exact mechanism is unclear.
In the respiratory system, opioids inhibit reflexes in the upper and lower airways, suppress cough reflex, and can cause respiratory depression. The respiratory depressant effect is dose-dependent and can be significant in conditions such as renal or hepatic impairment, necessitating careful monitoring.
Opioids have minimal cardiovascular effects, making them safe for use in patients with heart conditions. They may even reduce the volume of ischemic lesions in myocardial infarction. However, morphine can cause histamine release, leading to hypotension, which can be prevented by H1 and H2 receptor antagonists.
In the gastrointestinal system, opioids act on central and gastrointestinal opioid receptors, causing relaxation of the lower esophageal sphincter, inhibiting gastrointestinal motility, and often leading to constipation. Opioids may also stimulate the Oddi sphincter, causing increased bile duct pressure.
Opioids affect the urinary system by contracting the muscles of the ureters, bladder detrusor muscle, and urethral sphincter, leading to urinary retention. Opioids may cause histamine release, resulting in nausea and vomiting by acting on the chemoreceptor trigger zone in the medulla.
Opioids can induce skeletal muscle rigidity, particularly in high doses. The exact mechanism is unknown, but it may involve changes in the GABA and dopamine systems in the basal ganglia. Opioids do not directly affect neuromuscular junctions, so opioid-induced muscle rigidity is not reversed by muscle relaxants.
Opioids have an anti-stress effect, suppressing the excessive stress response induced by surgical trauma. This can be beneficial during anesthesia for surgery.
Drug interactions, both pharmacodynamic and pharmacokinetic, are discussed. Benzodiazepines combined with opioids can enhance respiratory depression, increasing the risk of unintentional death.
Oxycodone may interact with CYP2D6 inhibitors, potentially increasing its blood concentration. Fentanyl inhibits CYP3A4.
Opioid receptors include μ (mu), κ (kappa), δ (delta), σ (sigma), and ε (epsilon). μ and κ receptors are particularly significant in clinical medicine.
The text also briefly mentions the use of medical cannabis alongside opioids. Medical cannabis, when accessed, has been reported to enhance the analgesic effect of opioids, and states with legalized medical cannabis have seen a decrease in opioid overdose deaths.
Please note that this is a concise summary, and for more in-depth understanding, the original text should be referred to.