5.20
コリン作動阻害剤：薬物動態
コリン作動阻害剤、例えば抗ムスカリン薬などは、経口、局所、眼球、皮下、および吸入剤の形で利用可能です。多くの抗ムスカリン薬は経口剤であり、—方でスコポラミンはトピカルパッチとして、イプラトロピウムとチオトロピウムは吸入用エアゾルや粉末として利用可能です。アトロピン、トロピカミド、およびシクロペンタテ…
抗ムスカリン薬などのコリン作動性拮抗薬は、経口投与、点眼薬、経皮パッチ、エアロゾル、または注射剤として投与されます。
第四級抗ムスカリン薬はイオン性であるため、脂質溶解性が低く、BBBへの浸透が制限されていることを思い出してください。さらに、腸、皮膚、または目からの吸収が不十分です。
対照的に、三級誘導体は脂質溶解度が高く、中枢および末梢によく吸収されます。
これらの薬剤は作用持続時間が異なるため、SAMAおよびLAMAに分類されます。
それらは肝臓で加水分解または抱合によって代謝され、尿を介して排泄されます。
抗ムスカリン薬の効果は、抗ヒスタミン薬、抗精神病薬、抗うつ薬などの抗コリン作用を持つ薬物と同時投与すると、その相加的な副作用により顕著になります。.
最後に、抗ムスカリン薬は胃の蠕動運動を部分的に抑制し、胃内容排出を遅らせ、同時投与された薬物の吸収を遅らせることが知られています。
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Q1: What are the different routes of administration for cholinergic antagonists?
Cholinergic antagonists are administered through multiple routes including oral formulations, topical eye drops, transdermal patches, inhalational aerosols or powders, and injections. Most antimuscarinics are available as oral formulations, while scopolamine is delivered as a topical patch. Ipratropium and tiotropium are available as inhalation aerosols or powders, and atropine, tropicamide, and cyclopentolate are topically instilled in the eye.
Q2: How does the chemical structure of antimuscarinics affect their absorption and distribution?
Quaternary antimuscarinics are ionic with low lipid solubility, resulting in poor absorption from the gut, skin, or eye and restricted penetration to the blood-brain barrier. Tertiary derivatives have higher lipid solubility and are well-absorbed both centrally and peripherally. When inhaled, quaternary antimuscarinics have limited systemic absorption due to their reduced lipid solubility.
Q3: How are antimuscarinics metabolized and eliminated from the body?
Antimuscarinics undergo hepatic metabolism through hydrolysis or conjugation and are primarily excreted via urine. Atropine rapidly metabolizes in the liver and is excreted unchanged in the urine. Most swallowed ipratropium and tiotropium are excreted through feces, while elimination of quaternary compounds is generally slower than tertiary agents.
Q4: What is the difference between short-acting and long-acting antimuscarinics?
Antimuscarinics are classified based on their duration of action as short-acting or long-acting agents. Short-acting antimuscarinics include ipratropium, while long-acting agents include glycopyrrolate, tiotropium, and aclidinium. This classification helps determine dosing frequency and clinical application for different therapeutic conditions and patient needs.
Q5: Which drugs interact with antimuscarinics and why is this clinically significant?
Antimuscarinics interact with tricyclic antidepressants, antihistamines, antianxiety agents, and antipsychotics, exacerbating antimuscarinic side effects due to additive anticholinergic properties. Additionally, antacids can increase stomach pH and form complexes with antimuscarinics, reducing their absorption. These interactions require careful monitoring during co-administration.
Q6: How do antimuscarinics affect gastric motility and drug absorption?
Antimuscarinics partially suppress peristaltic movement of the stomach, delaying gastric emptying and slowing the absorption of co-administered drugs. This effect can significantly impact the bioavailability and onset of action of other medications taken concurrently with antimuscarinics, requiring dose timing adjustments.
Q7: Why do quaternary antimuscarinics have limited systemic absorption when inhaled?
Quaternary antimuscarinics are ionic compounds with low lipid solubility, which restricts their ability to cross biological membranes. When inhaled, this reduced lipid solubility results in limited systemic absorption, allowing these agents to act primarily at local respiratory sites with minimal systemic effects and reduced side effects.