Goofball Polypharmacy.
Goofball Polypharmacy.
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傻瓜多药房。
DOI：
10.1124/jpet.123.001930
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Cotten,JosephF
中科院分区：
文献类型：
--
作者：
Cotten,JosephF
$35.00 dx。doi。org/10.1124/jpet。123.001930药理学与实验治疗杂志[J] .药理与实验治疗杂志388:241-243，feb 2024版权©2024由美国药理学与实验治疗学会抑郁症。前药海洛因（二乙酰吗啡）可迅速转化为吗啡，尽管芬太尼的临床效价约为吗啡的100倍，但芬太尼和吗啡都具有相似的阿片受体亲和力，这与纳洛酮逆转密切相关（Volpe et al., 2011）。具有较高受体亲和力的其他临床有效芬太尼类似物（例如，舒芬太尼或卡芬太尼）可能对纳洛酮竞争性拮抗剂提供更大的抗性，或在与甲基苯丙胺共给药或与甲基苯丙胺共存时产生独特的毒性。最后，Hiranita等人（2024）对数据进行的大量平均，掩盖了在给药后最初几秒钟观察到的一些动态效应。我和其他人一样，怀疑一些阿片类药物过量死亡可能是由于药物施用后发生的短暂事件，如气道关闭或心源性慢速心律失常。这些迷走神经介导的事件可能是由肺伤害性c纤维（也称为j受体）上的阿片受体激活引发的（Willette和Sapru, 1982； Miner等人，2021）。全身体积脉搏描记包括将整个动物置于封闭的室内（Drorbaugh和Fenn， 1955）。动物吸气后，凉爽干燥的室内空气被吸入肺部，在那里被加热到体温，并与水蒸气饱和，导致室内压力的净增加。舱内压力的频率和幅度的变化，结合舱内温度和湿度的知识，被用来计算呼吸率和潮汐量。该技术的有用之处在于，动物不需要在腔室之外的任何限制，也不需要麻醉来定位，并且只要腔室用新鲜气流清除二氧化碳、热量和水蒸气，它就可以长时间连续地收集数据。然而，容积脉搏波描记术是有限的，因为它不能解决呼吸的功效（即动脉血氧合和二氧化碳消除），也不能突出通气模式之间效率差异的生理影响（例如，快速浅呼吸与缓慢深呼吸）。呼吸方式显著影响肺泡通气和血液氧合。在我看来，正如作者所承认的那样，动脉血气分析通常测量血液pH值和血氧、二氧化碳、碳酸氢盐和乳酸含量，对于理解和解释呼吸研究以及药物对呼吸和代谢的药理影响至关重要。例如，在目前的研究中，d-甲基苯丙胺，特别是在最高剂量（3.2 mg/kg iv）下，导致分钟通气量显著（100%）和持续（bbb60分钟）增加。为什么?代谢（氧气利用和二氧化碳产生）的平行增加可能是原因，因为这种程度的通气增加，没有增加代谢，将导致深度呼吸性碱中毒（即低碳酸血症）。人们可以理解，在d-甲基苯丙胺诱导的高代谢条件下，阿片类药物诱导的低通气是如何拮抗的，并且可能难以耐受。这类似于跑步时屏住呼吸，它的影响最好通过动脉血气分析来理解和量化。值得注意的是，大鼠的动脉血气研究…
1521-0103/388/2/241–243 $35.00 dx. doi. org/10.1124/jpet. 123.001930 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 388: 241–243, Feburary 2024 Copyright© 2024 by The American Society for Pharmacology and Experimental Therapeutics depression. Heroin (diacetylmorphine), a prodrug, is rapidly converted to morphine, and although fentanyl’s clinical potency is approximately 100-fold greater than that of morphine, both fentanyl and morphine have similar opioid receptor affinity, which is germane to naloxone reversal (Volpe et al., 2011). Other clinically potent fentanyl analogs (eg, sufentanil or carfentanil) with higher receptor affinities may provide greater resistance to naloxone competitive antagonism or yield unique toxicities when coadministered with or in the presence of methamphetamine. Finally, the heavy averaging of the data by Hiranita et al.(2024) obscures some of the dynamic effects observed in the first seconds following drug administration. I, as well as others, suspect that some opioid overdose deaths may occur as a result of transient events such as airway closure or cardiac bradyarrhythmias just after drug administration. These vagus nerve–mediated events are likely initiated by opioid receptor activation on pulmonary nociceptive C-fibers, also known as J-receptors (Willette and Sapru, 1982; Miner et al., 2021).Whole-body plethysmography involves placing an entire animal in a closed chamber (Drorbaugh and Fenn, 1955). Upon animal inspiration, cool, dry chamber air is drawn into the lungs, where it is heated to body temperature and saturated with water vapor, causing a net increase in chamber pressure. Variations in the frequency and amplitude of chamber pressure, combined with knowledge of chamber temperature and humidity, are used to calculate breathing rate and tidal volume. The technique is useful in that the animal requires no restraints beyond that of the chamber and no anesthesia for positioning and it enables data collection on a continuous basis for a prolonged period of time, provided that the chamber is cleared of carbon dioxide, heat, and water vapor with fresh airflow. Plethysmography is limited, however, in that it fails to address the efficacy of breathing (ie, arterial blood oxygenation and carbon dioxide elimination) and does nothing to highlight the physiologic impact of efficiency differences between ventilatory modes (eg, rapid shallow vs. slow deep breathing). Alveolar ventilation and blood oxygenation are significantly impacted by the breathing pattern. In my opinion and as acknowledged by the authors, arterial blood gas analysis, which typically measures blood pH and blood oxygen, carbon dioxide, bicarbonate, and lactate content, is essential for understanding and interpreting breathing studies and a drug’s pharmacological impact on breathing and metabolism. For example, in the current study, d-methamphetamine, particularly at the highest doses (3.2 mg/kg iv) caused a marked (100%) and sustained (> 60-minute) increase in minute ventilation. Why? A parallel increase in metabolism (oxygen utilization and carbon dioxide production) is the likely reason since an increase in ventilation of this magnitude, without increased metabolism, would cause profound respiratory alkalosis (ie, hypocapnia). One can appreciate how opioid-induced hypoventilation under conditions of d-methamphetamine–induced hypermetabolism would be antagonistic and likely poorly tolerated. It would be similar to holding your breath while running, and its impact is best appreciated and quantified by arterial blood gas analysis. Of note, arterial blood gas studies in rats by …
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两栖动物变态的激素控制
DOI：
--
发表时间：
1981
期刊：
影响因子：
--
作者：
B. White;C. S. Nicoll
通讯作者：
C. S. Nicoll
对非洲爪蟾的抑制：胸腺诱导剂、脾效应细胞。
影响因子：
6.4
作者：
Ruben,LN;Buenafe,A;Oliver,S;Malley,A;Barr,K;Lukas,D
通讯作者：
Lukas,D
凝集素对南非爪蟾蜍脾脏碎片体外血凝素产生的胸腺抑制作用。
DOI：
--
发表时间：
1985
期刊：
Thymus
影响因子：
--
作者：
Ruben,LN;James,HS;Clothier,RH;Barr,K;Balls,M
通讯作者：
Balls,M
小鼠和人类白细胞介素 2 可以替代非洲爪蟾（南非爪蟾）对 TNP-Ficoll 的免疫反应中的胸腺。
影响因子：
4.3
作者：
Ruben,LN;Clothier,RH;Balls,M
通讯作者：
Balls,M
非洲爪蟾（南非爪蟾）体外胸腺抑制抗体产生的一些特征。
DOI：
--
发表时间：
1983
期刊：
Thymus
影响因子：
--
作者：
Ruben,LN;Buenafe,A;Seivert,D
通讯作者：
Seivert,D