PubMed · 15564930
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Steven L Shafer. 2004. Picking safe combinations.. https://doi.org/10.1097/00000542-200412000-00003
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Microinjection of pentobarbital and GABA(A)-receptor agonists into a brainstem region we have called the mesopontine tegmental anesthesia area (MPTA; Devor and Zalkind [2001] Pain 94:101-112) induces a general anesthesia-like state. As in systemic general anesthesia, rats show loss of the righting reflex, atonia, nonresponsiveness to noxious stimuli, and apparent loss of consciousness. GABA(A) agonist anesthetics acting on the MPTA might suppress movement by engaging endogenous motor regulatory systems previously identified in research on decerebrate rigidity and REM sleep atonia. Anterograde and retrograde tracing revealed that the MPTA has multiple descending projections to pontine and medullary areas known to be associated with motor control and atonia. Prominent among these are the dorsal pontine reticular formation and components of the rostral ventromedial medulla (RVM). The MPTA also has direct projections to the intermediate gray matter and ventral horn of the spinal cord via the lateral and anterior funiculi. These projections show a rostrocaudal topography: neurons in the rostral MPTA project to the RVM, but only minimally to the spinal cord, while those in the caudal MPTA project to both targets. Finally, the MPTA has ascending projections to motor control areas including the substantia nigra, subthalamic nucleus, and the caudate-putamen. Projections are bilateral with an ipsilateral predominance. We propose that GABA(A) agonist anesthetics induce immobility at least in part by acting on these endogenous motor control pathways via the MPTA. Analysis of MPTA connectivity has the potential for furthering our understanding of the neural circuitry responsible for the various functional components of general anesthesia.
This review focuses on potential drug interactions between anaesthetic drugs or techniques and chronic medications in patients scheduled for surgery. The vast majority of therapeutics can be continued until the morning of surgery. However, for some drugs such as ACE inhibitors, there is strong evidence to recommend their discontinuation prior to surgery. When juged necessary, interruption of chronic therapeutic needs to be anticipated and planned. In the other hand, for other drugs such as beta-blockers or L-Dopa, acute withdrawal is associated with documented adverse outcome. As a result, such drugs have to be continuing throughout the operative period. Although a general consensus exists for many medications, there are still controverses as to the management of antithrombotic drugs and some central nervous system agents. Advances in anaesthesia include knowledge on the mechanisms involved in drug interactions, which allows us to improve the preoperative management of chronic therapeutics.
We describe a method for studying the interaction of two anesthetic agents, Morphine and Midazolam, acting simultaneously in the same individual. Representing the levels of the two chemicals by diffusion processes, we assume their interaction is governed by a linear combination of the separate components. Pharmacological data is used to estimate the model parameters and, in particular, to determine the coefficient in the linear combination. This leads to the conclusion that the two chemicals have a counteractive effect.