Pharmacotherapy A Pathophysiologic Approach 11e Pdf
Janean Mcconnaughhay
The #1 textbook in pharmacotherapy providing optimal patient outcomes using evidence-based medication therapies -- updated with the latest advances and guidances. For more than 30 years, 'Dipiro's Pharmacotherapy' has been the essential textbook for learning how to properly select, administer, and monitor drugs -- everything needed to provide safe, effective drug therapy across all therapeutic categories. This new edition has been fully updated with the latest evidence-based information and recommendations. With content from 300 expert contributors, this valuable resource offers detailed descriptions of common and uncommon disease states, including treatment by pharmacologic and non-pharmacologic means. Each disease chapter opens with a Patient Care Process, helping readers understand the collaborative care model in which pharmacists work and communicate with other healthcare providers for effective coordinated care. Here's why 'DiPiro's Phamacotherapy : A Pathophysiologic Approach' is the perfect learning tool for students, pharmacists, and other heathcare providers : all chapters provide the most current, reliable, and relevant information available ; Key Concepts are included at the beginning of each chapter ; Clinical Presentation boxes concisely outline disease signs and symptoms ; new Beyond the Book feature points readers to multimedia resources to deepen their understanding of the material ; diagnostic flow diagrams, treatment algorithms, dosing guideline recommendations, and monitoring approaches clearly distinguish treatment pathways ; new drug monitoring tables have been added ; Patient Care Process boxes help readers know how to communicate with other health care providers ; over 2,000 Review Questions to help prepare students! --
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Pain management is challenging for both clinicians and patients. In fact, pain patients are frequently undertreated or even completely untreated. Optimal treatment is based on targeting the underlying mechanisms of pain and tailoring the management modality for each patient using a personalized approach. This narrative review deals with pain conditions that have a complex underlying mechanism and need an individualized and frequently multifactorial approach to pain management. The research is based on previously conducted studies, and does not contain any studies with human participants or animals performed by any of the authors. This is not an exhaustive review of the current evidence. However, it provides the clinician with a perspective on pain therapy targeting the underlying pain mechanism(s). When dealing with complex pain conditions, the prudent physician benefits from having a deep knowledge of various underlying pain mechanisms in order to provide a plan for optimal pharmacological pain relief to patients.
Regardless of the origin of the pain or its duration, the central nervous system (CNS) is always involved. The CNS detects and interprets a wide range of thermal and mechanical stimuli as well as environmental and endogenous chemical irritants. Intense stimuli provoke acute pain, but recurrent stimuli, should protective reflexes fail, can lead to chronic pain through plasticity of the peripheral nervous system (PNS) and CNS as well as signal enhancement [6].
It is also important for clinicians to become aware of the multifactorial nature of chronic pain in order to make pharmacological decisions based on the underlying mechanistic factors of the pain [15]. Therefore, it is crucial that clinicians who treat patients with chronic pain are knowledgeable regarding current theories of the development of chronic pain, and understand the differences between nociceptive and neuropathic pain and how they develop. An understanding of peripheral sensitization and the local release of inflammatory mediators that attract immune cells after injury is crucial, as well as an understanding of the process of central sensitization. The latter is the result of persistent transmission of pain signals from the periphery to the spinal cord [17].
A number of different mechanisms are involved in central sensitization, which involves the peripheral input of a nociceptive stimulus to a dorsal horn synapse and the concomitant release of substance P and glutamate into the synaptic cleft. These include presynaptic N-methyl d-aspartate (NMDA) receptors and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and the signal is transmitted to the thalamus. There, microglial cells release inflammatory modulators, after activation of the toll-like receptor 4 (TLR4). The role of the NMDA receptors is crucial, because their prolonged activation after repetitive stimuli leads to their increasing density, which in turn enhances the signal to the thalamus [18, 19]. Allodynia, hyperalgesia, spontaneous pain, and secondary hyperalgesia indicate central sensitization. Another characteristic of central sensitization is the wind-up phenomenon, where the same unchanged stimulus causes increasingly intense sensations of pain [20]. Wind-up can be prevented up to a point by ketamine, an NMDA antagonist [21]. However, ketamine cannot fully reverse central sensitization [22, 23]. Another cause of central sensitization could be a defect of the descending inhibitory control (DIC) system, which is present in various pain conditions [24, 25] Therefore, knowledge of the multiple causative mechanisms of pain and pain syndromes, along with their molecular components, is fundamental in creating proper treatment plans, especially in complex patients [11, 17, 26].
Because a very important task for clinicians is the effective management of pain in their patients by targeting the causative triggering mechanisms, this review aims to bring together published work that has shed light on the above mechanisms and, at the same time, offers insight into current or promising pain-relieving pharmacological treatments.
We searched relevant articles within the PubMed, Scopus, and Cochrane databases, considering publications up to May 2019. All searches used the following research key words: (pathophysiology OR underlying mechanism OR cause) AND (pain OR painful OR pain syndromes) AND (pharmacological therapy OR pharmacological approach OR pharmacological treatment OR pharmacological strategy). The primary search was supplemented with a secondary search using the bibliographies of the articles retrieved. Only full-length original articles were accepted, and the search was limited to English-language publications. Because knowledge regarding pain mechanisms is evolving so rapidly, the primary search focused on articles within the last 15 years. All retrieved articles were reviewed by title, abstract, and the article itself when its content was not clearly indicated by the title and abstract. The inclusion criteria were as follows: (1) the article referred to acute or chronic pain, and a specific pathophysiological mechanism was suggested in the article, and (2) the authors suggested a treatment plan or a medication therapy that would target the underlying mechanism. We tried to focus on the main complex categories of pain, such as neuropathic pain, and special populations such as the elderly. The perspective suggested here can be used by clinicians to guide their efforts in dealing with pain experienced by their patients. This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.
The article selection process is shown in Fig. 1. According to the new classifications of chronic pain [5], we attempted to cover as many clinical conditions as possible, indicating a possible representative for each category. As a result, we elaborated on the pathophysiological mechanisms and the proposed pharmacological approach for the following: chronic neuropathic pain, chronic primary pain and more specifically fibromyalgia, chronic visceral pain, central post-stroke pain, pain in complex regional pain syndrome, and low back pain. Finally, a group of patients that is continually growing and, in our opinion, needs particular attention is the elderly population, who were included in our review.
Tricyclic antidepressants (TCAs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, which act through the potentiation of the descending nociceptive inhibitory pathways by presynaptic inhibition of the reuptake of serotonin and norepinephrine, two monoaminergic neurotransmitters. TCAs also block voltage-dependent sodium channels and have sympatholytic properties, and should be given in an individually titrated dose [30]. Both are considered first-line medications. The last update of the relevant Cochrane review also supports this, pinpointing diabetic neuropathy and postherpetic neuralgia as benefiting the most from this category of medication [31].
Gabapentinoids, which act on the α2-d-subunit and inhibit the activation of calcium influx [30], and are recommended as a first-line medication. The evidence suggests that although they are not expected to benefit more than half of the patients, this category of medications should always be considered [32].
Weak (e.g., tramadol) or strong opioids (e.g., morphine, buprenorphine) for resistant pain. Opioids act as agonists primarily at the -opioid receptors, which are located in both the CNS and PNS. Tramadol exerts an additional effect on the descending pain-suppressing system by inhibiting the reuptake of norepinephrine and serotonin [30]. The use of opioids, although controversial, is being reserved for occasions when either more rapid relief is necessary or when pain is significantly resistant, leaving them as a second-line recommendation. The 2013 Cochrane review regarding opioids for neuropathic pain does not conclude that opioids are better than placebo for long-term use and highlights their multiple side effects [33].
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