Handbook of experimental pharmacology
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Handb Exp Pharmacol · Jan 2009
ReviewClinical cough II: therapeutic treatments and management of chronic cough.
Chronic cough is a common and frequently disruptive symptom which can be difficult to treat with currently available medicines. Asthma/eosinophilic airway disease and gastro-oesophageal reflux disease are most commonly associated with chronic cough but it may also trouble patients with chronic obstructive pulmonary disease, pulmonary fibrosis and lung cancer. Over the last three decades there have been a number of key advances in the clinical approach to cough and a number of international guidelines on the management of cough have been developed. ⋯ The main objective of new treatments for cough would be to identify ways to downregulate this heightened cough reflex but yet preserve its crucial role in protecting the airway. The combined efforts of clinicians, scientists and the pharmaceutical industry offer most hope for such a treatment breakthrough. The aim of this chapter is to provide some rationale for the current treatment recommendations and to offer some reflections on the management of patients with chronic cough.
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Handb Exp Pharmacol · Jan 2009
ReviewCough sensors. I. Physiological and pharmacological properties of the afferent nerves regulating cough.
The afferent nerves regulating cough have been reasonably well defined. The selective effects of general anesthesia on C-fiber-dependent cough and the opposing effects of C-fiber subtypes in cough have led to some uncertainty about their regulation of this defensive reflex. But a role for C-fibers in cough seems almost certain, given the unique pharmacological properties of these unmyelinated vagal afferent nerves and the ability of many C-fiber-selective stimulants to evoke cough. ⋯ These "cough receptors" are distinct from the slowly and rapidly adapting intrapulmonary stretch receptors responding to lung inflation. Indeed, intrapulmonary rapidly and slowly adapting receptors and pulmonary C-fibers may play no role or a nonessential role in cough, or might even actively inhibit cough upon activation. A critical review of the studies of the afferent nerve subtypes most often implicated in cough is provided.
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Handb Exp Pharmacol · Jan 2009
ReviewSkin aquaporins: function in hydration, wound healing, and skin epidermis homeostasis.
Several aquaporins (AQPs) are expressed in mammalian skin. Some are directly involved in water transport, such as AQP5, which is involved in sweat secretion. In contrast, the physiological role of skin aquaglyceroporins, which permeate both water and glycerol, appears more and more complex. ⋯ Both water and glycerol transport by AQP3 appear to play an important role in hydration of mammalian skin epidermis. In addition, recent data suggest that glycerol transport by AQP3 is involved in the metabolism of lipids in skin as well as in the regulation of proliferation and differentiation of keratinocytes. Finally, AQP3 is also believed to be important in wound healing, as a water channel by facilitating cell migration, and as a glycerol transporter by enhancing keratinocyte proliferation and differentiation.
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For more than a half century, tobacco manufacturers have conducted sophisticated internal research to evaluate nicotine delivery, and modified their products to ensure availability of nicotine to smokers and to optimize its effects. Tobacco has proven to be a particularly effective vehicle for nicotine, enabling manipulation of smoke chemistry and of mechanisms of delivery, and providing sensory cues that critically inform patterns of smoking behavior as well as reinforce the impact of nicotine. ⋯ A review of internal documents indicates important historical differences, as well as significant differences between commercial brands, underscoring the effectiveness of methods adopted by manufacturers to control nicotine dosing and target the needs of specific populations of smokers through commercial product development. Although the focus of the current review is on the manipulation of nicotine dosing characteristics, the evidence indicates that product design facilitates tobacco addiction through diverse addiction-potentiating mechanisms.
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Handb Exp Pharmacol · Jan 2009
ReviewCough sensors. II. Transient receptor potential membrane receptors on cough sensors.
The transient receptor potential (TRP) family of channels is represented by at least six members in primary sensory neurons. These include the TRP vanilloid subtypes 1 (TRPV1), 2, 3, and 4, the cold and menthol receptor TRPM8, and TRPA1. ⋯ Evidence in experimental animals and in patients with airway diseases indicates a marked hypersensitivity to cough induced by TRPV1 agonists. Recent studies with newly developed high-affinity and selective TRPV1 antagonists have revealed that TRPV1 inhibition reduces cough induced by citric acid or antigen challenge.