10. Drugs and Local Chemical Mediators
Sheila A Doggrell
Discipline of Medical Sciences, Faculty of Science and Technology, Queensland University of Technology, Gardens Point, GPO Box 2434, QLD 4001, Australia
Phone +61 7 3870574 Fax +61 7 31381534 Email sheila.doggrell@qut.edu.au
Reviewer required
Key words: histamine, cytokines, drugs that modify, cyclooxygenase, lipooxygenase, action of eicosanoids, drugs that modify the actions of eicosanoids, 5-hydroxytryptamine (5-HT), nitric oxide, endothelin
10.1 Histamine and cytokines
10.1.1 Actions of histamine
10.1.2 Drugs that modify the actions of histamine
10.1.3 Cytokines
10.2 Eicosanoids
10.2.1 Cyclooxygenase (COX) and lipooxygenase system
10.2.2 Actions of eicosanoids
10.2.3 Drugs that modify the actions of eicosanoids
10.2.3.1 Inhibit phospholipase A2
10.2.3.2 Non-selective cyclooxygenase inhibitors
10.2.3.3 Selective COX-2 inhibitors
10.2.3.4 Agonists at prostaglandin receptors
10.2.3.5 Leukotriene receptor antagonists
10.3. 5-Hydroxtryptamine (serotonin), nitric oxide, and endothelin
10.3.1 5-HT and migraine
10.3.2 5-HT and the gastrointestinal tract
10.3.3 Nitric oxide and angina
10.3.4 Nitric oxide and erectile dysfunction
10.3.5 Endothelin and pulmonary hypertension
LOCAL CHEMICAL MEDIATORS
Cell-to-cell communication is the key to most processes in the body, and this cell-to-cell communication uses chemical mediators. Chemical mediators are classified into four groups: nervous, endocrine, paracrine, and autocrine (Table 10.1).
Table 10.1 Chemical mediators (modified from Table 29.1 in Bullock S et al)
Nerves secrete neurotransmitters that act over a short range, and have a relatively rapid action. The neurotransmitters in the peripheral nervous systems have already been discussed and drugs and the central nerve system will be discussed in future chapters. Endocrine glands secrete hormones into the blood, where they circulate until they find their target receptor. The actions of hormones are relatively prolonged. Various hormones are discussed further in Systematic pharmacology. The other groups of chemical mediators, paracrine and autocrine secretion, are involved in local actions. Paracrine secretions are of local hormones released into the circulation to have an effect on a neighbouring cell. These actions are relatively rapid. The local hormones to be discussed are the prostaglandins, nitric oxide and endothelin. Actually, some of the actions of the prostaglandins are autocrine, whereby the action is on the secreting cell. Histamine, 5-hydroxytryptamine (5-HT) and cytokines also have some autocrine activity. As there is overlap between the paracrine and autocrine actions of some chemical mediators, I prefer just to call the combination of local hormones and autocoids, local chemical mediators. In the following sections, some important local chemical mediators are discussed, and how drugs can modify the effects of these chemical mediators are considered.