By Bertram G. Katzung
The most modern, authoritative, and entire pharmacology ebook for clinical, pharmacy, and different wellbeing and fitness technology scholars. largely revered for its readability, comprehensiveness, and association, this pharmacology path e-book provides the basic recommendations that scholars want to know concerning the technology of pharmacology and their program. makes a speciality of the elemental ideas of every drug crew in addition to the scientific selection and use of gear in sufferers and the tracking in their results.
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Extra resources for Basic & Clinical Pharmacology, Ninth Edition
One measure, which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect, is the therapeutic index. In animal studies, the therapeutic index is usually defined as the ratio of the TD50 to the ED50 for some therapeutically relevant effect. The precision possible in animal experiments may make it useful to use such a therapeutic index to estimate the potential benefit of a drug in humans. Of course, the therapeutic index of a drug in humans is almost never known with real precision; instead, drug trials and accumulated clinical experience often reveal a range of usually effective doses and a different (but sometimes overlapping) range of possibly toxic doses.
The principle of drug selectivity may even apply to structurally identical receptors expressed in different cells, eg, receptors for steroids such as estrogen (Figure 2–6). Different cell types express different accessory proteins, which interact with steroid receptors and change the functional effects of drug-receptor interaction. For example, tamoxifen acts as an antagonist on estrogen receptors expressed in mammary tissue but as an agonist on estrogen receptors in bone. Consequently, tamoxifen may be useful not only in the treatment and prophylaxis of breast cancer but also in the prevention of osteoporosis by increasing bone density (see Chapter 40: The Gonadal Hormones & Inhibitors and Chapter 42: Agents That Affect Bone Mineral Homeostasis).
Down-regulation, which decreases the actual number of receptors present in the cell or tissue, occurs more slowly than rapid desensitization and is less readily reversible. This is because down-regulation involves a net degradation of receptors present in the cell, requiring new receptor biosynthesis for recovery, in contrast to rapid desensitization which involves reversible phosphorylation of existing receptors. Many G protein–coupled receptors are down-regulated by undergoing ligand-induced endocytosis and delivery to lysosomes, similar to down-regulation of protein tyrosine kinases such as the EGF receptor.
Basic & Clinical Pharmacology, Ninth Edition by Bertram G. Katzung