Basic & Clinical Pharmacology, Ninth Edition by Bertram G. Katzung

By Bertram G. Katzung

The most present, authoritative, and finished pharmacology booklet for scientific, pharmacy, and different future health technological know-how scholars. largely revered for its readability, comprehensiveness, and association, this pharmacology path e-book offers the fundamental ideas that scholars want to know in regards to the technological know-how of pharmacology and their software. makes a speciality of the fundamental ideas of every drug crew in addition to the medical selection and use of gear in sufferers and the tracking in their results.

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Added together, these separate clearances equal total systemic clearance: "Other" tissues of elimination could include the lungs and additional sites of metabolism, eg, blood or muscle. The two major sites of drug elimination are the kidneys and the liver. Clearance of unchanged drug in the urine represents renal clearance. Within the liver, drug elimination occurs via biotransformation of parent drug to one or more metabolites, or excretion of unchanged drug into the bile, or both. The pathways of biotransformation are discussed in Chapter 4: Drug Biotransformation.

Note that some doses of drug A can produce larger effects than any dose of drug B, despite the fact that we describe drug B as pharmacologically more potent. The reason for this is that drug A has a larger maximal efficacy, as described below. For clinical use, it is important to distinguish between a drug's potency and its efficacy. The clinical effectiveness of a drug depends not on its potency (EC50), but on its maximal efficacy (see below) and its ability to reach the relevant receptors. This ability can depend on its route of administration, absorption, distribution through the body, and clearance from the blood or site of action.

After reaching an initial high level, the response (eg, cellular cAMP accumulation, Na+ influx, contractility, etc) gradually diminishes over seconds or minutes, even in the continued presence of the agonist. This desensitization is usually reversible; a second exposure to agonist, if provided a few minutes after termination of the first exposure, results in a response similar to the initial response. Figure 2–12. Possible mechanism for desensitization of the -adrenoceptor. The upper part of the figure depicts the response to a -adrenoceptor agonist (ordinate) versus time (abscissa).

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