Modern Pharmacology With Clinical Applications pot

[...]... substances being tested, and the potential risks, benefits, and discomforts PHASES OF CLINICAL INVESTIGATION The clinical development of new drugs usually takes place in steps or phases conventionally described as clinical pharmacology (phase I), clinical investigation (phase II), clinical trials (phase III), and postmarketing studies (phase IV) Table 1.1 summarizes the four phases of clinical evaluation Phase... Combination of an agonist with its receptor (B) Combination of an antagonist with its receptor (C) Combination of a neurotransmitter with its receptor (D) Combination of a hormone with its receptor 3 Which of the following chemical bonds would create an irreversible combination of an antagonist with its receptor? (A) Ionic bond (B) Hydrogen bond (C) Van der Waals bond (D) Covalent bond 4 Potency is determined... subject 2 To conduct reliable clinical trials with a potential new drug, it is necessary to establish a dose level that toxicity first appears This is commonly determined in (A) Phase I Studies (B) Phase II Studies (C) Phase III Studies (D) Phase IV Studies 3 The history of pharmacology includes a long list of heroes The person considered to be the founder of American pharmacology is (A) Claude Bernard... The purpose of these studies is to broaden the experience with the drug and to compare the new drug with other agents that are being used clinically 3 C John Jacob Abel occupied the first chair of a department of pharmacology in the United States This was at the University of Michigan Abel subsequently left Michigan to chair the first department of pharmacology at Johns Hopkins University Claude Bernard... (eds.) Handbook of Phase I/II Clinical Drug Trials Boca Raton, FL: CRC, 1997 Parascandola J John J Abel and the emergence of U.S pharmacology Pharmaceut News 1995;2:911 Spilker, B Guide to Clinical Trials New York: Raven, 1991 2 Mechanisms of Drug Action William W Fleming RECEPTORS A fundamental concept of pharmacology is that to initiate an effect in a cell, most drugs combine with some molecular structure... predictable, for example, orthostatic hypotension with some antihypertensive agents, arrhythmias with certain cardioactive drugs, and electrolyte imbalance with diuretics Other adverse effects are not predictable and may occur rarely or be delayed for months or years before the association is recognized Examples of such reactions are aplastic anemia associated with chloramphenicol and clear cell carcinoma... many drugs may interact with the same binding site A drug with a higher affinity may displace a drug with weaker affinity Increases in the non–protein-bound drug fraction (i.e., free drug) can theoretically result in an increase in the drug’s intensity of pharmacological response, side effects, and potential toxicity However, in practice, changes in protein binding result in clinically significant effects... and marketed Such studies are intended to broaden the experience with the drug and compare it with other drugs SPECIAL POPULATIONS One of the goals of drug development is to provide sufficient data to permit the safe and effective use of the drug 8 I GENERAL PRINCIPLES OF PHARMACOLOGY Therefore, the patient population that participates in clinical trials should be representative of the patient population... resulting in local depolarization The local depolarization (end-plate potential) triggers the activation of large numbers of voltage-dependent sodium channels, causing the conducted depolarization known as an action potential The action potential leads to the release of calcium from intracellular binding sites The calcium then interacts with the contractile proteins, resulting in shortening of the muscle... channels as well as in the activation of other enzymes In this system, the receptor is in the membrane with its binding site on the outer surface The G protein is totally within the membrane while the adenylyl cyclase is within the membrane but projects into the interior of the cell The cAMP is generated within the cell (see Figure 10.4) Whether or not a particular agonist has any effect on a particular . class="bi x0 y0 w0 h0" alt="" T he sixth edition of Modern Pharmacology With Clinical Applications continues our commitment to enlisting experts in pharmacology to provide a textbook that is up-to-date. potential risks, benefits, and discomforts. PHASES OF CLINICAL INVESTIGATION The clinical development of new drugs usually takes place in steps or phases conventionally described as clinical pharmacology. broaden the experience with the drug and to compare the new drug with other agents that are being used clinically. 3. C. John Jacob Abel occupied the first chair of a de- partment of pharmacology in