Principles of pharmacodynamics and their applications in veterinary pharmacology
ABSTRACT Pharmacodynamics (PDs) is the science of drug action on the body or on microorganisms and other parasites within or on the body. It may be studied at many organizational levels--sub-molecular, molecular, cellular, tissue/organ and whole body--using in vivo, ex vivo and in vitro methods and utilizing a wide range of techniques. A few drugs owe their PD properties to some physico-chemical property or action and, in such cases, detailed molecular drug structure plays little or no role in the response elicited. For the great majority of drugs, however, action on the body is crucially dependent on chemical structure, so that a very small change, e.g. substitution of a proton by a methyl group, can markedly alter the potency of the drug, even to the point of loss of activity. In the late 19th century and first half of the 20th century recognition of these facts by Langley, Ehrlich, Dale, Clarke and others provided the foundation for the receptor site hypothesis of drug action. According to these early ideas the drug, in order to elicit its effect, had to first combine with a specific 'target molecule' on either the cell surface or an intracellular organelle. It was soon realized that the 'right' chemical structure was required for drug-target site interaction (and the subsequent pharmacological response). In addition, from this requirement, for specificity of chemical structure requirement, developed not only the modern science of pharmacology but also that of toxicology. In relation to drug actions on microbes and parasites, for example, the early work of Ehrlich led to the introduction of molecules selectively toxic for them and relatively safe for the animal host. In the whole animal drugs may act on many target molecules in many tissues. These actions may lead to primary responses which, in turn, may induce secondary responses, that may either enhance or diminish the primary response. Therefore, it is common to investigate drug pharmacodynamics (PDs) in the first instance at molecular, cellular and tissue levels in vitro, so that the primary effects can be better understood without interference from the complexities involved in whole animal studies. When a drug, hormone or neurotransmitter combines with a target molecule, it is described as a ligand. Ligands are classified into two groups, agonists (which initiate a chain of reactions leading, usually via the release or formation of secondary messengers, to the response) and antagonists (which fail to initiate the transduction pathways but nevertheless compete with agonists for occupancy of receptor sites and thereby inhibit their actions). The parameters which characterize drug receptor interaction are affinity, efficacy, potency and sensitivity, each of which can be elucidated quantitatively for a particular drug acting on a particular receptor in a particular tissue. The most fundamental objective of PDs is to use the derived numerical values for these parameters to classify and sub-classify receptors and to compare and classify drugs on the basis of their affinity, efficacy, potency and sensitivity. This review introduces and summarizes the principles of PDs and illustrates them with examples drawn from both basic and veterinary pharmacology. Drugs acting on adrenoceptors and cardiovascular, non-steroidal anti-inflammatory and antimicrobial drugs are considered briefly to provide a foundation for subsequent reviews in this issue which deal with pharmacokinetic (PK)-PD modelling and integration of these drug classes. Drug action on receptors has many features in common with enzyme kinetics and gas adsorption onto surfaces, as defined by Michaelis-Menten and Langmuir absorption equations, respectively. These and other derived equations are outlined in this review. There is, however, no single theory which adequately explains all aspects of drug-receptor interaction. The early 'occupation' and 'rate' theories each explain some, but not all, experimental observations. From these basic theories the operational model and the two-state theory have been developed. For a discussion of more advanced theories see Kenakin (1997).
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ABSTRACT: Abstract Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition distinguished by elevated pressure of pulmonary arteries and increased vascular resistance. The management of patients with PAH and CTEPH has advanced rapidly over last decade but despite the progress in the treatment, the survival of suffering patients remain unsatisfactory and there is no cure for the diseases. However, surgery is not a first choice for patients. Furthermore, some patients who undergo surgery have persistent pulmonary hypertension (HTN) as a side effect after surgery. Therefore, the search for an "ideal" therapy still goes on and it lead to the approval of riociguat as a potential agent for the treatment. It acts directly on soluble guanylate cyclase, exciting the enzyme, and elevating sensitivity to lower levels of NO. Riociguat, therefore, has potential as a novel therapy for PAH and CTEPH. This review is focused on various aspects of the recently approved "riociguat" including its efficacy and safety profiles with the clinical data highlighting its importance in the present scenario.Clinical and Experimental Hypertension 09/2014; DOI:10.3109/10641963.2014.960976 · 1.46 Impact Factor
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ABSTRACT: Drugs (medicines) are considered either the primary therapy or an adjunct to another modality. Physicians of all specialties prescribe drugs on a daily basis, and therefore they need to understand the mode and action by which drugs exert their therapeutic effects. Written records of the use of natural products as medicinal agents date back thousands of years. However, it was not until the early 1800s that the active principles from plants were isolated. Since then thousands of drugs have been introduced to the drugs market. With advances in drug design, molecular biology and genetics, the rate of developing new potent drugs is accelerated. Due to the vast progress in drug development and discovery, medical and pharmacy students, doctors, nurses and pharmacists in training need to learn the principles of therapeutics in order to follow up with the frequent changes in the therapeutics and adapt to them. With contributions from some of my colleagues, this book provides a clear and concise overview of the most important commonly used drugs with emphasis on the pharmacology aspects necessary for a basic understanding of the subject. It reviews the concepts, clinical applications, dosage forms, bioavailability, pharmacokinetics and side effects of a large number of drugs used to alleviate pain, lower cholesterol levels, and treat bacterial infections, diabetes, osteoporosis, bleeding, psoriasis and multiple Sclerosis. This book, with over 750 references, is an excellent pharmacology text for the student who is looking to broaden his/her strengths prior to the exam. The beauty of this text is that it includes essential pharmacology concepts in a compact book that can be quickly referenced and read multiple times during the course of a student's studies. In addition, this guide assists scientists trained in molecular biology, medicinal chemistry and related fields who need to know the basic theories, principles and practical applications of pharmacology. With the addition of pharmacokinetics coverage, ways to improve the bioavailability of commonly used drugs and sections on therapeutics that will help readers identify with diseases and drug treatments, this book provides better preparation of researchers in the basics of pharmacology.1 edited by Rafik Karaman, 01/2015; Nova Science Publishers, Inc., NY, USA., ISBN: 9781634638289
Chapter: DRUG OVERVIEW[Show abstract] [Hide abstract]
ABSTRACT: A drug is a chemical substance with known biological effects on humans or other animals. In the pharmacology field, a drug is defined as a chemical substance used in the treatment, cure, prevention, or diagnosis of disease or used to otherwise enhance physical or mental well-being. Drugs usually affect either normal or abnormal physiological processes. Drugs may be used for a limited duration, or on a regular basis for chronic disorders. The way drugs are classified or grouped are confusing. Therefore, a new approach of drugs classification is presented in this chapter along with general information on drugs which includes definition, drugs and diseases types, drugs administration, drugs interactions and drug names. In addition, the chapter describes some important aspects of drugs design and development, drug effectiveness and safety, and drug errors.Commonly Used Drugs - Uses, Side Effects, Bioavailability & Approaches to Improve it, 1 edited by Rafik Karaman, 01/2015: chapter 1: pages 1-40; Nova Science Publishers., ISBN: 978-1-63463-828-9