Veterinary Psychopharmacology

Sharon L. Crowell-Davis, Thomas F. Murray, Leticia Mattos de Souza Dantas

• Publisher: Wiley-Blackwell
• Year: 2019
• ISBN:
  9781119226239
• Edition: 2
• Topic: Medicina
• Subtopic: Medicina veterinaria

Offers an updated second edition of the comprehensive reference on the use of drugs for veterinary mental health care and behavior modification

This fully revised Second Edition of Veterinary Psychopharmacology offers an authoritative reference to the drugs prescribed to treat psychiatric, psychological, and behavioral disorders in pets. Designed to be an accessible resource, the text is divided into sections on psychopharmacologic principles and clinical psychopharmacology. Comprehensive in scope, the book contains detailed information on pharmacologic intervention for pet mental health and behavior issues, offers thorough explanations of options, and explores why a particular drug should be prescribed and why it works.

Updated to include the recent advances in psychopharmacology for pets, the Second Edition includes new chapters that cover the principles of psychopharmacology, miscellaneous serotonergic agents, anticonvulsants and mood stabilizers, sympatholytic agents, and NMDA antagonists. In addition, the text explains the drug options, including all the information necessary to correct dysfunctions in the brain's chemistry through pharmacologic treatment. This important resource:

• Presents an updated and comprehensive resource for pharmacologic treatments for pet, equine, and zoo animal psychiatric disorders and behavior problems
• Contains in-depth information on drugs that promote neurochemical changes that will alter the mood, emotional state, reactivity, and behavior of the patient, including prescribing options and mechanisms of action
• Includes new chapters on the principles of psychopharmacology, miscellaneous serotonergic agents, mood stabilizers, sympatholytic agents, and NMDA antagonists

Written for veterinarians, veterinary behaviorists, and veterinary students, the updated second edition of Veterinary Psychopharmacology is a complete source for current knowledge on pharmacologic behavior modification. "Overall, this book packs a substantial amount of useful data into approximately 300 pages. The scope of the book is comprehensive and may include more in-depth information than casual prescribers seek, but it will be a good resource for the practitioners who are interested in immersing themselves into veterinary psychopharmacology." - JAVMA Vol 255 No. 6

Part I
Principles of Veterinary Psychopharmacology

1
General Principles of Psychopharmacology

Thomas F. Murray

Creighton University, Omaha, NE, USA

Drug Action

Pharmacology is the science of drug action, and a drug is defined as any agent (chemical, hormone, peptide, antibody, etc.) that, because of its chemical properties, alters the structure and/or function of a biological system. Psychopharmacology is a sub‐discipline of pharmacology focused on the study of the use of drugs (medications) in treating mental disorders. Most drugs used in animals are relatively selective. However, selectivity of drugs is not absolute inasmuch as they may be highly selective but never completely specific. Thus, most drugs exert a multiplicity of effects.

Drug action is typically defined as the initial change in a biological system that results from interaction with a drug molecule. This change occurs at the molecular level through drug interaction with molecular target in the biologic system (e.g. tissue, organ). The molecular target for a drug typically is a macromolecular component of a cell (e.g. protein, DNA). These cellular macromolecules that serve as drug targets are often described as drug receptors, and drug binding to these receptors mediates the initial cellular response. Drug binding to receptors either enhances or inhibits a biological process or signaling system. Of relevance to the field of psychopharmacology, the largest group of receptors are proteins. These include receptors for endogenous hormones, growth factors, and neurotransmitters; metabolic enzymes or signaling pathways; transporters and pumps; and structural proteins. Usually the drug effect is measured at a much more complex level than a cellular response, such as the organism level (e.g. sedation or change in behavior).

Drugs often act at receptors for endogenous (physiologic) hormones and neurotransmitters, and these receptors have evolved to recognize their cognate signaling molecules. Drugs that mimic physiologic signaling molecules at receptors are agonists, that is, they activate these receptors. Partial agonist drugs produce less than maximal activation of activation of receptors, while a drug that binds to the receptor without the capacity to activate the receptor may function as a receptor antagonist. Antagonists that bind to the receptor at the same site as agonists are able to reduce the ability of agonists to activate the receptor. This mutually exclusive binding of agonists and antagonists at a receptor is the basis for competitive antagonism as a mechanism of drug action. One additional class of drugs acting at physiologic receptors are inverse agonists. At physiologic receptors that exhibit constitutive activity in the absence of activation by an endogenous agonist, inverse agonists stabilize an inactive conformation and therefore reduce the activation of the receptor. Thus, inverse agonists produce responses that are the inverse of the response to an agonist at a given receptor. Theoretical log concentration‐response curves for these four classes of drugs are depicted in Figure 1.1.

Figure 1.1 Theoretical logarithmic concentration‐response relationships for agonist, partial agonist, antagonist, and inverse agonist drugs acting at a common receptor. In this theoretical set of concentration‐response curves, the agonist produces a maximum response while the partial agonist is only capable of evoking a partial response. The antagonist binds to the receptor but is not capable of activating the receptor and therefore does not produce a response. Inverse agonists bind to an inactive form of the receptor and produce an effect which is in the inverse direction of that produced by the agonist.

Dose Dependence of Drug Interaction with Receptors

Receptor occupancy theory assumes that drug action is dependent on concentration (dose) and the attendant quantitative relationships are plotted as dose‐ or concentration‐response curves. Dose–response analysis is typically reserved to describe whole animal drug effects, whereas concentration‐response curves describe in vitro drug action where the actual concentration of the drug interacting with a receptor is known. Inspection of dose–response relationships reveals that for any drug, there is a threshold dose below which no effect is observed, and at the opposite end of the curve there is typically a ceiling response beyond which higher doses do not further increase the response. As shown in Figure 1.2, these dose‐ or concentration‐response curves are typically plotted as a function of the log of the drug dose or concentration. This produces an S‐shaped curve that pulls the curve away from the ordinate and allows comparison of drugs over a wide range of doses or concentrations.

Figure 1.2 Theoretical logarithmic concentration‐response relationships for three agonists which differ in relative potency. Drug A is more potent than Drug B, which in turn is more potent than Drug C.

A drug‐receptor interaction is typically reversible and governed by the affinity of the drug for the receptor. The affinity essentially describes the tightness of the binding of the drug to the receptor. The position of the theoretical S‐shaped concentration‐response curves depicted in Figure 1.2 reveals the potency of these drugs. The potency of a drug is a function of its affinity for a receptor, the number of receptors, and the fraction of receptors that must be occupied to produce a maximum response in a given tissue. In Figure 1.2, Drug A is the most potent and Drug C is least potent. The efficacy of all three drugs in Figure 1.2, however, is identical in that they all act as full agonists and produce 100% of the maximal effect. As a general principle in medicine, for drugs with similar margins of safety, we care more about efficacy than potency. The comparison of potencies of agonists is accomplished by determining the concentration (or dose) that produces 50% of the maximum response (Effective Concentration, 50% = EC₅₀). In Figure 1.2, the EC₅₀ values are 10⁻⁸, 10⁻⁷, and 10⁻⁶ M, respectively, for Drugs A, B and C; hence, the rank order of potency is Drug A > Drug B > Drug C, with Drug A being the most potent since its EC₅₀ value is the lowest. Figure 1.3 depicts three additional theoretical concentration‐response curves for drugs with identical potencies but different efficacies. In this example, Drug A is a full agonist, producing a maximum response, whereas Drugs B and C are partial agonists, producing responses, respectively, of 50% and 25% of the maximum. Similar to receptor antagonist drugs, partial agonists can compete with a full agonist for binding to the receptor. Increasing concentrations of a partial agonist will inhibit the full agonist response to a level equivalent to its efficacy, whereas a competitive antagonist will completely eliminate the response of the full agonis...

Table of contents

• Cover
• Table of Contents
• Contributors
• Preface
• Acknowledgments
• Part I: Principles of Veterinary Psychopharmacology
• Part II: Practice of Veterinary Psychopharmacology
• Index
• End User License Agreement