Table Of ContentSELECTED CHAPTERS OF PHARMACOLOGY
SELECTED CHAPTERS OF PHARMACOLOGY
Prof. Dr. Árpád Tósaki
Publisher• Budapest, 2011
© Árpád Tósaki
closed: 2011. okt. 31.
ISBN
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SELECTED CHAPTERS OF PHARMACOLOGY
Written
by
Arpad Tosaki
2011
University of Debrecen
Helath Science Center
School of Pharmacy
Debrecen
HUNGARY
Reviewed
by
David Donald Haines
University of Connecticut, Storrs, CT
USA
PREFACE
This book was written to provide students, researchers and educators with a user-
friendly tool for keeping pace with rapidly evolving drug discovery initiatives. The primary
content is based on the pharmacotherapy of various diseases, which has been an enormously
rewarding and fascinating adventure. In addition, the content is also based on my research and
teaching experience during the 3 decades prior to this writing in Hungary, England, France,
and United States of America, which has been an enormously rewarding and fascinating
adventure. Use of pharmacological agents to prevent or mitigate disease is an ancient skill
maintained during the entire history of all human societies in various forms. Hunter-gatherer
communities each developed culturally unique uses for plant, mineral and animal resources
locally available to populations in need that evolved into sophisticated and increasingly
efficacious medical traditions that persist to this day. The progressive integration of medical
traditions into written record allowed evolution of progressively powerful pharmacology
based increasingly on analysis of clinically valid precedent. As understanding of the
molecular-biological basis of diseases, drug design has become progressively driven by
consideration of how specific biochemical interactions may be modulated to achieve
therapeutic endpoints. Of particular interest in this respect, is identification of compounds
capable of modifying critical ligand-receptor interactions, enzyme activities and other events
in cellular signaling pathways that lead to enhancement or inhibition of major symptoms of
various diseases. Most descriptions of drug mechanisms given in this book focus on how
small-molecule drugs affect specific molecular targets to alter well-defined aspects of cellular
physiology in ways that in most cases are expected to result in improved prognosis of selected
disorders. In this respect, the book reflects “orthodoxy” of strategic thinking in the
pharmaceutical industry, which favors single site-acting “magic bullet” compounds that may
be highly effective in some treatment venues, but are highly toxic, often costly and provide
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only transitory remediation to serious chronic illness. A particularly exciting subject area
covered in this book is a description of novel treatment strategies that prevent or mitigate
serious diseases, particularly those with underlying inflammatory etiology, by strengthening
natural host immunoregulatory mechanisms, rather than intervening in activity of host
homeostasis. It is an honor and a pleasure to participate in the medical revolution, of which
this book is a vanguard.
Debrecen, 2011. Oct. 31.
Prof. Dr. Arpad Tosaki
Chairman, Department of Pharmacology
Faculty of Pharmacy, Health Science Center
University of Debrecen
Debrecen, Hungary
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CONTENTS
CENTRAL NERVOUS SYSTEM 7
General anesthesia 7
Intravenous anesthesia 9
Anesthetics for inhalation 11
Local anesthetics 13
Hypnotics and sedatives 17
(A) Benzodiazepines 17
(B) Barbiturates 19
( C ) Miscellaneous sedative-hypnotics 19
Depression and anxiety disorders, drugs 19
Psychosis and mania 22
Epilepsies 24
Mechanisms of seizures and antiepileptic drugs 25
(a) hydantoins 26
(b) barbiturates 26
(c) iminostilbenes 27
(d) succinimides 27
(e) valproic acid 27
(f) benzodiazepines 27
(g) other antiseizure drugs 28
Degenerative disorders 28
PD Diseases (paralysis agitans or shaking palsy) 29
Alzheimer‟s disease (AD) 32
Hungtinton disease (HD) 32
Amyotrophic lateral sclerosis (ALS) 33
Opioids 34
Effects of opioids 34
Morphine and opioid agonists 35
Opioid agonist/antagonists 37
Antitussive agents 38
CARDIOVASCULAR SYSTEM 40
1). Therapy of myocardial ischemia 40
(a) Nitrovasodilators 41
(b) Beta-adrenergic receptor blockers 43
(c) Calcium channel blockers 43
(d) Antiplatelet, antiintegrin, and antithrombotic agents
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combined with statins 44
2). Treatment of congestive heart failure 45
3). Antiarrhythmic drugs 50
4). Treatment of hypertension including the rennin-angiotensin system 56
5). Vasopressin and others affecting renal function 59
6). Diuretics 64
7). Therapy of hypercholesterolemia and dyslipidemia 70
8). Blood, pharmacology 74
(I) Hematopoietic growth factors 75
(II) Drugs effective against anemias 77
(III) Vitamin B12 and folic acid for the treatment of megaloblastic
anemias 80
CANCERS AND ANTINEOPLASTIC DRUGS 82
A). Alkylating agents 83
B). Antimetabolites 86
C). Natural extracts and products, and antibiotics 88
D). Miscellaneous agents 90
E). Hormones and Hormone-like agents 95
GASTROINTESTINAL TRACTS 99
(i)The stomach 99
a). Inhibitors of the proton pump (K+ -H+ pump) 100
b). H2 receptor antagonists 100
c). Antacids, ascid supressants and cytoprotectants 100
(ii) The bowel motility, laxatives, antinauseant,
and antiemetic agents, billary and pancreatic diseases 101
Bowel motility 101
Laxatives 102
Antinauseant and antiemetic agents 105
Billary and pancreatic diseases 108
(iii) Treatment of inflammatory bowel disease 108
ASTHMA AND PULMONARY PHARMACOLOGY 112
a). Beta adrenergic agonists (beta sympathomimetics) 114
b). Methylxanthine (e.g., theophylline) 115
c). Muscarin receptor antagonists 116
d). Corticosteroids 117
(e). Other asthma and COPD mediator antagonists 119
(f). Immunomodulators 119
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(g). Other future developments in asthma therapy 120
(h). Therapy of pulmonary arterial hypertension 121
ENDOCRINOLOGY, HORMONES, AND HORMONE ANTAGONISTS 123
The hypothalamic-pituitary endocrine system 123
Somatotrophic hormones: growth hormone (GH) and prolactin (PR) 124
Glycoprotein hormones: TSH and gonadotropins 127
Oxytocin and vasopressin (posterior pituitary hormons) 129
Thyroid and antithyroid drugs 130
ESTROGENS AND PROGESTINS 137
Estrogens 137
Progestins (gestogens, progestogens) 140
Anitprogestins and progesteron receptor modulators 141
Contraceptives 141
Testosterone and other androgenes 142
Antiandrogens 143
ACTH (adrenocorticotropic hormone) and adrenal steroids 144
Inhibitors of the biosynthesis of adrenocortical steroids 146
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CENTRAL NERVOUS SYSTEM
General anesthesia
General anesthesia depresses the central nervous system (CNS) at a sufficient degree
to permit the performance of various surgeries and other noxious or unpleasant procedures.
General anesthesia has low therapeutic indices, and therefore, it requires great care in
application. Although, general anesthetics produce a very similar anesthetic state, they are
relatively dissimilar in their adverse effects in various organs. To choose specific drugs and
routes of administrations to produce general anesthesia is based on their chemical and
pharmacological properties and on the adverse effects of various structures, in the context of
suggested diagnostic and surgical procedures with considerations of the patient‟s age,
conditions, and medications. Anesthesia usually is not carried out with a simple agent, thus,
anesthesiologists apply various combinations of sedatives, neuromuscular blocking agents,
and local anesthetics, as the actual clinical situation requires. The development of general
anesthesia and the application of anesthetics started in 1846 in the United States.
The first used anesthetic was (i) „ether anesthesia‟ achieving a revolution worldwide in
surgery and medical care. Currently ether is not used in medical care, but it was the „ideal‟
pioneer anesthetic which was relatively nontoxic to cells and organs. Furthermore, ether does
not compromise, in therapeutic doses, respiration and circulation. However, ether is not used
any longer in medical care, because it forms toxic peroxides in the presence of oxygen and
light, and ether is explosive.
Chloroform (ii) followed ether, introduced by a Scottish doctor, J. Simpson, in 1847,
as the next anesthetic used worldwide as a nonexplosive anesthetic. The chloroform molecule
contains halogens (Cl-), therefore it has hepatotoxic and cardiovascular depressive effects.
Nitrous oxide (N O) was the third (iii) and „light‟ anesthetic introduced in medical
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care started in 1868. N O cannot alone induce „deep‟ anesthesia allowing brain, cardiac or
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abdominal surgery, however, it was used for painless tooth extraction.
About sixty years later, in 1929, (iv) cyclopropane was discovered and used for the
next 30 years. This molecule was explosive and flammable. Therefore, British scientists
developed a new chemical structure, (v) halothane, which is nonflammable and possessing
anesthetic properties. Halothane was introduced in surgery as a general anesthetic agent in
1956, and since then it has been widely used for general anesthesia.
Principles of anesthesia:
a). Minimizing the harmful effects of the procedure (techniques) and agents.
b). Stabilize and sustain the homeostasis during surgery related to blood loss, metabolic shifts
and coagulation.
c). Improve postoperative recovery and treat surgery-induced stress responses.
Anesthesia and hemodynamics:
Anesthesia results in a reduction in the systemic arterial blood pressure. The cause of
blood pressure reduction is vasodilation, cardiac depression or both, a diminution of
baroreceptor control and a generalized reduction in central sympathetic tone. The reduction in
blood pressure is enhanced by volume depletion or myocardial dysfunction. Those anesthetics
which have hypotensive properties under physiological conditions should be used with
caution in trauma victims.
Anesthesia and respiration:
Oxygen supply is essential during anesthesia, therefore, ventilation must be assisted
and controlled. The gag reflex is disappeared, and lower esophageal sphincter tone is reduced.
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Description:covered in this book is a description of novel treatment strategies that . General
anesthesia depresses the central nervous system (CNS) at a sufficient degree.
