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Pharmacology of the benzodiazepines
Gen. Pharmac. Vol. 16, No. 4, pp. 427-432, 1985 Pergamon Press Ltd. Printed in Great Britain
BOOK REVIEWS Pharmacology of the Benzodiazepines---Edited by E. Usdin,
Fever was one of the first symptoms of infection to be recognised by ancient physicians, though it was based on how the patient felt. The scientific analysis of fever depended on the development of the thermometer which only came into use in the 1720s. Even today the regulation of body temperature at 37°C is one indication of adequate homeostasis, and the various conditions that lead to disruption of this control are described in the present multi-authored volume. The subjects described in each chapter are as follows. 1. Body heat. 2. Fever and its role in disease; rationale for antipyretics. 3. Thermoregulation; its changes during infection with endotoxin producing micro organisms. 4. Exogenous pyrogens. 5. Endogenous pyrogens. 6. Role of central neurotransmitters in fever. 7. Role of ions in thermoregulation and fever. 8. Electrophysiology of the anterior hypothalamus; thermoregulation and fever. 9. Cyclic nucleotides and fever. 10. Prostaglandins in fever and the mode of action of antipyretic drugs. 11. Protein synthesis and fever. 12. The chemistry of non steroid antipyretic agents: structure-activity relationships. 13. Therapeutic agents affecting body temperature. 14. Capsaicin type pungent agents producing pyrexia. 15. The pathophysiology of fever in the neonate. 16. The treatment of fever from a clinical viewpoint. 17. Malignant hyperthermia: a review. 18. Febrile convulsions. 19. The pyrogenie responses of non mammalian vertebrates. 20. The pyrogenic responses of invertebrates. As the chapter headings indicate pyrogens set off a chain of reactions involving prostaglandins, cyclic AMP, the anterior hypothalamus, and changes in metabolism. There are special conditions where temperature control fails such as in malignant hyperthemia (MH), the development of an unexpected fever during anaesthesia, which is inherited through an autosomal dominant gene. In one case of a family of 138 individuals, 21 developed MH during anaesthesia and 8 of these died during or shortly after completion of surgery. MH is also found in racing greyhounds, race horses, cattle, and some breeds of pig. Although aspirin is still the major treatment of mild pyrexia, and thousands of tons are consumed each year, the side effects are such that aspirin (like penicillin) if put forward as new drug today, would most probably not get approval from the FDA. A wide range of new antipyretic drugs have been developed partly through routine screening and partly through greater understanding of the development of pyrexia in the body. The present volume provides an excellent account of the scientific basis of pyrexia and also indicates lines for future research and development.
P. Skolnick, J. F. Tallman, D. Greenblatt and S. M. Paul. 670pp. 1983. Verlag Chimie, Weinheim, Basel; Deerfield Beach, Florida, US$91. This is the proceedings of a conference held in Bethesda in 1982. The volume is in 10 sections. (1) BZ in the treatment of anxiety and depression. (2) BZ receptors, biochemistry and pharmacology. (3) BZ and GABA. (4) BZ and sleep. (5) Pharmacokinetics and distribution. (6) BZ and animal behaviour. (7) BZ receptors and new drug development. (8) Neurophysiology of BZ. (9) Endogenous ligands and modulators. (10) Adverse effects, tolerance and dependence. The brain contains specific receptors sites or recognition sites for BZ and these receptors are tightly coupled to other regulatory units such as the GABA receptor and the barbiturate recognition sites. This supra-molecular complex can be activated by minor tranquilizers as well as BZ. It is possible that there may be an endogenous BZ ligand of a peptide nature (or possibly a purine derivative) more work is needed before any definite conclusion can be made. The 57 papers presented are well illustrated and contain detailed bibliographies with full titles of the papers. There is a good subject index and the volume will be very useful to those interested in the scientific basis of the pharmacology of the BZs. The Encyclopedia of Drug Abuse---R. O'Brien and S. Cohen. 454pp. 1984. Facts on File, Bicester, New York. £26.50. There are 500 entries about drugs, their use, abuse, and their role in modem society. The drugs treated range from alcohol, caffeine, cannabis, cocaine, heroin, through to nicotine, histamine, and strychnine. There are several useful appendices. These are on street language, 54 tables of incidence of drug use in different countries: drugs names and their equivalents: fines and convictions for drugs use and traffiking: sources of information; a detailed bibliography, and an Index. For example the article on caffeine tells you that a 5 oz cup of percolated coffee will contain 110 mg of caffeine and that 6 cups of coffee a day will provide over 600 mg of caffeine. A dose of 350 mg a day can lead to dependence. Caffeine is rapidly absorbed through the GI tract and reaches a peak blood level in 30 minutes. Its half life in the body is 3.5 hours. It increases the heart rate and rhythm, stimulates gastric acid secretion, may elevate blood pressure, inhibits glucose metabolism and may raise blood sugar levels. It is a CNS stimulant, and postpones and shortens sleep. Fatalities from caffeine poisoning are rare. Only 7 deaths have been recorded to date. It is present also in tea--45 mg a cup; cocoa 13 mg, and some soft drinks (30-60 mg). This and much more of interest will be found in the volume. The book is written in an easy style and it can be understood and enjoyed by the general reader as well as the pharmacologist and it provides data that would not be easy to find elsewhere.
Pyretics and Antipyretics--Edited by A. S. Milton. Handbook of Experimental Pharmacology. Vol. 60. 691 pp. 1982. Springer Verlag, Berlin, New York. DM440. G.P. 16/4~1
Glucocorticoid Effects and Their Biological Consequences--Edited by L. V. Avioli, C. Gennari and B. Imbimbo. Advances in Experimental Medicine and Biology, Vol. 171. 419 pp. 1984. Plenum Press, New York, London. US$57.50. The anti-inflammatory action of hydrocortisone (half life 8-12 hours) is associated with the undesirable side effect of sodium retention. This is reduced in the synthetic giucocorticoid analogues such as prednisone, prednisolone, methylprednisone (half lives 12-36 hours): dexamethasone, betamethasone, paramethosone (half lives 36-72 hours). Though the sodium retention is reduced, these drugs have metabolic, gastro-intestinal, cardiovascular, ocular, cutane-
427
BOOK REVIEWS Pharmacology of the Benzodiazepines---Edited by E. Usdin,
Fever was one of the first symptoms of infection to be recognised by ancient physicians, though it was based on how the patient felt. The scientific analysis of fever depended on the development of the thermometer which only came into use in the 1720s. Even today the regulation of body temperature at 37°C is one indication of adequate homeostasis, and the various conditions that lead to disruption of this control are described in the present multi-authored volume. The subjects described in each chapter are as follows. 1. Body heat. 2. Fever and its role in disease; rationale for antipyretics. 3. Thermoregulation; its changes during infection with endotoxin producing micro organisms. 4. Exogenous pyrogens. 5. Endogenous pyrogens. 6. Role of central neurotransmitters in fever. 7. Role of ions in thermoregulation and fever. 8. Electrophysiology of the anterior hypothalamus; thermoregulation and fever. 9. Cyclic nucleotides and fever. 10. Prostaglandins in fever and the mode of action of antipyretic drugs. 11. Protein synthesis and fever. 12. The chemistry of non steroid antipyretic agents: structure-activity relationships. 13. Therapeutic agents affecting body temperature. 14. Capsaicin type pungent agents producing pyrexia. 15. The pathophysiology of fever in the neonate. 16. The treatment of fever from a clinical viewpoint. 17. Malignant hyperthermia: a review. 18. Febrile convulsions. 19. The pyrogenie responses of non mammalian vertebrates. 20. The pyrogenic responses of invertebrates. As the chapter headings indicate pyrogens set off a chain of reactions involving prostaglandins, cyclic AMP, the anterior hypothalamus, and changes in metabolism. There are special conditions where temperature control fails such as in malignant hyperthemia (MH), the development of an unexpected fever during anaesthesia, which is inherited through an autosomal dominant gene. In one case of a family of 138 individuals, 21 developed MH during anaesthesia and 8 of these died during or shortly after completion of surgery. MH is also found in racing greyhounds, race horses, cattle, and some breeds of pig. Although aspirin is still the major treatment of mild pyrexia, and thousands of tons are consumed each year, the side effects are such that aspirin (like penicillin) if put forward as new drug today, would most probably not get approval from the FDA. A wide range of new antipyretic drugs have been developed partly through routine screening and partly through greater understanding of the development of pyrexia in the body. The present volume provides an excellent account of the scientific basis of pyrexia and also indicates lines for future research and development.
P. Skolnick, J. F. Tallman, D. Greenblatt and S. M. Paul. 670pp. 1983. Verlag Chimie, Weinheim, Basel; Deerfield Beach, Florida, US$91. This is the proceedings of a conference held in Bethesda in 1982. The volume is in 10 sections. (1) BZ in the treatment of anxiety and depression. (2) BZ receptors, biochemistry and pharmacology. (3) BZ and GABA. (4) BZ and sleep. (5) Pharmacokinetics and distribution. (6) BZ and animal behaviour. (7) BZ receptors and new drug development. (8) Neurophysiology of BZ. (9) Endogenous ligands and modulators. (10) Adverse effects, tolerance and dependence. The brain contains specific receptors sites or recognition sites for BZ and these receptors are tightly coupled to other regulatory units such as the GABA receptor and the barbiturate recognition sites. This supra-molecular complex can be activated by minor tranquilizers as well as BZ. It is possible that there may be an endogenous BZ ligand of a peptide nature (or possibly a purine derivative) more work is needed before any definite conclusion can be made. The 57 papers presented are well illustrated and contain detailed bibliographies with full titles of the papers. There is a good subject index and the volume will be very useful to those interested in the scientific basis of the pharmacology of the BZs. The Encyclopedia of Drug Abuse---R. O'Brien and S. Cohen. 454pp. 1984. Facts on File, Bicester, New York. £26.50. There are 500 entries about drugs, their use, abuse, and their role in modem society. The drugs treated range from alcohol, caffeine, cannabis, cocaine, heroin, through to nicotine, histamine, and strychnine. There are several useful appendices. These are on street language, 54 tables of incidence of drug use in different countries: drugs names and their equivalents: fines and convictions for drugs use and traffiking: sources of information; a detailed bibliography, and an Index. For example the article on caffeine tells you that a 5 oz cup of percolated coffee will contain 110 mg of caffeine and that 6 cups of coffee a day will provide over 600 mg of caffeine. A dose of 350 mg a day can lead to dependence. Caffeine is rapidly absorbed through the GI tract and reaches a peak blood level in 30 minutes. Its half life in the body is 3.5 hours. It increases the heart rate and rhythm, stimulates gastric acid secretion, may elevate blood pressure, inhibits glucose metabolism and may raise blood sugar levels. It is a CNS stimulant, and postpones and shortens sleep. Fatalities from caffeine poisoning are rare. Only 7 deaths have been recorded to date. It is present also in tea--45 mg a cup; cocoa 13 mg, and some soft drinks (30-60 mg). This and much more of interest will be found in the volume. The book is written in an easy style and it can be understood and enjoyed by the general reader as well as the pharmacologist and it provides data that would not be easy to find elsewhere.
Pyretics and Antipyretics--Edited by A. S. Milton. Handbook of Experimental Pharmacology. Vol. 60. 691 pp. 1982. Springer Verlag, Berlin, New York. DM440. G.P. 16/4~1
Glucocorticoid Effects and Their Biological Consequences--Edited by L. V. Avioli, C. Gennari and B. Imbimbo. Advances in Experimental Medicine and Biology, Vol. 171. 419 pp. 1984. Plenum Press, New York, London. US$57.50. The anti-inflammatory action of hydrocortisone (half life 8-12 hours) is associated with the undesirable side effect of sodium retention. This is reduced in the synthetic giucocorticoid analogues such as prednisone, prednisolone, methylprednisone (half lives 12-36 hours): dexamethasone, betamethasone, paramethosone (half lives 36-72 hours). Though the sodium retention is reduced, these drugs have metabolic, gastro-intestinal, cardiovascular, ocular, cutane-
427