THE FATE OF TOXIC DRUGS
Disposition of Toxic Drugs and Chemicals in Man 5th Edition by Randall C. Baselt. Hard Bound, 7" x 10"
Chemical Toxicology Institute, P.O. Box 8209, Foster City, California 94404. Publication Date 2000; xvi + 919 pages: ISBN 0-9626523-3-4: Library of Congress Catalog Card No. 99-72382: Hardback edition, 2001: Price $119.00
The single most important thing a toxicologist requires in his day-to-day life is a reliable data source on all drugs, poisons and toxins. Very frequently I have been called in an Emergency room, and asked to opine in the case of a patient, who has ingested, say, twenty tablets of Amitryptine. What is the fatal dose of Amitryptiline? What is going to be the fate of this drug in the body? What are its metabolites, and how can we test for them? What tests need to be conducted to know to know if the patient is in danger or not? What blood concentration is fatal, and which is the safe limit? These and several similar questions need to be answered before any meaningful advice can be given in such cases.
Dr. Randall C. Baselt is an analytical toxicologist with 35 years experience in forensic, clinical and industrial toxicology. For more information about him, click here.
The book under review serves this purpose beautifully well. Written in an A-Z dictionary style, this book deals with as many as 483 substances, ranging from Acebutolol (a beta-adrenoceptor antagonist used in the treatment of hypertension) to Zopiclone (a hypnotic agent). Each substance is dealt with in a separate section. The book is in its fifth edition now. It is interesting to note that in the first edition, which appeared some 22 years before, less than 200 substances were dealt with. But the work has proved so popular, that editions after editions appeared, and in each edition, the authors increased the amount of information. Robert Cravey, a forensic Toxicologist joined as a co-author in the third edition. But Cravey has since retired, so the current edition appears under the single authorship of Randall C. Baselt.
8. Acetylsalicylic Acid
45. Benzyl Alcohol
66. Butyl Nitrite
73. Carbon Disulfide
74. Carbon Monoxide
75. Carbon Tetrachloride
80. Chloral Hydrate
Open the book anywhere, and you would find all data pertaining to a particular drug neatly divided into five sub-headings: (i) Occurrence and Usage (ii) Blood concentrations (iii) Metabolism and excretion (iv) Toxicity and (v) Analysis. In addition, there are a number of useful references at the end of each section. In the beginning of each section, important information pertaining to that drug is given. These include the half life of the drug in plasma (T½), Volume of Distribution (Vd), Fraction bound to Plasma proteins (Fb) and Dissociation constant (Pka). The structure of the drug is also given which is very helpful. I tried finding several drugs and poisons which interested me, and the book never failed me. Strychnine is a very commonly talked about poison in India, and I was very curious to know if this poison is dealt with in this book. Sure enough I found detailed information on this poison on page 790. In a jiffy, I could get to know its exact structure, its volume of distribution (which by the way is 13 L/kg), its half life and its pKa. In some cases, (as in the case of strychnine), certain data are not known, and the author rightly uses the "?" mark to denote this. For instance, in the case of strychnine, the portion bound to plasma proteins (Fb) is not known, and the author denotes it like this: "Fb:?". This could perhaps spur on toxicologists looking for new subjects to start investigation on.
The first sub-title in each section is "Occurrence and Usage". Under this sub-title, the author tells us where the drug comes from and how is it used. This gives a very good "handle" to the reader to get some grasp on the subject. For instance, in the case of Strychnine, we are told that it comes from the seed of Strychnos nux-vomica, and is still used in certain countries as a tonic to improve circulation and muscle tone. I tried many exotic sounding names in this book, and every time got sound information which helped me "understand" the drug to go further on. What for instance is Tramadol, and how it is used? Well, it is a synthetic opioid-receptor agonist that has been used clinically as a narcotic analgesic since 1977. What is 4,4'-Methylenebis(2-chloroaniline)? Also known as MOCA, this substance is used as a curing agent for epoxy resins and isocyanate polymers. This substance, although solid at room temperatures, may be absorbed following inhalation or dermal contact.
180. Ethyl Chloride
181. Ethylene Glycol
182. Ethylene Oxide
200. 5-Fluorouracil .
226. Hydrogen Sulfide
240. Isosorbide Dinitrate
259. Lysergic Acid
266. Mefenamic Acid
293. Methyl Bromide
294. Methyl n-Butyl Ketone
295. Methyl Chloride
The second sub-title in each section is "Blood concentrations". Under this heading the author gives us the various blood concentrations under various different conditions. The figures are basically a summarization of various studies, the author has painstakingly collected from literature. Not only does he give you the result of the study, but he actually quotes that study, so if the results have intrigued you, you can always go back to the original paper, and dig out more information. Essentially what he does is to separate "chaff from the grain", and give you only the latter. Sample this in the section on d-Methamphetamine: A single oral dose of 0.125 mg/kg produces a peak plasma concentration of 0.020 mg/L at 3.6 hours. This is just one study by Cook et al. published in 1992. But surely this is not the only study related to d-Methamphetamine. Baselt goes ahead and gives you a number of other studies with results. For instance, in another study published in 1996 by Shappell et.al, a 30 mg oral dose produced an average peak serum methamphetamine concentration of 0.094 mg/L at times of 3-5 hours. If you are facing a case of d-Methamphetamine overdose, or if you are planning to conduct research on this drug, these figures are going to be of much help to you.
I was attracted by certain non-conventional poisons. Carbon monoxide, for instance, is a gas, and I wanted to know what the author had to offer us under this section. The first thing I realized was that the values Vd and Fb were unknown for Carbon Monoxide, because both had a question mark in front of them. The plasma half life is 4-5 hours. In the Title "Occurrence and Usage", we are told about the common sources (cigarette smoke, automobile exhaust etc), along with the concentration in each. Some interesting figures are offered under the sub-title "Blood concentrations". Carbon-monoxide is actually produced endogenously by the catabolism of heme at an average rate of 0.4 mL/hour in resting male subjects. This gives a blood concentration of about 0.4-0.7%. Non-smokers living in perfectly clean surroundings must thus have this as their minimum blood concentration. However urban non-smokers smell carbon monoxide through automobile exhausts too, and their concentration is around 1-2%. Smokers have a concentration of about 5-6%.
The third sub-title is quite interesting and tells us about "Metabolism and excretion". How is the drug metabolized in the body? What are its various metabolic products? How is it excreted? These and many other similar questions are dealt with in this section. We all know about the metabolism and excretion of methyl and ethyl alcohol, but how is benzyl alcohol metabolized? Well, the book comes to your rescue; it is rapidly metabolized to benzoic acid which is conjugated with glycine to form hippuric acid, which is excreted in urine. Try some exotic sounding drugs, and the book will not fail you. How is, say, Methyl n-Butyl Ketone (used as a solvent for plastic resins, inks and various cleaning agents) metabolized and excreted? Well, it is metabolized to 2-hexanol, 5-hydroxy-2-hexanone, 2,5-hexanedione, and carbon dioxide! Studies have been quoted where humans were given a labeled oral dose of this compound. It was found that 40% was excreted as carbon-dioxide in breath and 26% as metabolites in urine over an 8 day period.
|301. Methyl Ethyl Ketone
304. Methyl Salicylate
326. Nickel Carbonyl
336. Nitrous Oxide
362. Phencyclidine (PCP)
383. Polybrominated Biphenyls
384. Polychlorinated Biphenyls
|401. Propylene Glycol
The fourth sub-title is on "Toxicity". What are the adverse reactions to a drug? How much drug could prove fatal to a human being? Questions like these are dealt with under this sub-title. What is the fatal dose of Nitrazepam, a drug commonly used as a hypnotic agent in a dose of about 10mg. Several studies are quoted, and we are told that about 250 mg should be the fatal dose (or about 25 tablets. This gives important insights to the doctor and the toxicologist). Also given are the concentrations in various organs when the fatal dose is ingested. This is helpful to forensic pathologists, who want to know how the person has actually died. In the current case, we are told that the blood concentrations in a fatal case range from 1.2-9.0 mg/L, liver concentrations range from 0.7-4.0 mg/kg, and urine concentrations from 1-10 mg/L. We are also told that with this particular drug, post-mortem redistribution does not occur.
The final sub-title is "Analysis". Under this heading we are told the various methods employed to analyze that particular drug or poison. You could be faced with a case of a very strange substance, say, Phensuximide (an anticonvulsant succinimide derivative). How are you going to analyze the drug? This book comes to your rescue again. It is done by fluorometric method, and by gas chromatography of the underivatized drug by flame-ionization.
There is a big "Reference" sub-heading at the final part of each section, under which all references quoted in the section are given. The reader could go back to these references if he needs to delve more in a particular toxic substance of his interest. Thus the book serves as a good collection of important references too.
I was very curious to know about certain tradition poisons - tetrahydrocannabinol, morphine, Khat - and every time I delved in the book for these poisons, I emerged with interesting information. Khat, for instance, contains Cathinone, which is structurally and pharmacologically related to amphetamine. Khat (Catha edulis) is an ever green shrub, cultivated in East Africa and on the Arabian peninsula. Khat chewing, in several countries, is a social event and the user may consume 100-200 g of leaves over a 3-4 hour period. Chronic abusers may develop psychiatric symptoms such as paranoid psychoses.
464. Valproic Acid
470. Vinyl Chloride
I searched for some exotic poisons, and I found some amazing substances. Gold for example is given in detail as a toxic substance. Monovalent gold compounds are used in the treatment of rheumatoid arthritis. Side effects may include dermatitis and nephrotic syndrome. A person even died after gold injections given over a period of 6 days. The details of his tissue concentrations are given. He was found to have a concentration of 0.4 mg/L of gold in his blood, 2.6 mg/kg in his liver, 0.7 mg/kg in his spleen, 15.7 mg/kg in the kidney cortex and 11.0 mg/kg in the kidney medulla. Quite rare figures, but very useful, if you are dealing with a case of gold poisoning. Not many toxicology books would enlighten you on these poisons.
How would I rate this book? In one word, superb! This is going to be the single most important book in my toxicology library. I would heartily recommend this book to anyone who has anything to do with toxicology. Should be most useful to clinicians, pharmacologists, pharmacists, forensic pathologists, researchers, crime investigators, and any one who is interested in the science of drugs and poisons. The value of the book is enhanced because it deals with a multitude of drugs and poisons, which are not found in other regular texts.
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