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[Popular Books Section]
[Animated Reviews]
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THE FATE OF TOXIC DRUGS
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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
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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.
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Randall C. Baselt, the author 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.
| 1. Acebutolol 2. Acetaldehyde 3. Acetaminophen 4. Acetohexamide 5. Acetone 6. Acetonitrile 7. Acetylmethadol 8. Acetylsalicylic Acid 9. Acrylonitrile 10. Albuterol 11. Aldrin 12. Alfentanil 13. Alphaprodine 14. Alprazolam 15. Alprenolol 16. Aluminum 17. Amantadine 18. Amikacin 19. Amiodarone 20. Amitriptyline 21. Amlodipine 22. Amobarbital 23. Amoxapine 24. Amphetamine 25. Amygdalin 26. Anileridine 27. Aniline 28. Antimony 29. Antipyrine 30. Aprobarbital 31. Arsenic 32. Astemizole 33. Atenolol 34. Atracurium 35. Atropine 36. Azide 37. Baclofen 38. Barbital 39. Barium 40. Benzene 41. Benzidine 42. Benzonatate 43. Benzphetamine 44. Benztropine 45. Benzyl Alcohol 46. Beryllium 47. Betaxolol 48. Biperiden 49. Bismuth 50. Borate |
51. Bromazepam 52. Bromide 53. Brompheniramine 54. Buflomedil 55. Buformin 56. Bupivacaine 57. Buprenorphine 58. Bupropion 59. Buspirone 60. Butabarbital 61. Butalbital 62. Butane 63. Butaperazine 64. Butethal 65. Butorphanol 66. Butyl Nitrite 67. Cadmium 68. Caffeine 69. Camphor 70. Captopril 71. Carbamazepine 72. Carbaryl 73. Carbon Disulfide 74. Carbon Monoxide 75. Carbon Tetrachloride 76. Carbromal 77. Carisoprodol 78. Cathinone 79. Cetirizine 80. Chloral Hydrate 81. Chloramphenicol 82. Chlordane 83. Chlordecone 84. Chlordiazepoxide 85. Chlormethiazole 86. Chlormezanone 87. Chlorobenzene 88. Chloroform 89. Chloroprocaine 90. Chlorquine 91. Chlorothiazide 92. Chlorphenesin Carbamate 93. Chlorpheniramine 94. Chlorphentermine 95. Chlorpromazine 96. Chlorpropamide 97. Chlorprothixene 98. Chlorpyrifos 99. Chlorzoxazone 100. Chromium |
101. Cimetidine 102. Citalopram 103. Clenbuterol 104. Clobazam 105. Clomipramine 106. Clonazepam 107. Clonidine 108. Clorazepate 109. Clozapine 110. Cobalt 111. Cocaine 112. Codeine 113. Colchicine 114. Copper 115. Cresol 116. Cumene 117. Cyanide 118. Cyclizine 119. Cyclobenzaprine 120. Cyclohexane 121. Cyclopropane 122. Cyclosporine 123. Cyproheptadine 124. Dantrolene 125. DDT 126. Desipramine 127. Dexfenfluramine 128. Dextromethorphan 129. Dextromoramide 130. Diazepam 131. Diazinon 132. Dibenzepine 133. Dibucaine 134. p-Dichlorobenzene 135. Dichloromethane 136. 2,4-Dichlorophenoxy acetic Acid 137. Diclofenac 138. Dicumarol 139. Dicyclomine 140. Dieldrin 141. Diethylpropion 142. Diethyltoluamide 143. Diflunisal 144. Digitoxin 145. Digoxin 146. Dihydrocodeine 147. Diltiazem 148. Dimethylformamide 149. Dimethylsulfoxide 150. Dimethyltryptamine |
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.
| 151. Dinitro-o-Cresol 152. Dioxane 153. Dioxin 154. Diphenhydramine 155. Diphenoxylate 156. Diquat 157. Disopyramide 158. Disulfiram 159. Dothiepin 160. Doxapram 161. Doxepin 162. Doxylamine 163. Dyphylline 164. Emetine 165. Enalapril 166. Encainide 167. Endrin 168. Enflurane 169. Ephedrine 170. Epinephrine 171. Esmolol 172. Estazolam 173. Ethanol 174. Ethchlorvynol 175. Ether 176. Ethinamate 177. Ethosuximide 178. Ethotoin 179. Ethylbenzene 180. Ethyl Chloride 181. Ethylene Glycol 182. Ethylene Oxide 183. Etidocaine 184. Etodolac 185. Etorphine 186. Famotidine 187. Famprofazone 188. Felbamate 189. Felodipine 190. Fenfluramine 191. Fenoprofen 192. Fentanyl 193. Fexofenadine 194. Flecainide 195. Flumazenil 196. Flunitrazepam 197. Fluoride 198. Fluoroacetate 199. Fluorocarbons 200. 5-Fluorouracil . |
201. Fluoxetine 202. Fluphenazine 203. Flurazepam 204. Flurbiprofen 205. Flvoxamine. 206. Formaldehyde 207. Gabapentin 208. Gamma- Hydroxybutyrate 209. Gasoline 210. Gentamicin 211. Glutethimide 212. Glycopyrrolate 213. Gold 214. Guaifenesin 215. Halazepam 216. Haloperidol 217. Halothane 218. Heparin 219. Heroin 220. Hexachlorobenzene 221. Hexachlorophene 222. Hexane 223. Hydralazine 224. Hydrochlorothiazide 225. Hydrocodone 226. Hydrogen Sulfide 227. Hydromorphone 228. Hydroxychloroquine 229. Hydroxyzine 230. Ibogaine 231. Ibuprofen 232. Imipramine 233. Indomethacin 234. Insulin 235. Iron 236. Isoflurane 237. Isoniazid 238. Isopropanol 239. Isoproterenol 240. Isosorbide Dinitrate 241. Kanamycin 242. Kerosene 243. Ketamine 244. Ketobemidone 245. Ketoprofen 246. Ketorolac 247. Labetalol 248. Lamotrigine 249. Lead 250. Levorphanol |
251. Lidocaine 252. Lindane 253. Lisinopril 254. Lithium 255. Loperamide 256. Loratadine 257. Lorazepam 258. Loxapine 259. Lysergic Acid Diethylamide (LSD) 260. Magnesium 261. Malathion 262. Manganese 263. Maprotiline 264. MBDB 265. Medazepam 266. Mefenamic Acid 267. Melatonin 268. Meperidine 269. Mephenytoin 270. Mephobarbital 271. Mepivacaine 272. Meprobamate 273. Mercury 274. Mescaline 275. Mesoridazine 276. Metaldehyde 277. Metformin 278. Methadone 279. d-Methamphetamine 280. l-Methamphetamine 281. Methanol 282. Methapyrilene 283. Methaqualone 284. Metharbital 285. Methocarbamol 286. Methohexital 287. Methomyl 288. Methotrexate 289. Methotrimeprazine 290. p-Methoxy amphetamine 291. Methoxyflurane 292. Methsuximide 293. Methyl Bromide 294. Methyl n-Butyl Ketone 295. Methyl Chloride 296. Methyldopa 297. 4,4'-Methylenebis (2-chloroaniline) 298. Methylenedioxy amphetamine 299. Methylenedioxy ethylamphetamine 300. Methylenedioxy methamphetamine |
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 302. Methylfentanyl 303. Methylphenidate 304. Methyl Salicylate 305. Methyprylon 306. Metoclopramide 307. Metoprolol 308. Mexiletine 309. Mianserin 310. Midazolam 311. Mirtazapine 312. Moclobemide 313. Modafinil 314. Molindone 315. Moricizine 316. Morphine 317. Nabumetone 318. Nadolol 319. Nalbuphine 320. Naloxone 321. Naltrexoe 322. Naproxen 323. Nefazodone 324. Nicardipine 325. Nickel 326. Nickel Carbonyl 327. Nicotine 328. Nifedipine 329. Nimodipine 330. Nisoldipine 331. Nitrazepam 332. Nitrite 333. Nitrobenzene 334. Nitroglycerin 335. Nitroprusside 336. Nitrous Oxide 337. Nomifensine 338. Nortriptyline 339. Olanzapine 340. Omeprazole 341. Ondansetron 342. Orphenadrine 343. Oxalate 344. Oxazepam 345. Oxprenolol 346. Oxycodone 347. Oxymorphone 348. Oxyphenbutazone 349. Pancuronium 350. Papaverine |
351. Paraldehyde 352. Paraquat 353. Parathion 354. Paroxetine 355. Pemoline 356. Pentachlorophenol 357. Pentazocine 358. Pentobarbital 359. Pentoxifylline 360. Perphenazine 361. Phenacetin 362. Phencyclidine (PCP) 363. Phendimetrazine 364. Phenelzine 365. Phenethylamine 366. Phenfonnin 367. Pheniramine 368. Phenmetrazine 369. Phenobarbital 370. Phenol 371. Phensuximide 372. Phentermine 373. Phenylbutazone 374. Phenylephrine 375. Phenylpropanolamine 376. Phenytoin 377. Pholcodine 378. Phosphine 379. Pimozide 380. Pindolol 381. Piroxicam 382. Platinum 383. Polybrominated Biphenyls 384. Polychlorinated Biphenyls 385. Potassium 386. Prazepam 387. Prazosin 388. Prilocaine 389. Primaquine 390. Primidone 391. Procainamide 392. Procaine 393. Prochlorperazine 394. Procyclidine 395. Promethazine 396. Propafenone 397. Propane 398. Propofol 399. Propoxyphene 400. Propranolol |
401. Propylene Glycol 402. Propylhexedrine 403. Protriptyline 404. Pseudoephedrine 405. Psilocybin 406. Pyrilamine 407. Quazepam 408. Quetiapine 409. Quinidine 410. Quinine 411. Ranitidine 412. Remifentanil 413. Remoxipride 414. Risperidone 415. Salicylamide 416. Scopolamine 417. Secobarbital 418. Selegiline 419. Selenium 420. Sertindole 421. Sertraline 422. Sevoflurane 423. Sibutramine 424. Sildenafil 425. Silver 426. Sotalol 427. Strychnine 428. Styrene 429. Succinylcholine 430. Sufentanil 431. Sulindac 432. Sulpiride 433. Sumatriptan 434. Temazepam 435. Terbutaline 436. Terfenadine 437. Tetrachloroethylene 438. Tetraethyllead 439. Tetrahydrocannabino1 440. Thallium 441. Theophylline 442. Thiopental 443. Thioridazine 444. Thiothixene 445. Timolol 446. Tin 447. Tobramycin 448. Tocainide 449. Tolbutamide 450. Tolmetin |
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.
| 451. Toluene 452. Tramadol 453. Tranylcypromine 454. Trazodone 455. Triazolam 456. Trichloroethane 457. Trichloroethylene 458. 2,4,5-Trichloro phenoxyacetic acid 459. Trifluoperazine 460. Trihexyphenidyl 461. Trimipramine |
462. Tripelennamine 463. Tubocurarine 464. Valproic Acid 465. Vanadium 466. Vancomycin 467. Venlafaxine 468. Verapamil 469. Vigabatrin 470. Vinyl Chloride 471. Warfarin 472. Xylazine |
473. Xylene 474. Yohimbine 475. Zidovudine 476. Zileuton 477. Zimelidine 478. Zinc 479. Zipeprol 480. Zolmitriptan 481. Zolpidem 482. Zomepirac 483. Zopiclone |
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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Interested in toxicology, forensic toxicology, and related areas? Well try these books recommended by the Editor-in-chief.
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-Anil Aggrawal
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