臺灣博碩士論文加值系統

由於時代潮流與動物保護法之通過，致使流浪犬捕捉之問題成為現今社會注目之焦點。在人道主義及經濟考量下，本研究利用水化氯醛（Chloral hydrate）之催眠作用來捕捉流浪犬；由於它能降低動物對刺激（如：痛、癢及保定）之反應，以及它的藥性穩定，安全範圍大，投藥方便，價格便宜，故選用此劑。
實驗犬隻裝設咽胃管（Pharyngostomy tube）24小時後，水化氯醛經由該管投予。研究結果半致死劑量（Lethal dose 50%；LD50）為1,821.4 mg/kg，半有效劑量（Effective dose 50%；ED50） 為509.09 mg/kg，治療指數（Therapeutic index）為3.58，及確立有效催眠劑量為834.93 mg/kg。在年齡方面，求取催眠劑量與致死劑量時，發現該劑量與年齡無顯著相關性（p＞0.05）；劑量方面，致死劑量與死亡率則有顯著相關性（p＜0.05）。受催眠犬隻之平均催眠時間為246.88 ±25.17分鐘，在心肺血管之變化：血壓，心跳數，脈搏數，血氧（SpO2），呼吸數，心電圖及體溫皆屬正常範圍。比較催眠前後之心肺功能，發現催眠中之血壓及體溫有輕微受抑制之現象（p＜0.05）。給予催眠劑量後ALT, AST, ALKP，均有明顯上升；田間試驗時催眠劑量之死亡率為3/28（10.71%），其中2/28（7.14%）因吸入性肺炎窒息死亡，而1/28（3.57%）因呼吸抑制致死。
嘔吐是水化氯醛在催眠劑量下之主要副作用，在催眠過程所造成之嘔吐易引起吸入性肺炎,因此若將水化氯醛稀釋倍數提高便可降低嘔吐率、吸入性肺炎之發生率及死亡率。在人道考量下水化氯醛能減少動物之緊張及恐懼，且水化氯醛與食物充分混合稀釋後安全性高，可應用於現場流浪犬之捕捉。

For the stray dog’s well-being, the hypnotic effect of chloral hydrate was utilized to catch them. The drug increased the animal’s responsive threshold of the environmental stimulations. The chemical compound was stable, safe, convenient, and inexpensive. We tried to use those characteristics to arrest street dogs.
The experimental dog was pharyngostomy tubed, after 24 hours, we gave the medicine by the tube. The LD50 of acute toxicity was 1,821.4 mg/kg, the ED50 was 509.09 mg/kg, therapeutic index was 3.58 and hypnotic dosage was 834.93 mg/kg. The relationship between hypnotic dose and fatal dose was not significant difference (p > 0.05). The fatal dosage and mortality had significant difference (p < 0.05). The mean hypnotic time was 246.88 ±25.17 minutes. When the dog hypnotized, the blood pressure and heart rate, pulse rate, SpO2, respiratory rate, electrocardiography and body temperature were normal. We compared the blood pressure and the body temperature both before and after hypnosis, and found it had mild depressed effect (p < 0.05). After the hypnotic treatment, the activity of ALT, AST and ALKP in serum was obviously increased. In the field trial, the mortality with hypnotic treatment was 3/28 (10.71%); among the dead, two of which were caused by aspiratory pneumonia; and another one was killed by respiratory depression.
The major side-effect of chloral hydrate was vomiting, which might result in the aspirated pneumonia. Dilution of the agent by food or water could prevent lethal side-effect. For the animal’s welfare, the effect of chloral hydrate may reduce their nervousness and fear, so it could be an useful way for street dog capture.

中文摘要 ………………………………………………Ⅰ
英文摘要 ………………………………………………Ⅲ
誌 謝 ………………………………………………Ⅴ
目 錄 ………………………………………………Ⅵ
表 次 ………………………………………………Ⅶ
圖 次 ………………………………………………Ⅷ
第一章前言…………………………………………….1
第二章文獻探討……………………………………….3
第1節水化氯醛之介紹……………………………….3
第2節水化氯醛之理化性狀………………………….4
第3節給予方法……………………………………….5
第4節水化氯醛之藥物特性………………………….6
第5節水化氯醛之製劑………………………………13
第6節水化氯醛之治療劑量和不良作用……………13
第7節水化氯醛藥物過量給予之臨床症狀…………15
第8節水化氯醛中毒之治療…………………………15
第9節水化氯醛在鎮靜或催眠過程之注意事項……16
第10節水化氯醛於動物之使用……………………..17
第11節水化氯醛對各種生化檢驗之影響……………21
第三章實驗材料與方法………………………………22
第1節實驗材料………………………………………22
第2節實驗方法………………………………………24
第3節統計分析………………………………………27
第四章 結果..………………………………………28
第1節半致死劑量……………………………………28
第2節半有效劑量……………………………………29
第3節藥物安全範圍…………………………………30
第4節水化氯醛對心血管之作用……………………30
第5節水化氯醛對肝指數之影響……………………31
第6節田間試驗………………………………………32
第五章 討論..………………………………………33
參考文獻………………………………………………….42
附 錄 …………………………………………….62
表 次
表4-1 犬隻投予水化氯醛後以迴歸方程式預估劑量，
催眠啟始時間和催眠作用率三者之相關…………51
表4-2 犬隻水化氯醛給予催眠劑量（835 mg/kg）前後
生理變化之比較表…………………………………51
表4-3 犬隻水化氯醛口服投予前與投予24小時後肝指
數之比較….…………………………………..……….52
表4-4 水化氯醛於犬、貓及兔子急性中毒之比較表…..…..52
附表1 水化氯醛對人誘發之心律不整………………..….....63
附表2 水化氯醛對於各種動物之劑量………………..…….64
附表3犬年齡區分表…………………………….…..……….65
附表4 水化氯醛之物質安全資料表………………..…….…66
圖 次
圖4-1 犬隻投予水化氯醛之劑量與死亡率之迴歸直線圖…53
圖4-2 犬隻投予水化氯醛之劑量與催眠率之迴歸直線圖…54
圖4-3 犬隻投予水化氯醛之劑量與催眠啟始時間之迴歸
直線圖………………………………………………….55
圖4-4 犬隻投予水化氯醛後TSP之變化……………………56
圖4-5 犬隻投予水化氯醛後T.Bili之變化…………………..57
圖4-6 犬隻投予水化氯醛後ALB之變化….………………..58
圖4-7 犬隻投予水化氯醛後ALT之變化……………….….. 59
圖4-8 犬隻投予水化氯醛後AST之變化………………..…. 60
圖4-9 犬隻投予水化氯醛後ALKP之變化…………..…….. 61
附圖1 水化氯醛於人體內代謝過程之模式圖……………….75
附圖2 Halothane、水化氯醛及TCE之結構式………………76
附圖3 水化氯醛和乙醇代謝之相互作用模式圖………….…76附圖4 自製之鐵絲環………………………….……..…...….. 77
附圖5 歐美式捕狗環..…….………………………….…..…..77
附圖6 捕狗捍…………………………………..……….…..…78
附圖7 自製之捕狗套網..……………………………..…..…..78
附圖8 捕狗籠…………………………………….….……..….79

1.王學仕。水化氯醛。實用麻醉藥理學。台灣中華書局。114-116, 1968。
2.呂車鳳，況慧星，吳永惠。靜脈注射及其他注射型麻醉劑。獸醫藥理與治療學(上冊)。藝軒圖書出版社。243-247, 1981。
3.沈明來。迴歸分析。試驗設計學。九州圖書文物有限公司。383-422, 1995。
4.金明儒。安眠藥及鎮靜劑。藥物學。中華藥學研究基金會。249-250, 1981。
5.夏良宙。動物安樂死。動物保護檢查人員訓練。國立屏東科技大學技藝訓練中心。101-103, 1999。
6.陳長安。非巴比妥類之鎮靜---安眠藥。常用藥物治療手冊。合記出版社。221-222, 1994。
7.陳裕江。中樞神經抑制藥及抗驚厥藥。獸醫藥理學。43-47, 1966。
8.馮淇輝。含氯素之麻醉劑。獸醫藥理學。農業出版社。131-133，1992。
9.Abbas R, Fisher JW. A physiologically based pharmacokinetic model for trichloroethylene and its metabolites, chloral hydrate, trichloroacetate, dichloroacetate, trichloroethanol, and trichloroethanol glucuronide in B6C3F1 mice. Toxicol Appl Pharm. 147(1): 15-30, 1997.
10.Adams WL. The comparative toxicity of chloral alcoholate and chloral hydrate. J Pharmaco Exp Ther. 78: 340-345, 1943.
11.Adriani J, Ambre JJ. Chloral hydrate. Clinical management of poisoning and drug overdose second edition. W.B. Saunders Co. 835-838, 1990.
12.Alfred GG, Louis SG, Alfred G. Pharmacodynamics. The pharmacological basis of therapeutics sixth edition. 39,1980.
13.Andrews EJ, Bennett BT, Clark JD. Houpt KA, Pascoe PJ, Robinson GW, Boyce JR. Report of the AVMA panel on euthanasia. JAVMA, 202(2): 231-249, 1993.
14.Barnes D, Eltherington L. Drug dosage in laboratory animals. University of California Press, Berkeley. 69, 260, 1973.
15.Barone MA. The harriet lane handbook fourteenth edition. St.Louis: Mosby. 505, 1996.
16.Beland FA, Schmitt TC, Fullerton NF, Young JF. Metabolism of chloral hydrate in mice and rats after single and multiple doses. J Toxicol En Heal. 3(54): 209-226, 1998.
17.Berger J. A comparison of some anesthetic techniques in young calves. Brit. Vet. J. 122(2): 65-73, 1966.
18.Beuan JA. Influence of drugs on laboratory tests. Essentials of pharmacology. Quinn & Boden Co. 22, 579-598, 1978.
19.Binder LS, Leake LA. Chloral hydrate for emergent pediatric procedural sedation. AJEM.9: 530-534, 1991.
20.Birchard Sj, Sherding RG. Normal Values. Saunders manual of small animal practice. W.B. Saunders Co. 14, 511, 1994.
21.Booth NH, McDonald LE. Intravenous and other parenteral anesthetics. Veterinary pharmacology and therapeutics, sixth edition. Yi Hsien Publishing Co. 212-274, 1988.
22.Bowyer K, Glasser SP. Chloral hydrate overdose and cardiac arrhythmias. Chest. 77: 232-235,1980.
23.Brander GC, Bywater RJ, Jenkins WL, Pugh DM. Introduction and general pharmacology. Veterinary applied pharmacology & therapeutics fifth edition. W.B. Saunders Co. 20-21, 1991.
24.Bush BM. Clinical enzymology. Interpretation of laboratory results for small animal clinicians. B.W. Science Publications. 311~319, 1991.
25.Butler TC. The metabolic fate of chloral hydrate. J Pharm Exp Ther. 92: 49-57, 1948.
26.Buur T, Larsson R, Norlander B. Pharmacokinetics of chloral hdrate poisoning treated with hemodialysis and hemoperfusion. Acta Med Scand. 233(3): 269-274, 1988.
27.Clark. Contemporary drug abuse. Medical pharmacology twelfth edition. International Edition. 290, 351-2,751,771, 777-778, 1988.
28.Cote CJ. Sedation for the pediatric patient. A review. Pediatr Clin North Am. 41: 31-58, 1994.
29.Craig CR, Stitzel RE. General principles of pharmacology. Modern pharmacology second edition. Little, Brown Co. 14-15, 1986.
30.Csaky TZ. Sedatives and Hypnotics. Cutting's Handbook of Pharmacology: The actions and uses of drugs sixth edition. The National Book Co. 572, 1979.
31.Dahiya Z, Peshine P, Nigam J. Evaluation of promazine and chloral hydrate anesthesia in horses. Indian J Anim Sci. 55: 243-248, 1985.
32.David CL. Acute gastric perforation in a chloral hydrate overdose. AJEM. 5(16): 545-546, 1998.
33.Devarajan S. Interaction of fluoxetine and chloral hydrate [latter]. Can J Psych. 37: 590-591, 1992.
34.Ellenhorn MJ, Barceloux. Chloral hydrate. Medical toxicology diagnosis and treatment of human poisoning. Elserier Science Publishing Co. 119, 586-588, 785, 1988.
35.Eric WM, Louis EK, John NM, Osol A, Martin S, Linwood FT. Sedatives and Hypnotics. Remington's Pharmacology Sciences. Mack Publishing Co. 1154, 1965.
36.Ettinger SJ, Feldman EC. Hypertension. Textbook of Veterinary internal medicine fifth edition. W.B. Saunders Co. 179, 2000.
37.Fleischman RW, McCrackem D, Forbes W. Adynamic ileus in the rat induced by chloral hydrate. Lab Anim Sci. 27(2): 238-243, 1977.
38.Gass T. Denicola D. Veterinary reference guide. Eastman Kodak Co. 1993.
39.Gleich GJ, Moran ES, Vanles DW. Esophageal stricture following chloral hydrate poisoning. JAMA. 201: 266-267, 1967.
40.Goodman LS, Gilman A. The pharmacological basics of therapeutics seventh edition. New York: The McMillan Co, 1985.
41.Graham SR, Day RO, Lee R, Fulde GW. Overdose with chloral hydrate: a pharmacological and therapeutic review. Med J Aust. 149(11-12): 686-688, 1988.
42.Greenberg BS, Faerber EN, Aspinall CL. High-dose chloral hydrate sedation for children undergoing MR imaging: Safety and efficacy in relation to age. AJR.161: 639-641, 1993.
43.Grollman A. Hypnotics and sedatives. Pharmacology and therapeutics, fifth edition. 189-190, 1962.
44.Gustafson A, Svensson SE, Ugander L. Cardiac arrhythmias in chloral hydrate poisoning. Acta Med Scand. 201: 227-230, 1977.
45.Haddad LM, Winchester JF. Chloral hydrate. Clinical management of poisoning & drug overdose, second edition. W.B. Saunders Co. 835-839, 1990.
46.Hall L. Equine anesthesia. Textbook of veterinary anesthesia. Baltimore, Williams & Wilkins. 319-343, 1971.
47.Harvey SC. Hypnotics and sedatives. In: Gilman AG, Goodman LS, Gilman A. The pharmacological basis of therapeutics. New York: Macmillan. 364-365, 1990.
48.Hershenson M, brouillette RT, Olsen E, Hunt CE. The effect of chloral hydrate on genioglossus and diaphragmatic activity. Pediatr Res. 18:516-519, 1984.
49.Hobara T, Kobaysahi H, Kawamoto T, Iwamoto S, Sakai T. Intestinal Absorption of chloral hydrate, free trichloroethanol and trichloroacetic acid in dogs. Pharm & Toxicol.62 (5): 250-258, 1988.
50.Hobara T, Kobaysahi H, KawamotoT, Iwamoto S, Sakai T. Extrahepatic metabolism of chloral hydrate, trichloroethanol and trichloroacetic acid in dog. Pharm & Toxicol. 61(1): 58-62, 1987.
51.Hoffman RS, Nelson L. The toxic emergency: Chloral hydrate and other sleep-inducing agents. Emerg Med.4: 82-84, 1996.
52.Hubbel J, Hull B. Perianesthetic considerations in cattle. Compendium on continuing education for the practicing veterinarian. 8: 92-99, 1986.
53.Hunt CE, Hazinski TA, Gora P. Experimental effect of chloral hydrate on ventilator response to hypoxia and hypercarbia. Pedatr Res. 16:79-81, 1982.
54.Jastak JH, Pallasch T. Death after chloral hydrate sedation: report of case. JADA. 116(3): 345-348, 1988.
55.Jay P, Paul P, Michele N. Chloral hydrate: the good and the bad. Pediatr Emerg Care. 15(6): 432-435, 1999.
56.Keller DA. Mechanistic studies on chloral toxicity: relationship to trichloroethylene carcinogenesis. Toxicol Lett. 42:183-191, 1988.
57.Kimberly S, Timothy E, Yona A, Daniel H. Chloral hydrate toxicity from oral and intravenous administration. J Toxicol Clin Toxicol. 34(1): 101-106, 1996.
58.Larson J, Bull R. Effect of ethanol on the metabolism of trichloroethylene. J Toxicol En Health. 28: 395-406, 1989.
59.Laurence. Sleep, hypnotics, sedative, antiepileptics. Clinical pharmacology forth edition. Churchill Livingstone. 330, 1980.
60.Lee DO. Acute gastric perforation in a chloral hydrate overdose. AJEM. 5: 16, 545-546, 1998.
61.Lehmann G, Knoefel P. Trichlorethanol, tribromethanol, chloral hydrate and bromal hydrate. J Pharm Exp Ter. 63: 453-465, 1938.
62.Lichenstein R, King JC, Bice D. Evaluation of chloral hydrate for pediatric sedation. Clin Pediatr. 32: 632-633, 1993.
63.Lipscomb JC, Mahle DA, Brashear WT, Garrett CM. A species comparison of chloral hydrate metabolism in blood and liver. Biochem Biophys Res Commun. 227(2): 340-350, 1996.
64.Livingston H. Rectal anesthesia. Anesthesiology. Philadelphia. 363-377, 1954.
65.Ludwigs U, Divino Filho JC, Magnisson A, Berg A. Suicidal chloral hydrate poisoning. J Toxicol, Clin Toxicol. 34 (1): 97-99, 1996
66.Lumb W, Jones E. Veterinary anesthesia .Lea & Febiger, Philadelphia. 315-317, 643, 1987.
67.Mayer DJ, Hindmarsh KW, Gorecki DK, Sankaran K. Sedative/hypnotic effects of chloral hydrate in the neonate: trichloroethanol or parent drug? Develop Pharm Ther. 19(2-3): 141-146, 1992
68.Meyers FH. Effect of drugs on common laboratory tests. Review of medical pharmacology sixth edition. Lange Medical Publications. 714-715, 1978.
69.Muir WW, Hubbell John AE. Euthanasia. Handbook of veterinary anesthesia second edition. Mosby Co. 447, 1995.
70.Napoli KL, Ingall CG, Martin GR. Safety and efficacy of chloral hydrate sedation undergoing echocardiography. J Pediatr. 129(2): 287-291, 1996.
71.Ni YC, Wong TY, Lloyd RV, Heinze TM, Shelton S, Casciano D, Kadlubar FF, Fu PP. Mouse liver microsomal metabolism of chloral hydrate, trichloroacetic acid, and trichloroethanol leading to induction of lipid peroxidation via a free radical mechanism. Drug Metabolism & Disposition. 24(1): 81-90, 1996.
72.Nicholas HB, Leslie EM: Injectable anesthetics: Chloral hydrate. Veterinary pharmacology and therapeutics Fifth edition. Yi Hsien Publishing Co. 30-32, 239-242, 1982.
73.Ogino K, Hobara HK. Gastric mucosa injury induced by chloral hydrate. Toxicol Lett.52: 129-133, 1990.
74.Osol A. Sedatives and hypnotics: Chloral hydrate. Remington's pharmaceutical sciences sixteenth edition. Mack Publishing Co. 1015, 1980.
75.Paddleford RR. Arterial blood pressure. Manual of small animal anesthesia. W.B. Saunders Co. 140-2, 1999.
76.Paret G, Kassem R, Vardi A, Ben Zeev B, Barzilay Z. Chloral hydrate--is it safe? Harefuah. 130(1): 14-15, 71, 1996.
77.Philip D. Hansten. Oral anticoagulant interactions. Drug interactions forth edition. 39,202,215, 1979.
78.Poisindex(r). Toxicological management, vol 89. Micromedex Inc., 1974-1996.Denver, 1990.
79.Rall TW. Chloral Derivatives. In: Goodman & Gilman's: The pharmacological basis of therapeutics eighth edition. Gilman AG, Rall TW, Nies AS, Taylor P. New York: Pergamon Press. 346-345, 1990.
80.Ronald SL, Jennifer AK, Karen AV. Chloral hydrate sedation: The additive sedative and respiratory depressant effects of nitrous oxide. Anesth Aanalg. 4(86): 724-728, 1998.
81.Ronchera-Oms CL, Casillas C, Marti-Bonmati L. Oral chloral hydrate provides effective and safe sedation in pediatric magnetic resonance imaging. J Clin Pharm Ther. 19: 239-43, 1994.
82.Rossoff I. Handbook of veterinary drugs. Springer Publishing, New York. 93, 352, 1974.
83.Rumm PD, Takao RT, Fox DJ, Atkinson SW. Efficacy of sedation of children with chloral hydrate. SMJ. 83(9): 1040-1043, 1990.
84.Sacchetti A, Achafermeyer R, Geradi M. Pediatric analgesia and sedation. Ann Emerg Med. 23: 237-250, 1994.
85.Salmon AG, Kizer KW, Zeise L. Potential carcinogenicity of chloral hydrate: A review. J Toxicol. 33 (2): 115-121, 1995.
86.Sander VM, Kauffmann BM, White KL Jr, Douglas KA, Barnes DW, Sain LE, Bradshaw TJ, Borzelleca JF, Munson AE. Toxicology of chloral hydrate in the mouse. En Heal Per. 44: 137-146, 1982.
87.Seger D, Schwartz G. Chloral hydrate: A dangerous sedative for overdose patients? Pediatr Emerg Care. 10(6): 349-350, 1994.
88.Sellers EM, Lang BS, KochoWeser. Interaction of chloral hydrate and ethanol in man. Clin Pharmacol Ther. 13: 37-48, 1971.
89.Silverman J, Muir W. A review of laboratory animal anesthesia with chloral hydrate and chloralose. Lab Anim Sci. 43(3): 210-216, 1993.
90.Simpson M, Parrott El. Oral and rectal absorption of chloral hydrate and its betaine complex. J Pharm Sci. 69(2): 227-228, 1980.
91.Sing K, Erickson T, Amitai Y, Hryhorczuk D. Chloral hydrate toxicity from oral and intravenous administration. J Toxicol., Clin Toxicol.34 (1): 101-106, 1996.
92.Steinburg AD. Should chloral hydrate be banned? Pediatr.92: 442-446, 1993.
93.Strobel GE, Wollman H. Pharmacology of anesthetic agents. Fed Proc. 28(4): 1386-1403, 1969.
94.Tavernor WD. Equine anesthesia. Bir Vet J. 117: 392-404, 1961.
95.Thienes CH, Haley TJ. Central nervous system depressants. Clinical Toxicology Fifth edition. Henry Kimpton Publisher. 70-71, 1972.
96.Thurmon J, Benson G. Anesthesia in ruminants and swine. Current veterinary therapy 2. Food animal practice. W.B. Saunders Co. 51-71, 1986.
97.Valenstein E. A note on anesthetizing rats and guinea pigs. J Exp Anal Behavior. 4: 6, 1961.
98.Vellar ID, Richardson JP, Doyle JC. Gastric necrosis: Aware complication of chloral hydrate intoxication. Br J Surg. 59: 317-319, 1972.
99.Walton JG, Thompson JW, Seymour RA. Chloral hydrate. Textbook of dental pharmacology and therapeutics. Oxford Medical Publication. 298-299, 1989.
100.Wilson S. Chloral hydrate and its effects on multiple physiological parameters in young children: a dose-response study. Pediatr Dent. 14(3): 171-177, 1992.
101.Wladyslaw R. Pediatric cardiology reviewer acknowledgments. Pediatr Cardio. 17: 419-420, 1996.
102.Young JB, Vandermolen LA, Pratt CM. Torsades de Pointes: an unusual manifestation of chloral hydrate poisoning. Am Heart J. 112: 181-184, 1986.
103.Young LY, Koda-Kimble MA. Sedation and analgesia. The clinical use of drugs sixth edition. Applied therapeutics Inc. 20-28, 1995.
104.Zahedi A, Grant MH, Wong DT. Successful treatment of chloral hydrate cardiac toxicity with propranolol. AJEM. 17 (5): 490-491, 1999.
105.Zimmermann T, Wehling M, Schylz HU. The relative bioavailability and pharmacokinetics of chloral hydrate and its metabolites. Arzneimittelforschung. 48(1): 5-12, 1998.
106.Zimpfer M Sit S, Vatner S. Effects of anesthesia on the canine carotid chemoreceptor reflex. Circ Res. 48: 400-406, 1981.