Volume 6 | Issue 4 Article 7

1944 Barbiturates I. E. Peterson Iowa State College

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Recommended Citation Peterson, I. E. (1944) "Barbiturates," Iowa State University Veterinarian: Vol. 6 : Iss. 4 , Article 7. Available at: https://lib.dr.iastate.edu/iowastate_veterinarian/vol6/iss4/7

This Article is brought to you for free and open access by the Journals at Iowa State University Digital Repository. It has been accepted for inclusion in Iowa State University Veterinarian by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Barbiturates

Their applicatiolls to veterinary therapeutics

I. E. Peterson, '44

URING the last decade, a new group The barbiturates may be generally clas­ D of drugs, known as the barbiturates, sified as long or short acting, and the two has come into prominence in veterinary groups should not be used interchange­ medicine as hypnotics and anesthetics. ably. The choice of drug to be used de­ Today we find that these derivatives of pends on the type of patient, length of barbituric acid are used quite extensively time and rapidity of action desired, con­ in human medicine and in the small ani­ dition of the patient, and history of pre­ mal field of veterinary medicine. The vious medication. The barbiturates are therapeutic action of the derivatives of destroyed mostly in the liver and are ex­ this parent barbituric acid molecule, which creted to a certain extent by the kidneys. is weakly acid but has no sedative or In toxic doses, the respiratory system is hypnotic effect, has been made possible affected more quickly than is the cardiac because one or both of the hydrogens on system, but in animals which have a cir­ the side chains are replaceable. Thus, culatory disturbance, the barbiturates af­ barbital or diethyl barbituric acid was fect the heart and blood pressure even in obtained by replacing each hydrogen with light doses before the respiratory system an ethyl radical, forming a derivative shows any effects of overdosage. In gen­ which did possess hypnotic and sedative eral, the contraindications of the barbitu­ action. Similarly, by replacing one hydro­ rates are hepatic disease, renal impair­ gen with an ethyl radical and the other ment, circulatory disturbances, acidosis, with a phenyl radical, phenyl ethyl bar­ anemia, respiratory distress from any bituric acid or phenobarbital, was ob­ cause, toxemia, shocks, and previous ad­ tained. This had twice the potency of bar­ ministration of other sedatives, hypnotics, bital, yet possessed no greater toxicity. or anesthetics in large doses. Especially Further chemical research with barbituric those patients showing toxemia or shock acid produced pentobarbital or nembutal, should be watched very closely during by substituting an ethyl radical for one administration of the barbiturates for any hydrogen and a methyl-butyl group for idiosyncrasy to the drug. The barbiturates the other. This drug was not used phar­ are not usually considered to be habit macologically or clinically for many years forming in humans, but a few cases of this after it was first synthesized. An isomer occurrence have been reported. of pentobarbital called amytal, which had greater hypnotic effect, more rapid action, Advantages and faster elimination than pentobarbital, was produced by Shonle in 1920. The so­ The advantages of barbiturates are dium salts of these barbituric acid deriva­ enumerated as follows: tives were later shown to be more soluble 1. The degrees of action may be easily and more adapted to intravenous and in­ graded from very slightly sedative to com­ tramuscular injection, thus giving quicker plete anesthesia. and deeper, but shorter, effects. 2. The effect is very prompt, within a

198 The Veterinary Student few minutes after oral doses and imme­ and benezdrine sulfate. Picrotoxin seems diately after intravenous. to be quite superior due to its lasting ef­ 3. Full doses cause little effect on other fect but all of them must be given in re­ functions. peated dosage since they are eliminated 4. The respiratory system, circulation, from the body more quickly than the bar­ metabolism, and smooth muscle remain biturates. These should be supplemented almost normal until full toxic doses are by injections of hypertonic dextrose solu­ reached. tion and artificial respiration. The bar­ 5. Most of them have no serious after­ biturates have been used for euthanasia effects. in large doses to small animals and the 6. They produce no serious local ef­ younger large animals. The use for this fects so they may be administered by all purpose has been limited due to the cost channels. compared to that of saturated magnesium The disadvantages of the barbiturates sulfate solution. The barbiturates produce are the following: death without violent struggling as is 1. The response to the drug is not al­ seen in many other products used for this ways the same. purpose and thus are quite humane. 2. The hypnotic action is sometimes preceded by excitement, which is the rea­ Classification son for using a small dose of morphine in dogs before administering the barbitu­ The barbiturate drugs fall into two rates. general classifications, the short acting 3. As anesthetics they are administered group and slow acting group. The short at a single dose, thus making for error in acting group includes pentothal sodium, the concentration in the body, and they seconal sodium, pentobarbital sodium, require much safer handling when used amy tal, and sodium amy tal. This group for general anesthesia than when used as produces anesthesia very rapidly but is basal narcotics. short acting due to the rapid elimination 4. They require too large dosage and of the drug from the body. are therefore too expensive in large ani­ Pentothal sodium, or sodium ethyl thio­ mal practice. barbituric acid, is one of a series of new thiobarbiturates. It is rapidly destroyed Indications in the body, and although it is rapid in effect the duration of this effect is rela­ The barbiturates in general are indi­ tively short. It is an excellent anesthetic cated for the following conditions: for minor operations in small animals for 1. As a sedative in nervous conditions, the effect may be gone in 20 to 30 minutes. 2. As an analgesic in neuritis and pru­ The solution should be freshly made and ritis, slowly administered, a careful check be­ 3. To control nausea and vomiting, ing kept on the dose as injection proceeds. 4. As a motor depressant in convulsive When anesthesia is sufficiently advanced, states as in epilepsy, Glclampsia, and strych­ injection must cease; when the patient is nine poisoning, unconscious and respiration is shallow, 5. Preliminary to local anesthetics to anesthesia is usually present. The onset prevent accidents with cocaine and pro­ of anesthesia is usually so rapid that the caine, normal stages of anesthesia cannot be 0 b­ 6. As preanesthetic narcotic, and served during the administration of this 7. As anesthetics. drug. The dosage varies in different ani­ In poisoning with these drugs, respira­ mals; 7.0 to 11.0 mg. per pound body tory stimulants are used. The following weight injected intravenously with a drugs have been used as antidotes: picro­ standard dose of 10.0 mg. per pound of toxin or metrazol with ephedrine, picro­ body weight as an average is recom­ toxin, metrazol, ephedrine, coramine, mended. The anesthesia will persist for icoral, strychnine, caffeine, dinitrophenol, 25 to 30 minutes when an average dose of

Spring, 1944 199 pentothal sodium is injected following the intramuscular inejction. The 5 percent administration of 8 to 32 mg. of morphine weight-volume solution is prepared with and 0.4 to 0.6 mg. of atropine to dogs. sterile water in the ampoule for this pur­ Seconal sodium has been used in human pose. Discard any solution of this drug medicine much more extensively than in which exhibits slight opalescence or hazi­ veterinary medicine. However, it is of ness. some value as a hypnotic when given in Pentobarbital sodium in preanesthetic small repeated doses to small animals for medication has many advantages similar the period of recovery is much shorter to those of sodium amy tal in which it re­ than that of the longer acting barbiturates. lieves preoperative apprehension by the This drug causes less renal disturbance patient, affords more quiet induction of than other members of the short acting anesthesia, reduces the amount of general group, thus being indicated in those pa­ anesthetic required, and diminishes the tients in which pentobarbital sodium postoperative nausea and vomiting in small would have a detrimental effect on the animals. In comparison to sodium amytal renal system. There are no after effects in preanesthetic medication, only one-half following the administration of this drug. the dose need be used to produce the same It has a large margin of safety in dosage effect and the period of postoperative re­ but larger doses seem to produce restless­ covery is only about one-half as long as ness rather than the desired hypnosis. that following the use of sodium amy tal. This drug is recommended for preanes­ Overdosage of either drug will produce thetic medication in small animals. The respiratory distress and postoperative rest­ dosage is usually 48 mg. to cats and small lessness, so one must caution against use dogs. Large doses followed by toxic re­ of barbiturates in doses sufficient to pro­ actions of the drug may be counteracted duce a deep preanesthetic effect for such by injection of hypertonic dextrose with doses predispose to respiratory embarrass­ caffeine and ephedrine. ment especially when they are supple­ mented with ether to the point of full Nembutal anesthesia. Respiratory distress may also be more often noticed in those cases in Pentobarbital sodium or nembutal is which morphine and pentobarbital sodium a more slowly acting member of the short were used in conjunction in preanesthetic acting group. This is prepared in the forms medication, followed by complete ether of pentobarbital sodium and pentobarbital anesthesia. So morphine is commonly used calcium. The sodium salt is more readily alone as a preanesthetic medicament in soluble and, thus, probably acts more dogs. quickly than the calcium salt. There is no pharmacological difference in their re­ Applications action, and they may be used interchange­ ably. The sodium salt is hygroscopic and Pentobarbital sodium is used in doses cannot be prepared in the tablet form. of 50 to 100 mg. orally for preanesthetic The calcium salt of pentobarbital is not medication in cats since morphine is ex­ hygroscopic and is prepared in the tablet citing to this animal. If the patient will form for oral or rectal administration only. not take the drug by way of the mouth, Pentobarbital sodium is the only salt of it may be given in the form of an enema the two which is prepared in the ampoule when mixed with a little water and in­ form for intravenous or intramuscular in­ serted into the rectum. Suppositories of jection. Solutions to be used for this pur­ pentobarbital calcium in cacao butter base pose should only be prepared from the seem to give good results in controlling sterile anhydrous form which is supplied the convulsions of chorea and in control­ in sterile ampoules. Under no circum­ ling the nausea and vomiting complicat­ stances should the pentobarbital sodium ing roentgen therapy. These are most which is prepared in pulvule form for oral successful when administered per rectum administration be used for intravenous or immediately following x-ray treatment.

200 The Veterinary Student Pentobarbital sodium is not used to any venous injection but the circulatory and great extent in obstetrics since there are respiratory depression are less marked. limiting factors to the use of barbiturates Local reaction is usually slight or absent. in these cases regardless of the route of The intravenous route of administration administration. When used in dosage large of pentobarbital sodium offers the imme­ enough to produce complete analgesia or diate placing of the patient under the in­ complete anesthesia, this drug is quite apt fluence of the hypnotic and is the method to produce respiratory and vascular de­ of choice in emergency conditions. The pression in the pregnant female and en­ intravenous injection of this drug must tails great risk of producing narcosis in be made carefully and slowly. The rate of the newborn and intensive resuscitation injection should not exceed 1 cc. per min­ efforts are often necessary with close ute. The patient should be observed supervision for the first 12 hours after closely during the injection to make cer­ administration to the dam. This drug has tain that respiratory or circulatory dis­ been used to good advantage in the con­ turbances do not appear before the char­ trol of strychnine convulsions. It has acteristic sleep of general anesthesia. shown good results in the control of other Three to 5 minutes should elapse during nervous symptoms especially those shown the administration of the solution, for too in chorea of dogs following canine distem­ rapid injection has been the cause of many per complications of the nervous system. of the hazards of this drug which surgeons Pentobarbital sodium should not be used complain about. in cases of cardiac pr respiratory disturb­ ance, in case of generalized arteriosclero­ Pupillary Reflex sis or in cases of impaired liver or renal function. During the postoperative period The pupillary reflex should guide the the patient should be observed closely for anesthetist in the administration of the tendency towards choking. This drug drug. Dilatation of the pupil occurs first, should not be used following heavy mor­ followed by contraction. When the pupil phine sulfate medication since both of reaches one-fourth the size of the normal these drugs may produce undesirable re­ pupil, a sufficient dose has been given. spiratory depression. Morphine sulfate is The onset of narcosis may be immediate used hypodermically in low dosage to con­ or may take up to 30 minutes by the intra­ trol the postoperative restlessness due to venous route. The intravenous method is pain only. Some patients are much more now recognized as the best method and if susceptible to the toxic reactions of pento­ done properly, anesthesia with pentobar­ barbital sodium than others, and these bital sodium may be accomplished in all should be observed closely following medi­ types of patients without danger. When cation for toxic symptoms of an idiosyn­ administered per os, its action is some­ crasy or hypersensitivity to the drug. what uncertain and the dosage cannot be regulated as efficiently. The onset of nar­ Administration cosis may be delayed if the stomach is full. As a general rule the animal recovers Nembutal can be administered by a va­ in 12 hours, but narcosis may last from riety of methods. Under ordinary circum­ 24 to 48 hours. The dosage rate is from 8 stances the therapeutic effects of this drug to 12 mg. per pound body weight when can be obtained by oral administration, administered intravenously in small ani­ but there are certain advantages to paren­ mals. The animal should be weighed to teral administration. Nausea, vomiting, get the exact dosage. It must be increased diarrhea or other factors interfering with or repeated in larger dogs with a higher absorption of the orally administered drug metabolic rate with faster elimination of may make it desirable to give it by the the drug from the body. parenteral route. Intramuscular injection The use of nembutal in large animal shows a slower onset and lowered inten­ practice has been limited due to the cost sity of action of the drug than does intra- and to the undesirable postoperative ef-

Spring, 1944 201 fects of the drug, in which there is a long muscular injection in nervous and mental period of recovery from its effects. It has disorders. These slower acting barbitu­ been used with success for general anes­ rates have a definite value in convulsive thesia in foals in doses of 5 to 25 cc., de­ conditions, but the shorter acting members pending upon the size of the foal. In calves have been used in the treatment of strych­ and small cattle nembutal has been used nine convulsions and the toxemia of tet­ intravenously for general anesthesia in anus infection due to their advantage of doses of 50 to 125 cc. with good results. immediate action. Barbital or barbital In mature horses excellent results have sodium have been used in dosages of 0.3 been obtained in using pentobarbital so­ to 0.6 Gm. prior to the use of either pro­ dium as a sedative. Fifteen cc. per 1,000 caine or cocaine in local anesthesia. The pounds body weight in large horses will average dose of either of these drugs is facilitate the easy handling of the indi­ 0.16 to 1.0 Gm. for dogs and 0.1 to 0.25 Gm. vidual in a few minutes. The amount may in cats. They have not been used in large be increased for very large and nervous animals due to their cost and the prolonged horses. The sedative dose for a horse suf­ postoperative effects. fering from pain in the digestive tract is Phenobarbital and phenobarbital sodium usually 15 to 25 cc. administered intra­ or luminal are also members of the slower venously. The high cost of this drug com­ acting barbiturates. Their action is even pared to choral hydrate has limited its more prolonged than that of barbital. Their usefulness in the large animal field of suggested dosage is 0.03 to 0.2 Gm. Pheno­ veterinary medicine. barbital is especially useful in small re­ Amy tal and sodium amytal are quite peated doses of 0.03 to 0.1 Gm. through­ similar to nembutal in action but require out the day in preventing the occurrence greater dosage. Thus, their use in vet­ of attacks of epilepsy. They have the same erinary medicine has been limited to only objections for use as preanesthetic agents a few cases in the small animal field. as barbital and barbital sodium. If used for that purpose the average dose is 0.06 Slow Acting Group to 0.2 Gm. Large doses of phenobarbital in surgical cases have resulted in collapse The slow acting group includes barbital and pneumonia, due to abolition of the and phenobarbital, or luminal, and their cough reflex. A failing heart, bronchitis, sodium salts. These members of the bar­ renal disease, or tuberculosis contraindi­ biturates are indicated where a very slow cate the use of phenobarbital in anesthetic and long-acting agent is desired. doses. Because of these contraindications Barbital and barbital sodium may be which are similar to those of barbital, it used where prolonged effects are not a is seldom used in obstetrics. Tolerance to disadvantage. Their action is very pro­ the drug has been noticed on repeated longed and extends well into the post­ small doses. In dogs, not more than 0.4 operative period, thus complicating post­ Gm. of phenobarbital should be given operative medication. For that reason they daily, and that only in divided doses of are not as extensively used for preanes­ 0.05 to 0.1 Gm. each. The dosage for cats thetic medication in surgery as the shorter is usually 0.02 to 0.015 Gm. at a single acting members of the barbituric acid administration. The dosage is increased series. As the effects wear off, there may 10 percent when the sodium salt is used. be disturbing mental complications. In As with barbital, phenobarbital is seldom addition, they may place undue strain on used in large animal patients for similar the heart and kidneys and so are contra­ objections to cost and postoperative effects. indicated in any cardiac or renal disturb­ ance. Their use in obstetrics has not been REFERENCES very extensive probably due to their ef­ 1. E. R. Frank. 1942. Veterinary Surgery noies. Bur­ gess Publishing Co .• Minneapolis. Minn. fect on the renal system already over­ 2. H. J. Milks. 1943. Veterinary pharmacology. ma­ burdened by pregnancy. The sodium salt teria medica. and therapeutics. Alexander Eger and Co. Chicago. Ill. of barbital has been used as an intra- 3. Eli Lilly and Co. 1943. Therapy with the Barbiturates.

202 The Veterinary Student