- Email: [email protected]
Extrapyramidal reactions to prochlorperazine and similar antiemetic drugs
EXTBAPYRAMIDA-L AND SIMILAR
REACTIONS
ANTIEMETIC
TO PROCHLORPERAZINE
DRUGS
N0rma.n M. Yokras, Captain, USAF F.A.G.D.,*” Travis AFB, Calif.
(DC),*
and B. C. Kingsbury,
Jr., D.D.X.,
A
most, distressing postoperative complication, vomiting not only prevents normal intake of liquids and solids but also alters electrolyte and acid base balance. Moreover, retching paroxysms may alter t,he position of reduced fracture segments; aspiration of vomitus may well cause lung abscess or asphyxiation. Fortunately, newer surgical, anesthetic, and analgesic techniques have reduced the problem in recent years. Thus, surgical procedures are, to some extent, less traumatic; modern general anesthetics are less emetic; and narcotics may be prescribed in lower dosages because of the use of synergistic agents. Nevertheless, because vomiting may be a distressing and even a critical complication in the postoperative oral surgical patient, several of the newel phenothiazine derivatives are being used for prophylaxis and for treatment when necessary. Unfortunately, the excellent relief afforded by the use of these drugs is at times accompanied by side effects of a bizarre nature. In fact, the more therapeutically active the drug, the more frequent are the toxic side effects.l In the early days of therapy with the phenothiazine-derived drugs, extrapyramidal reactions were considered more of a diagnostic than a treatment problem. That is, side effects of this nature were looked upon as “. . . more of a shock to the physician than a threat to the patient.“” However, when reports began to appear in the literature of many of these reactions exhibiting such serious signs as laryngospasm, prolonged cyanosis, and subluxation of the mandible,‘-” the problem was viewed more soberly. A brief review of the extrapyramidal system and its relationship to this group of drugs seems appropriate. The extrapyramidal system functions by inhibiting overaction of the lower reflex centers’ which mediate striated muscle movements. It acts as a pathway which tra.nsmits and modifies “the complex motor regulatory influences of the basal ganglia . . . through the cerebellum and the cerebral cortex. “8 Thus, it plays a role in the formation of many specific bodily movements; gait, posture, and specific movements of the eyes, head, reactions to and trunk are all mediated through this system. 8 Extrapyramidal the phenothiazines mimic lesions found at all levels of this system. Higher-level *Formerly
**Consultant
Chief of Oral Surgery. Oral Surgeon.
Present
address:
1’61
2036
N. Eroatlway,
Santa
Ana.
Calif.
Jcsions? f’or example, “induce hypc~rkirrotie movc~mc~~lt.s,. ’ I(bsions o-1111~IOWC~V l~~!ls cause ” Parkinson trc>mors. ripitlit\-, akinGs, ” iIIlC1 c~omhincd lesions pKdUW ” athctotic and dgstonic syntiromcss.” The ph;rrrnacologic, basis for t tl(a INI ot’ this group 01’ antic,irlet ic drugs lies in the direct inhibitory :\ctioll which the)- tlsc‘rt on the om(6(* ccbntc’r in that midbrain. Howe~--car, their spccific~ pha rnracology is itnpc~rf(~ctl~ nnd(*rstood.” According to (Goldman,“’ th(l disturhanccs encountered through their usage arc not the result of ovcrdosagc but art’ the regular effect 01 such compounds on the subcortical motor system in Wrtain susceptible persons. (‘oncurrinp, b‘rt).vban” stat,es : “ The (~xtr;ll,!-rnrnidal SJ-ndromcc is a rcyIllal* cffcct 01’ t trrl ILPU~Olcptic drugs, suh,ject only to individl~al variations, rcaf4cJcting their inhibitory action on psychomotor behavior.” F‘reyhan believes that the specific site ot’ action is the striopallidal system. the s!-stcJmwhich regulates I)s~chonlotilit~. (~rollman’” limits these effects to chlorpronlaeirl(~ and ~~lrcnothiazinr~ cltlrivatives caontaining a piperazinc ring in their side chain. Many borderline castrap)-ramidal reactions go undiagnosed; for this reason, any estimate as to rate of occurr(Lnce must br coqjectural. .Judging from t,he paucit,v of literature on the subject, however, couplet1 with the wide use of these drugs, one must assume that t,his type of reaction is uncommon. On the other hand, six cases were seen at Xt. (‘arrncl Merq- Hospital in an X week period, and four of the pat,icnts were taking morC than one phenothiazinc agent, concurrently.5 Further investigation into t,liis area certainly seems indicated. (Ilinically, extrap~ramidal reac%ioris may occur as lat(J as 2-l hours after drug administration.” Premonitory signs may precc~de iln attack by 2-t hours. These signs include thickened spclech, protruded tongue, tightening of muscle groups, and pains cmanat,ing from partial muscle spas111.“~ In addition, dizziness, blurred vision, and fatignc have bran noted some 2-l hours before the more characteristic signs.” I,ater signs include tightness in pharynx and chest, t,endency to protrude the tongue, tendency to Starr upward, unblinking “reptilian” expression, chills, puckering of the lips, and drooping of the mouth.“. I3 If the condition is not treated at this stages the more charactc~ristic changes will bc seen. These include spasms involvin, w muscles mediating posture, mastication, facial expression, tongue and c\-e movements, arid locomotion. L,vnch and Hoover’” categorize these reactions into two main groupings; reactions of the parkinsonian type arc characterized by gait and postural abnormalitit+ while dyskinetic and dystonic syndromes are characterized by spasms or cramps of several muscle groups. Among the casts reported by Seimc and Tallant,” one or more of the following changes were seen : 1. Severe protrusion, loss of control, numbness, and athetoid movements of the tongue. 2. Spasms of the sternocleidomastoid and trapezius muscles. 3. Masklike facies. 4. Loss of associat,ed movements in walking. 5. Gross tremors and/or spasms of the upper extrcmitics. 6. Oculogyric crisis. 7. Spasms of the back muscles with opisthotonos.
Volume Number
16 IO
EXTRAPYRAMTDAL
DRUG
REACT IONS
1263
It is interesting to note that trismus was common to all. Involvement is usually greater on one side than on the other. O’Hara2 found blood chemistry to be unchanged during the attack. Stertorous breathing, with brief episodes of laryngospasm accompanied by cyanosis, was reported by Laugh and Mettsl and also by Christian and Paulson.” Attesting to the fact that the movements of the mandible are, indeed, forceful and involuntary is the occasional occurrence of mandibular subluxation and chipped teeth” during these episodes. Reactions have been known to last from 30 minutes to 48 hours.” Differential diagnosis is generally straightforward because of the very characteristic signs. In the absence of a reliable history, however, and in certain borderline cases, diagnosis may prove more troublesome. Among the conditions for which an extrapyramidal reaction may be mistaken are cerebral vascular accident, tetanus, hysterical reaction, catatonic schizophrenia, strychnine poisoning,3 meningitis, and encephalitis.‘” In the case described by Lynch and Hoover,‘” intermittent spasm and pain in the muscles of mastication led to a preliminary diagnosis of temporomandibular pain-dysfunction syndrome. According to O’Hara,2 the similarity of patient types was impressive; all patients seemed to be hyperreactivc to pain, with many minor complaints. As with drug reactions from any other source, the first consideration in treatment is withdrawal of the affecting agent. The importance of a sound psychological approach to these patients should not be underestimated. As soon as the diagnosis is made, the patient must be advised of the exact nature of the condition and the good prognosis which can be expected. Since the reaction is centrally based, any excitement may well increase the symptoms; it should be borne in mind that the symptoms of parkinsonism disappear with sleep. Smith, Kline, and French Laboratories advocate the use of any of the antiparkinsonism agents as specific therapy for these reactions.” The availability of these agents in parenteral form, however, may be limited. The most consistently effective agent for immediate action has been Amytal sodium (up to 750 mg. intravenously over a 5 minute period). According to Christian and Pau1son,G 1 mg. of atropine given intravenously was not found to be effective. Small doses of phenobarbital were advocated by Scime and Tallant” for mild reactions, while Freyhanll st,ated, paradoxically, that intravenous caffeine sodium benzoate sometimes relieved the severe dgskinetic disturbances within 10 minutes. In treating a marked reaction, Waugh and Mettsl relieved the symptoms within minutes with diphenhydraminr, 25 mg. intravenously. We observed complete remission in a cast within 5 minutes after injecting 0.5 mg. of scopolamine intravenously. The basis for the use of scopolamine in the treatment of motor disturbances lies not in its peripheral action but in its central action. One of the first specific medications for the treatment of Parkinsonism, scopolamine is thought to act on the cortex.16 Its exact mechanism is imperfectly understood, however. Electroencephalographic studies have supported the fact that atropine, a closely related parasympatholytic, prevents the manifestations of central nervous system stimulation.lG Both drugs are more potent than the synthetic antiparkinsonism agents, although scopolamine has been shown to be some ten times more potent than
Subsequent to an open reduction of a mandibular fractuw, a 24.year-oltl patient lb{%cw~~e nauseated and retched on oral secrrtions. Since intermaxillary fixation had I)ecn uwd, an antiemetic was considered. Compazine, 10 mg. intramuscularly twice daily, was orderc~d. The nausea and retching subsided, and no other postoperative srquelae WBW encountered until 2 days later. Immc~diately following a tIressing change the patient drvrlopc~d an taxtensor spasm of the neck and bark musclra which produced a postuw not unlike that of opisthotonos. His eyes rolled back to the right, anti his head ~vas hyperextc~nded in thch sanw direction. He was conscious but seemed unxbl~ to speak. Becauw of the intermaxillary fixatiou, trismus could not be demonstrated, although spasm of the mastic~atory mwwlrr was noted. A diagnosis of Compazine reaction was made following consultatiw with thca Department? of Neurology and Neurosurgery. The int,~awnouti administration of wopolaminr, 0.3 mg., within a 5minute period reversed the waction immediately. Compazint~ tl1erap.v \vas ~liscnw tinwrl, and the patient ‘P postoperative (wurw wts unrrmarkahlc thewafter.
The problem of cxtrappramidal reaction to prochlorperazine and related drugs has been presented, and reference has been made to the specific importance of em&s to the oral surgeon. The extrapyramidal syst,em has been briefly described, and its pharmacologic relationship to the phenothiazine derivatives has been outlined. The rate of occurrence of this complication has been suggested. The signs and symptoms of extrapyramidal react,ions have been describrd and early recognition, through an insight into prodromal signs, stressed. Among the several proposed considerations concerning patient, management was the suggestion that the pspchological approach to these patient)s is of the utmost importance. While a large number of drugs have been advocated for this condition, the consensus seems to support the USC of barbiturates, diphenvlhydramine, or scopolamine. A cast of c~xtrap~ramidal reaction following Compazinc therapy and its prompt reversal has been presented. This review has been presented to publicize a means of reducing the occasional untoward scyuelae of t,he phcnothiazine derivatives rather than to suggest the diminished use of this helpful group of drugs. The authors
gratefully
acknowledge
th(a help of 1)rs. n’idnrr.
Grrnhrw,
and Karnrs.
Motor Activity lnducrd by 1. \Vaugh, TV. H., and Metts, J. U., Jr.: Severe Extrapyramidal Prochlorperazine; Its Relief by Intravenous Tnjection of Diphenhydramine, New England J. Med. 262: 353, 1960. Reactions in Patients Kweiving Prochlorperazine, 2. O’Hara Vincent 8 . Extrapyramidal Ndw England j. Med. 259: 826, 1958. 3. Scime, I. A., and Tallant, E. J.: Tetanus-Like Reactions to Prochlorperazine; Report of 8 Cases Exhibiting Extrapyramidal Disturbances After Small Doses, J. A. M. A. 171: 1814, 1959. 4. GrafT, T. D., Phillips, 0. C:, and Gentry, \Y. D.: Clonic C!onvulsionn After the Oral Use of Perophenazine (Trllafon), J. A. M. A. 169: 834, 1959. Neuromuscular Reactions Due 5. Gailitis, J., Knowles, R. R., and Longobardi, A.: Alarming to Prochlorperazine, Ann. Int. Med. 52: 539, 3960.
Volume Number
16 IO
EXTRAPYRAMTDAL
DRUG
REACTTONS
1265
C. D., and Paulson, George: Severe Motility 6. Christian, Disturbance After Small Doses of Prochlorperazine, New England J. Med. 259: 830, 1958. Starling’s Human Physiology, ed. 12, Philadelphia, 1956, Lea & Febiger, 7. Evans, Levatt: p. 334. of Physiology, 8. Field, John, Magoun, H. W., and Hall, Victor E. (editors) : Handbook prepared by the American Physiological Society. Sect. 1, vol. II. Neurophysiology, Baltimore, 1960, Williams & Wilkins Company, pp. 920, 922. Drugs of Choice, 1960.1961 edition, St. Louis, 1960, The C. V. Moshy 9. Modell, Walter: Comnanv. D. 326. Com10. Goldman,&D. r ’Risults of Treatment of Psychotic States With Newer Phenothiazine pounds Effective in Small Doses, Am. J. M. Se. 235: 69, 1958. 11. Freyhan, F. A.: Observations on Clinical Use of Tranquilizing Agents, Delaware M. J. 29: 191-195. 1957. Arthur: Pharmacology and Therapeutics, ed. 4, Philadelphia, 1960, Lea & 12. Grollman, Febiger, p. 239. 13. Lynch, Burton, Jr., and Hoover, David E.: Extrapyramidal Syndrome Due to Compazinr Therapy, ORAL SURG., ORAL MED. & ORAL PATH. 14: 1143, 1961. Desk Reference to Pharmaceutical Specialties and Biologicals, ed. 15, Oradrll, 14. Physician’s N. J., 1961, Medical Economics, Inc., p. 735. 15. England, Albert C., and Schwab, Robert S.: The Management of Parkinson’s Disease, A. M. A. Arch. Int. Med. lQ4: 439, 1959. 16. Goodman, Louis S., and Gilman, Alfred: The Pharmacological Basis of Therapeutics, ed. 2, New York, 1958, The Macmillan Company, p. 855.
REACTIONS
ANTIEMETIC
TO PROCHLORPERAZINE
DRUGS
N0rma.n M. Yokras, Captain, USAF F.A.G.D.,*” Travis AFB, Calif.
(DC),*
and B. C. Kingsbury,
Jr., D.D.X.,
A
most, distressing postoperative complication, vomiting not only prevents normal intake of liquids and solids but also alters electrolyte and acid base balance. Moreover, retching paroxysms may alter t,he position of reduced fracture segments; aspiration of vomitus may well cause lung abscess or asphyxiation. Fortunately, newer surgical, anesthetic, and analgesic techniques have reduced the problem in recent years. Thus, surgical procedures are, to some extent, less traumatic; modern general anesthetics are less emetic; and narcotics may be prescribed in lower dosages because of the use of synergistic agents. Nevertheless, because vomiting may be a distressing and even a critical complication in the postoperative oral surgical patient, several of the newel phenothiazine derivatives are being used for prophylaxis and for treatment when necessary. Unfortunately, the excellent relief afforded by the use of these drugs is at times accompanied by side effects of a bizarre nature. In fact, the more therapeutically active the drug, the more frequent are the toxic side effects.l In the early days of therapy with the phenothiazine-derived drugs, extrapyramidal reactions were considered more of a diagnostic than a treatment problem. That is, side effects of this nature were looked upon as “. . . more of a shock to the physician than a threat to the patient.“” However, when reports began to appear in the literature of many of these reactions exhibiting such serious signs as laryngospasm, prolonged cyanosis, and subluxation of the mandible,‘-” the problem was viewed more soberly. A brief review of the extrapyramidal system and its relationship to this group of drugs seems appropriate. The extrapyramidal system functions by inhibiting overaction of the lower reflex centers’ which mediate striated muscle movements. It acts as a pathway which tra.nsmits and modifies “the complex motor regulatory influences of the basal ganglia . . . through the cerebellum and the cerebral cortex. “8 Thus, it plays a role in the formation of many specific bodily movements; gait, posture, and specific movements of the eyes, head, reactions to and trunk are all mediated through this system. 8 Extrapyramidal the phenothiazines mimic lesions found at all levels of this system. Higher-level *Formerly
**Consultant
Chief of Oral Surgery. Oral Surgeon.
Present
address:
1’61
2036
N. Eroatlway,
Santa
Ana.
Calif.
Jcsions? f’or example, “induce hypc~rkirrotie movc~mc~~lt.s,. ’ I(bsions o-1111~IOWC~V l~~!ls cause ” Parkinson trc>mors. ripitlit\-, akinGs, ” iIIlC1 c~omhincd lesions pKdUW ” athctotic and dgstonic syntiromcss.” The ph;rrrnacologic, basis for t tl(a INI ot’ this group 01’ antic,irlet ic drugs lies in the direct inhibitory :\ctioll which the)- tlsc‘rt on the om(6(* ccbntc’r in that midbrain. Howe~--car, their spccific~ pha rnracology is itnpc~rf(~ctl~ nnd(*rstood.” According to (Goldman,“’ th(l disturhanccs encountered through their usage arc not the result of ovcrdosagc but art’ the regular effect 01 such compounds on the subcortical motor system in Wrtain susceptible persons. (‘oncurrinp, b‘rt).vban” stat,es : “ The (~xtr;ll,!-rnrnidal SJ-ndromcc is a rcyIllal* cffcct 01’ t trrl ILPU~Olcptic drugs, suh,ject only to individl~al variations, rcaf4cJcting their inhibitory action on psychomotor behavior.” F‘reyhan believes that the specific site ot’ action is the striopallidal system. the s!-stcJmwhich regulates I)s~chonlotilit~. (~rollman’” limits these effects to chlorpronlaeirl(~ and ~~lrcnothiazinr~ cltlrivatives caontaining a piperazinc ring in their side chain. Many borderline castrap)-ramidal reactions go undiagnosed; for this reason, any estimate as to rate of occurr(Lnce must br coqjectural. .Judging from t,he paucit,v of literature on the subject, however, couplet1 with the wide use of these drugs, one must assume that t,his type of reaction is uncommon. On the other hand, six cases were seen at Xt. (‘arrncl Merq- Hospital in an X week period, and four of the pat,icnts were taking morC than one phenothiazinc agent, concurrently.5 Further investigation into t,liis area certainly seems indicated. (Ilinically, extrap~ramidal reac%ioris may occur as lat(J as 2-l hours after drug administration.” Premonitory signs may precc~de iln attack by 2-t hours. These signs include thickened spclech, protruded tongue, tightening of muscle groups, and pains cmanat,ing from partial muscle spas111.“~ In addition, dizziness, blurred vision, and fatignc have bran noted some 2-l hours before the more characteristic signs.” I,ater signs include tightness in pharynx and chest, t,endency to protrude the tongue, tendency to Starr upward, unblinking “reptilian” expression, chills, puckering of the lips, and drooping of the mouth.“. I3 If the condition is not treated at this stages the more charactc~ristic changes will bc seen. These include spasms involvin, w muscles mediating posture, mastication, facial expression, tongue and c\-e movements, arid locomotion. L,vnch and Hoover’” categorize these reactions into two main groupings; reactions of the parkinsonian type arc characterized by gait and postural abnormalitit+ while dyskinetic and dystonic syndromes are characterized by spasms or cramps of several muscle groups. Among the casts reported by Seimc and Tallant,” one or more of the following changes were seen : 1. Severe protrusion, loss of control, numbness, and athetoid movements of the tongue. 2. Spasms of the sternocleidomastoid and trapezius muscles. 3. Masklike facies. 4. Loss of associat,ed movements in walking. 5. Gross tremors and/or spasms of the upper extrcmitics. 6. Oculogyric crisis. 7. Spasms of the back muscles with opisthotonos.
Volume Number
16 IO
EXTRAPYRAMTDAL
DRUG
REACT IONS
1263
It is interesting to note that trismus was common to all. Involvement is usually greater on one side than on the other. O’Hara2 found blood chemistry to be unchanged during the attack. Stertorous breathing, with brief episodes of laryngospasm accompanied by cyanosis, was reported by Laugh and Mettsl and also by Christian and Paulson.” Attesting to the fact that the movements of the mandible are, indeed, forceful and involuntary is the occasional occurrence of mandibular subluxation and chipped teeth” during these episodes. Reactions have been known to last from 30 minutes to 48 hours.” Differential diagnosis is generally straightforward because of the very characteristic signs. In the absence of a reliable history, however, and in certain borderline cases, diagnosis may prove more troublesome. Among the conditions for which an extrapyramidal reaction may be mistaken are cerebral vascular accident, tetanus, hysterical reaction, catatonic schizophrenia, strychnine poisoning,3 meningitis, and encephalitis.‘” In the case described by Lynch and Hoover,‘” intermittent spasm and pain in the muscles of mastication led to a preliminary diagnosis of temporomandibular pain-dysfunction syndrome. According to O’Hara,2 the similarity of patient types was impressive; all patients seemed to be hyperreactivc to pain, with many minor complaints. As with drug reactions from any other source, the first consideration in treatment is withdrawal of the affecting agent. The importance of a sound psychological approach to these patients should not be underestimated. As soon as the diagnosis is made, the patient must be advised of the exact nature of the condition and the good prognosis which can be expected. Since the reaction is centrally based, any excitement may well increase the symptoms; it should be borne in mind that the symptoms of parkinsonism disappear with sleep. Smith, Kline, and French Laboratories advocate the use of any of the antiparkinsonism agents as specific therapy for these reactions.” The availability of these agents in parenteral form, however, may be limited. The most consistently effective agent for immediate action has been Amytal sodium (up to 750 mg. intravenously over a 5 minute period). According to Christian and Pau1son,G 1 mg. of atropine given intravenously was not found to be effective. Small doses of phenobarbital were advocated by Scime and Tallant” for mild reactions, while Freyhanll st,ated, paradoxically, that intravenous caffeine sodium benzoate sometimes relieved the severe dgskinetic disturbances within 10 minutes. In treating a marked reaction, Waugh and Mettsl relieved the symptoms within minutes with diphenhydraminr, 25 mg. intravenously. We observed complete remission in a cast within 5 minutes after injecting 0.5 mg. of scopolamine intravenously. The basis for the use of scopolamine in the treatment of motor disturbances lies not in its peripheral action but in its central action. One of the first specific medications for the treatment of Parkinsonism, scopolamine is thought to act on the cortex.16 Its exact mechanism is imperfectly understood, however. Electroencephalographic studies have supported the fact that atropine, a closely related parasympatholytic, prevents the manifestations of central nervous system stimulation.lG Both drugs are more potent than the synthetic antiparkinsonism agents, although scopolamine has been shown to be some ten times more potent than
Subsequent to an open reduction of a mandibular fractuw, a 24.year-oltl patient lb{%cw~~e nauseated and retched on oral secrrtions. Since intermaxillary fixation had I)ecn uwd, an antiemetic was considered. Compazine, 10 mg. intramuscularly twice daily, was orderc~d. The nausea and retching subsided, and no other postoperative srquelae WBW encountered until 2 days later. Immc~diately following a tIressing change the patient drvrlopc~d an taxtensor spasm of the neck and bark musclra which produced a postuw not unlike that of opisthotonos. His eyes rolled back to the right, anti his head ~vas hyperextc~nded in thch sanw direction. He was conscious but seemed unxbl~ to speak. Becauw of the intermaxillary fixatiou, trismus could not be demonstrated, although spasm of the mastic~atory mwwlrr was noted. A diagnosis of Compazine reaction was made following consultatiw with thca Department? of Neurology and Neurosurgery. The int,~awnouti administration of wopolaminr, 0.3 mg., within a 5minute period reversed the waction immediately. Compazint~ tl1erap.v \vas ~liscnw tinwrl, and the patient ‘P postoperative (wurw wts unrrmarkahlc thewafter.
The problem of cxtrappramidal reaction to prochlorperazine and related drugs has been presented, and reference has been made to the specific importance of em&s to the oral surgeon. The extrapyramidal syst,em has been briefly described, and its pharmacologic relationship to the phenothiazine derivatives has been outlined. The rate of occurrence of this complication has been suggested. The signs and symptoms of extrapyramidal react,ions have been describrd and early recognition, through an insight into prodromal signs, stressed. Among the several proposed considerations concerning patient, management was the suggestion that the pspchological approach to these patient)s is of the utmost importance. While a large number of drugs have been advocated for this condition, the consensus seems to support the USC of barbiturates, diphenvlhydramine, or scopolamine. A cast of c~xtrap~ramidal reaction following Compazinc therapy and its prompt reversal has been presented. This review has been presented to publicize a means of reducing the occasional untoward scyuelae of t,he phcnothiazine derivatives rather than to suggest the diminished use of this helpful group of drugs. The authors
gratefully
acknowledge
th(a help of 1)rs. n’idnrr.
Grrnhrw,
and Karnrs.
Motor Activity lnducrd by 1. \Vaugh, TV. H., and Metts, J. U., Jr.: Severe Extrapyramidal Prochlorperazine; Its Relief by Intravenous Tnjection of Diphenhydramine, New England J. Med. 262: 353, 1960. Reactions in Patients Kweiving Prochlorperazine, 2. O’Hara Vincent 8 . Extrapyramidal Ndw England j. Med. 259: 826, 1958. 3. Scime, I. A., and Tallant, E. J.: Tetanus-Like Reactions to Prochlorperazine; Report of 8 Cases Exhibiting Extrapyramidal Disturbances After Small Doses, J. A. M. A. 171: 1814, 1959. 4. GrafT, T. D., Phillips, 0. C:, and Gentry, \Y. D.: Clonic C!onvulsionn After the Oral Use of Perophenazine (Trllafon), J. A. M. A. 169: 834, 1959. Neuromuscular Reactions Due 5. Gailitis, J., Knowles, R. R., and Longobardi, A.: Alarming to Prochlorperazine, Ann. Int. Med. 52: 539, 3960.
Volume Number
16 IO
EXTRAPYRAMTDAL
DRUG
REACTTONS
1265
C. D., and Paulson, George: Severe Motility 6. Christian, Disturbance After Small Doses of Prochlorperazine, New England J. Med. 259: 830, 1958. Starling’s Human Physiology, ed. 12, Philadelphia, 1956, Lea & Febiger, 7. Evans, Levatt: p. 334. of Physiology, 8. Field, John, Magoun, H. W., and Hall, Victor E. (editors) : Handbook prepared by the American Physiological Society. Sect. 1, vol. II. Neurophysiology, Baltimore, 1960, Williams & Wilkins Company, pp. 920, 922. Drugs of Choice, 1960.1961 edition, St. Louis, 1960, The C. V. Moshy 9. Modell, Walter: Comnanv. D. 326. Com10. Goldman,&D. r ’Risults of Treatment of Psychotic States With Newer Phenothiazine pounds Effective in Small Doses, Am. J. M. Se. 235: 69, 1958. 11. Freyhan, F. A.: Observations on Clinical Use of Tranquilizing Agents, Delaware M. J. 29: 191-195. 1957. Arthur: Pharmacology and Therapeutics, ed. 4, Philadelphia, 1960, Lea & 12. Grollman, Febiger, p. 239. 13. Lynch, Burton, Jr., and Hoover, David E.: Extrapyramidal Syndrome Due to Compazinr Therapy, ORAL SURG., ORAL MED. & ORAL PATH. 14: 1143, 1961. Desk Reference to Pharmaceutical Specialties and Biologicals, ed. 15, Oradrll, 14. Physician’s N. J., 1961, Medical Economics, Inc., p. 735. 15. England, Albert C., and Schwab, Robert S.: The Management of Parkinson’s Disease, A. M. A. Arch. Int. Med. lQ4: 439, 1959. 16. Goodman, Louis S., and Gilman, Alfred: The Pharmacological Basis of Therapeutics, ed. 2, New York, 1958, The Macmillan Company, p. 855.