BETA-BLOCKERS IN ESSENTIAL TREMOR
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1280 tory blood-pressure monitor which requires the patient to inflate his own pressure cuff." In a group of patients whose casual clinic blood-pressures were broadly simi- lar, cardiovascular events were more frequent in those with higher ambulatory blood-pressures. This tech- nique, therefore, did seem to add appreciably to the prog- nostic information. The equipment is not cheap and needs refinement, but such devices may eventually prove valuable aids to prognostication and good management. BETA-BLOCKERS IN ESSENTIAL TREMOR TREMOR is reflex alternating contraction of muscle groups and their antagonists.’ A low-amplitude tremor of action and fixation (physiological tremor) is seen in all normal subjects. The tremor involves the limbs, the head, and the tongue and is best observed in the out- stretched fingers when the arms are held out and wrists hyperextended.2 In the adult, physiological tremor has a peak frequency at 6-12 Hz and increases in amplitude with anxiety and stress, and on administration of sym- pathomimetic drugs such as isoprenaline, ephedrine, and salbutamol. Essential tremor was originally regarded as an exag- geration of physiological tremor,3 but this view has been questioned.2,4 It has a similar peak frequency and body distribution to those of physiological tremor and, like the latter, disappears at rest and worsens in conditions associated with increased adrenergic discharge.4-6 It is sometimes familial and increases in prevalence and amplitude with increasing age.2 Although a benign con- dition, essential tremor may cause considerable social and occupational disability when it is severe. ’ Other types of pathological tremor are usually associ- ated with signs of underlying metabolic or neurological disease. Parkinsonian tremor is easily distinguished from essential tremor by its lower frequency (4-5 Hz) and by the presence of rigidity and akinesia. Furthermore it is mainly present at rest and may improve on action. 5 Action tremor, in contrast, is frequently associated with lesions of cerebellar and vestibular connections, and is most commonly seen in multiple sclerosis. In these con- ditions tremor is virtually never monosymptomatic.2 There is increasing evidence that p-adrenergic mech- anisms are implicated in the pathogenesis of tremor in Parkinson’s disease,7-10 essential tremor,4,6,11,12 thyro- 13. Sokolow M. Clinical applications of ambulatory blood pressures. In: Clement DL, ed. Blood pressure variability. Lancaster: MTP, 1979: 25-29. 1. Liversedge LA. Involuntary movements. In: Vinken PJ, Bruyn GW, eds. Handbook of clinical neurology, vol. I. Amsterdam: North Holland, 1969: 286. 2. Fahn S. Differential diagnosis of tremors. Med Clin N Am 1972; 56: 1363-75. 3. Marshall J. Observations on essential tremor. J Neurol Neurosurg Psychiatry 1962; 25: 122-25. 4. McAllister RG, Markesbery WR, Ware RW, Howell MA. Suppression of essential tremor by propranolol: correlation of effect with drug plasma level and intensity of &bgr;-adrenergic blockade. Ann Neurol 1977; 1: 160-66. 5. Ashenhurst EM. The nature of essential tremor. Can Med Assoc J 1973; 109: 876-78. 6. Young RR, Growdon JH, Shahani BT. Beta-adrenergic mechanisms in action tremor. N Engl J Med 1975; 293: 950-53. 7. Gerstenbrand F, Rainer J, Pouve W. The influence of &bgr;-adrenergic blocking agents on Parkinson syndrome. Can J Neurol Sci 1979; 6: 79. 8. Gilligan BS, Veale JL, Wodak J. Propranolol in the treatment of tremor. Med J Aust 1972; i: 320-22. 9. Owen DAL, Marsden CD. Effect of adrenergic beta-blockade on parkin- sonian tremor. Lancet 1965; ii: 1259-62. toxicosis," anxiety states,", 14 lithium toxicity, 15 and alcohol withdrawal.16 The p-adrenergic blocking drug propranolol has proved effective in reducing tremor as- sociated with each of these conditions. Although it has little effect on resting physiological tremor4 propranolol suppresses the increase of physiological tremor which is produced by adrenergic stimulation. to. 13 In the treatment of essential tremor, -adrenergic blocking drugs are the only effective agents, with the exception of ethanol. Ethanol may be valuable in tiding a patient over an important social engagement but the risk of excessive intake is a real one. The exis- tence of an alternative form of treatment is therefore welcome. In most studies of propranolol, therapeutic effects have been obtained in a substantial proportion of patients with daily doses ranging from 120 to 320 mg,6,S,12,IS-20 but as much as 800 mg has been used on some occasions.4 A positive correlation between reduc- tion of tremor and plasma propranolol concentration has been recorded after intravenous infusion of the drug4 but this was not confirmed when propranolol was given orally.21 In the latter study, optimal responses were obtained at plasma propranolol levels below 40 ng/ml, which are usually achieved on a regimen of 120-240 mg/day. By what mechanism does propranolol reduce essential tremor? Although an action on the central nervous sys- tem cannot be excluded,6 6 a peripheral action on -adrenoceptors situated in the muscle spindles and extrafusal muscle fibres is more likely The observation that relatively cardioselective p-adrenergic blocking drugs such as atenolol" and praCtolol22 are less effective in the suppression of tremor than propranolol or sota- lolll suggests that &bgr;2-adrenoceptors are involved. Simul- taneous blockade of bronchial &bgr;2-adrenoceptors, how- ever, leads to a risk of bronchoconstriction and therefore patients with a history of asthma should not be treated. In these patients, and in those in whom p-blockers are less helpful, alcohol will remain the sole form of phar- macological relief. 10. Marsden CD, Foley TH, Owen DAL, McAllister RG. Peripheral beta- adrenergic receptors concerned with tremor. Clin Sci Mol Med 1967; 33: 53-65. 11. Jefferson D, Jenner P, Marsden CD. &bgr;-adrenoreceptor antagonists in essen- tial tremor. J Neurol Neurosurg Psychiatry 1979; 42: 904-09. 12. Morgan MH, Hewer RL, Cooper R. Effect of the beta adrenergic blocking agent propranolol on essential tremor. J Neurol Neurosurg Psychiatry 1973; 36: 618-24. 13. Marsden CD, Gimlette TMD, McAllister RE, Owen DAL, Miller TN. Effect of &bgr;-adrenergic blockade on finger tremor and Achilles reflex time in anxious and thyrotoxic patients. Acta Endocrinol 1968; 57: 353-62. 14. Tyrer PJ, Lader MH. Effects of beta-adrenergic blockade with sotalol m chronic anxiety. Clin Pharm Ther 1973: 14: 418-26. 15. Krik L, Baastrup PC, Schou M. Propranolol treatment of lithium-induced tremor. Lancet 1973; ii; 1086-87. 16. Zilm DH, Sellers EM, MacLeod SM, Degani N. Propranolol effect on tremor in alcohol withdrawal. Ann Intern Med 1975; 83: 234-35. 17. Growdon JH, Shahani BT, Young RR. The effect of alcohol on essential tre- mor. Neurology 1975; 25: 259-62. 18. Dupont E, Hansen HJ, Dalby MA. Treatment of benign essential tremor with propranolol. Acta Neurol Scand 1973; 49: 75-84. 19. Teravainen MD, Larsen A, Fogelholm MD. Comparison between the effects of pindolol and propranolol on essential tremor Neurology 1977; 27: 439-42. 20. Tolosa ES, Loewenson RB. Essential tremor: treatment with propranolol. Neurology 1975; 25: 1041-44. 21. Jefferson D, Jenner P, Marsden CD. Relationship between plasma proprano- lol concentration and relief of essential tremor. J Neurol Neurosurg Psy- chiatry 1979; 42: 831-37. 22. Richens A. Propranolol in the control of tremor. A review of available evi- dence. In: The developing future of "Inderal" (propranolol) in CNS dis- orders. Macclesfield: ICI Ltd, 1977.
Transcript of BETA-BLOCKERS IN ESSENTIAL TREMOR
1280
tory blood-pressure monitor which requires the patientto inflate his own pressure cuff." In a group of patientswhose casual clinic blood-pressures were broadly simi-lar, cardiovascular events were more frequent in thosewith higher ambulatory blood-pressures. This tech-
nique, therefore, did seem to add appreciably to the prog-nostic information. The equipment is not cheap andneeds refinement, but such devices may eventually provevaluable aids to prognostication and good management.
BETA-BLOCKERS IN ESSENTIAL TREMOR
TREMOR is reflex alternating contraction of musclegroups and their antagonists.’ A low-amplitude tremorof action and fixation (physiological tremor) is seen inall normal subjects. The tremor involves the limbs, thehead, and the tongue and is best observed in the out-stretched fingers when the arms are held out and wristshyperextended.2 In the adult, physiological tremor has apeak frequency at 6-12 Hz and increases in amplitudewith anxiety and stress, and on administration of sym-pathomimetic drugs such as isoprenaline, ephedrine, andsalbutamol.
Essential tremor was originally regarded as an exag-geration of physiological tremor,3 but this view has beenquestioned.2,4 It has a similar peak frequency and bodydistribution to those of physiological tremor and, likethe latter, disappears at rest and worsens in conditionsassociated with increased adrenergic discharge.4-6 It issometimes familial and increases in prevalence andamplitude with increasing age.2 Although a benign con-dition, essential tremor may cause considerable socialand occupational disability when it is severe.
’
Other types of pathological tremor are usually associ-ated with signs of underlying metabolic or neurologicaldisease. Parkinsonian tremor is easily distinguished fromessential tremor by its lower frequency (4-5 Hz) and bythe presence of rigidity and akinesia. Furthermore it is
mainly present at rest and may improve on action. 5Action tremor, in contrast, is frequently associated withlesions of cerebellar and vestibular connections, and ismost commonly seen in multiple sclerosis. In these con-ditions tremor is virtually never monosymptomatic.2There is increasing evidence that p-adrenergic mech-
anisms are implicated in the pathogenesis of tremor inParkinson’s disease,7-10 essential tremor,4,6,11,12 thyro-
13. Sokolow M. Clinical applications of ambulatory blood pressures. In: ClementDL, ed. Blood pressure variability. Lancaster: MTP, 1979: 25-29.
1. Liversedge LA. Involuntary movements. In: Vinken PJ, Bruyn GW, eds.Handbook of clinical neurology, vol. I. Amsterdam: North Holland, 1969:286.
2. Fahn S. Differential diagnosis of tremors. Med Clin N Am 1972; 56:1363-75.
3. Marshall J. Observations on essential tremor. J Neurol Neurosurg Psychiatry1962; 25: 122-25.
4. McAllister RG, Markesbery WR, Ware RW, Howell MA. Suppression ofessential tremor by propranolol: correlation of effect with drug plasmalevel and intensity of &bgr;-adrenergic blockade. Ann Neurol 1977; 1: 160-66.
5. Ashenhurst EM. The nature of essential tremor. Can Med Assoc J 1973;109: 876-78.
6. Young RR, Growdon JH, Shahani BT. Beta-adrenergic mechanisms inaction tremor. N Engl J Med 1975; 293: 950-53.
7. Gerstenbrand F, Rainer J, Pouve W. The influence of &bgr;-adrenergic blockingagents on Parkinson syndrome. Can J Neurol Sci 1979; 6: 79.
8. Gilligan BS, Veale JL, Wodak J. Propranolol in the treatment of tremor.Med J Aust 1972; i: 320-22.
9. Owen DAL, Marsden CD. Effect of adrenergic beta-blockade on parkin-sonian tremor. Lancet 1965; ii: 1259-62.
toxicosis," anxiety states,", 14 lithium toxicity, 15 andalcohol withdrawal.16 The p-adrenergic blocking drugpropranolol has proved effective in reducing tremor as-sociated with each of these conditions. Although it haslittle effect on resting physiological tremor4 propranololsuppresses the increase of physiological tremor which isproduced by adrenergic stimulation. to. 13
In the treatment of essential tremor, -adrenergicblocking drugs are the only effective agents, with theexception of ethanol. Ethanol may be valuable in
tiding a patient over an important social engagementbut the risk of excessive intake is a real one. The exis-tence of an alternative form of treatment is thereforewelcome. In most studies of propranolol, therapeuticeffects have been obtained in a substantial proportion ofpatients with daily doses ranging from 120 to 320
mg,6,S,12,IS-20 but as much as 800 mg has been used onsome occasions.4 A positive correlation between reduc-tion of tremor and plasma propranolol concentrationhas been recorded after intravenous infusion of the
drug4 but this was not confirmed when propranolol wasgiven orally.21 In the latter study, optimal responseswere obtained at plasma propranolol levels below 40ng/ml, which are usually achieved on a regimen of120-240 mg/day.By what mechanism does propranolol reduce essential
tremor? Although an action on the central nervous sys-tem cannot be excluded,6 6 a peripheral action on
-adrenoceptors situated in the muscle spindles andextrafusal muscle fibres is more likely The observationthat relatively cardioselective p-adrenergic blockingdrugs such as atenolol" and praCtolol22 are less effectivein the suppression of tremor than propranolol or sota-lolll suggests that &bgr;2-adrenoceptors are involved. Simul-taneous blockade of bronchial &bgr;2-adrenoceptors, how-ever, leads to a risk of bronchoconstriction and therefore
patients with a history of asthma should not be treated.In these patients, and in those in whom p-blockers areless helpful, alcohol will remain the sole form of phar-macological relief.
10. Marsden CD, Foley TH, Owen DAL, McAllister RG. Peripheral beta-adrenergic receptors concerned with tremor. Clin Sci Mol Med 1967; 33:53-65.
11. Jefferson D, Jenner P, Marsden CD. &bgr;-adrenoreceptor antagonists in essen-tial tremor. J Neurol Neurosurg Psychiatry 1979; 42: 904-09.
12. Morgan MH, Hewer RL, Cooper R. Effect of the beta adrenergic blockingagent propranolol on essential tremor. J Neurol Neurosurg Psychiatry1973; 36: 618-24.
13. Marsden CD, Gimlette TMD, McAllister RE, Owen DAL, Miller TN. Effectof &bgr;-adrenergic blockade on finger tremor and Achilles reflex time inanxious and thyrotoxic patients. Acta Endocrinol 1968; 57: 353-62.
14. Tyrer PJ, Lader MH. Effects of beta-adrenergic blockade with sotalol mchronic anxiety. Clin Pharm Ther 1973: 14: 418-26.
15. Krik L, Baastrup PC, Schou M. Propranolol treatment of lithium-inducedtremor. Lancet 1973; ii; 1086-87.
16. Zilm DH, Sellers EM, MacLeod SM, Degani N. Propranolol effect on tremorin alcohol withdrawal. Ann Intern Med 1975; 83: 234-35.
17. Growdon JH, Shahani BT, Young RR. The effect of alcohol on essential tre-mor. Neurology 1975; 25: 259-62.
18. Dupont E, Hansen HJ, Dalby MA. Treatment of benign essential tremorwith propranolol. Acta Neurol Scand 1973; 49: 75-84.
19. Teravainen MD, Larsen A, Fogelholm MD. Comparison between the effectsof pindolol and propranolol on essential tremor Neurology 1977; 27:439-42.
20. Tolosa ES, Loewenson RB. Essential tremor: treatment with propranolol.Neurology 1975; 25: 1041-44.
21. Jefferson D, Jenner P, Marsden CD. Relationship between plasma proprano-lol concentration and relief of essential tremor. J Neurol Neurosurg Psy-chiatry 1979; 42: 831-37.
22. Richens A. Propranolol in the control of tremor. A review of available evi-dence. In: The developing future of "Inderal" (propranolol) in CNS dis-orders. Macclesfield: ICI Ltd, 1977.
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