Skip to main content
SpringerLink
Log in

Drug Treatment of Stroke

Current Status and Future Prospects

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Despite advances in the understanding of the mechanism of cerebral injury during focal ischaemia, the best treatment of cerebral ischaemia is still prevention. The pathophysiological mechanisms that contribute to cerebral ischaemia are discussed relative to the many therapeutic interventions that have been attempted. It is our impression that the treatment of such a complex multifactor process will require multimodal therapy, as most of the unifactorial therapies used to date have proven relatively unsuccessful in improving neurological outcome and survival.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams HP, Olinger CP, Barsan WG, Butler MJ, Graff-Radford NR, et al. A dose-escalation study of large doses of naloxone for treatment of patients with acute cerebral ischemia. Stroke 17: 404–409, 1986

    Article  PubMed  Google Scholar 

  • Agnoli A, Palesse N, Ruggieri S. Barbiturate treatment of acute stroke. Advances in Neurology 25: 269–276, 1979

    PubMed  CAS  Google Scholar 

  • Aldrich MS, Sherman SA, Greenberg HS. Cerebrovascular complications of streptokinase infusion. Journal of the American Medical Association 253: 1777–1779, 1985

    Article  PubMed  CAS  Google Scholar 

  • American-Canadian Cooperative Study Group. Persantine and aspirin in trial in acute cerebral ischemia, part II: risk factors of stroke. Stroke 16: 406–515, 1985

    Article  Google Scholar 

  • Anderson DC, Cranford RE. Corticosteroids in ischemic stroke. Stroke 10: 68–71, 1979

    Article  PubMed  CAS  Google Scholar 

  • Andree RA. Sudden death following naloxone administration. Anesthesia Analog 10: 782, 1980

    Google Scholar 

  • Asplund K. Hemodilution in acute ischemic stroke: randomized multicenter trial, Abstract 71, Stroke 17: 143, 1986

    Google Scholar 

  • Asplund K, et al. Multicenter trial of hemodilution in ischemic stroke-background and study protocol. Stroke 16: 885–890, 1985

    Article  Google Scholar 

  • Asplund K. Hemodilution in acute ischemic stroke: randomized multicenter trial, Abstract 71, Stroke 17: 143, 1986

    Google Scholar 

  • Barnett HJM. Antithrombotic therapy in cerebral vascular disease: antispasmodics and fibrinolysins. In Barnett et al. (Eds) Stroke: pathophysiology, diagnosis, and management. Churchill Livingstone, New York, 1986

    Google Scholar 

  • Baskin DS, Hosobuchi Y. Naloxone reversal of ischemic neurological deficits in man. Lancet 2: 272–275, 1981

    Article  PubMed  CAS  Google Scholar 

  • Bauer RB, Telleg H. Dexamethasone as treatment in cerebrovascular disease. Stroke 4: 547–555, 1973

    Article  PubMed  CAS  Google Scholar 

  • Bousser MG, Eschwege E, Haguenau M, et al. ‘AICLA’ controlled trial of aspirin and dipyridamole in the secondary prevention of athero-thrombotic cerebral ischemia. Stroke 14: 5–14, 1983

    Article  PubMed  CAS  Google Scholar 

  • Brain Resuscitation Clinical Trial I Study Group. Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest. New England Journal of Medicine 314: 397–403, 1986

    Article  Google Scholar 

  • Brandt L, Ljunggren B, Anderson KE. Effects of topical application of a calcium antagonist (nifedipine) on feline cortical pial microvasculature under normal conditions and in focal ischemia. Journal of Cerebral Blood Flow and Metabolism 3: 44–50, 1983

    Article  PubMed  CAS  Google Scholar 

  • Britton M, de Faire U, Miah K, Rane A. Lack of effect of theophylline on the outcome of acute cerebral infarction. Acta Neurologica Scandinavica 62: 116–123, 1980

    Article  PubMed  CAS  Google Scholar 

  • Brown MM, Hewazy AH, Pickles H, Redmond S, Myfanwy T, et al. Indomethacin, epoprostenol, and cerebral blood flow in normal subjects. Journal of Physiology 334: 52P, 1983

    Google Scholar 

  • Canadian Cooperative Study Group. A randomized trial of aspirin and sulfinpyrazone in threatened stroke. New England Journal of Medicine 299: 53–59, 1979

    Google Scholar 

  • Cerebral Embolism Study Group. Immediate anticoagulation of embolic stroke: brain hemorrhage and management options. Stroke 15: 779–789, 1984

    Article  Google Scholar 

  • Conley RF, Sundt TM. Effects of dexamethasone on the edema of focal cerebral ischemia. Stroke 4: 148–155, 1973

    Article  Google Scholar 

  • Cronberg S, Robertson B, Nilsson IM, Nilehn JE. Suppressive effect of dextran on platelet adhesiveness. Thrombosis et Diathesis Haemorrhagica 16: 384–394, 1966

    PubMed  CAS  Google Scholar 

  • Cutler JR, Bredesen D, Edwards R, Simon RP. Failure of naloxone to reverse vascular neurologic deficits. Neurology 33: 1517–1521, 1983

    Article  PubMed  CAS  Google Scholar 

  • Del Zoppo GJ, Copeland BR, Waltz TA, Zyroff J, Harker LA. Thrombolytic therapy in a baboon model of acute stroke, Abstract 31, Stroke 17: 133, 1986

    Google Scholar 

  • Demopoulous HB, Flamm ES, Seligman ML, Jorgensen E, Ransohoff J. Antioxidant effects of barbiturates in model membranes undergoing free radical damage. Acta Neurologica Scandinavica 56: 152–153, 1977

    Google Scholar 

  • Duke RJ, Turpie AG, Bloch RJ, Trebilcock RG, Bayer NH. A randomized controlled trial of heparin in acute partial thrombotic stroke, Abstract 29, Stroke 17: 133, 1986

    Google Scholar 

  • Fasten JD, Sherman DG. Management of cerebral embolism of cardiac origin. Stroke 11: 433–442, 1980

    Article  Google Scholar 

  • Eichner ER. Platelets, carotids, and coronaries: critique on antithrombotic role of antiplatelet agents, exercise, and certain diets. American Journal of Medicine 77: 513–523, 1984

    Article  PubMed  CAS  Google Scholar 

  • Faden AI. Opiate antagonists in the treatment of stroke. Stroke 15: 575–578, 1984

    Article  PubMed  CAS  Google Scholar 

  • Fallis R, Fisher M, Lobo R. A double-blind trial of naloxone in acute stroke, Abstract 14, Stroke 14: 124, 1983

    Google Scholar 

  • Flamm ES, Demopoulous HB, Seligman ML, Ransohoff J. Possible molecular mechanisms of barbiturate-mediated protection in regional cerebral ischemia. Acta Neurologica Scandinavica 56: 150–151, 1977

    Google Scholar 

  • Fletcher AP, Alkjaersig N, Lewis M, Tulevski V, Davies A, et al. A pilot study of urokinase therapy in cerebral infarction. Stroke 7: 135–142, 1976

    Article  PubMed  CAS  Google Scholar 

  • Furlan AJ, Cavalier SJ, Hobbs RE, Weinstein MA, Modie MT. Hemorrhage and anticoagulation after nonseptic embolic brain infarction. Neurology 32: 280–282, 1982

    Article  PubMed  CAS  Google Scholar 

  • Gelmers HJ. The effects of nimodipine on the clinical course of patients with acute ischemic stroke. Acta Neurologica Scandinavica 69: 232–239, 1984

    Article  PubMed  CAS  Google Scholar 

  • Gelmers HJ. Calcium-channel blockers: effects on cerebral blood flow and potential uses for acute stroke. American Journal of Cardiology 55: 144B–148B, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gelmers HJ, Gorter K, de Weerdt CJ, Wiezer JHA. Effect of nimodipine on clinical outcome in patients with acute ischemic stroke. Abstract 77, Stroke 17: 145, 1986

    Google Scholar 

  • Genton E, Barnett HJM, Fields WS, Gent M, Hoak JC. Report of the Joint Committee of Stroke Resources, XIV: cerebral ischemia: the role of thrombosis and of antithrombotic therapy. Stroke 8: 150–157, 1977

    Article  PubMed  CAS  Google Scholar 

  • Gilroy J, Barnhart M, Meyer JS. Treatment of acute stroke with Dextran-40. Journal of the American Medical Association 210: 2193–2198, 1969

    Article  Google Scholar 

  • Grotta JC, Ackerman R, Correia J, Fallick G, Chang J. Whole blood viscosity parameters and cerebral blood flow. Stroke 13: 296–301, 1982

    Article  PubMed  CAS  Google Scholar 

  • Grotta JC, Ostrow P, Fraifeld E, Hartman D. Reduction of fibrinogen and viscosity does not significantly alter ischemic injury. Journal of Cerebral Blood Flow and Metabolism 3: S349, 1983

    Google Scholar 

  • Grotta JC, Pettigrew LC, Allen S, Tonnesen A, Yatsu FM, et al. Baseline hemodynamic state and response to hemodilution in patients with acute cerebral ischemia. Stroke 16: 790–795, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gryglewski RJ, Nowak S, Kostka-Trabka E, Kusmiderski J, Dembinska-Kiec A, et al. Treatment of ischaemic stroke with prostacyclin. Stroke 14: 197–202, 1983

    Article  PubMed  CAS  Google Scholar 

  • Haley EC, Kassel NJ, Torner JC. Failure of heparin to prevent progression in progressing ischemic infarction, Abstract 28, Stroke 17: 132, 1986

    Google Scholar 

  • Hanaway J, Torack R, Fletcher AP, Landau WM. Intracranial bleeding associated with urokinase therapy for acute ischemic hemispheral stroke. Stroke 7: 143–146, 1976

    Article  PubMed  CAS  Google Scholar 

  • Harrison MJG, Pollock S, Kendell BE, Marshall J. Effect of haematocrit on carotid stenosis and cerebral infarction. Lancet 2: 114, 1981

    Article  PubMed  CAS  Google Scholar 

  • Hart RG, Sherman DG, Miller VT, Easton JD. Diagnosis and management of ischemic stroke: part II: selected controversies. Current Problems in Cardiology 8: 7–80, 1983

    Article  Google Scholar 

  • Hass WK, Kamm B. North American Ticlopidine aspirin stroke study: structure, stratification variables, and patient characteristics. Agents and Actions (Suppl. 15): 273–378, 1984

    Google Scholar 

  • Hossman V, Heiss WD, Berwermeyer H, Wiedemann G. Controlled trial of ancrod in ischemic stroke. Archives of Neurology 40: 803–808, 1983

    Article  Google Scholar 

  • Jabaily J, Davis JN. Naloxone partially reverses neurologic deficits in some but not all stroke patients. Abstract PP180, American Academy of Neurology, 34th Annual Meeting. Neurology 32: A197, 1982

    Google Scholar 

  • Kaste M, Fogelholm R, Waltimo O. Combined dexamethasone and low-molecular weight dextran in acute cerebral infarction. British Medical Journal 2: 1409–1410, 1976

    Article  PubMed  CAS  Google Scholar 

  • Koller RL. Recurrent embolic cerebral infarction and anticoagulation. Neurology 32: 283–285, 1982

    Article  PubMed  CAS  Google Scholar 

  • Linet O, Hsu CY, Faught RE, Hogan EL, Furlan AJ, et al. Epoprostenol in acute stroke, Abstract 54, Stroke 16: 149, 1985

    Google Scholar 

  • Lodder J, van der Lugt PJM. Evaluation of the risk of immediate anticoagulant treatment in patients with embolic stroke of cardiac origin. Stroke 14: 42–46, 1983

    Article  PubMed  CAS  Google Scholar 

  • Martin JF, Hamdy N, Nicholl J, Lewtas N, Bergrall U, et al. Double-blind controlled trial of prostacyclin in cerebral infarction. Stroke 16: 386–390, 1985

    Article  PubMed  CAS  Google Scholar 

  • Matthews WB, Oxbury JM, Grainger MR, Greenhall RCD. A blind controlled trial of dextran-40 in the treatment of ischemic stroke. Brain 99: 193–206, 1976

    Article  PubMed  CAS  Google Scholar 

  • McCalden TA, Nath RO, Thiele K. The effects of a calcium antagonist (nimodipine) on basal cerebral blood flow and reactivity to various agonists. Stroke 15: 527–530, 1984

    Article  PubMed  CAS  Google Scholar 

  • Michenfelder JD. Cerebral preservation for intraoperative focal ischemia. Clinical Neurosurgery 32: 105–113, 1985

    PubMed  CAS  Google Scholar 

  • Mikhailidis DP, Barradas MA, Mikhailidis AM, Magnani H, Dandona P. Comparison of the effect of a conventional heparin and a low molecular weight heparinoid on platelet function. British Journal of Clinical Pharmacology 17: 43–48, 1984

    Article  PubMed  CAS  Google Scholar 

  • Miller VT, Coull BM, Yatsu FM, Shah AR, Beamer NB. Prostacyclin infusion in acute cerebral infarction. Neurology 34: 1431–1435, 1984

    Article  PubMed  CAS  Google Scholar 

  • Mills DC, Smith JB. The control of platelet responsiveness by agents that influence cyclic AMP levels. Annals of the New York Academy of Sciences 210: 391–399, 1972

    Article  Google Scholar 

  • Moncada S. Biology and therapeutic potential of prostacyclin. Stroke 14: 157–168, 1983

    Article  PubMed  CAS  Google Scholar 

  • Mulley G, Wilcox RG, Mitchell JRA. Dexamethasone in acute stroke. British Medical Journal 2: 994–996, 1978

    Article  PubMed  CAS  Google Scholar 

  • Nenci GG, Gresele P, Taramelli M, Agnelli G, Signorini E. Thrombolytic therapy for thromboembolism of vertebrobasilar artery. Angiology 24: 561–571, 1983

    Article  Google Scholar 

  • Norris JEW. Steroid therapy in acute cerebral infarction. Archives of Neurology 33: 69–71, 1976

    Article  PubMed  CAS  Google Scholar 

  • Norris JEW, Hachinski VC. Megadose steroid therapy in ischemic stroke, Abstract 57, Stroke 16: 150, 1985

    Google Scholar 

  • O’Brien MD. Ischemic cerebral edema: a review. Stroke 10: 623–628, 1979

    Article  PubMed  Google Scholar 

  • Olesen J, Paulson OB. The effect of intra-arterial papaverine on regional cerebral blood flow in patients with stroke or intracranial tumor. Stroke 2: 148–159, 1971

    Article  PubMed  CAS  Google Scholar 

  • Ottonello GA, Primavera A. Gastrointestinal complication of high-dose corticosteroid therapy in acute cerebrovascular patients. Stroke 10: 208–210, 1979

    Article  PubMed  CAS  Google Scholar 

  • Patten BM, Mendell J, Bruun B, Curtin W, Carter S. Double-blind study of the effects of dexamethasone on acute stroke. Neurology 22: 377–383, 1972

    Article  PubMed  CAS  Google Scholar 

  • Regli F, Yamaguchi T, Waltz AG. Effects of vasodilating drugs on blood flow and the microvasculature of ischemic and nonischemic cerebral cortex microvasculature of ischemic and nonischemic cerebral cortex. Archives of Neurology 24: 467–474, 1971

    Article  PubMed  CAS  Google Scholar 

  • Rosenblum WI. Effects of calcium channel blockers on pial vascular responses to receptor-mediated constrictors. Stroke 15: 284–288, 1984

    Article  PubMed  CAS  Google Scholar 

  • Safar P. Amelioration of post-ischemic brain damage with barbiturates. Stroke 11: 565–568, 1980

    Article  PubMed  CAS  Google Scholar 

  • Sakuta S. Blood filtrability in cerebrovascular disorders, with special reference to erythrocyte deformability and ATP content. Stroke 12: 824–828, 1981

    Article  PubMed  CAS  Google Scholar 

  • Saltiel E, Ward A. Ticlopidine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states. Drugs 34: 222–262, 1987

    Article  PubMed  CAS  Google Scholar 

  • Salzman EW, Deykin D, Shapiro RM, Rosenberg R. Management of heparin therapy-controlled prospective trial. New England Journal of Medicine 292: 1046–1050, 1975

    Article  PubMed  CAS  Google Scholar 

  • Selman WR, Spetzler RF. Therapeutics for focal cerebral ischemia. Neurosurgery 6: 446–452, 1980

    Article  PubMed  CAS  Google Scholar 

  • Sinzinger H, Feigl W, Silberbauer K. Prostacyclin generation in atherosclerotic arteries. Lancet 2: 469, 1979

    Article  PubMed  CAS  Google Scholar 

  • Sixma JJ. The prethrombotic state. British Journal of Haematology 46: 515–522, 1980

    Article  PubMed  CAS  Google Scholar 

  • Skinhoj E, Paulson OB. The mechanism of action of aminophylline upon cerebral vascular disorders. Acta Neurologica Scandinavica 46: 129, 1970

    Article  PubMed  CAS  Google Scholar 

  • Spence JD, Del Maestro RF. Hypertension in acute ischemic stroke. Archives of Neurology 42: 1000–1002, 1985

    Article  PubMed  CAS  Google Scholar 

  • Spudis EV, De La Torre E, Pikula L. Management of completed stroke with dextran-40. Stroke 4: 895–897, 1973

    Article  PubMed  CAS  Google Scholar 

  • Steen PA, Michenfelder JD. Cerebral protection with barbiturates. Stroke 9: 140–142, 1978

    Article  PubMed  CAS  Google Scholar 

  • Strand T, Asplund K, Eriksson S, Hägg E, Lithner F, et al. A randomized controlled trial of hemodilution therapy in acute ischemic stroke. Stroke 15: 980–989, 1984

    Article  PubMed  CAS  Google Scholar 

  • Strandgaard S, Paulson OB. Cerebral autoregulation. Stroke 15: 413–416, 1984

    Article  PubMed  CAS  Google Scholar 

  • Thomas DJ. Hemodilution in acute stroke. Stroke 16: 763–764, 1985

    Article  PubMed  CAS  Google Scholar 

  • Van de Werf F, Ludbrook PA, Bergmen SR, Tiefenbrunn AJ. Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction. New England Journal of Medicine 310: 609–613, 1984

    Article  PubMed  Google Scholar 

  • Wade JPH. Transport of oxygen to the brain in patients with elevated haematocrit values before and after venesection. Brain 106: 513–523, 1983

    Article  PubMed  Google Scholar 

  • Wallace JD, Levy LL. Blood pressure after stroke. Journal of the American Medical Association 246: 2177–2180, 1981

    Article  PubMed  CAS  Google Scholar 

  • Weksler BB, Lewin M. Anticoagulation in cerebral ischemia. Stroke 14: 658–663, 1983

    Article  PubMed  CAS  Google Scholar 

  • Whisnant JP, Cartlidge NEF, Elveback LR. Carotid and vertebral-basilar transient ischemic attacks: effects of anticoagulants, hypertension, and cardiac disorders on survival and stroke occurrence — a population study. Annals of Neurology 3: 107–115, 1978

    Article  PubMed  CAS  Google Scholar 

  • Wood JH, Fleischer AS. Observations during hypervolemic hemodilution of patients with acute focal cerebral ischemia. Journal of the American Medical Association 248: 2999–3004, 1982

    Article  PubMed  CAS  Google Scholar 

  • Wood JH, Kee DB. Hemorheology of the cerebral circulation in stroke. Stroke 16: 765–772, 1985

    Article  PubMed  CAS  Google Scholar 

  • Wood JH, Simeone FA, Fink EA, Golden MA. Correlative aspects of hypervolemic hemodilution with low molecular weight dextran: relationships of cortical blood flow, cardiac output and intracranial pressure to fresh blood viscosity and plasma volume. Neurosurgery 11: 739–753, 1982

    Article  PubMed  CAS  Google Scholar 

  • Wood JH, Simeone FA, Fink EA, Golden MA. Hypervolemic hemodilution in experimental focal cerebral ischemia. Journal of Neurosurgery 59: 500–509, 1983

    Article  PubMed  CAS  Google Scholar 

  • Yatsu FM, Zivin J. Hypertension in acute ischemic strokes. Archives of Neurology 42: 999–1000, 1985

    Article  PubMed  CAS  Google Scholar 

  • Zeumer H, Hundgen R, Ferbert A, Ringelstein EB. Local intraarterial fibrinolytic therapy in inaccessible internal carotid occlusion. Neuroradiology 26: 315–317, 1984

    PubMed  CAS  Google Scholar 

  • Zivin J, Fisher M, DeGirolami U, Hemenway C. Tissue plasminogen activator therapy for embolic stroke, Abstract 30. Stroke 17: 133, 1986

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH, 44106, USA

    Cathy A. Sila & Anthony J. Furlan

Authors
  1. Cathy A. Sila
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony J. Furlan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sila, C.A., Furlan, A.J. Drug Treatment of Stroke. Drugs 35, 468–476 (1988). https://doi.org/10.2165/00003495-198835040-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-198835040-00005

Keywords

Search

Navigation