Volume 11, Issue 1, March 2009

Pharmacotherapy of stroke

Dániel Bereczki


Annually about 50.000 patients are hospitalized for acute stroke in Hungary. Of all stroke cases 85% are ischemic, and 15% are hemorrhagic (intracerebral or subarachnoid). In acute ischemic stroke the only registered causal treatment with proven efficacy is thrombolysis with intravenous administration of recombinant tissue plasminogen activator with a 3-hour time window. The indication areas of intraarterial thrombolysis are currently being established for selected cases in selected centers. Other studies examine the options to extend the time window and to test new thrombolytic agents. Despite the large number of studies none of the neuroprotectant agents have been found beneficial in randomized controlled clinical trials in acute stroke. According to the results of studies to date anticoagulant therapy (heparin) cannot be recommended for the routine treatment of acute stroke. Aspirin may be safely administered within 48 hours of ischemic stroke and results in a 1% decrease of death or disability at 6 months after stroke. There were no large studies on the use of other antiplatelet agents in acute stroke. If thrombolysis is performed, antiplatelet or anticoagulant agents should not be administered in the first 24 hours. Further studies are needed to test the efficacy and safety of anticoagulants in special cases of stroke (e.g. crescendo TIA-s, progressing stroke), and to test combined antiplatelet treatment in the acute phase of stroke. In acute intracerebral hemorrhage the beneficial effect of recombinant coagulation factor 8 Neuropsychopharmacologia Hungarica 2009, XI/1, 7-13 found in a small study could not be proved in a large phase III trial. Currently there is no evidence based pharmacotherapy for the specific treatment of intracerebral hemorrhage. In subarachnoid hemorrhage nimodipine was found effective in preventing vasospasm and thus secondary ischemic cerebral damage. Although the results of individual trials are conflicting, a systematic review on the effects of statins suggests a similar effect. Due to the limited options of evidence based treatments of acute stroke primary prevention has utmost importance.

KEYWORDS: ischemic stroke, cerebral hemorrhage, pharmacotherapy


Migraine attacks are characterized by unilateral throbbing, pulsating headache associated with nausea, vomiting, photophobia, phonophobia and allodynia. Peripheral sensitization is an acute, chemical-induced form of functional plasticity, which converts high-threshold nociceptors into low-threshold sensory neurons. This form of sensitization occurs when the nerve terminals (meningeal nociceptors) of the neurons of the trigeminal ganglion are soaked with the “inflammatory” soup (prostaglandin E2, bradykinin, serotonin and cytokines) along the vasculature of the cerebral dura mater. Peripheral sensitization in migraine attacks is explained clinically by intracranial hypersensitivity (the headache worsens during coughing or physical activity) and by a throbbing element in the pain of migraine (sensitized nociceptors become hyperresponsive to the otherwise innocuous and unperceived rhythmic fluctuation in intracranial pressure produced by normal arterial pulsation). The essence of central sensitization is that the second-order neurons in the trigeminocervical complex become hyperexcitable. The altered behavior of the second-order neurons is based on the increased glutamate sensistivity of the NMDA receptors and the neuronal nitric oxide synthase activity stimulated by nitric oxide. This process is explained clinically by face and scalp ollodynia and by neck stiffness (extracranial tenderness).

Keywords: migraine, peripheral sensitization, central sensitization


Multiple sclerosis (MS) is one of the most frequent neuroimmunological disorders of the central nervous system. It is a multifactorial disease with possible causes including genetic and environmental factors. MS is characterized in essence by an autoimmune inflammation in the central nervous system, resulting in the damage of the myelin sheath and the axons. There are four pathological subtypes of the disease. Its clinical course can either be of the relapsing-remitting or primary and secondary progressive type. All structures of the central nervous system may be involved, but the longest tracts are affected the most often. According to the revised McDonald criteria, the diagnosis of MS is based on the clinical course and the MRI findings. Its therapy can be divided into the acute treatment of relapses, symptomatic relief and long-term immunomodulatory treatment. With respect to differential diagnosis, it is of special concern to distinguish between MS and neuromyelitis optica, as early diagnosis and appropriate treatment of the latter may prevent the development of severe residual symptoms associated with this disease.

Keywords: multiple sclerosis, McDonald criteria, immunomodulatory treatment


Dementia is one of the most important health problems in the aging populations. The most frequent cause of it is Alzheimer’s disease (AD) which is characterized by intracellular neuro-fibrillary tangles (NFT) and the extracellular senile plaques. The NFTs are mainly formed by the hyperphosphorylated microtubule-binding protein, the tau, while the senile plaques are composed of beta-amyloid protein cleaved from the amyloid precursor protein (APP) by the beta- and gamma-secretases. The pharmacotherapy of AD consists of symptomatic and disease-modifying therapies. The most frequently used therapeutic agents are the nootropic drugs supported by personal rather evidence based experiences. The leading-edge therapy of AD at present is the inhibition of the acetylcholine-esterase enzyme (AChEI) with mainly cognitive symptomatic and weak disease-modifying effects; they are licensed in the mild and middle stages of AD (MMSE 26-10), but their effect is proved in the severe stage of the disease and they are effective in the management of the neuropsychiatric symptoms too. Memantine (which is an inhibitor of the N-metil-D-aspartate receptor) is used in the middle and severe stages of AD and it can be effectively combined with AChEIs. The future therapy of AD will possibly be a “causative” therapy. The most frequent directions are therapies aiming to decrease the production or the deposition of beta-amyloid peptide. The active vaccination study of AN-1792 was terminated because of immunological side-effects, but several active and passive immunisation therapies are in development nowadays. It is also possible to inhibit the aggregation of the beta-amyloid peptide with peptide fragments or with Cu2+ and Zn2+ ion chelators. A promising direction is the inhibition of the enzymes responsible for the production of the beta-amyloid peptide: beta-secretase inhibitors with low molecular weight and penetrability through the blood-brain barrier are developed while the inhibitors of the gamma-secretase (some of them are the derivatives of the non-steroid anti-inflammatory drug ibuprofen) are tested in phase III trials. The inhibition of NFT formation might be promising too and inhibitors of the enzymes responsible for the hyperphosphorylation of the tau (like the glycogen synthase kinase-3) are in develo ment. Several other therapeutic methods are studied. NSAIDs and statins are useful in the prevention of the disease but they are failed in symptomatic treatment. There are promising studies in few patients using nerve growth factor therapy and some studies proved that peroxisome proliferator activated receptor (PPAR) agonist rosiglitazone (which is used to the treat diabetes mellitus) is effective in AD. The presently modest therapeutic interventions of AD will explode in the near future and together with the improved diagnostics of the disease they will cause further specialization with increased treatment and caring costs amplified by the ever growing number of the patients. This means that AD is and will be one of the most important diseases for the health care systems.

KEYWORDS: Alzheimer’s disease, cholinesterase inhibitors, memantine, ß-amyloid, tau, ß-secretase,



Schizoprenia is not a consistent illness, but the symptoms free state do may achive with different methods. During the last fifty years the clinical psychopharmacology improved very quickly, but the psychotherapy and sociotherapy as well. The complex therapy of schizophrenia is a new method: the psychopharmacons together with psychotherapy (first of all with cognitive one), sociotherapy and psychiatric rehabilitation. During the acute or chronic phase of schizophrenia the psychopharmacons are the first line treatment, but the complex therapy is better. In the last forty years we tested this new therapy, finally conducted a clinical trial: with one psychopharmacon (monotherapy), with two or three psychopharmacons (combination) and with the complex therapy (one psychopharmacon together with psychotherapy, sociotherapy and psychiatric rehabilitation). The antipsychotics, first of all the second generations have a very good efficacy. Risperidone is proven to be an efficient product. Fields of indication: first psychotic episode, acut schizophrenic exacerbation, chronic schizophrenia, the treatment of behavior disorder in dementia, maniac phase of bipolar disorder, treatment of behavioral disorders.

Keywords: schizophrenia, biological psychiatric therapy, complex therapy, risperidone