Neurological side effects and plasma and CSF levels

Author(s):  
Göran Sedvall
Keyword(s):  
1996 ◽  
Vol 84 (5) ◽  
pp. 860-866 ◽  
Author(s):  
Gary K. Steinberg ◽  
Teresa E. Bell ◽  
Midori A. Yenari

✓ Experimental studies have shown that dextromethorphan, a noncompetitive N-methyl-d-aspartate antagonist is neuroprotective in experimental models of ischemic cerebral injury. The authors studied the safety and tolerability of oral dextromethorphan (DM) in humans, and correlated serum levels of this drug with cerebrospinal fluid (CSF) and brain levels. Neurosurgical patients undergoing intracranial surgery or endovascular procedures were given ascending doses of oral DM prior to and 24 hours after surgery. Serum, CSF, and brain levels of DM and its active metabolite, dextrorphan, were measured. One hundred eighty-one patients received a total of 212 courses of DM treatment in dose ranges of 0.8 to 9.64 mg/kg. Serum DM levels correlated highly with CSF and brain DM levels. Brain levels were 68-fold higher than serum levels, whereas CSF levels were fourfold lower than serum levels. The maximum DM levels attained were 1514 ng/ml (serum), 118 ng/ml (CSF), and 92,700 ng/g (brain). The maximum dextrorphan levels were 501 ng/ml (serum), 167 ng/ml (CSF), and 6840 ng/g (brain). In 11 patients, brain and plasma levels of DM were comparable to levels that have been shown to be neuroprotective in animal studies. Frequent side effects occurring at neuroprotective levels of DM included nystagmus (64%), nausea and vomiting (27%), distorted vision (27%), feeling “drunk” (27%), ataxia (27%), and dizziness (27%). All symptoms were reversible and no patient suffered severe adverse reactions. This study demonstrates that potentially neuroprotective doses of DM can be administered safely to neurosurgical patients. Brain and CSF levels of DM can be estimated from serum levels of the drug. Side effects, even at the highest levels, proved to be tolerable and reversible. Administration of DM to patients at risk for cerebral injury should be further explored.


2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Cinzia Auriti ◽  
Fiammetta Piersigilli ◽  
Iliana Bersani ◽  
Sara Cairoli ◽  
Paolina Giuseppina Amante ◽  
...  
Keyword(s):  

Author(s):  
S.K. Aggarwal ◽  
J. San Antonio

Cisplatin (cis-dichlorodiammineplatinum(II)) a potent antitumor agent is now available for the treatment of testicular and ovarian cancers. It is however, not free from its serious side effects including nephrotoxicity, gastro intestinal toxicity, myelosuppression, and ototoxicity. Here we now report that the drug produces peculiar bloating of the stomach in rats and induces acute ulceration.Wistar-derived rats weighing 200-250 g were administered cisplatin(9 mg/kg) ip as a single dose in 0.15 M NaCl. After 3 days the animals were sacrificed by decapitation. The stomachs were removed, the contents analyzed for pepsin and acidity. The inner surface was examined with a dissecting microscope after a moderate stretching for ulcers. Affected areas were fixed and processed for routine electron microscopy and enzyme cytochemistry.The drug treated animals kept on food and water consistently showed bloating and lesions (Fig. 1) with a frequency of 6-70 ulcers in the rumen section of the stomachs.


Author(s):  
George D. Pappas ◽  
Jacqueline Sagen

We have been interested in the use of neural transplants mainly as a local source of neuroactive substances, rather than as a replacement for damaged neural circuities. In particular, we have been exploring the possibilities of reducing pain by transplants of opioid peptide producing cells, and reducing depression by transplants of monoamine-producing cells. For the past several years, work in our laboratory has demonstrated in both acute and chronic pain models that transplantation of adrenal medullary tissue or isolated chromaffin cells into CNS pain modulatory regions can reduce pain sensitivity in rodents. Chromaffin cells were chosen as donor source since they produce high levels of both opioid peptides and catecholamines, substances which independently, and probably synergistically, reduce pain sensitivity when injected locally into the spinal cord. The analgesia produced by these transplants most likely results from the release of both opioid peptides and catecholamines, since it can be blocked or attenuated by opiate or adrenergic antagonists, respectively. Furthermore, CSF levels of met-enkephalin and catecholamines are increased by the transplants.


Author(s):  
J.M. Fadool ◽  
P.J. Boyer ◽  
S.K. Aggarwal

Cisplatin (CDDP) is currently one of the most valuable antineoplastic drugs available. However, it has severe toxic side effects of which nephrotoxicity is the major dose limiting factor in its use. It induces morphological changes in the kidney with hampered urine output. The present study is an effort to determine the influence of the drug on the neurohypophysis for any antidiuretic effects on the kidney.


2012 ◽  
Vol 21 (1) ◽  
pp. 15-21
Author(s):  
Merete Bakke ◽  
Allan Bardow ◽  
Eigild Møller

Severe drooling is associated with discomfort and psychosocial problems and may constitute a health risk. A variety of different surgical and non-surgical treatments have been used to diminish drooling, some of them with little or uncertain effect and others more effective but irreversible or with side effects. Based on clinical evidence, injection with botulinum toxin (BTX) into the parotid and submandibular glands is a useful treatment option, because it is local, reversible, and with few side effects, although it has to be repeated. The mechanism of BTX is a local inhibition of acetylcholine release, which diminishes receptor-coupled secretion and results in a flow rate reduction of 25–50% for 2–7 months.


2001 ◽  
Vol 26 (1) ◽  
pp. 67-71 ◽  
Author(s):  
S. A. Ahmadi-Abhari ◽  
S. Akhondzadeh ◽  
S. M. Assadi ◽  
O. L. Shabestari ◽  
Z. M. Farzanehgan ◽  
...  

1977 ◽  
Vol 113 (3) ◽  
pp. 376-376
Keyword(s):  

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