Drugs neurotoxic

Drug Membrane Uptake Carrier Involved in Neurotoxicity Drug Metabolite Involved in Neurotoxicity... 

Rats that have lost dopamine and/or serotonin terminals following treatment with amphetamine, methamphetamine, MDMA, MDA, / -chloroamphetamine, or fenfluramine show little in the way of overt ehanges in appearanee or behavior. Dr. Rieaurte (this volume) emphasized the need for more studies in primates, since MPTP-treated miee also show little in the way of observable functional changes, whereas MPTP-treated monkeys show marked neurologie deficits. It may be neeessary to do more detailed analysis of speeifie behaviors and other funetional outputs that are influeneed by dopamine and/or serotonin neurons, to detect functional deficits induced by some neurotoxic drugs. For instance, specific behaviors sueh as appetite-eontrolled behavior (Leibowitz and Shor-Posner 1986), murieidal behavior (Katz 1980), and sexual behavior (Tucker and File 1983) elieited by drugs... 

Neurodegeneration Localised or widespread death of neurons, a feature of a number of brain disorders, such as Alzheimer s disease, Parkinson s disease and cerebrovascular stroke. It can also be caused by neurotoxic drugs like MDMA/Ecstasy, although there is debate over whether this occurs in humans as well as laboratory animals. 

Anand SS, Kim KB, Padilla S, Muralidhara S, Kim HJ, Fisher JW, Bruckner JV (2006) Ontogeny of hepatic and plasma metabolism of deltamethrin in vitro role in age-dependent acute neurotoxicity. Drug Metab Dispos 34 389-397... 

Saito, T., Zhang, Z. J., Ohtsubo, T., et al. (2001) Homozygous disruption of the mdrla P-glycoprotein gene affects blood-nerve barrier function in mice administered with neurotoxic drugs. Acta Otolaryngol. 121, 735-742. 

Coadministration of didanosine buffered tablets, buffered powder for oral solution, and pediatric powder for oral solution with drugs that are known to cause peripheral neuropathy or pancreatitis or patients who have a history of neuropathy or neurotoxic drug therapy may have increased risk of toxicities. Closely observe patients who receive these drugs or have a history of neuropathy or neurotoxic drug therapy. 

Neurologic symptoms Motor weakness has been reported rarely. Most of these cases occurred in the setting of lactic acidosis. The evolution of motor weakness may mimic the clinical presentation of Guillain-Barre syndrome (including respiratory failure). Symptoms may continue or worsen following discontinuation of therapy. Stavudine therapy has been associated with peripheral neuropathy, which can be severe and is dose-related. Peripheral neuropathy has occurred more frequently in patients with advanced HIV disease, a history of neuropathy, or concurrent neurotoxic drug therapy, including didanosine (see Adverse Reactions). 

Ethambutol (Myambutel) [Antitubercular Agent] Uses Pulm TB other mycobacterial Infxns, MAC Action i RNA synth Dose Adults Feds >12 y. 15-25 mg/kg/d PO single dose X in renal impair, take w/ food, avoid antacids Caution [B, +] Contra Unconscious pts, optic neuritis Disp Tabs SE HA, hyperuricemia, acute gout, abd pain, T LFTs, optic neuritis, GI upset Interactions T Neurotox W/ neurotoxic drugs X effects W/ A1 salts EMS May affect glucose (hypoglycemia) may cause vision problems OD Sxs unknown activated charcoal may be effective symptomatic and supportive... 

The concomitant or previous use of potentially neurotoxic drugs (for example paclitaxel, vinca alkaloids, or hexam-ethylmelamine) can increase the risk of peripheral neuropathy due to platinum compounds (68,69). 

Encephalopathy, peripheral neuropathy, cerebellar syndromes, autonomic neuropathy, and cranial nerve toxicity represent the range of neurological complications associated with cancer chemotherapy. Dose, route of administration, age of the patient, hepatic and renal function, prior and/or concomitant use of other neurotoxic drugs, and the concurrent use of cranial or CNS radiotherapy can each influence the incidence rate and severity of neurologic symptoms associated with selected chemotherapy drugs. 

Tacrolimus is metabolised by CYP3A4, the induction and inhibition of which may affect the serum levels of tacrolimus. The manufacturers also issue cautions about the concurrent use of tacrolimus and anticoagulants, antidiabetics, nephrotoxic and neurotoxic drugs. 

The cells of the blood brain barrier (BBB) are closely linked by tight junctions, which practically prevent hydrophilic molecules to diffuse between the cells into the central nervous system (CNS). However, as hydrophobic substances might diffuse through the membrane, it is the role of P-gp to keep those out as well (Neuhaus Noe, 2009). The protecting function of P-gp at the BBB has been observed with mdrl knock-out mice and the dog breed collie, which naturally lacks functional P-gp because of a mutated mdrl gene. Collies are extremely susceptible to neurotoxic drugs and thus show dramatic adverse reactions after treatment with the antiparasitic drug ivermectin (Mealey et al., 2001). 

Makhaeva, G.R, Radchenko, E.V., Baskin, I.L, et al., 2012. Combined QSAR studies of inhibitor properties of O-phosphorylated oximes toward serine esterases involved in neurotoxicity, drug metabolism and Alzheimer s disease. SAR QSAR Environ. Res. 23, 627-647. 

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