A variety of factors that affect drug metabolism may affect the individual’s sensitivity to neurotoxicity, such as: individual’s nutritional status, self-protective response to drugs, local blood flow and tissue uptake, as well as the influence of the blood-brain barrier, drug absorption The rate of drug transport to the target tissue, activation, elimination and metabolism, and other related factors include: genetics, patient’s renal function and the passage of the central nervous system barrier.
Different production mechanisms
At present, common antibiotics are: aminoglycosides, β-lactams, quinolones, macrolides, polymyxins, etc. These drugs have been reported in the literature to have neurotoxicity and are produced through different mechanisms.
Aminoglycosides (gentamicin, streptomycin, kanamycin, amikacin, etc.)
The production of aminoglycoside neurotoxicity usually includes the following mechanisms: (1) activation of aspartate (NMDA) receptors; (2) lysosome abnormalities; (3) axon loss; (4) infection caused by Inflammation; (5) Inhibition of acetylcholine release; (6) The binding of the drug to the receptor after protruding. Among them, NMDA receptors play an important physiological role in the development of the nervous system, such as regulating the survival of neurons, regulating the development of neuronal dendrites and axon structures, and participating in the formation of synaptic plasticity. Formation also plays a key role. Lysosomes play a role in digestion in cells, and while engulfing foreign macromolecules, they also affect the metabolism of macromolecules in the cell.
β-lactams (penicillin G, amoxicillin, cefazolin, ceftriaxone, imipenem, meropenem, etc.)
The neurotoxicity mechanism of this type of antibiotics includes: the release of γ-aminobutyric acid (GABA) and the inhibition of receptors; the increase of glutamate release; the production of endotoxin; the release of cytokines, etc. Gamma-aminobutyric acid is a naturally occurring non-protein amino acid and an important inhibitory neurotransmitter in the central nervous system of mammals. about 50% of central nervous system synapses use GABA as a transmitter. The hippocampus, thalamus, basal ganglia and cerebellum play important roles, and have a regulatory effect on various functions of the body.
Quinolones (Norfloxacin, Ciprofloxacin, Levofloxacin, etc.)
The mechanism of neurotoxicity: the activation of aspartate receptors; the release of γ-aminobutyric acid and the inhibition of receptors.
The above-mentioned antibiotic-related neurotoxicity that occurs in the clinic includes: peripheral nerve paresthesia, dyskinesia, neuromuscular junction blockage, delayed epilepsy, nonconvulsive status epilepticus (NCSE), myoclonus, fluttering tremor, headache , Ataxia, dysarthria, chorea, etc. In a study, 42 cases of neurotoxicity caused by cefepime and 12 ceftazidime were included in the systematic review. After the clinical characteristics and diagnostic time passed the criteria, the neurotoxic reactions that occurred were: disorientation (96%), Myoclonus (33%), epilepsy (13%). These neurological dysfunctions usually occur in uremia patients and the elderly, and they are more likely to have delayed diagnosis. The time interval from symptom onset to diagnosis is 5 days and 3 days for cefepime and ceftazidime, respectively (P=0.005). The reason for the delayed diagnosis of neurotoxicity may be the lack of awareness of the side effects of neurotoxicity. It reminds clinicians that only by being vigilant can the diagnosis efficiency be improved.
Pay attention to risk factors
After theoretical analysis of the relative neurotoxicity of antibiotics, the diagnosis and treatment effects in clinical work should be further improved to better improve the efficacy of drugs and reduce the impact of drug side effects. First of all, clinicians should accurately understand the potential risk factors related to neurotoxicity, including age, renal impairment, central nervous system history, blood-brain barrier integrity, individual body surface area, neurotoxicity, in addition to those mentioned above. Or the combination of nephrotoxic drugs, the possibility of epilepsy, etc. In addition to the psychological changes caused by the use of antibiotics, the nephrotoxicity after the drug is also related to its neurotoxicity. Therefore, early diagnosis is very important to reduce the neurotoxicity of the drug, and more importantly, to avoid the application of neurotoxicity in patients with the above-mentioned high-risk factors. drug.
It is easier to make a correct diagnosis when the application of antibiotics after infection causes mental changes or for patients with metabolic disorders (such as renal failure). When symptoms appear, ECG can sometimes also play a role. For example, NCSE caused by drugs can be diagnosed by ECG. Because NCSE is sometimes fatal, emergency treatment should be considered after the patient has symptoms of adverse reactions due to the use of neurotoxic antibiotics. ECG or ECG monitoring; once the diagnosis is /confirm/ied, the related inducing drugs should be discontinued and replaced with non-neurotoxic drugs. When epilepsy or NCSE occurs, antiepileptic drugs should be considered. In cases of renal impairment, once it is confirmed that neurotoxicity is caused by related antibiotics, hemodialysis should be considered to remove drugs, such as high flux continuous venous hemodialysis (CVVHF), and appropriate drug dosages should also be considered before then. .
For clinical practice, it is impractical to abandon the use of neurotoxicity-related antibiotics, but the clinical manifestations of adverse drug reactions can better serve clinical practice through learning, and the understanding of relevant high-risk factors in the population can enable patients Benefit more from visits. In recent clinical observations, there have been more studies on the relationship between drug exposure and adverse reactions. As a medical worker, you should deal with potential adverse reactions with a high degree of occupational vigilance, so that patients can get better treatment.