CNS adverse effects

Peak blood levels are reached in 2 to 3 hours. The therapeutic range is approximately 0.5 to 2 mcg/mL. An increase in the frequency of CNS adverse effects has been observed when plasma levels exceed 2 mcg/mL. It is 50% to 60% bound to plasma protein with a volume of distribution of 5 to 7 L/kg. 

Geriatric Considerations - Summary Systemic absorption of ophthalmic drugs may occur and cause adverse effects in older adults. Since betaxolol is beta-selective, cardiovascular, respiratory and CNS adverse effects occur less frequently than with beta-nonselective topical opthalmics. These effects may still occur therefore close monitoring for systemic side effects is warranted. Betaxolol maybe less effective than the nonselective topical beta-blockers with an average lOP reduction of 18%-26%. Tachyphylaxis may occur after long-term therapy. 

Review and reinforce prevalence of CNS adverse effects early in treatment (reason for gradual fifrafion regimens) with tolerance developing with continued adherence... 

Patients should exercise caution with initiation and dosage titration when driving, operating hazardous machinery, or other activities requiring mental concentration patients should be advised to take the medication with food, to delay peak effecfs to avoid many CNS adverse effects... 

SR) anti-inflammatory drugs, this drug produces the most CNS adverse effects. ... 

Pentazocine (Talwin) Narcotic analgesic that causes more CNS adverse effects, including confusion and hallucinations, more commonly than other narcotic drugs. Additionally, it is a mixed agonist and antagonist. High... 

Clonidine (Catapres) Potential for orthostatic hypotension and CNS adverse effects. Low... 

CNS adverse effects can be the result of toxic serum levels, which may result from accidental or intentional patient ingestion of lithium doses exceeding clinical needs (334). Patients with organic brain impairment are also at increased risk of neurotoxicity. Toxicity may also be caused by reduced clearance of lithium from the body. 

Various CNS adverse effects have been reported with CBZ and include sedation, dizziness, ataxia/clumsiness, blurred vision/diplopia, and impaired task performance. Although uncommon, fatal CBZ toxicity does occur. CBZ overdose is characterized by neurological symptoms such as diplopia, dysarthria, ataxia, vertigo, nystagmus, and coma. Infrequently, cyclic coma with biphasic fluctuations of consciousness, seizures, respiratory depression, cardiac conduction defects, and the need for artificial ventilation may occur. Plasma levels are only moderately correlated to severity, but as noted earlier, more than 15 pg/ml in children or 20 pg/ml in adults should be considered serious. Charcoal hemoperfusion or gastric lavage with activated charcoal has been used in such cases, whereas benefit from plasmapheresis is controversial (77, 114, 368). 

The use of antihistamines can be traced back to the beginning of 1940s. The applications of the first-generation antihistamines were limited since they cause significant adverse effects such as sedation, memory impairment and psychomotor dysfunction. The second-generation antihistamines have significantly fewer central nervous system (CNS) adverse effects because they penetrate the blood-brain barrier much less extensively. 

Dose-related factors A dose-response relation is most evident with the CNS adverse effects of sedation, cognitive impairment, hallucinations, myoclonus. 

Convulsions have occurred after inadvertent intravenous injection of ropivacaine during regional anesthesia (4,5). CNS adverse effects from ropivacaine occur before or without severe cardiovascular toxicity, as there have been several similar reports of CNS toxicity, but not yet one with severe or fatal cardiotoxicity. This reinforces the claim of increased safety from cardiovascular toxicity with this enantiomeric local anesthetic compared with racemic bupivacaine. 

B Advantages. Gabapentin has multiple mechanisms of action and is mechanistically different from first-generation AEDs. It is not metabolized and is excreted unchanged by the kidney. Gabapentin has the additional advantages of a broad therapeutic index with minimal CNS adverse effects and no drug interactions. Doses can be escalated rapidly. 

I Disadvantages. Dose adjustments are needed for patients with decreased renal functioning, and slower dose escalation may be needed to avoid CNS adverse effects. Behavioral problems may hmit therapy in some patients. Currently, there is no parenteral formulation, but one is in development. 

Possible CNS adverse effects of TCAs include dizziness, aggressiveness, excitement, nightmares, insomnia, forgetfulness, and irritability. Signs of CNS toxicity are confusion, impaired concentration, hallucinations, and delusions. 

In the elderly, secondary to a decreased capacity for oxidation and alterations in the volume of distribution, drug accumulation can result. Patients with hepatic disease also are at risk for drug accumulation and subsequent complications. Therefore, intermediate- or short-acting benzodiazepines without active metabolites are preferred for chronic use in the elderly and those with liver disorders. Elderly patients are also sensitive to the CNS adverse effects of benzodiazepines (regardless of half-life) and their use is associated with a high frequency of falls and hip fractures. 

C. Toxicity Cardiovascular adverse effects, which are extensions of the beta blockade induced by these agents, include bradycardia, atrioventricular blockade, and congestive heart failure. Patients with airway disease may suffer severe asthma attacks. Premonitory symptoms of hypoglycemia from insulin overdosage, eg, tachycardia, tremor, and anxiety, may be masked, and mobilization of glucose from the liver may be impaired. CNS adverse effects include sedation, fatigue, and sleep alterations. Atenolol, nadolol, and several other less lipid-soluble beta-blockers are claimed to have less marked CNS action because they do not enter the CNS as readily as other members of this group. 

B) Guanethidine causes fewer CNS adverse effects (such as sedation) than methyldopa... 

Reserpine has been used in the management of mild to moderate hypertension, but because of very significant CNS adverse effects and its cumulative action in the adrenergic neurons, reserpine is rarely used. Reserpine and related Rauwolfia alkaloids have been used in the symptomatic treatment of agitated psychotic states, such as schizophrenic disorders, although other antipsychotic agents generally have replaced reserpine and the alkaloids. 

Pethidine is metabolised via several eytoehrome P450 isoenzymes. If the metabolism of pethidine is increased it ean lead to increased production of the toxic metabolite, norpethidine, and increased CNS adverse effects. 

A study in 16 healthy subjects showed that diflunisal 500 mg twice daily raised the steady-state plasma levels and the AUC of indometacin 50 mg twice daily about twofold. Combined use was associated with more gastrointestinal and CNS adverse effects, but there was no clear effect on blood loss in the faeces. Another study produced similar findings. ... 

The CNS adverse effects and the weight-reducing effects of phenmetrazine are reduced by amobarbital. 

Both lidocaine and cocaine exhibit class I antiarrhythmic effects and are proconvulsants. Lidocaine may potentiate the cardiac and CNS adverse effects of cocaine. Therefore the use of lidocaine for cocaine-associated myocardial infarction is controversial. The lack of adverse effects in this study may have been due to delays of more than 5 hours between last exposure to cocaine and lidocaine therapy. These authors and others consider that the cautious use of lidocaine does not appear to be contraindicated in patients with cocaine-associated myocardial infarction who require antiarrhythmic therapy. However, extra care should be taken in patients who receive lidocaine shortly after cocaine. ... 

Propafenone has minimal effects on the pharmacokinetics of intravenous lidocaine, but the severity and duration of the CNS adverse effects of lidocaine are increased. 

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