Modafinil for Awareness in Critical Units
Modafinil is a wakefulness-enhancing agent that has been shown to improve cognition in critically ill patients. However, the available data on its use in the ICU are limited.
A retrospective cohort study examined the effects of modafinil on awareness in critical units. The study included 60 patients admitted to the ICU without any ventilator support.
Modafinil is a benzodiazepine
Modafinil is a central nervous system stimulant that acts as a wakefulness agent, improving alertness and cognitive function. It has been shown to be effective in a number of neuropsychiatric conditions, including various fatigue syndromes and treatment-resistant depression. It also has a much-improved side-effect profile than amphetamine, with a lower risk of heart disease and a lower liability for abuse. This has led to increased interest in the potential for modafinil to remediate cognitive dysfunction in neuropsychiatric illnesses, particularly those requiring attentional control.
Modafinil has multiple neurochemical actions that are related to its primary wake-promoting effects. These include inhibition of dopamine transporter and reuptake, elevation of extracellular catecholamines (DAT and NET), activation of orexinergic systems, and decrease in GABA. However, unlike conventional neuro stimulants, modafinil does not increase norepinephrine levels in the nucleus accumbens or induce addiction or euphoria. It is also devoid of dopaminergic effects, which may be important in the treatment of post-stroke fatigue and encephalopathy.
It is well absorbed from the gastrointestinal tract and is rapidly metabolized by the liver, mostly by CYP3A4. This drug has a low likelihood of developing tolerance and has few side effects. It is also safe for long-term use in patients with narcolepsy and other chronic disorders of sleepiness.
The use of modafinil in critically ill patients is associated with reduced duration of delirium and length of stay in the intensive care unit. This is due to its ability to improve wakefulness and cognition, reduce sedation, and promote early mobilization. This can result in decreased ICU length of stay and greater patient and family satisfaction. However, the efficacy of this medication in improving awareness in ICUs remains controversial.
Modafinil is a benzodiazepine receptor agonist
Modafinil is a wake-promoting agent that has been found to be efficacious in the treatment of narcolepsy, shift work sleep disorder, and obstructive sleep apnea. It has also shown initial promise for the treatment of a number of neuropsychiatric disorders, including attention-deficit/hyperactivity disorder and schizophrenia. This has been attributed to the combination of its direct and indirect dopamine modulator actions, as well as its partial alpha 1-adrenergic agonist properties.
Modafinil has been found to increase wakefulness in narcoleptic patients by increasing the rate of depletion of catechol-O-methyltransferase (COMT), a key enzyme in the catabolism of dopamine. The drug is a racemate and its two enantiomers are equipotent in behavioral effects but have different pharmacokinetic profiles in mice. The R-enantiomer of the drug is more potent than modafinil and is absorbed more rapidly reaching higher plasma concentrations within 6-14 h post-administration.
A number of studies have characterized the neurochemical and cognitive actions of modafinil in animal models, healthy human subjects, and clinical populations. The drug has been found to be a non-selective dopamine inhibitor, inhibiting the reuptake of dopamine in rat frontal cortex synaptosomes, and enhancing extracellular levels of dopamine in the nucleus accumbens in rats. Modalert 200 mg is also a weak antagonist of the NMDA receptor and enhances orexin activation in the hypothalamus.
Unlike other stimulants, modafinil does not have important pleasurable or euphoric actions and is unlikely to be misused as a recreational drug. Despite its relatively low abuse potential, the drug is known to induce psychiatric side effects in some patients, such as anxiety, agitation, and mania. It is thought that these side effects occur in a minority of patients and can be minimized by administering the medication at the recommended doses.
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