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Generalized anxiety disorder is a persistent, reoccurring, and paralyzing condition connected to a remarkable occupational and social debility of life changes such as death, accident, and loss of a job. GAD primarily involves a continuous feeling of extreme anxiety and a sense of impending doom which may affect activities of daily living. People with generalized anxiety disorder have a hard time managing their anxiety. Symptoms include extreme worry, anxiety, difficulty concentrating, anger, palpitations, chest pains, amnesia, nervousness, and restlessness. This usually occurs for as long as months or even years. GAD starts around middle age but can occur during the childhood years and is more prevalent in females than in males (Reinhold et al., 2011). There are multiple treatment modalities for GAD. The success of these treatments depends on the pharmacodynamics and pharmacokinetics processes as well as genetics, ethnicity, age-related changes, gender, behavioral patterns, and changes in pathophysiology due to disease processes and medication compliance. Anxiolytics are used in the treatment of GAD to decrease the frequency, severity, and duration of symptoms of anxiety. Anxiolytic medications used in the treatment of generalized anxiety disorder include benzodiazepines, azapirones, antipsychotics, and antidepressants (SSRI). Pharmacokinetics include absorption, distribution, metabolism, and excretion. It is the onset of action and duration of the effect. Pharmacodynamics parameters which are the degree of sedation and adverse effects are critical in deciding which medication and dosage should be used. It is described as the dosage response of the medication on the patient and the resulting effect. Various disease processes such as previous drug exposure, hepatic, and kidney diseases influence the choice of drug and dosage (Hidalgo & Davidson, 2001).
Benzodiazepines such as clonazepam, lorazepam and alprazolam are used to manage GAD. Benzodiazepines are psychoactive drugs that work to enhance GABA by reducing anxiety, seizures as well as insomnia. It calms the brain by decreasing the excitability of neurons. Due to its addictive properties, it is not recommended for long-term use, however, it is recommended to be safe and effective for short-term use. Pharmacokinetics and pharmacodynamics vary among the various drugs. Because of its high lipid solubility, it can easily cross the blood-brain barrier to get to the central nervous system giving an immediate response (Rosenthal, 2021)
Clonazepam
Clonazepam is an anti-anxiety medication that may be used to treat panic attacks or seizures. The process by which clonazepam applies its anti-panic and antiseizure is not yet known, however, it is known to be connected to its capabilities to heighten the gamma-aminobutyric acid activity which is a vital inhibitory neurotransmitter in the central nervous system.
This medication is quickly absorbed immediately after oral administration. The bioavailability is close to ninety percent and eighty-five percent bound to plasma protein. Maximum plasma concentration is gained in about one to four hours after administration. Clonazepam is metabolized with less than two percent of unchanged medication being eliminated via the urine. Biotransformation only happens by a decrease of seven nitro groups to a four amino derivative. The elimination half-life is usually thirty to forty hours when taken orally. Its pharmacokinetics are dose-dependent all through the dosing span (Basit et al, 2022).
Lorazepam
It is a long-acting benzodiazepine with a half-life of twenty-four hours and a duration of eight to twelve hours. It starts to work within thirty minutes of ingestion. The inhibitory action in the amygdala is beneficial in anxiety disorders and its activity in the cerebral cortex is beneficial in controlling seizure disorders. Lorazepam is metabolized by hepatic glucuronidation into inactive metabolites and excreted through biliary action (Ghiasi et al, 2022).
Alprazolam
This drug is mostly metabolized by renal microsomal oxidation. It has a peak plasma concentration of twelve to twenty-two micrograms/L happening 0.7 to 1.8 hours post-dose, a volume of distribution of 0.8 to 1.3L/kg, and an excretion half-life of nine to sixteen hours. Absolute bioavailability orally averages eighty to one hundred percent. Pharmacokinetics are dose-dependent and do not change with multiple dose-treatment. It is not significantly influenced by gender, but clearance is decreased in the elderly even for those who are considered healthy and individuals with cirrhosis (Ibanez et l, 2014).
Buspirone
Buspirone is also an anxiolytic that is completely different from benzodiazepine as it is not a CNS depressant. It binds with a high affinity to serotonin and a lower affinity to dopamine. It has no potential for abuse, therefore it is recommended for long-term therapy. Its effects build up slowly and take many weeks before it reaches its peak. Due to its delayed response, it is not recommended for as needed use for individuals who need instant relief. It does not show inter-dependence with benzodiazepines
Selective Serotonin Reuptake Inhibitor (SSRI)
SSRIs are a class of medications for the treatment of GAD. They are first-line drugs for depression. Examples include sertraline, citalopram, and escitalopram. Anti-depressants can reduce cognitive symptoms related to anxiety. It increases the neurotransmitters serotonin in the brain. SSRIs take about two to four weeks to see their effectiveness. These drugs also do not have the potential for abuse, but sudden discontinuation can bring about withdrawal symptoms (Sangkuhl et al, 2009).
References
Basit, H., & Kahwaji, C.I. (2021). Clonazepam. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK556010/
Ghiasi. N., Bhansali, R.K. &, Marwaha, R. Lorazepam. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK532890/
Hidalgo, R.B., & Davidson, J.R. (2001). Generalized Anxiety Disorder. An Important Clinical Concern. Med Clin North Am. Doi: 10.1016/s0025-7125(05)70336-9.
Ibáñez, J., González de la Aleja, J., Gallego, J.A., Romero, J.P., Saíz-Díaz, R.A., Benito-León, J., & Rocon, E. (2014). Effects of Alprazolam on Cortical Activity and Tremors in Patients with Essential Tremor. Doi: 10.1371/journal.pone.0093159.
Millan, M.J. (2022). Agomelatine for the Treatment of Generalized Anxiety Disorder: Focus on Its Distinctive Mechanism of Action. Sage Journals. Http://doi.org/10.1177/20451253221105128.
Reinhold, J.A., Mandos, L.A., Rickels, K. & Lohoff, F.W. Pharmacological Treatment of Generalized Anxiety Disorder. Doi: 10.1517/14656566.2011.618496.
Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s Pharmacotherapeutics for Advanced Practice Nurses and Physician Assistants (2nd ed.) St. Louis, MO: Elsevier.
Sangkuhl, k., Klein, T.E, & Altman, R.B. (2009). Selective Serotonin Reuptake Inhibitors Pathway. Pharmacogenet Genomics. Doi: 10.1097/FPC.0b013e32833132cb.
