DISCUSSION: COMPARING AND CONTRASTING PHARMACOLOGIC OPTIONS FOR THE TREATMENT OF GENERALIZED ANXIETY DISORDER
DISCUSSION: COMPARING AND CONTRASTING PHARMACOLOGIC OPTIONS FOR THE TREATMENT OF GENERALIZED ANXIETY DISORDER
Post a discussion of pharmacokinetics and pharmacodynamics related to anxiolytic medications used to treat General Anxiety Disorder (GAD). In your discussion, utilizing the discussion highlights, compare and contrast different treatment options that can be used.
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Options for the Treatment of Generalized Anxiety Disorder
Generalized anxiety disorder (GAD) is a common diagnosis in psychiatric practice. Patients present the hospital with symptoms such as excessive fear and worry that affect their daily functioning. Psychiatric mental health practitioners adopt both pharmacological and non-pharmacological interventions to improve patient outcomes in the affected populations. Practitioners should understand the pharmacokinetics and pharmacodynamics of the different anxiolytics used in GAD to ensure optimum care outcomes. Therefore, this paper explores the pharmacokinetics and pharmacodynamics of anxiolytics used in GAD.
Several types of anxiolytics are recommended for use in GAD. Benzodiazepines are the first category of anxiolytics largely used due to their high safety and efficacy profiles. Benzodiazepines have a high lipophilicity level, which enhance their rapid movement across membranes to produce its effects. Its resorption rate depends largely on the route of administration and form. The routes of administration include oral, intramuscular, and rectal. Their volume of distribution depends on water/fat ratio in a patient. Metabolism of benzodiazepines occurs in the gastrointestinal lumen while elimination is via the urine in hydroxylated conjugated metabolites(Skidmore-Roth, 2022). Its half-life depends on volume of distribution, renal and metabolic clearance.
Buspirone is another anxiolytic that is used in the treatment of GAD. Buspirone works by binding to 5-HT1A receptors and acts s an antagonist of dopamine receptors. It has almost complete absorption orally with a significant first-pass effect. The administration of a 10 mg dose is associated with plasma peak being reached in less than an hour. It has 95% protein binding. Its elimination half-life ranges between 2 and 4 hours. The metabolism of buspirone occurs in the liver with its elimination being with urine. Hydroxyzine is another anxiolytic that may be considered for GAD. The drug is a piperazine derivative that blocks histamine receptors. It is administered orally with rapid gastrointestinal absorption. It is fully metabolized in the liver after its rapid absorption. Hydroxyzine is considered an alternative treatment to bromazepam, which is a benzodiazepine. Patients with psychosomatic medications are often prescribed etifoxine. Etifoxine is an anxiolytic that belongs to benzoxazines class. It works on 5-HT2A and GABA system receptors. Etifoxine is readily absorbed orally with hepatic metabolism and renal elimination(Learning, 2022). It crosses the placenta, hence, not recommended in pregnant women.
Antidepressants are also used as anxiolytics in the treatment of GAD. Antidepressants such as clomipramine have demonstrated some effectiveness in GAD and other mental disorders besides depression. These drugs work by inhibiting the reuptake of serotonin and to some extent norepinephrine. The resulting effect is symptom improvement. Clomipramine is administered orally, absorbed in the gastrointestinal tract, and eliminated through the renal system (Tucker, 2022). Hepatic and renal impairments translate into careful dosing for safety and efficiency.
Anticonvulsants also have enhanced benefits when used in treating GAD. Placebo-controlled trials have consistently shown that anticonvulsants that include pregabalin are effective against GAD and social phobia. Some studies have also shown gabapentin to be effective against social phobia while valproic acid in panic disorder. However, the mainly considered anticonvulsants for GAD are gabapentin and pregabalin. Pregabalin is a GABA analog that acts on alpha 2 gamma protein. It is well-tolerated with a rapid onset of action. Its efficacy in GAD is comparable to that of benzodiazepines. It has dose dependent side effects such as dizziness, somnolence, and ataxia. Pregabalin is administered orally, absorbed rapidly in the gastrointestinal tract, with bioavailability of at least 90% irrespective of its dosage (Skidmore-Roth, 2022). It has high penetration rate to the central nervous system, not metabolized in the liver andis excreted vi the renal system in its unchanged form.
Gapabentin is also a GABA analog with antiepileptic and analgesic properties. It is effective against anxiety disorders and patients with somatic complains. It is administered orally and absorbed in the proximal small intestines via the L-amino acid transport system. It has bioavailability of about 60% with a non-linear relationship between its dosage and plasma levels. Gabapentin reaches its peak plasma level within 2-3 hours of administration. Food does not affect its absorption(Learning, 2022). Its elimination half-life is 5-7 hours and is not metabolized in the body. It is eliminated in its unchanged form via the renal system.
The last category of anxiolytics that are least utilized in GAD are antihypertensives. Beta adrenergic blockers are the specific drugs that are considered for use in GAD. The drugs work by blocking the activity of the endogenous catecholamines adrenaline and noradrenaline through their action on beta-adrenergic receptors. The beta adrenergic receptors are activated in fight and flight responses via the sympathetic nervous system. Propranolol and atenolol are the main beta-adrenergic blockers used in GAD. Propranolol is administered orally, completely absorbed in the small intestines, and have a half-life of 5-10 minutes. It is metabolized in the liver, and eliminated in the renal system. Atenolol is also administered orally, with 50% being absorbed in the gastrointestinal system and another 50% excreted unchanged in feces. It can also be administered intravenously to achieve peak plasma levels within 5 minutes(Tucker, 2022). Most of the atenolol is excreted through the renal system.
In summary, several classes of anxiolytics are available for use in GAD. Benzodiazepines are largely considered the first-line because of their safety and efficacy. The different anxiolytics have varying pharmacokinetics and pharmacodynamics that influence their selection. Therefore, practitioners should prioritize safety when prescribing patients these agents for GAD.
References
Learning, J. & B. (2022). 2023 Nurse’s Drug Handbook. Jones & Bartlett Learning.
Skidmore-Roth, L. (2022). Mosby’s 2023 Nursing Drug Reference—E-Book. Elsevier Health Sciences.
Tucker, R. G. (2022). 2023 Lippincott Pocket Drug Guide for Nurses. Lippincott Williams & Wilkins.