Read a selection of your colleagues’ responses and respond to at least two of your colleagues on two different days by suggesting additional factors that might have interfered with the pharmacokinetic and pharmacodynamic processes of the patients diagnosed with GAD. In addition, suggest different treatment options you would suggest to treat a patient with the topic of discussion.

RESPONSE 1

Generalized Anxiety Disorder (GAD) is a chronic disorder characterized by uncontrollable and continuous worrying, with the main characteristic being an abnormally high degree of anxiety that lasts for at least six months. A significant majority of individuals with GAD also experience depression (Rosenthal & Burchum, 2021). 

During this past year, a patient came under my treatment who was in mental distress. She was a 55-year-old white female brought in by the police on an involuntary hold for being a danger to herself and gravely disabled. The patient was reported by family to have locked herself in the bathroom, crying incessantly, stating she wanted to hurt herself and not wanting to leave the house. Upon assessment the patient stated that she was ‘worrying all the time, and couldn’t sleep, eat or enjoy life anymore’.  The patient also admitted to drinking alcohol to cope with here severe anxiety. The psychiatrist diagnosed the patient with GAD, major depressive disorder, and alcohol abuse.

When it comes to treating anxiety disorders, combining psychotherapy and anxiolytic medication is generally more effective than using either method alone. There are three main categories of anxiolytic medications that are often used to treat anxiety: Serotonin Reuptake Inhibitors (SRIs), Benzodiazepines, and Buspirone (Non-Benzodiazepine Anxiolytic). SRI’s include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (Rosenthal & Burchum, 2021). 

To better understand what medication would be best for the client, it is beneficial to understand the pharmacokinetics and pharmacodynamics of anxiolytic medications commonly used for treating GAD. Benzodiazepines are well-absorbed after oral administration, and the onset of action is relatively fast. They have a rapid distribution into various tissues, including the central nervous system, due to their lipophilic nature. Most benzodiazepines undergo hepatic metabolism, primarily through the cytochrome P450 system. Elimination half-lives vary among benzodiazepines, influencing their duration of action and dosing frequency. The mechanism of action of benzodiazepines enhances the inhibitory effects of gamma-aminobutyric acid (GABA) by binding to the GABA-A receptor, resulting in increased chloride conductance and neuronal hyperpolarization. They produce anxiolytic, sedative, hypnotic, and muscle relaxant effects. However, they are associated with a risk of tolerance, dependence, and withdrawal.

Buspirone is classified as a non-benzodiazepine anxiolytic. Buspirone is well-absorbed after oral administration, with a slower onset of action compared to benzodiazepines. It undergoes first-pass metabolism, and its active metabolite has a higher affinity for serotonin receptors. Buspirone is metabolized in the liver, mainly by the cytochrome P450 system. The elimination half-life is relatively short. Buspirone’s exact mechanism of action is not fully understood, but it is believed to involve serotonin (5-HT1A) receptor partial agonism. Buspirone produces an anxiolytic effect without sedative or muscle relaxant properties. It may take several weeks to achieve the full therapeutic effect.

SRIs are well-absorbed after oral administration, with varying rates among different medications. They are distributed throughout the body, including the central nervous system. Metabolism occurs in the liver, primarily through the cytochrome P450 system. Elimination half-lives vary, and steady-state concentrations may take several weeks to achieve. The Mechanism of Action for SRIs is they inhibit the reuptake of serotonin, leading to increased synaptic serotonin levels resulting in anxiolytic and antidepressant effects. They are considered a first-line treatment for GAD due to their efficacy and lower risk of dependence.

In individuals with a history of alcohol use, such as the client mentioned above, there may be concerns about the potential for substance misuse with benzodiazepines. Patients who were older, white, and of lower socioeconomic position were more likely to participate in harmful alcohol use while taking benzodiazepines and had higher doses and prescription durations than others (Hirschtritt et al., 2019). Additional factors affecting pharmacokinetics and pharmacodynamics include liver function, drug to drug interactions, and drug tolerance. Chronic alcohol consumption affects liver function by altering the processing of medications via inhibition of certain enzymes needed for metabolism and can interact with medications, either enhancing or inhibiting their effects. Lastly, chronic alcohol usage can cause tolerance and dependence impacting the therapeutic effects of drugs, necessitating dosage modifications.  Given this, the benefits of SRIs as a safer long-term option to benzodiazepines would outweigh the dependency risks associated with benzodiazepines. Additionally, behavioral therapies and counseling will also be important components of the overall treatment plan for GAD, as Cognitive Behavioral Therapy (CBT) has produced significant improvements to quality of life for GAD patients (Bandelow, Michaelis, & Wedekind, 2017).

References

Bandelow, B., Michaelis, S., & Wedekind, D. (2017). Treatment of anxiety disorders. Dialogues in clinical neuroscience, 19(2), 93–107. https://doi.org/10.31887/DCNS.2017.19.2/bbandelow

Hirschtritt, M. E., Palzes, V. A., Kline-Simon, A. H., Kroenke, K., Campbell, C. I., & Sterling, S. A. (2019). Benzodiazepine and unhealthy alcohol use among adult outpatients. The American journal of managed care, 25(12), e358–e365.

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.

RESPONSE 2

Generalized Anxiety Disorder (GAD) is a complex condition that can be approached with various pharmacological treatments, each having unique characteristics, efficacy, and side effects. The primary goal of these treatments is to manage symptoms effectively while minimizing adverse effects (Showraki et al., 2020).

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) are generally the first-line options for treating GAD. These medications are chosen for their safety and tolerability. However, it is important to start with small doses to minimize potential side effects like jitteriness. These medications work by impacting neurotransmitters in the brain, specifically targeting serotonin, norepinephrine, and gamma-aminobutyric acid (GABA), which are believed to play significant roles in GAD. The response to these treatments is usually assessed over a period of 4-6 weeks, and if there’s at least a partial response, the dosage may be adjusted for optimal effect. It’s estimated that 61-67% of patients might not achieve remission with the initial SSRI treatment (Leshem et al., 2021).

Other medications, like duloxetine, venlafaxine, benzodiazepines, hydroxyzine, buspirone, pregabalin, or second-generation antipsychotics (SGAs), may also be considered depending on the patient’s comorbidities and clinical features. For instance, in cases where SSRIs or SNRIs are not effective, or where specific symptoms or comorbidities are present, these alternatives or augmentation strategies might be more suitable (Sapra et al., 2020).

Pharmacogenetics, the study of how genetics affect a person’s response to drugs, is also an important consideration in the treatment of GAD. Variations in pharmacokinetic genes can influence the efficacy and safety of pharmacological treatments. This means that a patient’s genetic makeup can impact how well they respond to a certain medication, and what side effects they might experience (Craske & Bystritsky, 2022).

In addition to medication, lifestyle changes and psychotherapy are important aspects of treating GAD. Exercise, healthy eating, good sleep hygiene, and avoiding substances like alcohol and recreational drugs can all contribute to better management of anxiety symptoms.

To sum up, the treatment of GAD involves a multi-faceted approach that includes careful selection of pharmacological agents, consideration of patient-specific factors such as comorbidities and genetics, and incorporation of lifestyle modifications and psychotherapy

References
 

Craske, M., & Bystritsky, A. (2022). Generalized anxiety disorder in adults: Management. UpToDate. Accessed September, 8. https://medilib.ir/uptodate/show/101879

Leshem, R., Bar-Oz, B., Diav-Citrin, O., Gbaly, S., Soliman, J., Renoux, C., & Matok, I. (2021). Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) during pregnancy and the risk for autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) in the offspring: A true effect or a bias? A systematic review & meta-analysis. Current Neuropharmacology, 19(6), 896–906.

Sapra, A., Bhandari, P., Sharma, S., Chanpura, T., & Lopp, L. (2020). Using generalized anxiety disorder-2 (GAD-2) and GAD-7 in a primary care setting. Cureus, 12(5). https://www.cureus.com/articles/31476-using-generalized-anxiety-disorder-2-gad-2-and-gad-7-in-a-primary-care-setting.pdf

Showraki, M., Showraki, T., & Brown, K. (2020). Generalized Anxiety Disorder: Revisited. Psychiatric Quarterly, 91(3), 905–914. https://doi.org/10.1007/s11126-020-09747-0