Respond to two of your colleagues 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.
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Peer 1
Rose Marie Victor
The term “generalized” refers to those who suffer from generalized anxiety disorder (GAD) and are afraid of many different things rather than just one or two. Besides the obvious psychological effects, this can also have real-world repercussions, including feeling drained, tense, and anxious. Constant worrying can wear a person down, but effective remedies are available. Therefore, symptoms like excessive worrying about various things are characteristic of GAD, making it the most prevalent kind of anxiety disorder. The pharmacokinetics and pharmacodynamics of commonly used antianxiety drugs are discussed.
Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs)
The benefit-to-risk ratio of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin-norepinephrine reuptake inhibitors (SNRIs) makes them a top choice for the first treatment. Patients taking these antidepressants should be advised that it can take anywhere from 2 weeks to 6 weeks for the medication to start working to reduce anxiety (Nanjappa et al., 2022). The first two weeks are when adverse effects could be at their worst. Patients’ compliance with treatment may suffer if they experience a spike in anxiety or agitation at the outset. If you have any of these unwanted effects, it may be helpful to start with a lower dose of the antidepressant. However, clinical evidence suggests tolerance varies by patient and that a given patient may experience fewer side effects by moving from an SSRI to an SNRI. Several SSRIs and SNRIs are inhibitors of the cytochrome P450 enzyme, which means they could potentially interact with other psychopharmacological medications and medical treatments (Nanjappa et al., 2022). Stopping SSRI treatment abruptly can cause withdrawal symptoms. While unpleasant, these symptoms pale in comparison to those of benzodiazepine withdrawal. These adverse effects may occur more frequently with paroxetine than with sertraline or fluoxetine.
Tricyclic Antidepressants (TCAs)
Both imipramine and clomipramine, which belong to the first generation of tricyclic antidepressants (TCAs), help treat anxiety disorders. To a greater extent than with SSRIs and SNRIs, TCAs tend to cause unwanted side effects. Thus, these drugs should be tested first before TCAs are used. The suggested dosage for treating depression is reached by progressively increasing the starting dose. Patients at risk of suicide should be treated with TCAs with caution due to the potential for deadly toxicity following an overdose. All TCAs are readily absorbed after oral administration and bind to therapeutic plasma concentrations of albumin with an affinity of 90–95% (Asensi-Cantó et al., 2022). Because of their affinity for binding to extravascular tissues, they have incredibly high distribution volumes (10-50 l kg1). There are several ways tertiary TCAs are rendered inactive by CYP450 enzymes, including demethylation to secondary amine metabolites, hydroxylation, glucuronidation, and urinary excretion. As a rule of thumb, plasma values between 50 and 300 ng ml1 (molecular weights between 263 and 314) are considered therapeutically effective.
Benzodiazepines
The molecular structure of benzodiazepines is highly individualized, and they all share the same primary pharmacological effects. Their pharmacokinetics and metabolism define them significantly; thus, they should be utilized with care. These acids are rather weak, but their high lipophilicity and varying constant dissociation allow them to rapidly cross membranes (including the blood-brain and placental barriers and the milk-to-baby barrier). All benzodiazepines are insoluble in water except for chlordiazepoxide, dipotassium clorazepate, and midazolam; hence, organic solutions are required for parenterally administrable forms (Gale et al., 2019). Sedatives like these are often reserved for emergency situations where immediate calm is required. These medications are not recommended for anyone with a history of, or current struggles with, alcoholism or drug addiction. In rare cases (such as severe heart disease, contraindications to traditional drugs, suicidality, and other illnesses), benzodiazepines may be used for a short period (Gale et al., 2019). On the other hand, patients with a benzodiazepine or substance misuse history should not be treated. To hasten the onset of the antidepressant’s effects, benzodiazepines can be taken in tandem with SSRIs/SNRIs in the weeks prior to treatment.
Buspirone
In addition to selective serotonin reuptake inhibitors (SSRIs) and/or norepinephrine reuptake inhibitors (SNRIs), the FDA has approved azapirone buspirone to treat anxiety. It is the only FDA-approved azapirone in the country. A Cochrane review indicated that buspirone was more effective than a placebo for generalized anxiety disorder (GAD). However, its effect size was smaller than benzodiazepines and antidepressants (Howe et al., 2022). Additionally, those who had previously used benzodiazepines showed decreased efficacy and worse tolerance (nausea and dizziness). Almost all buspirone taken orally is absorbed and has a sizeable first-pass effect. The plasma peak is attained in less than an hour after a 10 mg dose. It has a 95% binding efficiency to proteins in plasma. The metabolic pathways of hydroxylation and oxidative degradation of buspirone produce inactive metabolites. The body gets rid of buspirone through the biliary and urinary systems. The apparent elimination half-life is typically between 2 and 4 hours. When given multiple doses, plasma concentrations scale linearly with each additional dose.
References
Asensi-Cantó, A., López-Abellán, M. D., Castillo-Guardiola, V., Hurtado, A. M., Martínez-Penella, M., Luengo-Gil, G., & Conesa-Zamora, P. (2022). Antitumoral effects of tricyclic antidepressants: Beyond neuropathic pain treatment. Cancers, 14(13), 3248. https://doi.org/10.3390/cancers14133248
Gale, C., Glue, P., Guaiana, G., Coverdale, J., McMurdo, M., & Wilkinson, S. (2019). Influence of covariates on heterogeneity in Hamilton Anxiety Scale ratings in placebo-controlled trials of benzodiazepines in generalized anxiety disorder: systematic review and meta-analysis. Journal of Psychopharmacology, 33(5), 543–547. https://doi.org/10.1177/0269881118822146
Howe, Y. J., Thom, R. P., Notson, E. E., McDougle, C. J., & Palumbo, M. L. (2022). Buspirone for the Treatment of Generalized Anxiety Disorder in Down Syndrome: 3 Cases. Journal of Developmental & Behavioral Pediatrics, 43(1), 38–43. DOI: 10.1097/DBP.0000000000000970
Nanjappa, M. S., Voyiaziakis, E., Pradhan, B., & Thippaiah, S. M. (2022). Use of selective serotonin and norepinephrine reuptake inhibitors (SNRIs) in the treatment of autism spectrum disorder (ASD), comorbid psychiatric disorders and ASD-associated symptoms: A clinical review. CNS spectrums, 27(3), 290-297. doi:10.1017/S109285292000214X
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Peer 2
Luis Arencibia
Discussion
Generalized Anxiety Disorder (GAD) is characterized by chronic, unrealistic experiences of excessive anxiety and worry most of the time (DeMartini et al., 2019). The DSM-5 Criteria for a diagnosis of Generalized Anxiety Disorder: Excessive anxiety and worry, occurring more days than not for at least six months, about some events or activities (such as work or school performance); the individual finds it difficult to control the worry; it is characterized by motor tension, hypervigilance, motor tension, restlessness, and irritability. The Food Drug Administration recommends SSRIs and SNRIs as the first line of treatment for generalized anxiety disorder (Octaviani, 2020). These drugs have almost the same efficacy levels. Still, SSRIs are the most preferred drug of choice because SNRIs are associated with adverse effects such as orthostatic hypotension, hyponatremia, sexual dysfunction, and bleeding.
Factors that influence pharmacokinetics and pharmacodynamics
Many factors influence the pharmacodynamics and the pharmacokinetics of the drugs for treating Generalized Anxiety Disorder. Several impacts occur to patients when using pharmacotherapeutics while treating general anxiety disorder. Fast drug administration, such as selective serotonin reuptake inhibitors and Serotonin and norepinephrine reuptake inhibitors, may cause adverse effects when administered to patients (Rosenthal & Burchum, 2021). These effects include headache, agitation, blurred vision, insomnia, and drowsiness. Moreover, Selective serotonin reuptake inhibitors may cause decreased bone mineral density, increasing the risk of fractures.
Pharmacodynamics and pharmacokinetics depend on many drug and patient factors. Pharmacokinetics is the movement of drugs into the body, how the body interacts with the drug, its metabolism, and its movement out of the body. Pharmacodynamics describes how a drug interacts with an individual’s body and hence refers to the relationship between a drug and the site of action. Psychopharmacotherapy requires clinicians to consider some specific factors before drug administration. Additionally, genetics can influence efficacy and drug bioavailability (Geddes & Andreasen, 2020). Certain genes influence drug absorption and distribution within the body of individuals taking SSRIs and SNRIs. Therefore, drug dosage should depend on pharmacodynamics and pharmacokinetics.
My past experiences have taught me that pharmacokinetics and pharmacodynamics are influenced by factors such as gender. These factors alter the response to which a drug responds when it binds to its receptor. For example, women are more prone to getting adverse drug reactions than men after the administration of treatment. Drugs compete for receptor sites and have different pharmacodynamics and pharmacokinetics (Rosenthal & Burchum, 2021). Moreover, age influences pharmacotherapy; older patients have increased serum concentrations of drugs such as sertraline compared to younger patients.
A personalized plan of care
A plan of care is determined after patient information has been obtained by performing a mental status examination and history. The two main treatment modalities for generalized anxiety disorder, pharmacotherapy, and psychotherapy become part of the treatment plan (Geddes & Andreasen, 2020). The patient’s physical symptoms determine the combination of these two modalities. Knowledge of drug interactions, pharmacokinetics, and pharmacokinetics is important in determining the best drug for treatment. Moreover, factors such as age, gender, ethnicity, and genetics influence the pharmacokinetics and pharmacokinetics of different drugs and should be considered before administering Food Drug Administration drugs. The interventions for the patient would include administering drugs such as sertraline, acknowledging the patient’s feelings, maintaining a therapeutic relationship, and offering relaxation techniques.
References
DeMartini, J., Patel, G., & Fancher, T. L. (2019). Generalized anxiety disorder.
Annals of internal medicine,
170(7), ITC49-ITC64.
Geddes, J. R., & Andreasen, N. C. (2020).
New Oxford textbook of psychiatry. Oxford University Press, USA.
Octaviani, P. (2020, February). Drugs Interaction in Clinical Management for (Generalized Anxiety Disorders) Inpatients: A Retrospective Study. In
1st International Conference on Community Health (ICCH 2019) (pp. 79-81). Atlantis Press.
Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.
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