DQ reply 14

DQ 1

Gabapentin was initially utilized as a muscle relaxer and anti-spasmodic medication but is now utilized as anticonvulsive medication, and other purposes including postherpetic neuralgia, partial seizure, and restless leg syndrome (RLS) (Yasaei, Katta, & Saadabadi, 2020). There is also an off-label use for neuropathic pain, fibromyalgia, anxiety, mood disorders, migraine prophylaxis, diabetic neuropathy, and post-traumatic stress disorder. Gabapentin is similar to gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, but does not bind to GABA receptors or promote the synthesis or uptake of GABA (Yasaei et al., 2020). Instead, it binds to its binding sites located throughout the brain and corresponds to the voltage-gated calcium channels inhibiting the release of excitatory neurotransmitters, which contributes to epileptogenesis and nociception (“Gabapentin,” 2020). The general dosing for neuropathic pain for immediate release is 100 – 300 mg PO 1 to 3 times daily and for extended release is 300 mg at bedtime. Dosages may be increased depending on targeted therapy and tolerability as the max dosage is 3600 mg per day (“Gabapentin,” 2020). Gabapentin may cause CNS depression including dizziness, drowsiness, and somnolence, and may cause suicidality, depression, and abnormal thinking. Other adverse effects include Steven-Johnson syndrome, ataxia, angioedema, diarrhea, asthenia, tremor, infection, and nystagmus disorder (“Gabapentin,” 2020). It is important to monitor for renal functions, including creatinine levels, throughout treatment, as well as, screening patients for depression, mood/behavioral changes, and suicidal ideation (Yasaei et al., 2020). Gabapentin should be used with caution in patients with myasthenia gravis as it may exacerbate symptoms/condition, renal impairment, and respiratory issues, such as COPD as risks of respiratory depression are increased. Drug interactions include alcohol, buprenorphine, cannabis, CNS depressants, kava kava, magnesium salts, opioid agonists, and SSRIs (“Gabapentin,” 2020). Although gabapentin is considered non-addictive and doesn’t have increase risks for overdose, it may enhance CNS depressant effects and may block the effects of addiction treatment medications.

One of the most common types of neuropathy is diabetic peripheral neuropathy (DPN) with symptoms of burning, shooting, tingling, and allodynia (Chandra et al., 2017). Studies have shown gabapentin has been effective in the treatment of DPN. Chandra et al. (2017) compared the effectiveness and safety between gabapentin and amitriptyline, a tricyclic antidepressant also utilized for neuropathy and concluded that gabapentin improved neuropathic sign and symptoms at a rapid onset as long-term treatment and had less adverse effects than amitriptyline (Chandra et al., 2017). A meta-analysis recommended the use of gabapentin as it reduced neuropathic pain by more than 50% in DPN and improved sleep for patients with diabetic neuropathy (“Gabapentin,” 2020).

 

References

Chandra, M., Garg, r., Kaur, J., Santram, Kaur, N., & Pal. R. (2017). Evaluation of efficacy of amitriptyline vs. gabapentin in diabetic peripheral neuropathy. Al Ameen Journal of

Sciences, 10(3), 194-200. Retrieved from https://doaj.org/article/306e1e40f0e34ae6b29fb184fe97d0e7?

Gabapentin. (2020). Retrieved from https://www.drugs.com/ppa/gabapentin.html

Yasaei, R., Katta, S., & Saadabadi, A. (2020). Gabapentin. StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK493228/

DQ-2

Aripiprazole (Abilify) is an atypical antipsychotic medication, mainly used for symptoms of psychosis in patients with schizophrenia, acute manic episodes associated with bipolar disorder, and major depressive disorder (Gettu & Saadabadi, 2020). It may also be used for irritability associated with autism in pediatrics and Tourette syndrome. As a quinolinone, Abilify is a partial agonist at the D2 and 5HT-1A receptors and antagonist activity at 5HT-2A receptors that has a high affinity for dopamine D2 and D3 and serotonin 5-HT-1A and 5-HT 21 receptors, and a moderate affinity for dopamine D4, serotonin 5-HT 2c and 5-HT7, alpha-1 adrenergic, and histamine H1 receptors (Gettu & Saadabadi, 2020). However, Abilify has no affinity for cholinergic muscarinic receptors. In patients with schizophrenia, Abilify stabilizes dopamine and serotonin within the brain including the nucleus accumbens, ventral tegmental area, and frontal cortex resulting in the management of symptoms. It demonstrates functional selectivity as it acts as an antagonist in areas of high dopamine while remaining inactive in areas where dopamine levels are normal. Abilify has been replacing first-generation antipsychotics due to a decrease in psychiatric hospitalization and adverse effects, such as reducing symptoms of tardive dyskinesia, decreasing alcohol craving, improving cognitive function, and reducing cardiovascular risk factors (Gettu & Saadabadi, 2020).

Treatment guidelines depend on symptoms. In adult patients with schizophrenia, the targeted dosage is 10 or 15 mg/day with or without meals and should not be increased prior to 2 weeks of initial treatment as steady-state serum concentrations are about 14 days (“Abilify,” 2020). The initial dose for patients with bipolar 1disorder is 15 mg/day as monotherapy or as adjunctive therapy and can be increased to 30 mg/day. Prior to dosage change, is important to continuously monitor and assess clinical response. In children and young adults with major depressive disorder, Abilify may worsen mood and behavioral changes, such as depression and suicidal ideation (“Abilify,” 2020). Patients may also experience intense urges including gambling and sexual urges, binge eating, or compulsive shopping. Although there are less adverse effects of Abilify compared to first-generation antipsychotics, there is still some degree of extrapyramidal symptoms (EPS) and metabolic syndromes including tremor, shuffling gait, akathisia, tardive dyskinesia, weight gain, dyslipidemia, hyperprolactinemia, and hyperglycemia, and cardiovascular abnormalities and orthostatic hypotension (Gettu & Saadabadi, 2020). The most common adverse effects include somnolence, nausea, vomiting, dizziness, anxiety, and, in rare cases, neuroleptic malignant syndrome. Abilify should not be given to elderly patients with dementia-related psychosis due to increased risk stroke, cognitive decline, and mortality. Patients should be monitored for side effects and clinical response. Additionally, baseline blood pressure, weight, height, BMI, electrolytes, liver functions, plasma glucose levels, and lipid panel should be measured and monitored every three months and annually (Gettu & Saadabadi, 2020). Serum sodium levels should be monitored in older adults, as well as, CBC in patients with preexisting leukopenia or neutropenia. Important drug interactions with Abilify include CYP3A4 inhibitors, such as clarithromycin, and CYP2D6 inhibitors including fluoxetine and quinidine, as it may increase the effects of Abilify, while strong CYP3A4 inducers may decrease therapeutic effects of Abilify (“Abilify,” 2020). Other drug interactions include antihypertensive drugs as Abilify may enhance antihypertensive effects and benzodiazepines, in which intensity of sedation was enhanced when concomitant with Abilify.

 

References

Abilify. (2020). Retrieved from https://www.drugs.com/pro/abilify.html#s-34090-1

Gettu, N., & Saadabadi, A. (2020). StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK547739/

DQ-3

Citalopram is a selective serotonin reuptake inhibitor (SSRI) that has been favorite to treat panic disorders, depression, and other psychiatric disorders (Jiang et al., 2019). However, the primary use as defined by the FDA is for depression in adults (Jiang et al., 2019). There are non-FDA approved uses which include alcohol use disorder, coronary arteriosclerosis, OCD, postmenopausal flushing, and premenstrual dysphoric disorder (Jiang et al., 2019).

Citalopram's mechanism of action is to potentiate the serotonergic activity in the central nervous system as an SSRI without having an effect on norepinephrine or dopamine reuptake (Shoar & Padhy, 2020). Citalopram also has a low affinity for muscarinic acetylcholine receptors, but there is no significant effect on alpha or beta-adrenergic receptors, or dopamine 1, dopamine 2, histamine, 5ht1a, 5ht1b, gamma-aminobutyric acid, opioid, or benzodiazepine receptors (Shoar & Padhy, 2020). As an SSRI, there is a lag time in terms of response time and full response time. The onset of action for depression is about 1 to 4 weeks, while full response may take 8-12 weeks (Shoar & Padhy, 2020). Bioavailability of the oral route is 80%, and the half-life is 24 to 48 hours but increases in patients with hepatic impairment, mild-to-moderate renal impairment, in elderly patients, and patients with poor CYP2C19 metabolizers (Shoar & Padhy, 2020).

Common adverse effects include drowsiness, insomnia, dizziness, headache, diaphoresis, nausea, vomiting, xerostomia, constipation, and diarrhea (Shoar & Padhy, 2020). Rarer side effects include MI, prolonged QT interval, Torsades de pointes, hemorrhage, CVA, suicidal thoughts, suicide, hypokalemia, and serotonin syndrome (Shoar & Padhy, 2020).

Contraindications of Citalopram include a history of hypersensitivity to this drug (Shoar & Padhy, 2020). Another contraindication includes monoamine oxidase inhibitors like linezolid, IV methylene blue, and pimozide (Shoar & Padhy, 2020). It is important to note that you should not start citalopram within 14 days of discontinuing an MAOI due to the risk of serotonin syndrome (Shoar & Padhy, 2020).

Monitoring includes for QT-prolongation and bradycardia (Shoar & Padhy, 2020). A drug-drug interaction includes medications like Haldol and Protonix that prolong the QT interval (Shoar & Padhy, 2020). This can lead to R on T phenomenon and QT-prolongation (Shoar & Padhy, 2020). Other monitoring includes electrolytes as Citalopram can cause electrolyte disturbances (Shoar & Padhy, 2020).

There is a black box warning with Citalopram. Suicidality and worsening depression, especially in children, adolescents, and young adults have occurred in patients (Shoar & Padhy, 2020). For this reason, the administration of citalopram should be accompanied by close monitoring for clinical worsening, suicidality, or unusual changes in behavior (Shoar & Padhy, 2020).

Toxicity can occur in the form of serotonin toxicity even with therapeutic doses, especially with concomitant administration of another medication that can increase the CNS serotonin (Shoar & Padhy, 2020). Excessive ingestion of citalopram leads to extended monitoring, for example, 600mg ingested leads to 8 hours of cardiac monitoring and 1000mg ingested includes 13 hours of monitoring (Shoar & Padhy, 2020). If patients who have prolonged QT intervals even at the end of the observation period, extended observation is required (Shoar & Padhy, 2020). References:

Jiang, J., Zheng, Y., Chen, Y., Zahra, A., Long, C., & Yang, L. (2019). Exposure to prenatal antidepressant alters medial prefrontal-striatal synchronization in mice. Brain Research, 1717, 27–34. https://doi-org.lopes.idm.oclc.org/10.1016/j.brainres.2019.04.008

Shoar, S. N., Padhy, R.K. (2020). Citalopram. StatPearls Publishing. Retrieved from: https://www.ncbi.nlm.nih.gov/books/NBK482222/