Pharmacology

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/30450

Browse

Now showing 1 - 4 of 4

Synthesis and Bioactivity of Nitric Oxide Donor and Antioxidant Drug Hybrid
(2021) Khowaja, Sanober; Nguyen, Maria; Weston, Courtney; Acharya, Suchismita
Purpose: In ischemic stroke or peripheral artery disease, there is a blockage of the arteries that results in increased free radicals and cell death. Our goal was to synthesize a hybrid compound SA-9-01 and assess its NO releasing and reactive oxygen species (ROS) scavenging ability using chemical assays. We hypothesize that the hybrid compound will prevent cell death by improving blood circulation and neutralizing ROS. Methods: SA-9-01 was synthesized using a synthetic procedure similar to a previously designed analog SA-2 and structure was verified by 1HNMR. The NO releasing activity was determined using the Griess assay by measuring the total nitrite formation. The xanthine oxidase assay was used to measure the ROS scavenging activity. Results: Compound SA-9 (25 mM) released NO at concentrations between 1.35-1.40 µM at t=90 mins sufficient to provide therapeutic activity, while a known NO donor SIN-1 released between 2-15 µM at same concentration and time point. From the xanthine oxidase assay, the scavenging ratio for SA-9-01 (250 µM) was about 20-25% at t=100 mins and comparable to previously described compound SA-2 and Baicalein (the positive control). Conclusion: Compound SA-9-01 was synthesized successfully with the correct chemical structure and was found to be a tautomer of the first batch SA-9. The Griess assay demonstrated that SA-9 releases physiological level of NO. SA-9-01 also demonstrated ROS scavenging activity. The testing of SA-9-01 in cells is under progress.
Hyperbaric Oxygen Therapy: a potential Alzheimer's disease modifier?
(2021) Sumien, Nathalie; Mensah-Kane, Paapa; Dory, Lad; Vann, Philip
Purpose: Current treatment of Alzheimer's disease (AD) is symptomatic, involving anti-cholinesterase and an NMDA antagonist. Over time, this increase in AD incidence, will bring dire consequences not just on the quality of life but also as an economical burden, as Medicare spending for AD is projected to increase to 1 trillion by the year 2050. Based on these numbers, it necessary to identify a solution. It is therefore, not surprising that the Alzheimer's Project Act was passed about 9 years ago to support this course. Though a complex disease, oxidative stress and neuroinflammation are key factors in the pathogenesis. Procedures or treatments that tend to reduce these two factors could probably reverse/modify the progression of the disease. Hyperbaric Oxygen Therapy (HBOT) seems promising for neurological conditions. Therefore, we aim to explore whether HBOT can improve cognition Methods: Young and adult mice were each divided into 4 groups consisting of control-HBOT, control+HBOT, 5xFAD-HBOT and 5xFAD+HBOT. HBOT was started at either 4 or 9 months and continued until the mice were euthanized. Two behavioral tests to study cognition were used. Results: HBOT reversed the deficits in the 5xFAD in the adult mice but not in the young ones. Conclusion: This work though preliminary does support HBOT as a viable option. More work is needed to determine the optimal timing and frequency of the treatment, as well as the mechanism of action underlying its benefits.
Severe Hyponatremia Secondary to Escitalopram Therapy: A Case Study
(2021) Aziz, Hadia; Escobedo, JD
Background: Hyponatremia secondary to syndrome of inappropriate antidiuretic hormone (SIADH) secretion is a well-known complication of selective serotonin reuptake inhibitors (SSRI), however it is rarely seen with the new generation SSRIs. There have only been fifteen reported cases of hyponatremia with the newest SSRI, escitalopram. Case Presentation: A 77-year-old female was admitted to the hospital for altered mental status and hyponatremia. Her past medical history was significant for anxiety treated by escitalopram oxalate 10 mg daily. Patient reported increased weakness and use of walker due to recent history of falls. On exam, she was communicating slower than her baseline but otherwise speech, memory, and orientation seemed unchanged. Mucous membranes were dry and skin tenting was present. A diagnosis of SIADH was made based on clinical findings, laboratory findings of severe hyponatremia, hypotonicity, elevated urine osmolality, and after ruling out other causes of hyponatremia due to normal renal, adrenal, and thyroid function. Patient's SIADH was attributed to the escitalopram she was started on for anxiety fourteen days before admission. After treatment, patient was asymptomatic and discharged with a sodium level of 121 mEq/L. Repeat sodium levels were 130 mmol/L eleven days after discharge and patient was started on mirtazapine for anxiety. She has had no episodes of hyponatremia since discontinuing escitalopram. Conclusion: Physicians should be aware of SIADH development secondary to SSRIs in the elderly even with new generation SSRIs such as escitalopram. Electrolytes should be monitored regularly, especially in the first two weeks after starting the medication.
A Study of Pharmacologic Therapy in Patients with Chronic Low Back Pain
(2021) Powell, Jake; Licciardone, John C.
Purpose: This study aimed to examine the effects of different pharmacologic therapies on patients with chronic low back pain, including nonsteroidal anti-inflammatory drugs(NSAIDs), opioids, antidepressants, muscle relaxants, antipsychotics, and anticonvulsants. Outcomes included low back pain intensity, back-related functioning, and quality of life. Methods: This was a cross-sectional study of patients within the PRECISION Pain Research Registry who met criteria for chronic low back pain established by the National Institutes of Health. Pharmacologic therapy was self-reported by patients. Back pain intensity was measured with an 11-point numerical rating scale (NRS). Back-related functioning was measured using the Roland-Morris Disability Questionnaire (RMDQ). Quality of life was measured using the SPADE cluster (sleep disturbance, pain interference with activities, anxiety, depression and low energy/fatigue) derived from the Patient-Reported Outcomes Measurement Information System (PROMIS-29). Higher scores represent worse health on all outcome measures. Results: Of 977 eligible patients, 323(33.1%) used opioids, 593(60.7%) used NSAIDs, 222(22.7%) used antidepressants, 160(16.4%) used muscle relaxants, 44(4.5%) used atypical antipsychotics, and 153(15.7%) used anticonvulsants. Mean NRS score for patients using opioids was 6.5 vs. 5.9 for non-users (p=0.13,95%CI(-0.925 - -0.390)). Mean RMDQ score for opioid users was 16.7 vs. 13.2 for non-users (p< 0.001,95%CI(-4.287 - -2.720)). Mean SPADE score for opioid users was 59.4 vs. 56.4 for non-users (p=0.15,95%CI(-3.910 - -1.9798)). Conclusion: Patients used a variety of pharmacologic therapies for chronic low back pain. Opioid users reported worse outcomes than non-users, including significant deficits in back-related functioning.

Browse

Recent Submissions