The Snow Man by Wallace Stevens

Post has two assignments

1:Digoxin interaction

Order Description

” You are developing a new drug JP789 for treatment of heart failure, It is proposed to conduct an interaction study in humans to investigate whether your new drug affects plasma concentrations of digoxin. JP 789 is considered to be effective in doses of 50 mg – 150 mg once daily. It is cleared by a mixture of hepatic metabolism and renal excretion and has a
half life of about 20 hours. JP789 is known to inhibit the activity of P-glycoprotein in concentrations that approximate to the maximum concentrations seen in patients treated with 50 mg daily.
Describe briefly the potential effects of JP789 on the pharmacokinetics of digoxin with reference to examples published in peer-reviewed journals. part 2 of the question is “Write a synopsis of the study protocol for the interaction study with details of design such as
population, dosing regimen and sampling schedule; provide justification for your proposals.” . for first part of question it has to about digoxin and other drugs that induce or decrease its action, while part 2 pf the question it has to be about the study protocol like which population ” inclusion and exclusion criteria ” and examples of number of patients and study design ( is it parallel or cross over and sampling and dosing regimen , half life time, c max , t max and AUC and relation to cyp3a4. here are some articles may be helpful
1- Brazzell, R. K and Colburn, W. A. (1986). Controversy I: Patients or healthy volunteers for pharmacokinetic studies? The Journal of Clinical Pharmacology.
2- Gheorghiade, M., Adams, K. F and Colucci, W. S. (2004). Digoxin in the management of
cardiovascular disorders. Circulation.”
3- Rodrigues, A.D. (2008). Digoxin. In Drug-drug interactions.
4- Silverberg, D., Wexler, D., Blum, M., Schwartz, D and Iaina, A. (2004). The association between congestive heart failure and chronic renal disease. Current opinion in nephrology and hypertension.
5-Srivalli, K. M. R and Lakshmi, P. K. (2012). Overview of P-glycoprotein inhibitors: a rational outlook. Brazilian Journal of Pharmaceutical Sciences.
6- Vamos, M., Erath, J. W and Hohnloser, S. H. (2015). Digoxin-associated mortality: a systematic review and meta-analysis of the literature. European heart journal.
7- Wang, Z. Y., Chen, M., Zhu, L. L., Yu, L. S., Zeng, S., Xiang, M. X and Zhou, Q. (2015). Pharmacokinetic drug interactions with clopidogrel: updated review and risk management in combination therapy. Therapeutics and clinical risk management.
8- Wessler, J. D., Grip, L. T., Mendell, J and Giugliano, R. P. (2013). The P-glycoprotein transport system and cardiovascular drugs. Journal of the American College of Cardiology.
9- EMA: Note for guidance on the evauluation of the pharmacokineitcs of medicinal products in patients with impaired renal function [Online]. Committee for medicinal products for human use (CHMP) (2004) .
10-FDA: Drug interaction studies – study design, data analysis, implications for dosing and labeling recommendations [Online] Guidace for industry.

2: The Snow Man by Wallace Stevens

Order Description

Analysis and deep look inside the poem “The Snow Man” by Wallace Stevens.
-Begin with an introduction, ending in a general thesis statement that sums up the main idea of your poem. Everything discussed will come back to this point.
-Begin with the large elements and work towards the finer. The structure of the poem. Talk about stanza, line length, that kind of thing. Don’t forget the Why? is incredibly important. Move onto punctuation. How much is there? Why is it important? Why are spondees there? What are they doing? Why is is left aligned? Look at syntax. Some other topics include meter, rhyme (or lack of), sounds, metaphor/simile, imagery, etc. Pay close attention to sound, this will probably be the most difficult section of the paper, but it is considered the most important.

heart failure