Insomnia

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Use APA 6th Edition Format and support your work with at least 3 peer-reviewed references within 5 years of publication. Remember that you need a cover page and a reference page. All paragraphs need to be cited properly. Please use headers.  All responses must be in a narrative format and each paragraph must have at least 4 sentences. Lastly, you must have at least 2 pages of content, excluding cover page and reference page.Case Study: Insomnia and Sleep Disorders. S.H., age 47, reports difficulty falling asleep and staying asleep. These problems have been ongoing for many years, but she has never mentioned them to her health care provider. She has generally “lived with it” and selftreated the problem with OTC Tylenol PM. Currently, she is also experiencing perimenopausal symptoms of night sweats and mood swings. Current medical problems include hypertension controlled with medications. Past medical history includes childhood illnesses of measles, chickenpox, and mumps. Family history is positive for diabetes on the maternal side and hypertension on the paternal side. Her only medication is an angiotensinconverting enzyme inhibitor and diuretic combination for hypertension control. She generally does not like taking medication and does not take any other OTC products.

Diagnosis: InsomnIa.

1. List specific goals of therapy for S.H.

2. What drug therapy would you prescribe? Why?

3. What are the parameters for monitoring the success of the therapy?

4. Discuss specific patient education based on the prescribed therapy

5. List one or two adverse reactions for the selected agent that would cause you to change therapy.

6. What would be the choice for second-line therapy?

7. What OTC and/or alternative medicines might be appropriate for this patient?8. What dietary and lifestyle changes might you recommend?

9. Describe one or two drug–drug or drug–food interactions for the selected agent.

Drug Information Question

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PS: The 4 sources are already selected by me. The are attached with my rough draft. There are 3 articles and a website (Lexicomp).

page limit is 3 pages, including references***

 

 

Here is the rubric used for grading:

 

 

 

 

 

 

 

 

 

 

For citation (AMA style):

 

 

 

 

Here is my PICO: Use this in the literature summary (25% of the grade)

Step Item Response
Step 1: Original Question

 

 Can 3% sodium chloride (3% hypertonic saline) be safely administered through a peripheral IV line?

 

 
Step 2: Population Patient with elevated intracranial pressure. Patient with severe hyponatremia.

 
  Intervention/Exposure A typical initial rate of infusion of 3% sodium chloride is approximately 15 to 80

mL/hr. (1mL/kg/hour) for 2 to 3 hours.
  Comparator (if applicable) 0.9%NS, 0.45% NS administration through peripheral IV Line, 5% dextrose in normal saline, Lactated Ringer’s solution. Central line administration for hypertonic saline.
  Outcome Adverse reactions of hypertonic saline through Peripheral line compared to Central line.

 
Step 3: Well-developed clinical question What are the risks when hypertonic saline (3% saline) is administered through a peripheral IV Line? (Feel free to change to a better

Clinical question if you like)

 

 

HERE IS MY DRAFT that I submitted for review

· Notice that I did not integrate my Pico in my Intro/background

Question:

Can 3% sodium chloride (3% hypertonic saline) be safely administered through a peripheral IV line?

Saline solutions are mixtures of Nacl and water. They are mainly classified into hypotonic 0.18-0.3%, isotonic or normal saline 0.9% and hypertonic saline 3% or more. Saline solutions are widely used in medicine from wound cleaning, rehydration to cosmetic. According to Lexicomp, 3% sodium chloride has an osmolality of 1025 mOsm/L which is higher than the 900 mOsm/L recommended for parenteral nutrition4. 3% Hypertonic saline is mostly used in clinical settings. They are used in intracranial hypertension management and hyponatremia2. Traditionally, Hypertonic saline are administered via central line due to risk of damages to small veins if given via peripheral central line. However, it is common to see 3% sodium chloride used in clinical settings due to central line association with risk of complications such as infections, thrombosis, pneumothorax and delay of therapy for a patient in need of a time-sensitive therapy2,3. Therefore, is it safe for patients to get 3% sodium chloride through a peripheral IV line?

In a retrospective review study conducted on 66 patients who received 3% sodium chloride via Peripheral Venous Catheters (PVC) in Intensive care unit, Infusion-related adverse events (IRAEs) were collected from patients for analysis1. Complications such as Hyponatremia (29%) and cerebral edema (29%) were common. 6.1 % (4 of 66 patients) of patients experienced an IRAEs were aged between 38-82 years old and resulted with no permanent tissue damage1. 50% of patients who experienced IRAEs had their infusion restarted peripherally at another location1. Minimal damage was shown when the location was a large vein (80%) and 20-22 gauge catheters were used1. The onset time of IRAEs ranged from 2 to 94 hours (the median was 19 hours) after the start of the 3% Nacl infusion at a rate of 30 mL/h ( median 32ml/h, IR 30-35). Serum sodium at the beginning was 124 1.4 mEq/L compared to 131 1.3 mEq/L ( P< .0001) at the end of the infusion which shows a rise in serum sodium1. Central line infusion is an invasive procedure that requires skills to perform but allows instant distribution and minimal vascular wall damages. PVC provides patients with acute symptomatic hyponatremia and elevated intracranial pressure rapid access and prompt distribution of the 3% Nacl1.This article shows that using PVC for hypertonic saline is not always dangerous. The risks of tissue damage and invasiveness of central line can be good arguments for the use of PVC.

In a retrospective cohort study that evaluated adult and pediatric patients who were given 3% NaCl or mannitol via Peripheral IV line in the emergency department to manage intracranial pressure elevations with a primary outcome of extravasation incidence (leakage around the site of injection)3. 192 patients were included in the study. 85 (44%) received 3% Nacl and 107 (56%) received mannitol with no extravasation in either group3. In hospital mortality was higher in the mannitol group (54.7% vs. 32.9%; p = 0.003)3. In conclusion, since neither group experienced an extravasation, it is safe to use 3% sodium chloride peripherally in patients with elevated intracranial pressure at the ED.

In another article, a prospective study of patients admitted to Parkland Hospital Surgical ICU and who were treated with 3% NaCl via the peripheral IV catheter was collected from October 2013 to May 2014. 28 patients and 34 peripheral lines were monitored2. Infusion rates ranged from 30 to 50 ml/L for all subjects. The duration of the infusion was 1 to 124 hours (mean 36 hours)2. 2 patients presented complications which included infiltration, with an incidence of 6%, and 1 patient with thrombophlebitis, with an incidence of 3% 2. The complications rate was 10.7% (n=3) among the patients and 11.7% (n=4) on assessed peripheral lines for 3 patients. According to the article, thrombophlebitis is the most common complications of Peripheral IV line2. Duration of catheterization is an important indicator for thrombophlebitis with most patients at risk after 5 days of IV therapy2. The study concluded that 3% hypertonic saline peripheral administration presented low risk and non-life threatening complications and that any concern and risk are therefore unfounded2.

In conclusion, according to current literature using hypertonic saline (3% NaCl) presents a low risk when administered via a peripheral IV line. Even though hypertonic saline is traditionally administered through a central line because of the osmolarity of 3% sodium chloride exceeds 900 mOsm/L and puts patient at risk of thrombophlebitis, tissue damage, and extravasation reactions, peripheral administration is preferred in emergencies and time sensitive therapies1,2,3,4. Peripheral administration requires less skill and is less invasive than the central line. However, all the studies present limitations that could be reduced by conducting a randomized control trial or a prospective cohort study. Without a control group, it is hard to definitely say that 3% sodium chloride is safer when administered via a peripheral IV line versus central line.

I appreciate this drug information question and will follow up within 72 hours with any further questions.

 

Please read those articles and make they are correctly referenced.

 

References

1. Dillon, R. C., Merchan, C., Altshuler, D., & Papadopoulos, J. (2018). Incidence of Adverse Events During Peripheral Administration of Sodium Chloride 3%. Journal of Intensive Care Medicine, 33(1), 48–53.

 

2. Perez, C., & Figueroa, S. (n.d.). Complication Rates of 3% Hypertonic Saline Infusion Through Peripheral Intravenous Access. Journal of Neuroscience Nursing, 49(3)(0888-0395), 191–195. doi: 10.1097/JNN.0000000000000286

 

3. Mesghali, E., Fitter, S., Bahjri, K., & Moussavi, K. (n.d.). Safety of Peripheral Line Administration of 3% Hypertonic Saline and Mannitol in the Emergency Department. The Journal of Emergency Medicine, 56(4), 431–436.

 

 

4. Lexicomp® AHFS Drug Information®. © Copyright, 1959-2020, Selected Revisions January 1, 2009, American Society of Health-System Pharmacists®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

 

 

 

 

 

 

 

 

 

 

 

 

 

Example of a well written Drug Information question response:

· As long as my paper looks like this (format and answers all the rubric question I’m happy)

 

 

 

Let me know if you have any other questions.

Its due on the 04/08/ by midnight

Drug Development Process

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1

PJ4012 – Drug Development

Developability of drugs This coursework is 1800±10%. Submission will be online on Turnitin folder on Blackboard. The date of submission will be on Sunday 6th December 11:59PM.

1. Introduction

Selective serotonin 2C (5-HT2C) antagonists, that enhance mesocortical dopamine signaling in the brain, are under development as fast-onset antidepressants. You are part of a drug development team that is working on a potential blockbuster drug for the treatment of depression. There are synthetic chemists, formulation scientists, pharmacologists, toxicologists, clinical scientists, regulatory affairs specialists, marketing and a principal scientist acting as the project manager who oversees the drug development process.

 

2. Objectives

• To develop skills to construct and provide a critical rationale for appropriate product design.

• To evaluate chemical data presented in the drug discovery process.

• To analyse physicochemical and pre-formulation data for the design of a suitable formulation.

• To be able to apply formulation science and principles to select appropriate excipients including solvents, suspending agents, viscosity emulsifiers, surface active agents, preservatives, colouring agents and sweeteners etc. to give desirable properties of a formulation of the given drug for the proposal of a “Dosage Form Nomination”.

• To devise an appropriate clinical trial strategy based on the given data.

3. To develop a working plan for the marketing authorisation application.Supporting data

Sections 3.1 to 3.4 provide information on the chemical studies (drug discovery), formulation development, in vitro and in vivo studies, and Marketing Authorisation Application of the investigational drug, OPTIMISIMX. [X refers to a to f, depending on your chosen candidate drug.]

 

 

 

2

 

3.1. Drug discovery

The chemists in your team have synthesised a series of compounds with potential antagonism to 5-HT2C receptor as an anti-depressant. The profiles of each of the possible candidate drugs (OPTIMISIMa, b, c, d, e and f) for development are shown in Table 1. One of these compounds needs to be selected to be progressed into Phase I clinical trials following suitable formulation testing.

 

OPTIMISIM

a OPTIMISIM b

OPTIMISIM c

OPTIMISIM d

OPTIMISIM e

OPTIMISIMf

Affinity towards h5-HT2C

high high high high high high

Selectivity vs h5- HT2B, h5-HT2A

>150 >80 >150 >100 >100 >100

Function

2

Potent Inverse agonist/ant agonist

 

Potent antagonist

 

Potent antagonist

 

Potent antagonist

 

Potent antagonist

 

Potent antagonist

Oral activity 3

3 mg/kg 5.0 mg/kg 10 mg/kg 1mg/kg 2.0 mg/kg 15 mg/kg

MW (g/mol) 400.4 409.2 520.5 511.4 493.0 412.8

Half-life >3h ~4h >10h ~2h ~7h >10h

Salt form Di-HCl Mono-HCl Mono-HCl N/A Mono-HCl Mono-HCl

cLogP 4.2 4.8 2.3 6.1 3.5 -1.2

Metabolites 2 major 1 major 3 major 4 major 1 major N/A

Active metabolites none none 1 active 1 active none none

Cytochrome P450 Interaction

Inhibits 4

Inhibits 5

Weak inhibition

6

Weak inhibition

6

Induces 7

none

Tolerance None N/A Slight 8

None none none

Withdrawa l symptoms

None N/A N/A None slight none

Anxiogenicity None v. weak None weak none none

 

 

3

 

Teratogenicity 9

None None None Marginal 10

none none

Uticaria 9

Mild Mild None mild mild none

Relative Weight gain

None Not significant

Not significant

None none modest

 

Notes: 1. vs other h5-HT, dopamine and adrenergic receptors.

2. Order of potency OPTIMISIMe> OPTIMISIMf~ OPTIMISIMa~ OPTIMISIMb> OPTIMISIMd~ OPTIMISIMc.

3. Rat model. 4. Partial of CYP2C9; 3A4, 3A5 and 3A7. 5. CYP2C9; 3A4, 3A5 and 3A7. 6. Weak at CYP2C9. 7. At high concentrations CYP2C9. 8. Develops after 12 days continuous dosing. 9. Rabbit model. 10. At highest dose of 30 mg/kg.

 

Based on the profiles presented, select ONE possible candidate compound to be taken to late-stage evaluation in the drug discovery process and justify your selection. Critically discuss the rationale and any adjustments that may need to be considered to take that compound forward for development if necessary. You should use references from journals / textbooks to help support your decision.

 

3.2. Formulation development

Following optimisation and further development of your chosen candidate drug, some further physical data and properties of the optimised candidate drug (a weak base) are shown in Table 2, and Figures 1, and 2. At this stage, the data provided in Table 2 and 3, Figures 1 and 2 are considered as the FINAL characteristics profiles.

 

Table 2: Characteristics of the chosen candidate drug.

pKa 8.1

Physical state at 25ºC Pink odourless, crystalline powder

Salt form Hydrochloride (non-hygroscopic)

Mesylate (hygroscopic)

Particle size 460 – 810 µm

Melting point 231ºC

UV absorbance (max) 520 nm

Chemical properties Stable between pH 3 – 8

Photosensitive

Taste Strong bitter taste

 

 

4

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

HCl salt

Mesylate salt

 

 

 

 

 

 

Figure 1. Solubility of hydrochloride and mesylate salts of the chosen candidate drug in purified water (pH 3) at different temperatures.

 

 

HCl sal t Mesylate sal t

 

 

 

 

 

 

Figure 2: Solubility of hydrochloride and mesylate salts of the chosen candidate drug in purified water (pH 8) at different temperatures.

Evaluate the physicochemical data provided for the optimised chosen candidate drug (OPTIMISIMX) and design a suitable formulation for this drug using ‘powder-in-a- bottle’ approach to be used for subsequent Phase I clinical trials. It is predicted that a daily dose of 30 mg may be suitable for clinical use. Based on the principles you have learnt so far about formulation science, you should first analyse the solubility and compatibility data. Then design a suitable formulation and explain the function of each excipient you have chosen. You must be able to justify your choice with supporting information. Finally you should consider the Dosage Form Nomination for subsequent development.

S o

lu b

il it

y (

m g

/m l)

S

o lu

b il

it y

( m

g /m

l)

 

 

5

Avoid using excessive excipients unnecessarily. Only use essential excipients at suitable quantities and provide reasons for the quantities chosen.

Information about the necessary excipients and liquid dosage form design can be found in the following resources:

– Medicines Complete (online) – Handbook of Pharmaceutical Excipients (Raymond C Rowe) – The Science of Dosage Form Design (M. E. Aulton) – Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems

(Loyd V. Allen) – BP – http://www.ncbi.nlm.nih.gov/sites/entrez – http://wos.mimas.ac.uk/ – http://www.sciencedirect.com – http://www.ipecamericas.org/public/faqs.html#question1 – http://www.faia.org.uk/enumbers.php (information on E numbers)

 

3.3. In vitro and in vivo studies

Both in vitro and in vivo animal studies on this leading compound showed promising 5-HT2C antagonism. Toxicological studies in rodents and dogs have been well tolerated with a predicted MTD of between 10-20 mg/kg. The candidate drug is 20% bound to plasma proteins. In vitro metabolism studies using human liver microsomes indicated that the candidate drug is a substrate of CYP 3A4. It is believed that the compound will be slowly metabolised and toxic metabolites are likely to be accumulated in patients with hepatic and renal impairment. A daily dose of 30 mg is the recommended clinical trial dose.

Devise an appropriate first-in-man study by describing the recruitment process (subject number, participant exclusion and inclusion criteria etc.), trial design (e.g. parallel or cross-over; randomization, blinding and masking), aims and objectives, and clinical outcomes / endpoints etc.

 

3.4. Marketing Authorisation Application

Data obtained from Phase I to III clinical trials supports the use of the drug for the treatment of depression.

Discuss the essential information that is required and relevant for this particular product for the submission of a Marketing Authorisation Application for a new active substance. E.g. if a drug name is required, then give it a drug name, rather than stating “a drug name is required”.

 

 

 

4. Support

You should use your lecture / workshop notes as well as the recommended textbooks and journal articles on drug discovery, pharmaceutical dosage form design, clinical trials, regulatory affairs and other relevant required texts to help you analyse the data. Please note that you may need to refer back to your learning in your MPharm Programme!

You may also find online searches such as Pubmed, ScienceDirect and Web of Knowledge useful for compiling references for writing this report. In particular, information from regulatory bodies such as the MHRA, FDA and the EMEA would also be useful to provide regulatory guidelines for the licensing and marketing of medicinal products. You are also strongly recommended to start doing the case study early before the deadline!

MHRA

http://www.mhra.gov.uk/

European Medicines Agency http://www.ema.europa.eu/

 

US Food and Drug Administration http://www.fda.gov/

 

Association of the British Pharmaceutical Industry (ABPI) http://www.abpi.org.uk/

 

International Conference on Harmonization (ICH) guidelines http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html

 

Public Spiritually

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You have been assigned required readings on spirituality in your course. You may choose one or more chapters from each assigned book to read. You will then write a reflection paper regarding your thoughts, meaningful ideas, feelings, and/or reactions, and the application of these to nursing practice or your own spiritual growth and self-care.

 

1. Paper is typed in at least 3 pages, double spaced and turned in on time via D2L or email to your professor, with coversheet title page in APA format; thoughtful, suitable title 10 Points  
2. Introductory paragraph is attention-getting

 

 10 Points  
3. Spelling, grammar, mechanics, and usage are correct throughout paper 10 Points  
4. Thoughts are expressed in a coherent and logical manner. 20 Points  
5. Viewpoints and interpretations are insightful, demonstrating an in-depth reflection. 20 Points  
6. Concluding paragraph sums up information, reiterates ideas and opinions, and leaves reader with a call to action or something meaningful to remember 10 Points  
7. Pertinent reference sources are skillfully woven throughout paper without over use of quotations but, rather, attempt to paraphrase 10 Points  
8. References are properly cited in APA format with no plagiarism. 5 Points  
9. At least 3 references are cited in paper, including a reference from current class assigned chapter readings in Mauk, a reading in an assigned chapter in White, and one journal article of your own choice. 5 Points  
Total 100 Possible Points Actual Points =

References:

Mauk, K. L., & Schmidt, N. K. (2004). Spiritual care in nursing practice. Philadelphia, PA: Lippincott.

White, E. G. (2011). The Ministry of healing. Guildford, UK: White Crow Books.

Journal article:

APA format reference that you may use for free:

https://owl.english.purdue.edu/owl/resource/560/01/

 

It is recommended that you upload your paper into Turnitin on D2L to check for plagiarism prior to submission to your professor. Also, to check for correct grammar, use the Grammar Tutor on D2L.