Analysis of NSAIDs non-selective take (Ibuprofen and Naproxen)
Health impact of many diseases leaves a potential consequence on the quality of life (QOL). The frequency at which such impact occurs could vary from one disease condition to the other. Affected individuals need to encounter physical and psychological distress. However, scientific advancements have made a progress in alleviating such problems. Especially, pharmaceutical science has become a reliable branch to cater the needs of people who suffer from illnesses. Understanding the efficacy and other properties of various drugs is important for the better therapeutic application of pharmacy. In such context, the present description deals with highlighting about Analysis of NSAID take by considering Ibuprofen and Naproxen as examples.
Briefly, Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs of common occurrence. They are widely available at the retail shops/counters and are sold even without a doctors’ prescription. Their widespread occurrence is due to their efficacy in decreasing
a) High body temperature due to fever
b) Pain, and
c) Inflammation (NSAIDs, 2007).
a) Decreasing the synthesis of components that offer protection to stomach
b) Ceasing the fucntions of platelets and
c) Decreasing the blood flow quantity that reaches the kidney by constricting the arteries.
Thesis statement: It is not known if Ibuprofen and Naproxen could be the reliable NSAID drugs of choice for the health care community. NSAIDs work by suppressing the action of an enzyme called cyclooxygenase (COX). COX enzyme is vital for the synthesis of special class of chemicals, the prostaglandins. These are the secretions with diverse roles, say to promote inflammation. Hence, the enzyme inhibition leads to the reduced production of prostaglandins that in turn causes less pain and inflammation (NSAIDs, 2007).
There are two classes of NSAIDS, non-selective and selective. Non-selective NSAIDs are those that suppress the two forms of COX such as COX 1 and COX 2 enzymes. COX-1 is mainly responsible for protecting the gastric mucosa whereas COX-2 is the responsible for fever and inflammation. Selective NSAIDS only inhibit the COX-2 enzyme thus facilitating the synthesis of the prostaglandins (NSAIDs, 2007).
Ibubrofen: Ibuprofen is class of nonselective NSAID. It’s chemical name is (2RS)-1[4-(2-methyl propyl) phenyl] propionic acid (BP. 2004) and is the earliest substance from the propionic acid family (Bushra & Aslam, 2010).
Ibubrofen has antipyretic and analgesic properties, say it reduces fever and inflammation. Its pharmacodynamics is mainly associated with its mechanism of inhibition. It non-selectively and reversibly inhibits both COX-1 and COX- 2. Ibubrofen has two enantiomers, R and S.
S-ibuprofen is the important suppressor of COX enzymes than its R counterpart with a higher inhibitory action on COX-1 than COX-2 (Mazaleuskaya et al., 2014). Here, the inhibitory effects of COX-1 and COX-2 start when they both catalyse the synthesis of most vital substances from the arachidonic acid. These include thromboxane (Tx) A2, prostanoids - prostaglandin PGI2 (prostacyclin), PGF2alpha, PGD2, and (PG) E2.The release of Arachidonic acid is very crucial for the prostaglandin synthesis (Mazaleuskaya et al., 2014). Arachidonic acid release occurs from the plasma membrane by PLA2G2A (in synovial fluid and platelets) and PLA2G4A (in cytoplasm, relies on calcium). The conversion of Arachidonic acid to the prostaglandin H2 (PGH2), an intermediate and unstable form, occurs by the action of prostaglandin G/H synthases of cytosol. Such synthases are cyclooxygenases, COX. Various tissue-specific synthases thus convert PGH2 to several prostanoids. COX-1 preferably couples enzymes such as cytosolic (c) prostaglandin E synthase (PGES) isozymes prostaglandin F synthase and thromboxane synthase (TXS). COX-2 preferably couples with microsomal (m) PGES isozymes and prostaglandin I synthase (PGIS). The production of prostanoid depends on the expression variations of these enzymes at inflammation sites within a given cell (Ricciotti & FitzGerald, 2011).
The pharmacokinetics of Ibubrofen mainly relies on its isomers/enantiomers, S and R.
In vitro and in vivo studies describe that the [+] S-isomer of ibubrofen plays role in clinical activity. The pharmacological effect of [-] R-form is weak. It undergoes a slow, insufficient inter-conversion into a strong [+]S species in adult individuals. In children, such inter-conversion remains undiscovered but is believed to be identical. The [-] R-isomer plays role as a circulating source to sustain the drug activity levels. Ibuprofen undergoes a good oral absorption and its excretion through urine is just below 1% at a stable level. Ibubrofen has a plasma half-life of nearly 2 hours accompanied with a biphasic elimination time curve. In febrile children, a dose of 5 and 10 mg/kg of Ibubrofen was established by the researchers. In adult individuals, a single oral drug dose ranging from 50 to 800 mg was been established by the research studies (Motrin (Ibuprofen), 2014).
Some of ibuprofen brand names are Motrin and Advil.
The common uses of ibubrofen are therapeutic applications. It is used an antipyretic, anti-inflammatory and analgesic agent.
S(+) enantiomer and recemic ibuprofen are commonly employed for treating
moderate pain associated with soft tissue diseases, rheumatoid arthritis, osteoarthritis, management of spondylitis, postoperative dental pain, migraine, headache
and dysmenorrheal problems (Bushra and Aslam, 2010).
In addition, its therapeutic uses are exploited for managing
a) Cystic fibrosis
b) Orthostatic hypotension
c) Dental pain
d) Alzheimers disease
e) Parkinson’s disease
f) Breast cancer (Bushra and Aslam, 2010).
The adverse effects of ibubrofen include are reported to be low. But, ibubrofen could disturb, gastrointestinal tract, coagulation system and kidneys. It could cause vomiting, diarrhea, dizziness, constipation, drowsiness or dizziness (Ibubrofen, 2014).
Upset stomach, nausea, vomiting, headache, diarrhea, constipation, dizziness, or drowsiness may occur. It could increase the risk for heart failure, apoptosis, confusion and bronchospasm epistaxis , gastric ulcers and damage (Bushra and Aslam, 2010).
Interactions: The interaction of ibubrofen involves various types. These include:
The interactions of ibuprofen with NSAIDs are both pharmacodynami and pharmacokinetic in nature. Ibubrofen interacts seriously with diuretics, β-blockers, angiotensin converting enzyme inhibitors, antihypertensives, high dose methotrexate, oral hypoglycemic and warfarin (Ibubrofen, 2014). The outcome of such interactions would induce the risk of bleeding in people (Ibubrofen, 2014).
The examples of drugs that interact with Ibubrofen and alter its functions are St. John’s wort, Desmopressin,voriconazole and fluconazole(Bushra and Aslam, 2010).
Drug- food: Ibubrofen when combined with other drugs and consumed could interact with food Say, the combination of ibuprofen and oxycodone could be malabsorbed when a simultaneous food absorption occurs.
On the other hand, food consumption prior to single dose combination administration did not affect absorption of ibubrofen, However, oxycodone absorption remained unchanged. Some other studies mention that Tamarindus indica fruit extract facilitated the increased bioavailability of Ibuprofen at a significant rate damage (Bushra and Aslam, 2010).
Drug- lab interactions : These interactions are not known or documented properly for Ibubrofen.
Further available research evidence mentions that drugs falling under the class non-selective NSAID are the most potential drugs of clinical relevance. However, spectrum of randomized controlled trials (RCTs) have described that this class could predispose the individuals to the risk of gastric and renal toxicties.
This class could inhibit the aldosterone metabolism.
Research evidence suggests a decreased dose and routine monitoring of individuals who use this class of ibubrofen for long-term. Especially, they must consider the patient profiles at the individual level in view of adverse reactions. Inter-individual variation could be observed due to the pharmcagenomics of this class of drugs. Cytochrome P450 (CYP) metabolizing enzyme,
CYP2C8 was reported to play key role in metabolism/ disposition of ibubrofen in humans (Daily & Aquilante, 2009).
So, gene polymorphisms in this enzyme could account for a varied individual effect.
The research data appears to orient the people who use these drug class agents, to the precautionary measures.
Next, the analgesic and anti-inflammatory properties of Ibubrofen had been exploited by researchers while studying the efficacy of physical therapy.
Pajareya et al (2004) examined the efficacy of combined ibubrofen and physical therapy and only ibubrofen in pateitns with adhesive capsulitis. The findings reveal improvements with physical therapy combination at 3-week. But at 12-week follow-up, there was no difference between the two groups in the success rates. So, physical therapists should have no concerns in choosing physical therapy intervention regardless of ibubrofen (Pajareya et al., 2004).
Implications and role of physical therapist in pharmacological management:
Another example of drug class non-selective NSAID is Naproxen. It belongs to the class of phenylpropionic acid and is member of arylacetic acid group (Naproxen, 2013). It’s chemical name is (2S)-2-(6-methoxynaphthalen-2-yl)propanoic acid. It is available as Naproxen sodium
Pharmacodynamics: Naproxen has both antipyretic and analgesic properties. It is able to suppress the prostaglandin synthesis like that of other NSAIDS and induce an anti-inflammatory effect (Naproxen, 2013).
Mechanism of action: Naproxen’s mechanism of action is concerns with the cyclooxygenase activity inhibition. Inhibition of COX-1 is related with renal and gastrointestinal whereas inhibition of COX-2 promotes anti-inflammatory effect.
Naproxen undergoes a very fast and complete absorption from the gut. It’s bioavailability is 95% in vivo (Naproxen - Description and Clinical Pharmacology, 2014). With regard to the magnitude of peak concentration (Cmax) and absorption (AUC), naproxen’s various dosage forms remain bioequivalent.
But certain variations in the absorption patterns exist with the products of naproxen.
Such variations between naproxen products have an association with the naproxen’s chemical form that is in use and its formulation. In addition, the differences in absorption pattern do not alter the elimination half‑life of naproxen in all its products for a duration of 17 hours.
Within four to five days, naproxen reaches its steady‑state levels and the magnitude of its accumulation is persistent with such half-life period. So, the variations in the pattern of naproxen’s release play only a least role in achieving a steady-state plasma level.
Some of its brand names include Aleve, Anaprox, Naprsyn, Naprelan.
Indications: Naproxene indications are for treating tendinitis, acute gout, ankylosing spondylitis, osteoarthritis and rheumatoid arthritis (Naprosyn, 2014).
The dose of naproxen sodium, for instance NAPRELAN® is either two 375 mg once daily or two 500 mg once daily. But, according to a given patient’s clinical response, the dose of naproxen sodium could need up or down adjustments during long-term administration (Naprosyn, 2014).
Caution is needed when higher dose appear mandatory.
The adverse reactions of naproxen are two to ten times more frequent in patients who receive a chronic treatment than those receiving short‑term treatment for mild to moderate pain.
The reactions involve aberrations of gastrointestinal tract involving nausea, constipation, diarrhea, abdominal pain, stomatitis, heartgurn and dyspepsia. Other problems include
headache, drowsiness, dizziness, vertigo, skin eruptions, pruritis, tinnitus, edema, dyspnea palpitatation and thirst (Naprosyn, 2014).
a) Drug- Drug: Davies and Anderson (1997) have demonstrated that drug interactions of naproxen with methotrexate and lithium,
Naproxen could induce increased plasma level elevation of lithium levels and decreases renal clearance. Likewise, Naproxen was shown to suppress the methotrexate accumulation competitively in animal models. It also decreased the tubular secretion of methotrexate.
When taken with selective serotonin reuptake inhibitors (SSRIs), they enhance the bleeding risk (Naprosyn, 2014).
So, the drug interactions of naproxen appear to improve the toxic reactions in patients. Hence, they should be observed carefully.
b) Drug- lab: Naproxen was shown to reduce the aggregation of platelets and increase the bleeding time. Further, the urinary levels of 17- ketogenic steroids for were increased with Naproxen administration (Naprelan, 2007).
The reason is that Naproxen interacted with m-di-nitrobenzene that were employed in the assay. If the Porter-Silber test is to be used for patients, naproxen administration needs to be stopped temporarily for 72 hours prior to any adrenal function tests (Naprelan, 2007).
c) Drug food: Naproxen could interact with alcohol which later could increase the stomach bleeding risk. It could interact with milk or food and leads to irritation of stomach (Bushra, Aslam & Khan, 2011).
Available research evidence mentions that Naproxen is potent anti-inflammatory and anti-pyretic drug. Especially, its antipyretic effect was shown to be significant in overcoming the
palliation of fever-associated symptoms in women suffering from gynecologic cancer (Economos et al., 1995). A special combination, Nitric oxide (NO)-naproxen was shown to be reliable in managing colon and urinary bladder carcinogenesis (Steele et al., 2009).
Next, the analgesic and anti-inflammatory properties of Naproxen had been exploited by researchers while studying the efficacy of physical therapy. Here, in a randomized trial carried out for 14 days, Borenstein, Lacks and Wiesel (1990) used the combination of naproxen regimen and Cyclobenzaprin as an adjunct to the physical therapy. The trial was on patients with painful, musculoskeletal aberrations.Combination therapy contributed to increased tenderness, lumbar spine motion and low objective muscle spasm, thus indicating its benefits (Borenstein, Lacks & Wiesel, 1990).
So, the effects of naproxen could be of special concern to the physical therapist who must be
a) Aware of its benefits when used in combination mode as an adjunct and
b) Cautious of its adverse reactions when used alone.
The implications of physical therapy and Physical therapist’s role:
The implications of physical therapy are bright in terms of pain management during problematic situations associated with musculoskeletal, neurological and psychiatric domains (Kumar& Saha, 2011) Physical therapist could play vital role in relieving the pain. Physical therapy involves manual therapy, actinotherapy, electrotherapy and exercise therapy. Physical therapists understand, evaluate and treat patients by applying specific mechanism-based clinical reasoning of pain (Kumar& Saha, 2011). However, research shows that physical therapists do not rely on pharmacological management at a significant rate.
For instance, patients with arthritis could get relief when the treatment is tailored. It may involves both physical therapy and analgesics like ibubrofen (deAngelo & Gordin,2004). The objective of physical therapists for such patients is to minimize the adverse effects of pharmacologic therapy and manage the pain.
So, a physical therapist could attempt to reduce a dependence on NSAIDs (Ibubrofen or Naproxen) and improve the strength through approaches that are comparatively efficacious and safe.
It can be concluded that non-selective NSAIDs are potent therapeutic drug agents. They have proven anti-inflammatory and antipyretic properties that make them promising candidates for clinical therapeutics. Especially, drugs like Ibubrofen and Naproxen have a well established pharmaceutical profile supported with research data. Their clinical relevance could not be under-estimated. However, certain adverse reactions appear to raise concerns among the health care professionals and the users. If the users/patients practice the precautionary measures, then NSIADS could cater their needs though it may be a conventional drug therapy or physical therapy. Therefore, Ibuprofen and Naproxen could be the reliable NSAID drugs of choice for the health care community.
Borenstein, D.G., Lacks, S. & Wiesel, S.W. (1990). Cyclobenzaprine and naproxen versus
naproxen alone in the treatment of acute low back pain and muscle spasm. Clin
Bushra, R.and Aslam, N. (2010). An Overview of Clinical Pharmacology of Ibuprofen. Oman
Med J, 25(3), 155–1661.
Bushra,R., Aslam, N.& Khan, A.Y. (2011).Food-Drug Interactions.
Oman Med J, 26(2),77–83.
Daily, E.B. & Aquilante, C.L. (2009). Cytochrome P450 2C8 pharmacogenetics: a review of
clinical studies. Pharmacogenomics, 10 (9), 1489–1510.
Davies, N.M. & Anderson, K.E.(1997). Clinical pharmacokinetics of naproxen. Clin
De Angelo,N.A. & Gordin,V. (2004). Treatment of Patients With Arthritis-Related Pain.
J Am Osteopath Assoc November,104,2S-5S.
Economos, K., Lucci, J.A., Richardson, B., Yazigi, R. & Miller, D.S. (1995).The effect of
naproxen on fever in patients with advanced gynecologic malignancies. Gynecol Oncol.
Ibubrofen. (2014). Retrieved
Kumar,S.P.& Saha,S .(2011).Mechanism-based Classification of Pain for Physical Therapy
Management in Palliative care: A Clinical Commentary. Indian J Palliat Care,17(1),80–86.
Mazaleuskaya,L., Theken, K.N., Gong,Li., Thorn, C.F., FitzGerald, G.A., Altman,R.S. &Klein.,
T.E. (2014). Ibuprofen Pathway, Pharmacodynamics. Retrieved
Motrin (Ibuprofen) - Description and Clinical Pharmacology .(2014). Retrieved
Naprelan. (2007). Retrieved
Naprosyn. (2014). Retrieved
Naproxen - Description and Clinical Pharmacology. (2014).
Naproxen. (2013). Retrieved http://www.drugbank.ca/drugs/db00788
NSAIDs, (Non-Steroidal Anti-Inflammatory Drugs) (2014). Retrieved
Pajareya, K., Chadchavalpanichaya, N., Painmanakit, S., Kaidwan, C., Puttaruksa, P. &
Wongsaranuchit, Y. (2004). Effectiveness of physical therapy for patients with adhesive
capsulitis: a randomized controlled trial. J Med Assoc Thai, 87(5),473-80
Steele, V.E., Rao, C.V., Zhang, Y., Patlolla, J., Boring, D., Kopelovich, L., Juliana, M.M.,
Grubbs, C.J. & Lubet, R.A. (2009). Chemopreventive efficacy of naproxen and nitric oxide-
naproxen in rodent models of colon, urinary bladder, and mammary cancers. Cancer Prev
Res (Phila),2 (11),951-6.