Drugs are chemical substances used to prepare medications or is used as a medication. “According to the Food, Drug, and Cosmetic Act, drug is a substance used in the diagnosing, curing, mitigation, treatment, or prevention of a disease.”1 Drug nomenclature, also known as naming of drugs is the system that puts drug into classification. The drugs are classified into three name categories mainly Chemical name, the Generic name or Non-Proprietary name, and the Brand or Trade or Proprietary name. 2
A chemical name is given when a new chemical entity is developed. It is the name given to the drug by the International Union of Pure and Applied Chemistry (IUPAC) accordance with rules of chemical nomenclature. Chemical name is useful or chemists or technical personnel as it provide the precise arrangement of atoms and atomic groups in the molecule. However, it is not used to identify the drug in a clinical or marketing situation. 3
The generic or non-proprietary name is a short name given to a drug that is not subjected to proprietary rights. The non-proprietary name or generic name should always be incisive and significant. “In 1948, British Approved Names (BANs) system is established by United Kingdom (UK) to provide convenient generic names. Other countries including the USA, France, Italy and Japan developed similar systems after it. BAN system gives the pharmaceutical substances the official non-proprietary name or generic name based on the British Pharmacopeia. Besides, BAN is used as the official name in the countries of British Commonwealth. Normally, BANs will be approved from the applications of the inventor or manufacturer. United States Adopted Names (USAN) is the American system of nomenclature administered by the USAN Council. USAN Council is sponsored by the American Medical Association (AMA), the United States Pharmacopeial Convention (USPC) and the American Pharmacists Association (APA). The non-proprietary name selected by World Health Organization (WHO) is known as International Non-Proprietary Names (INN). The selection of INN is between the collaboration of WHO and INN experts and national nomenclature committees For each active substance to be marketed as pharmaceutical, the name selected is worldwide acceptable. INN system is aimed to identify the active pharmaceutical ingredients and the pharmaceutical substances . The name selected by the INN system is unique and universally available to be easily identified from each pharmaceutical substance. Clear identification of INN helps in ensuring safe prescription and dispensing of medicines to patients.” 4 “There are two classes of non-proprietary names, approved name and official name. Approved name is the name given to drug by bodies like USAN and BAN after its introduction. This name is sometimes referred to as generic name. However, this term is used to designate a chemical or pharmacological class of drugs such as Sulphonamide and Penicillin. Whereas official names are included in official book and is approved by National Pharmacopeia Commission. This official name must be identical to approved name.” 3
Brand name or proprietary name or trade name is the name given to a drug by the pharmaceutical firm which sells the drug. Once a drug proves successful, it is marketed as a medicine by a company using a proprietary name or trade name. This trade name can be used only by the company which markets the medicine. Thus, a single drug is sold under many proprietary names by different firms. 3 Trade names are specific to the preparation or formulation of the drug rather than the active constituent. When the patent for the drug expires then other companies can produce and market the drug as generic drug however they cannot use the trade name used by the company that invented it. 5
“According to the National Cancer Institute, anti-inflammatory agents are drug or substances that reduce inflammation (redness, swelling and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation. They are used to treat many different conditions. Some anti-inflammatory agents are being studied in the prevention and treatment of cancer.” 6 There are many types of anti-inflammatory agents. The most commonly used anti-inflammatory drugs are the non-steroidal anti-inflammatory drugs (NSAIDs). Non-steroidal anti-inflammatory drugs (NSAIDs) are classification of medicines that have analgesic , anti-inflammatory and antipyretic effects. 7 There are many types of NSAID for example, aspirin, celecoxib, ibuprofen and many more. NSAIDs are often used to relieve symptoms such as headache, sprains and strains, arthritis and even painful periods. Aspirin is considered as an NSAID with ‘blood-thinning’ properties which can reduce the risk of heart attack, reduce fever as well as relieve pain and swelling conditions like arthritis. Ibuprofen often functions to block prostaglandin, a protein that worsens the condition of heavy menstrual bleeding. By blocking the protein, it aids in relieve cramping as well as blood loss from heavy menstrual bleeding. Celecoxib is used to treat pain and inflammation by reducing prostaglandins that cause inflammation and pain in the body.
Even though different NSAIDs have dissimilar structures, they all function by hindering cyclo-oxygenase (COX) enzymes. 7 There are two major forms of COX enzymes which are COX-1 and COX-2. Both two types of COX enzymes produce prostaglandins which has the effect of regulating inflammation. Patients must be very careful while taking NSAIDs as these drugs are not suitable for everyone. Mistaken these drugs may sometimes cause certain side effects for instance, indigestion, feeling sick or nausea and stomach ulcer. In this assignment, we are going to give emphasis to two non-steroidal anti-inflammatory drugs which are ibuprofen and celecoxib.
2.0 Literature Review
The World Health Assembly resolution WHA3.1120 has initiated the INN (International Nonproprietary Names) system that exists now. INN system enables the health professionals to identify each pharmaceutical substance. It also helps to provide safe prescription and dispensing of medication to the patients. INN is unique and is distinctive in sound and spelling. INN is to be used in pharmacopoeias, labeling, drug regulation and others. World Health Organization (WHO) will select the INN on the advice of experts from the WHO Expert Advisory Panel. There are mainly three steps in selecting the INN. Firstly, a request of the INN is made by the inventor of the particular medicine. Next, a review of the request is carried out and a proposed INN will be selected and published. The INN name is free to be comment and after some time, a recommended INN will be published if there is no objection. Usually, INN is designated for the active part of the molecule to prevent any multiplication of names.
According to S. Kopp-Kubel21, World Health Organization (WHO) collaborates with national nomenclature committees to identify the INN that is accepted worldwide for the pharmaceutical product to be marketed. Trade-marks or brand names are given to the marketed product to enable easier identification. Although INNs and trade-marks seem identical to outsider, there is actually a big difference. For example, trade-marks stand for the final drug product whereas nonproprietary names identify the active substances in a pharmaceutical product. In the past, the pharmaceutical products use natural origin and simple names. The use of trade-marks begins when there is introduction of the synthetic substances. As for recent developments in drug nomenclature, the name of the drug is usually requested during the development phase. This means that the WHO will receive the request during the clinical trials of the pharmaceutical substance. In the past few years, the selection process of INN has evolved to be more complex. This is due to the new discovery of the new receptors and pharmacological actions. Besides, new mode of action is also discovered. The protection of INN is made by the WHO Expert Committee. A resolution, WHA46.19 was adopted to make sure the INN is always displayed prominently. Besides, WHA46.19 encourages the investors to use their corporate name and the nonproprietary names. Trade-marks are not encouraged to ensure market multicourse products introduced after the patent of the pharmaceutical substances is expired. Lastly, WHA46.19 aims to develop guidelines for the use of INN.
Based on the guidelines on the use of INN for pharmaceutical substances introduced by WHO22, the INN for radicals and groups has already exist since 1975. However, some radicals and groups what is very complex composition are inconvenient to have chemical nomenclature. Cumulative list is where all INNs are published. Cumulative list is updated periodically. The entry of cumulative list includes equivalent nonproprietary names of the pharmaceutical substances in various languages such as Latin, Russian and English. Next, cumulative list requires a reference of details in which the INN was proposed and last amended. Cumulative list also requires the molecular formula of the pharmaceutical substances. There are many more other criteria to be needed to enter the cumulative list. In this article also, it discuss about the general principles for guidance in devising International nonproprietary names for pharmaceutical substances which includes the characteristics of INN. For examples, the INN should be distinctive, one-word names, short and easily conveyed to patient. Some list of common stems used in the INN selection such as –ac stands for anti-inflammatory agents, -arit that stands for antiarthritic substances and –bradine that represents bradycardiac agents. For the naming of peptides or proteins, the INN experts adopted some general scheme. Firstly, select a stem for the main compound such as –poetin, -irudin and -cog. Next, design a subgroup by expanding the stem. Lastly is the selection of prefix and Greek letter for the compound. There are some national authorities for the application for INN in different countries. Some examples includes Japanese Accepted Names (JAN), British Approved Names (BAN) and United States Adopted Names (USAN).
K. Calvo Campoverde and M. Rojas Volquez commented that hypersensitivity reactions to non-steroidal anti-inflammatory drugs ( NSAIDs) are the most common reactions to drugs.13 The prevalence varying from 0.6-5.7% in the general population towards the hypersensitivity reactions to NSAIDs has proven that there is a risk of being hypersensitive towards an anti-inflammatory drug. Campoverde and Volquez seek to determine the frequency of hypersensitivity to NSAIDs in patients and their clinical characteristics towards the reaction. Their method of research was to separate patients into two groups to determine the diagnosis. The first group included those patients with a single episode that underwent a DPT (Drug Provocation Test) with the suspected drug while the second group the patients with a history of more than one episode cause by a single drug diagnosed with hypersensitivity to NSAIDs based on clinical data that did not undergo DPT with the suspected drug. Their field of patients consists of 1-18 years old patients.13 Ibuprofen was found to be consistent in inducing HS among the children.13 All patients tolerated paracetamol except for one patient diagnosed with multiple HS towards two or more chemically non-related NSAIDs. Out of a total of 93 children studied, 26 were diagnosed with hypersensitivity to NSAIDs: 7 confirmed by oral DPT, and 19 based on clinical data. Multiple hypersensitivity was diagnosed in 50% of patients. Ibuprofen was involved in all reactions. The most common clinical manifestation was angioedema (44%). Acetaminophen was the best tolerated alternative drug. Paracetamol may be considered a safe alternative to ibuprofen, as 96.2%of children tolerated it. However, tolerance to it must be confirmed by a DPT.13 Meloxicam may be an option in patients that do not tolerate paracetamol, but it is not indicated in children younger than 15 years of age. In conclusion, more than one quarter (28%) of the population studied was diagnosed with hypersensitivity to NSAIDs, and 50% had multiple hypersensitivity. Acetaminophen is a safe alternative in children with hypersensitivity to NSAIDs. Meloxicam may be an alternative in cases that do not tolerate acetaminophen.13
J. K. Buer14 reported on a historical appraisal of the name non-steroidal anti-inflammatory drugs. It has the acronym which is NSAIDs. The term NSAID reminds that pharmaceutical designations and classes are complicated national and social products that have been made by particular society, for particular reasons, throughout particular chronological procedures. The first two letters of the NSAIDs acronym place the directions for query to the origin of the phrase. Corticosteroid treatment was first presented in 1949 and became the miracle cure, and then found to have many side-effects.14 The term “non-steroid” then arose in early 1960s, after the fall of steroid and before the revival of low-dose steroid treatment in 1980s. the earliest appearance of the word “non-steroid anti-inflammatory” was in 1963 by Professor Michael W Whitehouse of Griffith University, Brisbane Australia in his article “A biochemical distinction between non-steroid anti-inflammatory and analgesic drugs”. From then, the phrase non-steroid anti-inflammatory drugs have been worked on for wider research. An “International symposium of non-steroidal anti-inflammatory drugs” was held in Milan in September 1964, followed by the printing of a publication with this term in its title. The acronym NSAIDs was first used in 1973, and subsequently gained popularity with widespread use of it.14 Buer stated that in medical literature and everyday language and practices, drug categories such as NSAIDS are often taken at face value, which is seen as a phenomenon existing in their own right. NSAIDs being created as complex cultural, social, historical invention which have worked in our world for many years and may years to come.14
H. E. Paulus and M. W. Whitehouse15 reported that the testament of the anti-rheumatic properties of recent medication in patients founds to certain extent the rationality of rat oedema assays in favour of choosing moderately potent non-steroidal “anti-inflammatory” drugs (NSAIDs). However, the clinical requirement for extra homologous compounds will reduce, and it will then be imperative to evolve truly new categories of agents as more new NSAIDs reach general use. E-type prostaglandins (PGEs) have been found to be possible cause of inflammation, and NSAID is able to impede the making of PGE from arachidonic acid. Aspirin, indomethacin, and salicylate have shown their effectiveness in preventing the synthesis of PGE. The effectiveness of NSAIDs as prostaglandin synthetase inhibitor resemble their effectiveness against carrageenin-induced inflammation. It was found that the outcome of NSAIDs is on PGE synthesis or release, rather than an immediate antagonism on produced PGE. NSAIDs have paradoxical effects, where labialization of enzyme release from lysosomes has been reported. Aspirin impedes adenosine diphosphate (ADP) liberation from platelet, and other NSAIDs also affect platelets, such as Indomethacin which is more potent than aspirin, mefenamic acid, flufenamic acid, and phenylbutazone.15 Other NSAIDs use after aspirin intake did not impedes platelet accumulation to considerable extend compared to aspirin itself, indicating that both NSAIDs and aspirin incorporate with common receptor, but only aspirin persistently blocks the receptor. NSAIDs may interact with one another that the interaction does not enhance the pharmacological activity, but the incorporation of hydrocortisone with one NSAID results in considerable impediment of paw oedema.15 Besides, plasma binding of a second NSAID might be altered prior to aspirin ingestion. NSAIDs are unable to preserve bovine serum albumin (BSA) from chemical denaturation but able to preserve canine erythrocytes to certain extent of detergent-induced and thermal denaturation.15
J. K. Buer24 reported on a historical appraisal of the name non-steroidal anti-inflammatory drugs. It has the acronym which is NSAIDs. The term NSAID reminds us that pharmaceutical designations and classes are not a priori given; they are complicated national and social products that have been made by particular society, for particular reasons, throughout particular chronological procedures. The first two letters of the NSAIDs acronym place the directions for query to the origin of the phrase. Corticosteroid treatment was first presented in 1949 and became the miracle cure, and then found to have many side-effects. The term “non-steroid” then arose in early 1960s, after the fall of steroid and before the revival of low-dose steroid treatment in 1980s. the earliest appearance of the word “non-steroid anti-inflammatory” was in 1963 by Professor Michael W Whitehouse of Griffith University, Brisbane Australia in his article “A biochemical distinction between non-steroid anti-inflammatory and analgesic drugs”. From then, the phrase non-steroid anti-inflammatory drugs have been worked on for wider research. An “International symposium of non-steroidal anti-inflammatory drugs” was held in Milan in September 1964, followed by the printing of a publication with this term in its title. The acronym NSAIDs was first used in 1973, and subsequently gained popularity with widespread use of it.
The use of aspirin and other nonsteroidal anti-inflammatory drugs have been studied by Diana C. Farrow and Thomas L. Vaughan in the risk of oesophageal and gastric cancer.25 Farrow and her researches noted that regular uses of aspirin and other NSAIDs are at reduced risk of colon cancer, but the evidence for protective effects of NSAIDs elsewhere in digestive tract is scant.25 Farrow studies the association between the use of NSAIDs and risk of esophageal and gastric cancer using data from a large population-based, case-control study. Their area of study included individuals, ages 30-79 years, diagnosed with esophageal adenocarcinoma, esophageal squamous cell carcinoma, gastric cardia adenocarcinoma and noncardiac gastric adenocarcinoma.25 The findings of this research add to the growing evidence that the risk of cancers of the esophagus and stomach is reduced in users of NSAIDs, although whether the associations are causal in nature remained unclear. The use of aspirin and other NSAIDs was associated with an approximately 50% decrease in risk of both squamous cell carcinoma and adenocarcinoma of the esophagus. Aspirin and other NSAIDs act as cyclooxygenase inhibitors and thereby inhibit the synthesis of prostaglandins. These prostaglandins affect tumor cell growth, metastatic potential, and host immune function in experimental systems. The risk of NSAIDs use may outweigh the potential benefits in preventing esophageal and gastric tumor in low-risk populations. A randomized trial of NSAIDs might be appropriate in patients with high-risk conditions such as Barrett’s esophagus. A chemoprevention trial might also be targeted in geographic areas with exceptionally high rates of squamous cell cancer of the esophagus, particularly among residents with chronic esophagitis.25

3.0 Discussion
3.1 Ibuprofen
Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and fever-reducing effect. Ibuprofen is widely used to relieve symptoms of pain, fever and inflammation.

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Structure formula of ibuprofen
Ibuprofen is basically the non-proprietary name. The non-proprietary name for ibuprofen can also be (RS)-ibuprofen. The chemical name for Ibuprofen is known as (2RS)-14-(2-methylpropyl) phenyl propanoic acid. Trade names of ibuprofen include, Amibufen, Brufen and Ibumetin.11
Ibuprofen is derived from structure of arylacetic acids. These compounds are usually known as “profens”. The profens are a category of non-selective, non-steroidal anti-inflammatory drugs (NSAIDs). 9 All of the agents are strong organic acids which have pKa between 3 to 5. Therefore, the agents can form water soluble salts if it is mixed with alkaline reagents. At physiologic pH, the compounds are mainly ionized. Moreover, the compounds are more lipophilic than salicylic acid.
In order to enhance cyclooxygenase inhibitory activity and decreases toxicity of profens, ?-CH3 substituent present in profens. Chiral ?-carbon is found in the compounds. Cyclooxygenase inhibitor is less potent than S-(+)- enantiomer of profens. 8 Normally, profen products are available mostly as their racemates, which means equal mixture of the R and S stereoisomers, 9 except for naproxen (NaprosynTM). On the chiral carbon, there is stereospecific transformation of the out of action R-enantiomers to the in action S-enantiomers. Profens go through a metabolic inversion. 8 Activation of additional acidic ?-carbon thioester intermediate proceeds. Generally, S-(+) isomer is the only one present in plasma.
Normally, profens are studied to be a little “COX-1 selective”. For COX-2, other members of this sequence showed less selective than naproxen. 8 They are used for rheumatoid arthritis, osteoarthritis and as analgesics and antipyretics. It can go into fetal circulation and breast milk, thus it should not be used during pregnancy or nursing. It produces more salicylates than GI ulceration. Nevertheless, it may cause some headache, dizziness, thrombocytopenia and fluid retention edema.
Most of the profens are bound by plasma proteins. Metabolic transformations that the profens experience is mainly depend on the structure of the lipophilic functionality existing in the compound. It is reviewed as alkyl substituted for ibuprofen, ?, ?-1 and benzylic oxidation which results in the loss of activity. Electron rich aryl for flurbiprofen and fenoprofen undergo ring oxidation which is a loss of activity. Electron deficient aryl for ketoprofen which has no additional metabolism and methoxynaphthyl go through oxidative-O-dealkylation.
The profens is eliminated by way of metabolites and the elimination is mainly in the urine. Flurbiprofen and ibuprofen contain important non-renal component of elimination. In this category, half-lives of all drugs will be less than 4 hours. 8
Ibuprofen is a non-selective inhibitor of cyclo-oxygenase-1 (COX-1) and Cyclooxygenase-2 (COX-2). 10 It may contain weaker anti-inflammatory properties than some of other NSAIDs. However, it has a noticeable antipyretic and analgesic which is pain-relieving function. During the synthesis of prostaglandins, inhibitory actions on cyclo-oxygenase are concerned. Prostaglandins have significant function in the production of fever, pain and inflammation. 10
Ibuprofen is provided as suspension or tablets with a potency of 200 to 800 mg. Generally, the dose of ibuprofen between 400 to 800 mg is used each day for three times. It has good absorption through oral administration route. Through a serum half-life of 1.8 to 2 hours, it is quickly bio-transformed. 10 Ibuprofen is eliminated through metabolism. Within 24 hours after the last dose, it can be eliminated entirely. Ibuprofen is more than 99% protein bound. In the liver, it is highly metabolized and small quantity of it is excreted unchanged. 10
If patients have allergic response to ibuprofen, severe allergic reaction after taking aspirin or others NSAIDs, or have asthma attack histories, ibuprofen should be avoided. Patients with cardiovascular diseases, connective tissue diseases (Sjogren’s syndrome, lupus or Marfan syndrome), chronic kidney disease, high blood pressure, diabetes, high cholesterol, heart attack history, stomach bleeding and ulcers history, asthma, stroke or liver disease should consult health care professions to ensure that ibuprofen is safe to use. Unborn baby may be harmed during the last 3 months of pregnancy if ibuprofen is taken. 12 Therefore, pregnant woman should not take ibuprofen without health care professions guidance.
There are some unwanted side effects caused by ibuprofen. The common major side effects are indigestion, nausea, vomiting, noisy and rapid breathing, rash with flat lesions, diarrhea, swelling of body parts, weigh gain, heart burn, small raised lesion, unusual weakness and tiredness and abdominal pain. The minor side effects are depression, have no pleasure or interest, runny nose, paranoia, overreact or fast to react, swiftly changing moods and loss of appetite. However, there are some very rare side effects such as bleeding gums, agitation, peeling, loosening of skin, blistering, blood in urine, bloody, black, or tarry feces, blurred vision, burning feeling in chest or stomach, pain in chest, coma, confusion, constipation, coughing, urine is dark in colour and reduced of urine output.
The symptoms of overdose are bluish skin, insomia, disorientation, hallucination, dizzy, headache while getting up from a lying or sitting position suddenly, drowsy, profound coma and fainting.
There are some drug-drug interactions, drug-food interactions and drug-disease interactions with the use of ibuprofen. There are sum of 424 drugs are recognised to have interactions with ibuprofen.20 There are major, moderate and minor drug interactions. For instances, aspirin, cidofovir, danaparoid, iopamidol and omacetaxine are the medications known to react with ibuprofen. The example of drug-food interaction is the interaction of ibuprofen with alcohol. Alcohol should not be taken while taking ibuprofen because the risk of stomach bleeding will be increased. The disease that interact with ibuprofen are hypertension, asthma, ,hepatotoxicity, anemia, heart failure and hyperkalemia.
3.2 Celecoxib

Structural Formula of Celecoxib
Celecoxib is known as a non-steroidal anti-inflammatory drug (NSAID). Celecoxib works as a COX-2 ( cyclooxygenase 2) inhibitor.16 The general use of Celecoxib is to relieve discomfort and swelling (inflammation). Celecoxib is used to treat osteoarthritis, rheumatoid arthritis, acute pain, and menstrual pain. Prostaglandins are chemical substances that are important contributors to the inflammation of arthritis that causes pain and swelling. Celecoxib blocks the enzyme COX-2 that makes prostaglandins.17 This lowers the concentrations of prostaglandins. The therapeutic effect induced is the reduction of pain, fever, swelling and tenderness. Celecoxib varies from other Non-Steroidal Anti-Inflammatory Drugs (NSAID) because it causes less inflammation and formation of stomach and intestine ulcers with short-term use. It also does not interfere with the clotting of blood.18
NSAIDs have been found to prevent the formation and reduce the size of polyps in patients.16 Patients suffering from polyps are closely associated with the genetic disease, familial adenomatous polyposis (FAP).17 In FAP, patients develop large numbers of polyps in their colons, and the polyps have a risk of becoming malignant. The only cure of FAP is the removal of the entire colon.16 Celecoxib is approved as an adjunctive (secondary) treatment among patients with FAP. The cramping and pain during menstrual periods is due to prostaglandins. The usage of celecoxib reduces the cramps and pain by blocking the production of prostaglandins. Celecoxib was approved by the FDA in December 1998.17
There are various trades name for Celecoxib.18 The chemical structure of Celecoxib is 4-5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-ylbenzene-1-sulfonamide with the chemical formula of C17H14F3N3O2S. The trade names or proprietary names include Celebrex and Act Celecoxib as the prescription products. Celebrex was labelled by the company Pfizer while Act Celecoxib was labelled by the Actavis Pharma Company. Some generic prescription products names include Accel-celebrex and Apo-celecoxib. Accel-celebrex was introduced by Accel Pharma Inc. while Apotex Corporation started marketing Apo-celecoxib in November 2014.18
COX-2 inhibitors contain analgesic, antipyretic as well as inflammatory activity.19 They are used therapeutically for example osteoarthritis, rheumatoid arthritis, acute pain and primary dysmenorrhea. In addition, the selectivity of COX-2 may cause less production of GI ulceration and hemorrhage as compared to other NSAIDs. Besides, COX-2 inhibitors have minimal renal and cardiovascular side effects plus they do not inhibit platelet aggregation too. Patients should be very careful while consuming these drugs as the side effects may risk a patient’s life. The side effect of Celecoxib includes kidney failure, blurred vision and water retention. Patients who are pregnant should not take these drugs as they endorse closure of ductus arteriosus.19
COX-2 inhibitors have good absorption and they are able to produce peak plasma levels within 3 hours. When sulfonamide is present in celecoxib, it will be more acidic as compared to sulfone.19 Besides, plasma protein is highly bound to celecoxib. Celecoxib contains benzyl group which is the only functional group that is present in celecoxib which they can be metabolized efficiently. Drug inactivation and clearances are caused by complete oxidation and conjugation at this position.
The duration of action of COX-2 inhibitors is quite long which may be longer than 10 hours due to the slow clearance. Celecoxib is usually eliminated in the feces while both compounds actually show balanced excretion. Some of the drugs, for instance, valdecoxib are considered weak inhibitors of cytochromic enzymes.19
Celecoxib often used to treat pain or inflammation that is caused by conditions for example arthritis, ankylosing spondylitis as well as menstrual pain. It works by reducing the production of hormones that cause the inflammation and pain in the body. Moreover, celecoxib can also be used to treat a disease known as juvenile rheumatoid arthritis which occurs in children who are at least 2 years old. Furthermore, it also used in the therapy of hereditary polyps in the colon.
If a patient uses the celecoxib for a long term, while taking it with high doses or having heart disease, the risk of fatal heart attack or stroke will increase. Even though for people without heart disease or any risk factors, there are still minimal chances of getting shock or maybe heart attack when consuming this medicine.23
Celecoxib can also contribute to the reasons of stomach or intestinal bleeding, which can put patients’ health in danger. Patients may be unaware of the conditions that occur as the conditions may occur without warning while taking these medicines, particularly older adults.19
Celecoxib must not be used before or after heart bypass surgery (coronary artery bypass graft, or CABG). Besides, one should not take celecoxib if he or she is allergic to it or have stomach or intestinal bleeding. Furthermore, if a patient has history of asthma attack as well as allergy to sulfa drugs must not take celecoxib too. Some patients who have allergic reaction after taking aspirin or an NSAID should avoid taking celecoxib too.
Patients should inform their health care professions about their health conditions such as high blood pressure, high cholesterol, diabetes, consuming cigarettes, a history of congestive heart failure, stroke, or blood clot, a history of stomach ulcers or hemorrhage, asthma, liver or kidney disease or fluid retention to ensure celecoxib is safe to use. While for a pregnant woman, she must inform the doctor that she is pregnant, particularly if it is the last few months of the pregnancy. If you plan to become pregnant or breastfeeding, celecoxib intake has to be avoided. Consuming celecoxib before the last 3 months of labour may hostile the fetus.23 A nursing baby could be harmed by celecoxib due to it passing through breast milk. The use of celecoxib is only encouraged for infants who are older than 2 years old.23
There are some side effects caused by celecoxib. The major side effects are cough, fever, skin rash, sneezing, sore throat and swelling of the face, fingers, feet, or lower legs. The rare common effects are abnormal growth in the breast, bloody or black, tarry feces, blurred vision, burning feeling in the chest or stomach, burning or stinging of the skin, burning, tingling, numbness, chest tightness, chills, confusion, congestion in the chest, cramps, diarrhea, dry mouth, earache, fast or irregular heartbeat, heartburn and heavy bleeding. Moreover, there are some symptoms of overdose. For instances, continuing thirst, dizziness, drowsiness, headache, severe or continuing, shortness of breath, sudden decrease in the amount of urine, troubled breathing and weight gain.19
Celecoxib is normally taken by mouth as capsule. Generally, it is taken once or twice a day. When taking up to 200 mg of celecoxib at once, medication could be taken with or without food. However, when taking more than 200 mg of celecoxib at once, medication should be taken with food. Celecoxib is also sometimes used with surgery and other treatments to reduce the number of polyps in the large intestine and rectum in patients who have familial adenomatous polyposis, which is a condition that hundreds or thousands of polyps form in the colon and cancer may develop.
There are 628 drugs which sold under 3606 brand names will interact with celecoxib.22 The level of drug interactions can be differentiated into minor, moderate and major.The examples of major drug interactions are interactions of celecoxib with adefovir, diatrizoate, eliglustat, and ioxilan. The minor drug interactions are interactions of celecoxib with delavirdine, donepezil, plavix, raneza and tolterodine. The diseases that have interactions with celecoxib are rash, GI toxicity, asthma, thrombosis, anaemia, hepatotoxicity and fluid retention.
3.2.1 Pharmacokinetics of Celecoxib19
After oral administration, celecoxib is rapidly absorbed and obtains peak serum concentration in approximately 3 hours. It is extensively metabolized in the liver, with very little drug (< 3%) being eliminated unchanged. The major routes of excretion for celecoxib are feces and urine. Celecoxib is metabolized primarily through methyl hydroxylation to form hydroxycelecoxib. This reaction is largely catalyzed by CYP2C9, although CYP3A4 also plays a minor (< 25%) role. Hydroxycelecoxib is further oxidized to form carboxycelecoxib by cytosolic alcohol dehydrogenases ADH1 and ADH2, then conjugated with glucuronic acid by UDP glucuronosyltransferases to form the 1-O-glucuronide. None of the metabolites are pharmacologically active. The biotransformation of celecoxib in the liver is to ease the elimination of the drug out of the body.
As celecoxib metabolism is predominantly mediated by CYP2C9, polymorphisms in CYP2C9 are likely to have a direct impact on celecoxib pharmacokinetics and variability in drug responses. Individuals who are poor metabolizers of CYP2C9 substrates (e.g. CYP2C9*3 allele carriers) have an increased exposure to celecoxib when compared with those with normal CYP2C9 activity. Drug-drug interactions may occur in cases where drugs that inhibit CYP2C9 activity should be used with caution in patients who are taking celecoxib. The other drug-enzyme interactions are the interrelation between CYP2D6 enzyme. Celecoxib inhibits CYP2D6 enzyme although it not being a substrate of the metabolic enzyme. The metabolic activity of CYP2D6 (metabolism of metoprolol) can be inhibited by celecoxib. Thus, patients using celecoxib must be cautious in taking other drugs due to a potential risk of drug interactions.19
3.2.2 Pharmacodynamics of Celecoxib19
Celecoxib exerts its anti-inflammatory and analgesic activities through blocking the synthesis of various inflammatory prostanoids (PG). The prostanoids, which include PGs and thromboxane, are the end products of fatty acid metabolism produced by tissue-specific COX enzymatic activity. These products are important physiological and pathological mediators that are involved in a wide range of biological processes including inflammation, pain, cancer, glaucoma, osteoporosis, cardiovascular diseases, and asthma. The production of the prostanoids (PG) is dependent on the availability of arachidonic acid (AA). Following stimulation of the cell membrane by inflammatory or mitogenic signals, the first step in PG synthesis is the release of AA from the cellular phospholipids through the action of either secretory (sPLA2, encoded by gene PLA2G2A) or cytoplasmic (cPLA2, encoded by gene PLA2G4A) phospholipases. Once AA is released, the two isoenzymes, COX-1 (encoded by PTGS1) and COX-2 (encoded by PTGS2), catalyze the production of the prostanoids (Fig. 2) 25. As indicated above, this involves two sequential reactions. The initial COX reaction converts AA into PGG2. The second reaction reduces PGG2 to PGH2. PGH2 is then converted into active metabolites PGE2, prostacyclin (PGI2), thromboxane (T×A2), PGD2, and PGF2? by the action of tissue-specific PG synthases 26,27. These active metabolites interact with specific prostanoid G-protein-coupled receptors to mediate diverse physiological responses, such as inflammation, fever, blood pressure regulation, clotting, and gastrointestinal protection.
The COX-1 and COX-2 enzymes exhibit distinct expression profiles and roles in physiological processes. COX-1 is constitutively expressed in many cell types and is the major COX isoform in gastric tissue. It is responsible for the protection of the gastric mucosa, which led to the development of the ‘COX-2 hypothesis’ that drugs targeted against COX-2 only would have reduced upper gastrointestinal toxicity.19 Although COX-2 is highly inducible by inflammatory stimuli such as cytokines, growth factors, and tumor promoters, it is also constitutively expressed in some tissues, such as the vessel wall, the kidney, or the heart. Indeed, the depression of the physiological formation of COX-2-dependent prostanoids in these tissues has been identified as the molecular mechanism underlying the thrombotic cardiovascular complications of COX-2 inhibition. Seven placebo-controlled, randomized trials with three chemically distinct pdCOX-2 inhibitors, including celecoxib, have documented the cardiovascular risk. Of note, celecoxib is now used at lower doses than in the trials that showed its cardiovascular hazard. Celecoxib has 30-fold greater inhibitory activity against COX-2 compared with COX-1, and inhibits COX-1 only minimally at therapeutic concentrations. Although the selectivity for COX-2 measured in vitro is lower for celecoxib compared with other drugs in the coxib class (e.g. rofecoxib, valdecoxib, lumiracoxib, and etoricoxib), it is very similar at therapeutic concentrations in vivo. Celecoxib also retains more ability to inhibit COX-1 compared with other coxibs; however, the consequences of this with regard to its therapeutic efficacy and toxicity are not well understood.19

3.3 Ketorolac
Ketorolac is a non-steroidal anti- inflammatory drug (NSAIDs) which is used to treat pain and inflammation by reducing hormones in body that causes pain and inflammation. Other drug of anti-inflammatory drugs include naproxen, aspirin and ibuprofen, but ketorolac is more effective comparing to the other NSAIDs in the therapeutic effects.25
Ketorolac is the non-proprietary name of the drugs. The other name of ketorolac is ketorolac tromethamine. It comes from the pyrrolopyrrole group in non-steroidal anti- inflammatory drug NSAIDs. The chemical name of ketorolac is (±)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1).

Chemical structure of ketorolac

Ketorolac exist in three solid crystal form which has an experimental melting point of 160.5 °C. All forms are equally soluble in water. It has a pKa of 3.5 and an n-octanol/water partition coefficient of 0.26. Molecular weight of Ketorolac is 376.41. Its molecular formula is C19H24N2O6. The trade names of ketorolac are Toradol, Acular, Sprix and others. Ketorolac is derived from heterocyclic acetic acid, analgesic used, and is commonly known as a first generation NSAID. An analgesic is the group of drugs to relieve pain.
Ketorolac is widely used as a short term management on pain in the emergency department for severe pain. It is not recommend to be prescribed for more than five days. It is available commonly in three forms which is the oral, intranasal and intramuscularly in solution form to relieve pain in both animals and human beings.
Orally used ketorolac is packaged as a round white, red printed, film-coated tablets. Under normal condition, 10mg of active ingredients, ketorolac tromethamine is added with magnesium stearate, lactose and microcrystalline cellulose in each tablet. Hydroxypropyl methylcellulose, titanium dioxide and polyethylene glycol is the ingredients of the white film coated.
Risk of life-threatening heart or circulation problems, including heart attack or stroke will increase if ketorolac is used for long term medication. Ketorolac is not recommended for patient undergoing heart bypass surgery. The patient is recommended to seek for help from the professionals when there are symptoms regarding heart or circulation problems. For example, the symptoms possible are chest pain, weakness, hardness on breathing, shortness of breath, or problems with vision or balance. Besides that, there is also risk of gastrointestinal side effect such as bleeding and perforation may occurs especially on senior citizens .28

Pharmacodynamics of ketorolac
The mechanism action of Ketorolac tromethamine is like any other NSAIDs. It is not completely similar but may be related to prostaglandin synthetase inhibition. In ketorolac, biological activity is associated by (-)S-form. No anxiolytic or sedative properties is possessed by ketorolac tromethamine. 26 Within 2 to 3 hours, the peak analgesic effect of ketorolac occurs and it differs within different age range human and also human and animals over the recommended dosage range. The duration of analgesia is the biggest difference between different dosage of ketorolac. 29
Pharmacokinetics of ketorolac
The racemic mixture of ketorolac is in -S- and +R-enantiomeric forms. The -S-enantiomeric forms performs analgesic activity. For adults, a single dose of ketorolac either with oral, IM or IV route is recommended because the clearance of racemate does not change. Therefore, it is proposed that the pharmacokinetics of ketorolac tromethamine in adult is linear in single or multiple doses in different administration. Proportional increase in the concentrations of free and bound racemate happens when the dosage is increase. 26
Absorption
Ketorolac is 100% absorbed after oral administration. The peak and time-to-peak concentrations of oral administration ketorolac will be decreased upon intake of fatty meal. Antacids did not affect the extent of absorption. 27
Distribution
From a single dose data, the mean apparent volume (V) of ketorolac tromethamine upon complete distribution is approximately 13 litres. 99% of the ketorolac tromethamine racemate will bound with the protein. However, only 5% of the albumin will be binded. Thus, the unbound fraction for each enantiomer will be constant over the therapeutic range. A decrease in serum albumin, however, will result in increased free drug concentrations27
Metabolism
Ketorolac tromethamine is largely metabolized into hydroxylated and conjugated forms in the liver. The products of metabolism, and some unchanged drug, are excreted in the urine. 27
Excretion
Renal excretion is the principal route of elimination of ketorolac and its metabolites. About 92% of a given dose is found in the urine and 6% of a dose is excreted in the feces. Study has shown that the excretion of S-enantiomer is two times faster than the R-enantiomer The clearance depends on the route of administration. This means that the ratio of S/R plasma concentrations decreases with time after each dose. In human, there is little or no inversion of the R- to S- form. The clearance of the racemate in normal subjects, elderly individuals and in hepatically and renally impaired patients. 27
4.0 Conclusion
In conclusion, drug nomenclature is categorized into three main types which are the chemical name, proprietary name and non-proprietary name. Medication errors often occur due to the existence of confusing drug names during health care practice. The confusion in proprietary names and non-proprietary names are giving a potential of error. Each classes of drug are associated with different common stem which reflects the action that carry out by the drug molecules itself. However, some confusion still occurs in the naming system of drugs as the pharmacological effect may similar to each other. Hence, develop a good nomenclature system is essential in order to avoid the occurrence of errors that might cause dangerous effect as well as put patients safety at risk. The issue of medication errors shows that the nomenclature of drugs plays a vital role in the prescription and dispensing process.
Out of the four types of drug nomenclature, non-proprietary name is the most appropriate system to be used to classify each drug by using their specific ‘stem’. The INN system that was developed by WHO had succeed in overcome a lot of problems till today. This system also gave a standard in the method of drugs nomenclature that are been followed all over the world. They have to follow strictly to the guidelines provided while they wish to register their drugs. In addition, there are also a certain selection criteria in choosing an INN of a drug. These includes that the name should not be too long and also should be distinctive in sound and spelling. The new name also should not conflict with any existing common name or trademarks. Besides, new rules and guidelines must be established by the WHO in order to adopt with the world that was extremely having modernization in every aspects nowadays.
Non-steroidal anti-inflammatory drugs (NSAIDs) are the medications that were used in order to lessen inflammation, relieve pain, as well as any other symptoms that are related. Despite it was commonly consumed but on some cases they are not suitable for everyone because each individual carries different genetic and their body react on medicine would also be different from one and another. Some of the patient that consumes those drugs might experience side effects such as indigestion, nausea and stomach ulcer. However, for some other people, the same drug might help to boost their health very well. Thus, every drug has their own pros and cons where not all the consumer experience the same reaction towards the drugs even though they are using the exact same drugs with the same concentration and indication.

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