Prostaglandin inhibitors are drugs that inhibit the synthesis of prostaglandin in human body.^[1] There are various types of prostaglandins responsible for different physiological reactions such as maintaining the blood flow instomach andkidney, regulating the contraction ofinvoluntary muscles andblood vessels, and act as a mediator ofinflammation andpain.^[2][3]Cyclooxygenase (COX) andPhospholipase A2 are the majorenzymes involved in prostaglandin production, and they are the drug targets for prostaglandin inhibitors.^[3] There are mainly 2 classes ofprostaglandin inhibitors, namelynon- steroidal anti- inflammatory drugs (NSAIDs) andglucocorticoids. In the following sections, the medical uses,side effects,contraindications,toxicity and thepharmacology of these prostaglandin inhibitors will be discussed.

NSAIDs are used asanti- inflammatory,antipyretic andanalgesic agents.^[4] They can be administered through different routes, namelyoral, rectal andtopical.^[4] They can relieve mild to moderate pain.^[5] The dosage forms available for different NSAIDs and their respective medical uses are discussed as follows.

The available dosage forms for oral NSAIDs, rectal NSAIDs and topical NSAIDs are shown in the following table.

The common medical uses of oral NSAIDs, rectal NSAIDs and topical NSAIDs are shown in the following table.

	Oral NSAIDs	Rectal NSAIDs	Topical NSAIDs
Medical Uses	1. Common Cold and Flu Oral NSAIDs are commonly prescribed for relieving the symptoms ofcommon cold andflu.[9] They are shown to be effective to alleviate symptoms such assneezing,[9]headache,ear pain,muscle pain andmalaise.[10] However, studies show that NSAIDs are not effective in treatingcough andblocked nose.[10] 2.Postoperative Pain The American Society of Anesthesiologists Task Force on Acute Pain Management recommended the use of oral NSAIDs for managing postoperative pain in 2012.[5] The commonly used NSAIDs for postoperative pain arecelecoxib andibuprofen.[5] Trials have shown that these drugs can reduce pain to at least 50% and they are tolerable by most patients.[5] 3. Migraine The therapeutic goals for migraine treatment aremigraine prevention and symptomatic relief.[11] The majority of oral NSAIDs such as ibuprofen,mefenamic acid, andindomethacin are shown to be effective to treat and prevent migraine.[11] They do not have significant differences in terms of their therapeutic effects and are almost equally potent in migraine therapy.[11] NSAIDs with less side effects are more preferred in migraine therapy.[11]	Prevention of pancreatitis Rectal NSAIDs such asdiclofenac andindomethacin are administered for the prevention ofpancreatitis due toendoscopic retrograde cholangiopancreatography (ERCP).[12] ERCP is a technique for treating liver and pancreatic disease.[7]Acute pancreatitis is the most common complication of ERCP. Therefore, rectal NSAIDs are given to patients before ERCP as a measure to prevent post- ERCP pancreatits. Trials showed that rectal NSAIDs are more effective than oral NSAIDs to prevent post ERCP pancreatitis as it exerts its effects faster and its degree of absorption is higher.[7]	Osteoarthritis Topical NSAIDs, mainly diclofenac, are prescribed for patients withosteoarthritis.[8] They are effectively absorbed in arms and knees. As osteoarthritis is a disease commonly found in the elderly (>65 years old), oral NSAIDs are seldom used as their systemic side effects are more severe in elderly patients.[8] Therefore, topical NSAIDs are used for osteoarthritis to exert its localanalgesic effects and minimize their systemic side effects in elderly patients.[8]

Glucocorticoids are potent anti- inflammatory drugs.^[10] They are mainly administered via oral and pulmonary route.^[10] Oral glucocorticoids are mainly prescribed for the prevention ofchronic disease exacerbation. Inhalable glucocorticoids are effective in treating small airways inflammations.^[10] They are commonly used in the maintenance of chronic diseases, and to relieve symptoms duringacute flare up of airway inflammations such asasthma.^[10] The dosage forms available for different glucocorticoids and their medical uses are discussed as follows.

The available dosage forms for oral glucocorticoids and inhalable glucocorticoids are shown in the following table.

The common medical uses of oral glucocorticoids and inhalable glucocorticoids are summarized in the following table.

	Oral Glucocorticoids	Inhalable Glucocorticoids
Medical uses	Rheumatoid arthritis Rheumatoid arthritis is anauto- immune disorder that affectjoints.[15] The common symptoms are warm, painful and swollen joints.[15] Glucocorticoids exert anti- inflammatory effects to relieve the symptoms by inhibiting the synthesis of prostaglandin andleukotriene, and the release ofcollagenase andlysosomal enzymes.[16]	Asthma Inhalable glucocorticoids are the major drugs used for asthma treatment and maintenance.[13] They suppress airwayinflammation in asthma by inhibiting prostaglandin synthesis, enhancinggene expression of anti- inflammatory proteins, and suppressing inflammatory genes.[17] They also dilate airway by reducing the production ofleukotriene, a potent bronchoconstrictor in the circulation.[17]

The short term use of NSAIDs are rather safe, the manifestations of severe side effects are more commonly seen in the chronic use of NSAIDs.^[16]

The chronic use of NSAIDs inhibit the synthesis of prostaglandins andthromboxanes, which leads to renalvasoconstriction.^[18] This results in a decreased blood flow to the kidneys.^[18] Therefore, patients taking NSAIDs in long term are in higher risk of developing chronic renal diseases andnephrotoxicity due to reduced renal perfusion.

As NSAIDs inhibit prostaglandin synthesis, it reduces the blood flow to the stomach and weakens the stomachmucous membrane, making it more prone togastric acid attack.^[18] This increases the risk of developinggastric ulcers.^[18] This can be prevented by taking drugs such asproton pump inhibitors,H2 receptor antagonists which suppress gastric acid secretions together with NSAIDs.^[18]

NSAIDs retain sodium and water in the circulation, which in turn increase the blood volume andblood pressure in the body.^[18] The production of naturalvasodilator (prostaglandin) is also inhibited at the same time.^[18] Hence, the use of NSAIDs is associated with an increased risk ofcongestive heart failure andhypertension especially for elderly patients.^[18][19]

The chronic use of glucocorticoids suppress the activity ofhypothalamic- pituitary-adrenal (HPA) axis. The severity of HPA axis suppression is directly proportional to the dose and the duration of therapy.^[20] HPA axis suppression results in a weakened immune system, making the patients more prone to infections in long term.^[20]

Short- term use of glucocorticoids creates minor disturbance in human body. The examples of short- term effects created by glucocorticoids arehyperglycemia, oscillation in blood pressure, psychiatric events and electrolyte disorders.^[21] These effects usually can be reversed once the glucocorticoids therapy is stopped.^[20]

As NSAIDs inhibitcyclooxygenase, the production ofthromboxane, a natural coagulator, is inhibited.^[22] Therefore, the risk of bleeding during the use of NSAIDs is intensified by concomitant use ofanticoagulants.^[22]

As NSAIDs reduce blood flow to kidney by inhibiting prostaglandin synthesis, it leads torenal ischemia and a decrease inglomerular filtration pressure.^[22] As a result, the kidney functions of patients withchronic renal diseases is further worsen.^[22]

Glucocorticoids reduces the number of healthyneutrophils in human body, leading toneutropenia.^[23] Neutropenia reduces the efficacy ofantifungal drugs.^[23] Studies show that neutropenia together with high cumulative glucocorticoid concentration in circulation reduce the efficacy of invasive fungal infection treatment.^[23] Therefore, patients with fungal infections are not recommended with the use of glucocorticoids.^[23]

Glucocorticoids raise blood glucose level via different mechanisms. They can stimulateendogenous glucose production by activating the genes involved; reduce glucose uptake by muscle andadipose tissue; induce muscle and adipose tissues to produce substrates involved in glucose production and inhibit the section and production ofinsulin in pancreaticβ cells.^[24] All these raise blood glucose level and exacerbatediabetes mellitus.^[24] Thus, the use of glucocorticoids should be minimized or avoided for diabetes patients.

The most common signs of NSAIDs overdose arenausea,vomiting, blurred vision anddrowsiness.^[16] NSAIDs toxicity can be reversed bygastric lavage.^[16] In severe cases, NSAIDs toxicity can lead to the following clinical conditions.

NSAIDs overdose can lead to acutecentral nervous system toxicity.^[16] It can create CNS effects ranging fromdrowsiness tocoma.^[16] Other symptoms such asataxia,nystagmus,headaches,seizure, anddisorientation are also the reported manifestations of CNS toxicity.^[16]

A large dose of NSAIDs, particularlyibuprofen,naproxen can lead tometabolic acidosis.^[16] Metabolic acidosis can further deteriorate intocardiac arrhythmia andelectrolyte imbalance which can be fatal.^[16]

The overdose of glucocorticoids exacerbate its side effects. Most of the toxicities induced can be reversed by discontinuing the therapy.^[16]

A high dose of glucocorticoids suppress the release ofcorticotropin from thepituitary, leading toCushing's Syndrome.^[16] The symptoms are weight gain on the upper back and the area between shoulders, thinning of arms and legs, and moon face.^[16]

High- dose glucocorticoids increase the risk of patients' infection bybacteria,virus andfungus.^[16] The cells involved in theimmune system are mainlyphagocytes,neutrophils,monocytes,macrophages,natural killer cells,B cells,T cells,eosinophils,basophils andmast cells. Glucocorticoids significantly reduce the production of these cells in the human body, thereby weakening the immune system.^[16]

Pharmacokinetics refers to the study of absorption, distribution, metabolism and elimination of drugs in human body.^[25]

Pharmacodynamics refers to the study of how the drugs exert their actions in human body.^[27]

NSAIDs inhibits the synthesis of prostaglandin by inhibitingcyclooxygenase (COX-1 andCOX-2). NSAIDs with higher selectivity onCOX-2 such asindomethacin,zomepirac anddiclofenac have potent anti- inflammatory activity and fewer side effects on stomach and kidney.^[28][29]

Phospholipase A2 is an enzyme to catalyze the release ofarachidonic acid in our body. After arachidonic acid is released, it can be converted to prostaglandins by cyclooxygenase.^[28] Glucocorticoids work by inhibiting phospholipase A2, hence indirectly inhibiting prostaglandin synthesis.^[28]

• Anti-inflammatory agents