Drug Information about Commonly Used Drugs

By P.P. Sharma

Drug information is something that is needed by all pharma professionals whether in practice, industry, pharmacy education or regulatory. Drug information in this title has been compiled based on their use in disorders of different body systems like gastro-intestinal tract (GIT), respiratory tract, cardio-vascular system. In the introductory section of each part, there is general discussion on different classes of drugs, which are used in the treatment of disorders of the system. Later, there is drug information on individual drugs. There are two chapters, which are not specific to system but deal with common factor, for example pain. These chapters include drugs used in pain, fever, and inflammation and anti-infective drugs. The book has been divided into eight parts. Many pharma professionals may not be conversant with medical terms, therefore, abbreviations and glossary of medical terms have been given in the beginning of the book. There are three appendices in the book. Appendix I contains the list of drugs and their FDC, manufacture and sale of which have been banned in India. Appendix II contains list of schedule X drugs for which separate licence is required for manufacture and sale. Appendix III contains list of medical devices, which have been notified as drugs by Govt. of India.
 

• Language: English
• Publisher: Vandana Publications
• Release date: Aug 27, 2022
• ISBN: 9788190595735

Book preview

PART 1

DRUGS USED IN

PAIN, INFLAMMATION AND FEVER

DRUGS USED IN PAIN, INFLAMMATION AND FEVER

This class of drugs constitutes a number of drugs which are commonly used. Drugs used in inflammatory conditions like arthritis are used for a long period and as such has potential for side effects more than those which are used as and when needed. Drugs used in pain inflammation and fever can be classified broadly into the following classes.

♦Salicylates

♦Non-Steroidal Anti-Inflammatory Drugs (NSAIDS)

♦Narcotic Analgesics

♦Corticosteroids

There are some muscle relaxants (e.g. chlorzoxazone) which though are not analgesic or anti-inflammatory but are often used in pain and inflammation and therefore, these will be discussed in this section only. Muscle relaxants are often combined with analgesics so that pain caused by muscular spasm is relieved.

Analgesic abuse is prevalent almost the world over. Nephropathy (kidney problems) associated with the abuse of analgesics has been recognized from early fifties. A significant number of cases of chronic renal failure can be attributed to the abuse of analgesics. The characteristic features of nephropathy include fever, dys-urea, and protein urea, reduced urine concentrating ability and passage of large number of leucocytes in the urine. Pathological features include papillary necrosis (death or decay of tissue) and interstitial fibrosis of renal cortex and medulla. Often, the condition is associated with peptic ulceration, urinary tract infection, anaemia (low haemoglobin), and hypertension and sodium loss.

In mild cases of analgesic abuse the condition is reversible, if the offending analgesic is withdrawn. But in the serious cases, even if the analgesic is withdrawn, renal function may continue to deteriorate. Patients should be warned to be careful while using analgesics for long time.

1. SALICYLATES

Salicylates have analgesic, antipyretic and anti-inflammatory activity. Aspirin and other salicylic acid derivatives are hydrolyzed to salicylic acid. Although salicylamide and difinusal are structurally related but are not hydrolyzed to salicylic acid. Because of their hydrolysis salicylates are potential gastric irritants. Efforts have been made to synthesize salicylates with less gastric irritant properties, for example, choline salicylate, magnesium salicylate.

The pharmacological actions of salicylates are qualitatively similar. These lower elevated body temperature through vasodilatation of peripheral vessels enhancing dissipation of excess heat. The analgesic and anti-inflammatory actions of salicylates may be mediated through inhibition of prostaglandin synthetase enzyme complex.

Out of this group of salicylates, aspirin differs from others in that it more potently inhibits prostaglandin synthesis, has greater anti-inflammatory activity and irreversibly inhibits platelet aggregation. These distinctions have made aspirin as one of the most commonly used salicylates.

After oral administration, salicylates are rapidly and completely absorbed from gastrointestinal tract. However, bioavailability is dependent on dosage form, presence of food, gastric emptying time (GET), gastric pH, presence of antacids and particle size. Food slows down absorption of salicylates. After absorption, aspirin is distributed extensively to body fluids and tissues. Highest concentrations are found in plasma, liver, renal cortex, heart and lungs. At low doses, half-life of aspirin is 15-20 min. and that of salicylic acid in 2-3 hours. At higher doses, half-life of salicylic acid may be as high as 20 hours. In therapeutic anti-inflammatory doses, half-life ranges from 6-12 hours.

Indications of salicylates include mild to moderate pain, fever, inflammatory conditions like rheumatoid arthritis and osteoarthritis. Out of the salicylates, aspirin has been used for its anti-platelet aggregation activity in heart patients.

Contraindications of salicylates include hypersensitivity to salicylates or other non-steroidal anti-inflammatory drugs (NSAIDs), haemophilia, bleeding ulcers and haemorrhagic status. Magnesium salicylate is contraindicated in advanced chronic renal insufficiency due to magnesium retention. Hypersensitivity is manifested by symptoms like acute bronchospasm, generalized urticaria, severe rhinitis or shock. Incidence of hypersensitivity in asthmatics is about 5-20%. Symptoms occur within three hrs.

Salicylates in general and aspirin in particular may be associated with development of Reye’s syndrome in children and teenagers. Reye’s syndrome is a life threatening condition and is characterized by vomiting, lethargy and belligerence which may progress to delirium and coma. Mortality rate ranges between 20-30%. The condition is so serious that permanentbrain damage has been reported in survivors. Aspirin/salicylates should not be used in children and teenagers particularly in chickenpox or influenza symptoms.

Another important warning in case of salicylates is dizziness and tinnitus (ringing in ears). Probably, tinnitus represents blood salicylic acid levels reaching or exceeding the upper limit of therapeutic range. This probably could be used as helpful guide to dose titration. Use of salicylates should be discontinued if dizziness and tinnitus occurs. Temporary loss of hearing disappears gradually after the use of salicylates is discontinued.

Salicylates cross placenta readily. Salicylates may cause constriction of ductus arteriosus and other foetal effects. Use of aspirin by pregnant women during the later stages may cause adverse foetal effects like low birth weight, incidence of intracranial haemorrhage in premature infants, stillbirths, neonatal death. Therefore, salicylates should not be used during pregnancy, particularly during the last trimester.

Salicylates are excreted in breast milk, the levels range from 1.0-10.0 mcg/ml and could be potential risk to nursing infants.

There are some precautions which should be exercised during the use of salicylates. These include:

♦Salicylates should be used with caution in patients with chronic renal insufficiency. If magnesium salicylate is being taken, all other drugs containing magnesium should be discontinued and serum magnesium levels should be monitored.

♦Salicylates should be used with caution in patients of gastric ulcers, septic ulcers, mild diabetes, gout, erosive gastritis or bleeding tendencies.

♦When long term therapy has been prescribed, patients should be warned not to take other analgesics to avoid potentially toxic concentrations of analgesic. During long term treatment with salicylates, periodically plasma levels should be monitored. Therapeutic levels are 100-300 mcg/ml. Toxic manifestations are seen when concentrations exceed 300 mcg/ml. It is advisable to monitor urinary pH regularly as a drop of pH from 6.5 to 5.5 can double the plasma level resulting in toxicity.

♦Mild salicylism may occur following repeated use of large doses of salicylates. Manifestations of salicylism include dizziness, tinnitus, difficulty in hearing nausea, vomiting, diarrhoea, mental confusion, CNS depression, headache, sweating, hyperventilation and lassitude. Acute lethal dose is 10-30 gm in adults and 4 gm in children.

As stated above, aspirin is the most commonly used drug, it affects certain drugs and is affected by certain drugs. The drug which affect aspirin include:

–activated charcoal (decreases absorption of aspirin, therefore, can be used in salicylate toxicity within 2 hours of ingestion);

–ammonium chloride, ascorbic acid etc. urinary acidifiers (decrease salicylate excretion resulting in higher plasma levels);

–carbonic anhydrase inhibitions (if used concomitantly salicylate intoxication can occur)

–corticosteroids (increase salicylate clearance resulting in lower serum levels);

–nizatidine (increase in serum levels of salicylates).

The drugs which are affected by aspirin include:

–alcohol (risk of GI ulceration increases and may also prolong bleeding time);

–ACE (Angiotension converting enzymes) inhibitors (antihypertensive efficacy of these is reduced);

–oral anticoagulants (impaired platelet function may prolong bleeding time);

–beta-adrenergic blockers (efficacy of these is reduced);

–heparin (can increase bleeding risk);

–loop diuretics (may be less effective);

–methotrexate (increased drug levels of methotrexate);

–nitro-glycerine (may result in unexpected hypotension);

–NSAIDs (decrease in NSAIDs serum concentration and may increase incidence of GI effects);

–probenecid and sulphinpyrazone (small amounts may reduce uricosuric effects of these but large doses of salicylates themselves have uricosuric effect);

–spironolactone (diuretic effect is reduced);

–sulphonylurea and exogenous insulin (salicylates in doses of more than 2 gm per day have hypoglycaemic action and thus may enhance their effect);

–valproic acid (enhances effects of valproic acid).

Of the salicylates, two commonly used drugs are aspirin and methyl salicylate. Drug information about only these two drugs will be covered in this section.

2. NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

This is a broad class of anti-inflammatory drugs and includes drugs of varying chemical structure e.g. analgin, ibuprofen, indomethacin, naproxen, nimisulide etc. These antiinflammatory drugs also have analgesic and antipyretic actions. Exact mode of action of these drugs is not known. Mechanism of action of these drugs is believed to be inhibition of cyclooxygenase (COX) activity and prostaglanelin synthesis. Other mechanisms may also be there, such as inhibition of lipoxygenase, leukotriene synthesis, lysosomal enzyme release, neutrophil aggregation and various cell membrane functions. NSAIDs, after oral use are readily absorbed from gastrointestinal tract. Although food slows down their absorption but does not affect the total amount absorbed. Therefore NSAIDs can be taken with meals or after meals to minimize GI effects. Some NSAIDs can be given with acid neutralizing antacids like aluminium hydroxide, magnesium hydroxide. NSAIDs are highly protein bound. Elimination of NSAIDs mainly depends on hepatic biotransformation. Excretion is through kidney primarily as metabolites.

Indications

Indications of NSAIDs include:

–rheumatoid arthritis (except etodolac ketorolac, ketorolac and mefenamic acid);

–osteoarthritis (except ketorolac and mefenamic acid);

–juvenile rheumatoid arthritis (tolmetin, naproxen);

–mild to moderate pain (etodolac, fenoprofen, ibuprofen, ketoprofen, ketorolac, meclofenamate, mefenamic acid, naproxen).

Contraindications

Because of potential of cross-sensitivity among NSAIDs, these should not be used in patients in whom aspirin, iodides or other NSAIDs have induced symptoms of asthma, rhinitis, urticaria, nasal polyps, angioedema, bronchospasm and other symptoms of allergic or anaphylactoid reactions.

Some conditions which warrant warnings are:

GI Effects: Long term NSAID, therapy can cause GI toxicity like bleeding, ulceration and perforation and it may occur with or without warning symptoms. Indomethacin or sulindac should not be given to patients with active GI lesions or with a history of recurrent GI lesions.

To reduce the GI effects, NSAIDs can be given after meals or with meals or with antacids.

If diarrhoea occurs with mefenamic acid or meclofenamate either dose should be reduced or use should be discontinued temporarily.

CNS Effects: Indomethacin can aggravate depression or other psychiatric disturbances, epilepsy and Parkinsonism. If severe CNS adverse reactions develop, its use should be discontinued. Some of the NSAIDs can cause headache. If headache persists even after reduction of the dose, their use should be discontinued.

Renal Effects: Prolonged use of NSAIDs can cause acute renal insufficiency, interstitial nephritis, hyperkalemia, hyponatremia and renal papillary necrosis. Patients with history of renal disease or compromised renal perfusion are at greatest risk. The elderly patients are also at risk. Minimum effective dose should be used in elderly persons.

Pregnancy and Lactation: Safety for use of NSAIDs in pregnant woman has not be established. Therefore, use of NSAIDs is not recommended in pregnant women. Those drugs which inhibit prostaglandin synthesis may cause closure of the ductus arteriosus and other untoward effects to the foetus.

Use of NSAIDs is also not recommended in nursing mothers as several NSAIDs are excreted in breast milk and may affect the infant adversely.

Children: Safety for use of Indomethacin in children of 14 years or less in age has not been established and therefore, should not be used. Use of Mefenamic acid and meclofenamate is not recommended in children of 14 years or less age. Use of nimesulide in children is prohibited in India. In general, use of NSAIDs in children is not recommended.

Tolmetin and naproxen are the only drugs which are labelled for juvenile rheumatoid arthritis.

Side Effects

GI side effects are the most common and include nausea/ vomiting, diarrhoea, constipation, abdominal distress (cramps/ pain), dyspepsia, flatulence, anorexia and stomatitis. As stated above, gastric or duodenal ulcer with bleeding or perforation can occur. There may also be occult bleeding in the stool.

Hepatic side effects include cholestatic hepatitis, jaundice, toxic hepatitis.

As stated in the introductory part of analgesics, prolong use is likely to manifest renal side effects which include haematuria, cystitis, urinary tract infection, azotemia, nocturia proteinuria, increased serum creatinine, polyuria, dysuria, oliguria, renal insufficiency including renal failure in patients with impaired renal function, renal papillary necrosis, nephrosis, nephritic syndrome, glomerular and interstitial nephritis.

CNS side effects of NSAIDs include dizziness, headache, drowsiness, nervousness, paresthesia, peripheral neuropathy, tremor, convulsions, aggravation of epilepsy and parkinsonism, inability to concentrate, depression, psychic disturbances including psychotic episodes, hallucinations, sleep disturbances, involuntary muscle movements.

Cardiovascular side effects of NSAIDs include hypotension, hypertension, palpitation, arrhythmias, tachycardia, vasodilation, peripheral oedema and congestive heart failure.

Haematologic side effects of NSAIDs include neutropenia, eosinophilia, leucopenia, thrombocytopenia, agranulocytosis, aplastic anaemia, haemolytic anaemia, decrease in haemoglobin and haemetocrit.

Ocular side effects of NSAIDs include visual disturbances, blurred vision, photophobia, and amblyopia, swollen, dry or irritated eyes, corneal deposits, retinal haemorrhage and pigmentation changes.

Dermatological side effects of NSAIDs include rash, erythema, urticaria, cutaneous vasculitis, toxic epidermal necrolysis, exfoliative dermatitis, angioneurotic oedema, alopecia, pruritis, eczema and skin discolouration.

Respiratory side effects of NSAIDs include dyspnoea, pharyngitis, bronchospasm, rhinitis, shortness of breath and pulmonary infiltrates.

There are several precautions which should be observed during the use of NSAIDs. These may include the following:

♦GI tract ulceration and bleeding can occur in patients being treated for long time. As such, patients should be followed up and checked for these.

♦Though less than aspirin, NSAIDs can also inhibit platelet aggregation resulting in prolonged bleeding time. Therefore, NSAIDs should be used with caution in patients with intrinsic coagulation defects and in those who are on anticoagulant therapy.

♦Long term therapy may cause decrease in haemoglobin and haemocrit values. Low white blood cell count may occur rarely and is transient in nature. However, when persistent leukopenia, granulocytopenia or thrombocytopenia occurs, it should be evaluated and the drug should be discontinued.

♦NSAIDs can cause fluid retention and peripheral oedema. Therefore, NSAIDs should be used with caution in patients with compromised cardiac function, hypertension and other conditions predisposing to fluid retention.

♦NSAIDs can cause blurred or diminished vision, scotomata, corneal deposits, retinal disturbances. Ophthalmological studies should be carried out in patients who complain of eye problems.

♦There may be liver function test elevation which may progress or remain unchanged or become transient with continued therapy. If symptoms and signs of liver dysfunction occur or an abnormal test occurs, evaluation should be carried out for severe hepatic reaction.

♦In case of patients with inpaired hearing, periodic auditory function tests should be carried out particularly when the patient is being treated with fenoprofen.

♦If rashes occur, use of mefenamic acid, if being taken, should be stopped.

Drug Interactions

Drug interactions of NSAIDs can occur with several drugs. Some of the important drugs are given below:

–anticoagulants (may prolong prothrombin time);

–ACE inhibitors (antihypertensive effect may be reduced); - beta blockers (antihypertensive effect may be impaired); - cyclosporin (nephrotoxicity may be enhanced);

–digoxin (ibuprofen and indomethacin may increase digoxin serum level);

–dipyridamole (indomethacin may augment water retention);

–hydantoin (phenytoin serum levels may be enhanced);

–loop diuretics (their effect may be reduced);

–methotrexate (risk of methotrexate toxicity may be increased);

–penicillamine (indomethacin may enhance the bioavailability of penicillamine);

–sympathomimetics (coadministration of indomethacin and phenylpropanolamine may result in increased blood pressure);

–thiazide diuretics (activity of thiazides may be reduced);

–probenecid (toxicity of NSAIDs may be enhanced);

–salicylates (plasma levels of NSAIDs may be lowered).

There is a large number of NSAIDs but drug information about only those NSAIDs will be covered which are commonly used in India.

3. NARCOTIC ANALGESICS

The main use of narcotic analgesics is for the relief of moderate and severe pain and for postoperative medication. Most of them are likely to produce dependence in users if used continuously. The main narcotic analgesic is morphine. Morphine is one of the alkaloids isolated from opium. Codeine and diamorphine are closely related to morphine. Although, use of morphine declined because of its potential for dependence and the restrictions imposed by State Excise laws, however, it is being used in terminally ill cancer patients for relief of pain.

Many synthetic drugs having morphine like action are now available e.g. pethidine, anileridine, dextropropoxyphene, dihydrocodeine, methadone, pentazocine.

Narcotic analgesics are classified as agonist, mixed agonist-antagonists, or partial agonist by their activity at opioid receptors. There are five major categories of opioid receptors i.e. mu (μ), kappa (κ), sigma (σ), delta (δ) and epsilon (ε). Action of narcotic analgesics can be defined by their action on three specific receptor sites, namely mu, kappa and sigma. The mu receptors mediate morphine like supraspinal analgesia. Other effects associated with analgesia include euphoria, respiratory and physical depression. The kappa receptors mediate pentazocine like spinal analgesia, sedation and miosis. The sigma receptors mediate dysphoria, psychotomimetic effects (i.e. hallucinations) and respiratory and vasomotor stimulation because of antagonistic drugs.

3.1 Narcotic Agonist Analgesics

This group of analgesics include drugs like codeine, meperidine, methadone, oxycodone, oxymorphone, dextropropoxyphene.

Indications

Narcotic agonist analgesics are used to relieve moderate to severe pain, as preoperative medication, as analgesic adjuncts during anaesthesia. Some agents are also used as antitussive (e.g. codeine).

Contraindications

Contraindication include hypersensitivity to narcotics, diarrhoea caused by poisoning, acute bronchial asthma and upper airway obstruction, head injuries.

Side Effects

The most common side effects include light-headedness, dizziness, sedation, nausea/vomiting, sweating. Other side effects which may occur include bronchospasm, depression of cough reflex, facial flushing, chill, faintness, tachycardia bradycardia, arrhythmia, drowsiness, sedation, lethargy, impairment of physical and mental performance, confusion, euphoria, blurred vision, psychic dependence, increased intracranial pressure, tremor, convulsions, coma.

Precautionss

♦Narcotic agonist analgesics should be used with caution in patients those suffering from conditions accompanied by hypoxia or hypercapnia, debilitated patients and elderly.

♦They should also be used with caution in patients who are sensitive to CNS depressants.

♦When used post-operatively caution should be exercised particularly in patients with pulmonary disease.

♦Some patients may develop tolerance to these drugs on prolonged use and there may be need for increase in the dose.

♦These drugs have abuse potential also. Psychological and physical dependence may develop on repeated use.

♦Severe overdose, mainly by IV route, can lead to apnoea, circulatory collapse, convulsions, cardiopulmonary arrest and even death. While treating patient for overdosage primary attention should be adequate respiratory exchange and assisted or controlled ventilation should be provided. A narcotic antagonist should be administered. Naloxone is the antagonist of choice. Repeated doses may be required.

Drug Interactions

Narcotic agonist analgesics may have interactions with several drugs. Important drugs are mentioned below:

–anticoagulants (anticoagulant effect may be enhanced by propoxyphene);

–barbiturate anaesthetics (respiratory and CNS depressant action may be enhanced);

–carbamazepine (propoxyphene may increase the pharmacological effect of carbamazepine);

–chlorpromazine (analgesic effect may be potentiated and higher incidence of toxic effects may occur);

–diazepam (may produce cardiovascular depression with high doses of fentanyl and alfentanil);

–hydantoin (may decrease the effects of meperidine and methadone);

–Monoamine oxidase inhibitors (MAOIs) and furazolidone (meperidine is known to have precipitated unpredictable, sometimes fatal reactions in patients on MAOIs and furazolidone or who have received such drugs within 14 days);

–Nitrous oxide (may cause cardiovascular depression with high doses of sufentanil and fentanyl);

–Rifampicin (may reduce methadone plasma levels).

3.2 Narcotic Agonist-Antagonist Analgesics

Narcotic agonist-antagonist analgesics compete with substances at the site of mu receptors. The mu receptors mediate morphine like supraspinal analgesia, euphoria and respiratory and physical depression. There are two types of narcotic agonist-antagonists:

–drugs which are antagonists at the mu receptor and are agonist at the other receptors;

–drugs which are partial agonists at mu receptor.

Pentazocine represents the former type and the buprenorphine represents the later type. The narcotic agonistantagonist analgesics are potent analgesics with a lower potential for abuse than the pure narcotic agonists. These analgesics may precipitate withdrawal symptoms in those with opiate dependence. Some important narcotic agonist-antagonist analgesics are pentazocine, buprenorphine, butorphanol, dezocine and nalbuphine.

Since morphine and pethidine have great potential for abuse and have restrictions under NDPS Act and State Excise law, their use is limited. In this book some commonly used narcotic analgesics like dextropropoxyphene, pentazocine, and buprenorphine. Codeine will be covered under drugs used for cough and cold.

4. CORTICOSTEROIDS

The adrenal cortex produces a number of chemicals which are steroidal in nature and hence the name corticosteroids. The corticosteroids can be divided into three classes:

(i) those whose pharmacological actions are on gluconeogenesis, glycogen deposition, and protein and calcium metabolism;

(ii) those whose main actions are on electrolyte and water metabolism;

(iii) sex corticosteroids

The corticosteroids mentioned at S.No. (i) are known as corticosteroids. Examples of this class are cortisone, hydrocortisone. The corticosteroids mentioned at S.No. (ii) are known as mineralocorticoid. Examples of this class of corticosteroids are deoxycortone and aldosterone. The third class is sex corticosteroids and their examples are oestrogens and androgens.

The naturally occurring corticosteroids of first two classes (i.e. glucocorticoids and mineralo-corticoids) except aldosterone are secreted under the influence of the anterior pituitary corticotrophic hormone. In addition to the naturally occurring corticosteroids several synthetic steroids have been developed with similar properties. In developing the synthetic steroids the main aim has been to produce steroids of enhanced potency and to separate two main pharmacological actions i.e. glucocorticoid activity and mineralocorticoid activity.

In therapeutics, mineralocorticoid is used in conditions such as Addison’s disease and glucocorticoids are used in conditions like asthma, rheumatoid arthritis.

In this section, information on glucocorticoids will be given as this section relates to drugs used in inflammatory and other painful conditions.

Naturally occurring corticosteroids have both glucocorticoid (anti-inflammatory) and mineralocorticoid (salt-retaining) activities. Glucocorticoids have profound and varied metabolic effects. In addition they also modify the body’s immune responses.

Glucocorticoids like cortisone, hydrocortisone are used as replacement therapy in adrenocortical deficiency conditions and may also be used for their anti-inflammatory activity. The synthetic steroidal compounds like prednisolone, prednisone and fludrocortisone although have both glucocorticoid and mineralocorticoid activities but prednisolone and prednisone are mainly used for their glucocorticoid activity.

A group of synthetic compounds is distinguished by absence of any significant salt-retaining activity. This group includes dexamethasone, methyl prednisolone, betamethasone, triamsolone. These steroids are used for their potent antiinflammatory activity.

Contraindications

Use of glucocorticoids is contraindicated in systemic fungal infections, hypersensitivity to drug, intramuscular use in idiopathic thrombocytopenic purpura, administration of live viral vaccines and patients who are receiving immunosuppressive corticosteroid doses.

Side Effects

The side effects associated with the use of large doses of glucocorticoids involve action on electrolyte balance and other metabolism including gluconeogenesis and the action on tissue repair and healing. These also have inhibitory effect on the secretion of corticotrophin by the anterior lobe of pituitary gland. Disturbance of electrolyte balance results in retention of water and sodium with oedema and hypertension and in the increased excretion of potassium with the possibility of hypokalaemic alkosis. In very serious cases, cardiac failure may occur.

Disturbances of electrolyte balance are common with naturally occurring steroids like cortisone, hydrocortisone but are much less in synthetic derivatives like prednisolone, prednisone, dexamethasone.

Other metabolic effects lead to mobilization of calcium and phosphorus resulting in osteoporosis and spontaneous fractures. These may also cause nitrogen depletion and hyperglycemia.

The effect on tissue repair is manifested in delayed wound healing and increased liability for infection. The topical application of corticosteroids to the eyes has been reported to produce corneal ulcers, raised intraocular pressure and reduced visual function.

Susceptibility to all kinds of infection including sepsis, fungus infections, viral infections has been reported in patients on corticosteroid therapy.

Large doses of corticosteroids may produce symptoms of hyperactivity of adrenal cortex: moon face, hirsutism, buffalo hump, flushing, increased bruising, striae and acne, sometimes leading to fully developed Cushing’s syndrome. The symptoms are usually reversible, if therapy is discontinued. But sudden discontinuation may be dangerous.

Other side effects include amenorrhoea, mental and neurological disturbances, increase in intracranial pressure, increase in coagulability of blood leading to thromboembolic complications, reduction circulating lymphocytes.

Muscular weakness is an occasional side effect of corticosteroids. It is most evident with use of fludrocortisone, triamcinolone.

Though side effects may occur equally with all corticosteroids but their incidences rise sharply, if doses are increased much above 8 mg daily of prednisolone or its equivalent. However, short courses at higher doses for emergencies appear to cause less side effects than prolonged courses of lower doses.

During the treatment with corticosteroids there is likelihood of suppression of secretion of corticotrophin and the adrenal cortex may become atrophied. If there is sudden withdrawal or change in route of administration, this may precipitate acute adrenal insufficiency with symptoms like muscle weakness, hypotension, hypoglycaemia, headache, nausea, vomiting, restlessness and pain in joints and muscles. Severe symptoms are treated with administration of hydrocortisone sodium succinate by IV route.

Administration of corticosteroids on alternate days or a single dose in the morning will allow recovery of pituitary function.

Precautions

♦Patients on long duration therapy should be observed for weight increase, oedema, hypertension and excessive potassium secretion. Monitoring may be necessary for a negative nitrogen balance.

♦Patients on corticosteroid therapy for long duration should be asked to take proteins liberally.

♦Lowest possible dose should be used while treating patients with corticosteroids.

♦Corticosteroids should be used with caution in patients of non-specific ulcerative colitis, abscess or other pyrogenic infection; latent peptic ulcers.

♦Corticosteroids should also be used with caution in patients of hypertension and patients with thrombo-embolitic tendencies.

♦Patients on corticosteroids should be monitored for osteoporosis.

♦Steroid psychosis may occur. It is characterized by a delirious or toxic psychosis with clouded sensorium. The onset of symptoms usually occurs within 15-30 days. Predisposing factors include dose (more than 40 mg of prednisolone or its equivalent) female predominance and also the family history of psychic illness.

♦Massive doses of corticosteroids, if required to be given intravenously should be given slowly over a period of 10 minutes. Rapid administration of large doses of corticosteroids, sometimes may cause cardiovascular collapse.

Glucocorticoids are used more in replacement therapy and inflammation associated with allergic symptoms. The effects of corticosteroids in rheumatic arthritis are suppressive and palliative. But, symptoms return on discontinuation of therapy. Not many corticosteroids are used in rheumatoid arthritis. One synthetic steroid that is used is prednisolone and its derivative methylprednisolone. Therefore, only prednisolone will be covered in this section.

5. MUSCLE RELAXANTS

Skeletal muscle relaxants do not have analgesic or ani-inflammatory activity but these are often used along with analgesic/anti-inflammatory drugs because spasm of muscles causes pain. There are two main types of muscle relaxants -one, those with action on the central nervous system, and two, those affecting neuromuscular transmission. The former are used principally for relieving painful conditions and the latter are used as adjuncts in anaesthesia with object of muscle relaxation to be achieved with light anaesthesia.

The drugs used in the treatment of muscle spasm reduce skeletal muscle tone and involuntary movements by selective action on CNS. Examples of this group are mephenesin, carisoprodol, chlorzoxazone, methocarbamol.

In this section, drug information only on few of them which are used commonly will be covered.

After general discussion on the group of drugs used for pain, fever and inflammatory condition, drug information on individual commonly used drug will be given in the proceeding pages.

SALICYLATES

ASPIRIN

Synonyms: Acetylsalicylic Acid

General information

Aspirin is a one of the salicylates group of drugs. Salicylates have analgesic, antipyretic and anti-inflammatory effects. Aspirin and other salicylic acid derivatives are hydrolyzed to salicylic acid. Thus salicylic acid derivatives have potential of hydrolysis in stomach resulting in gastric irritation and erosive gastritis or bleeding tendencies. Salicylates are rapidly absorbed after oral use. However, food slows the absorption of salicylates. Aspirin, in low doses inhibit platelet aggregation. It is because of this property that it finds use in patients of myocardial infarction (medical term for heart attack). Since aspirin is hydrolyzed in presence of moisture, its packing should be such as to prevent the access of moisture. Advanced hydrolyzed preparations may show presence of crystals of salicylic acid and may have smell of acetic acid. It is an over the counter drug and can be purchased without the prescription from RMP.

Action, uses and dosage

Salicylates lower elevated body temperature through vasodilation of peripheral vessels. Their analgesic and anti- inflammatory activity may be because of inhibition of prostaglandin synthetase enzyme complex. Aspirin differs from other members of this group in that it more potently inhibits synthesis of prostaglandins and inhibits irreversibly platelet aggregation.

It is used for the relief of moderate pain like headache, neuritis (peripheral nerve inflammation), myalgia, chronic rheumatoid arthritis, toothache etc. It is also used as antipyretic to lower the temperature in fevers. The dose range for analgesic and antipyretic action is 300 mg to 1 gm which may be repeated according to clinical needs. The maximum dose is 4 gm daily.

Although aspirin has been used for the treatment of chronic gout because of its analgesic and uricosuric actions but it is less effective than allopurinol or probenecid. For this purpose, daily dose is 4 gm or more. Lower doses can cause uric acid retention.

Aspirin as an antiplatelet agent has been used in the patients with thromboembolic disease. Low doses of aspirin inhibit platelet aggregation and thus may be more effective than higher doses. Usually 100 mg dose is used for this purpose

Possible side effects

One of the side effects which may occur even with small doses is irritation of gastric mucosa and dyspepsia (indigestion) and ulceration. Side effects which are either mild or infrequent with lower doses but common with anti-inflammatory doses include gastrointestinal discomfort (nausea), ulceration with bleeding, tinnitus (constant buzzing or ringing in the ears), vertigo, confusion and hypersensitivity reactions. Hypersensitivity reactions are more prevalent in patients with asthma, nasal polyposis and chronic urticaria (skin conditions characterized by irritation, burning, stinging and spontaneous appearance of patches).

Precautions

Aspirin should be used with caution in children under 16 years of age particularly for chickenpox or flu symptoms and should always be in consultation with medical doctor as they run the risk of Reye’s syndrome (a rare but life threatening condition - it is characterized by vomiting, lethargy and belligerence that may progress to delirium and coma).

♦Aspirin should not be used in:

–patients hypersensitive to salicylates or nonsteroidal anti-inflammatory drugs (NSAIDs) as crosssensitivity may exist;

–patients prone to dyspepsia or patients known to have gastric lesions;

–patients with haemophilia (a disease with impaired blood clotting);

–infants under one year of age;

–patients in last stages of pregnancy as aspirin may cause adverse fetal effects such as low birth weight, stillbirths, neonatal death etc.

♦Aspirin should be used with caution in patients with impaired hepatic functions.

♦Some of the effects of aspirin are enhanced by alcohol.

♦Aspirin may enhance the activity of:

–coumarin anticoagulants;

–sulphonylurea hypoglycaemic agents.

♦Haemorrhagic effect of aspirin may be enhanced by anticoagulants.

♦Activity of methotrexate can be enhanced markedly and its toxicity may be enhanced.

♦Aspirin reduces the effects of uricosuric agents like probenecid and sulphinpyrazone

♦Barbiturates and other sedatives may mask respiratory symptoms of overdosage of aspirin and may also enhance its toxicity.

♦Use of aspirin should be stopped one week before surgical operation.

♦Urinary acidifiers such as ammomum chloride, ascorbic acid, and methionine may enhance the effects of aspirin.

♦Aspirin passes into breast milk; therefore, lactating mothers should use it only in consultation with medical doctor.

Preparations and some trade names

In India aspirin is available in tablet form. Some preparations contain a small amount of caffeine also. Soluble aspirin tablets contain calcium carbonate and citric acid (3:1 ratio) in addition to aspirin.

Anacin tablets (GM) - Aspirin 400 mg, caffeine 30 mg

Aspin-100 tablets (Cipla) - Aspirin 100 mg

Colsprin tablets (RB) - soluble aspirin tablets, 100 mg, 325 mg and 650 mg (contain calcium carb. and citric acid beside aspirin)

Disprin tablets (RB) - soluble aspirin tablets, 350 mg

Micropyrin tablets (Nicholas) - Aspirin (micro fined) 350, Caffeine 20 mg

Storage

Aspirin preparations are hydrolyzed by moisture. These should be stored in cool and dry place.

METHYL SALICYLATE

Synonyms: Oil of wintergreen

General information

Methyl salicylate is drug of salicylates group. It is used externally. It is absorbed readily from skin. It should be stored in airtight containers. Some plastic containers such as those made from polystyrene are unsuitable for storing liniments or ointments containing methyl salicylate. It has been combined with other analgesic and anti-inflammatory drugs. One of the drugs with which a number of preparations are available is diclofenac.

Action, uses and dosage

Salicylates have analgesic, antipyretic anti-inflammatory and antirheumatic actions. These bring down body temperature through vasodilation of peripheral blood vessels. Their analgesic and anti-inflammatory activity may be mediated through inhibition of prostaglandin synthetase enzyme complex.

Methyl salicylate is used externally to relieve pain in lumbago (pain in the lower back region), sciatica (pain in the back and down in one leg along the sciatica nerve and its branches) and rheumatic conditions. The most commonly used concentration is 10%. As stated above, it has been combined with other analgesic and anti-inflammatory drugs like diclofenac.

Possible side effects

For side effects see general discussion on salicylates.

Precautions

For precautions see general discussion on salicylates.

Preparations and some trade names

Earlier preparations included methyl salicylate liniment/ ointment. Now most of the preparations are in combination either with counter irritant or with analgesic and antiinflammatory agents.

Ethnorub ointment (Johnson & Johnson) - Methyl salicylate 4%, Mephenesin 5%, Iodine 0.5%

Muslax cream (BE) - Methyl salicylate 183 mg, Menthol 160 mg per gm

Moov ointment (Parag Pharma) - an Ayurvedic preparation - Oil of wintergreen (methyl salicylate) 15%, Podina ka phool (menthol) 5%, Tarpin ka tel (turpentine oil) 3%, Nilgiri oil 2%

Combinations with other analgesic/anti-inflammatory drugs

Acks gel (BPL) - Ibuprofen 50 mg, Mephenesin 50 mg, Methyl salicylate 5 mg, Menthol 5 mg per gm

Butaproxyvon gel (Wockhardt) - Diclofenac diethyl ammonium 1.16%, Linseed oil 3% Methyl salicylate 10%, Menthol 5%

Jusgo gel (Indi Pharma) - Diclofenac diethyl ammonium 1.16%, Linseed oil 3% Methyl salicylate 10%, Menthol 5%

Religel gel (RPG) - Diclofenac diethyl ammonium 1.16%, Linseed oil 3% Methyl salicylate 10%, Menthol 5%

Volini gel (Croosland) - Diclofenac diethyl ammonium 1.16%, Linseed oil 3% Methyl salicylate 10%, Menthol 5%

Storage

Preparations containing methyl salicylates should be stored in air-tight containers in cool and dry place. These preparations should also be protected from light.

NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)

ANALGIN

Synonyms: Dipyrone, Metamizol

General information

Dipyrone (analgin) is the sodium sulphonate of amidopyrine. Import, manufacture and sale of amidopyrine were banned in India in 1983 because of its toxic effect. Analgin has been used extensively as an analgesic and antipyretic in past. Novalgin was a famous trade name. Now with availability of several other analgesic and antipyretic drugs its use has gone down. This drug has been in controversy regarding its safety. Therefore, fixed dose combinations of other drugs with analgin have been banned in India. Recommendations in the literature are that it should be used only in serious or life threatening situations where no alternative antipyretic is available. It is a Schedule H drug and is required to be dispensed only on the prescription of RMP by retail pharmacies.

Action, uses and dosage

Analgin has analgesic and antipyretic actions similar to phenazone. It has been used for relief of pain in migraine, facial neuralgia, dysmenorrhoea (women menstruation), rheumatism and sciatica. It has also been used as antipyretic in catarrhal infections and in influenza.

The usual dose is 500 mg three or four times daily, the dose range being 300-600 mg. It can also be given by subcutaneous/ intramuscular/intravenous injection in doses of 0.5 to 1.0 gm

Possible side effects

Its side effects are same as with the amidopyrine. One major side effect is risk of agranulocytosis (absence of white blood cells which are natural defence of the body to fight microbes). Onset of agranulocytosis may be sudden and is unpredictable. It is for this reason that use of amidopyrine was banned in India. Large doses have been associated with renal tubular necrosis.

Precautions

♦Analgin should not be used by patients who are allergic to it.

♦It should not be used by patients who are using salicylates.

♦It should not be used in patients having haemorrhagic disorders.

♦It should be used with caution in patients with impaired hepatic or renal functions.

♦Concomitant use with chlorpromazine can result in severe hypothermia.

Preparations and some trade names

The most common dosage form in which analgin is available is tablet form. It is also available in injection form.

Baralgan-M tablets (Sanofi Aventis) - Analgin 500 mg

Novalgin injection (Sanofi Aventis) - Analgin 0.5 gm/ml

Ultragin injection (Wyeth) - Analgin 0.5 gm/ml

Storage

Analgin preparations can be stored at room temperature in a cool and dry place. The preparations are required to be protected form sunlight.

DICLOFENAC

General information

Diclofenac is available as Diclofenac sodium or Diclofenac potassium. It is one of the nonsteroidal anti-inflammatory drugs (NSAIDs). It has analgesic, antipyretic and anti-inflammatory activity. It has better anti-inflammatory activity than ibuprofen. Enteric coated granules are available which can be used in making tablets. Enteric coating reduces gastric irritation by the drug as the dosage form does not disintegrate in stomach, but disintegrates in the intestines. If enteric coated granules have been used in making tablet, it need not be taken with or after meals which is generally recommended for NSAIDs. Diclofenac and paracetamol fixed dose combinations have become more popular than diclofenac alone. It is a schedule H drug and is required to be dispensed on the prescription of RMP by retail pharmacies.

Action, uses and dosage

The mode of action of NSAIDs is not clear. However, possible mechanisms could be interference with cyclooxygenase activity and its inhibition, inhibition of prostaglandin synthesis, inhibition of lipoxygenase, even suppression of rheumatoid factor production.

Diclofenac can be used for chronic and acute treatment of signs and symptoms of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis. It can also be used for analgesia and primary dysmenorrhea (menstruation). For this purpose diclofenac potassium should be used.

Daily dose of 100-150 mg has been recommended for rheumatoid arthritis and osteoarthritis (50 mg twice or thrice a day or 75 mg twice a day). Doses in excess of 225 mg are not recommended.

Daily dose of 100-125 mg has been recommended for ankylosing spondylitis (25 mg four times a day, if necessary another dose of 25 mg can be given at bedtime)

Daily dose of 150 mg has been recommended for analgesia and dysmenorrhea (50 mg thrice a day). In some patients an initial dose of 100 mg followed by a dose of 50 mg will provide better relief.

Diclofenac is also used externally in minor aches or pains of muscles and joints as an adjunct therapy in the management of stiffness associated with arthritis, rheumatism, lumbago, sciatica, stiff neck etc.

Possible side effects

Diclofenac may have all the side effects associated with NSAIDs including gastric irritation, ulceration or even bleeding, nausea, vomiting. Children taking these drugs may vomit blood, may develop rashes and may suffer kidney failure. However, these effects are reduced to great extent by using enteric coated granules. Other side effects include constipation, dizziness, rashes, distress. For the first few days there may be problem of gas. Less common but with continuing therapy there may be side effects like protein in blood, nervousness, fainting, depression, disorientation, sweating, drying of mouth and nose, heart palpitation, chest pain, breathing difficulties and cramps in the muscles.

Precautions

♦Diclofenac should not be taken by patients who are either allergic to it or are allergic to other NSAIDs, aspirin or iodides.

♦Alcohol should be avoided during the therapy with diclofenac; it may aggravate risk of bleeding.

♦Aspirin should not be taken during the treatment with diclofenac.

♦Concomitant use of diclofenac and cyclosporin may enhance the kidney related side effects of both the drugs.

♦Probenecid may enhance the side effects of this drug.

♦It may enhance the effect of oral anti-coagulant and the dose of anti-coagulant might need adjustment.

♦Safety of NSAIDs including diclofenac during pregnancy has not been established. Therefore, use of diclofenac should be avoided.

♦During studies of NSAIDs, it was observed that differing concentrations of these appear in breast milk. In general, these should not be used in breast feeding mothers, as these may affect cardiovascular system of infant.

Preparations and some trade names

Diclofenac is usually available in tablet dosage form. It is also available in cream or gel form for external applications. There are many products where it has been combined with methyl salicylate (for list of such products, see methyl salicylate). As stated above, fixed dose combinations of diclofenac and paracetamol have become more popular than diclofenac alone.

Diclofenac preparations

Diclomax tablets (Torrent) - Diclofenac sod. 25, 50 mg

Diclomax injection (Torrent) - Diclofenac sod. 25 mg/ml

Dicloran tablets (Unique) - Diclofenac sod. 50 mg, 100 mg (SR)

Dicloran injection (Unique) - Diclofenac sod. 25 mg/ml

Exflam tablets (E.Merck) - Diclofenac sod. 50 mg

Exflam injection (E.Merck) - Diclofenac sod. 25 mg/ml

Movonac tablets (Nicholas Piramal) - Diclofenac sod. 50 mg, 100 mg (SR)

Movonac injection (Nicholas Piramal) - Diclofenac sod. 25 mg/ml

Voveran tablets (Novartis) - Diclofenac sod. 50 mg, 75 mg (SR), 100 mg (SR)

Voveran-D (Novartis) - Diclofenac free acid 46.5 mg

Voveran injection (Novartis) - Diclofenac sod. 25 mg/ml

Diclofenac and Paracetamol preparations

Anaida tablets (Dr. Reddy) - Diclofenac sod. 50 mg + Paracetamol 500 mg

Diclogesic tablets (Torrent) - Diclofenac sod. 50 mg + Paracetamol 500 mg

Jonac Plus (Grman Remedies) - Diclofenac sod. 50 mg + Paracetamol 500 mg

Oxalgin-DP (Cadila Health) - Diclofenac sod. 50 mg + Paracetamol 500 mg

Relaxyl Plus (Franco Indian) - Diclofenac sod. 50 mg + Paracetamol 500 mg

Diclofenac gel

Diclomax gel (Torrent) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Dicloric gel (Dolphin) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Fensaid gel (Nicholas) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Jonac gel (German Remedies) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Mobinak gel (Crossland) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Oxalgin gel (Cadila-H) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Voveran Emmul gel (Novartis) - Diclofenac diethyl ammonium salt 1.16% equivalent to diclofenac sod. 1% w/w

Storage

Diclofenac preparations can be stored at room temperature in a cool and dry place.

IBUPROFEN

General information

Ibuprofen is one of the nonsteroidal anti-inflammatory drugs (NSAIDs). Ibuprofen has less adverse reactions than other NSAIDs but is weak in anti-inflammatory action. As is the case with other NSAIDs, it has analgesic and antipyretic activity also. Ibuprofen can also be used to reduce pain in children. After oral administration, it is absorbed from the gastrointestinal tract and peak concentrations occur in one and half hour after ingestion. All NSAIDs cause gastric disturbance and ibuprofen is no exception. It may be taken with or after meals. It is a Schedule H drug and is required to be dispensed on the prescription of RMP by retail pharmacies.

Action, uses and dosage

Mode of action of NSAIDs is not known. Major mechanisms believed to be including inhibition of cyclooxygenase activity and inhibition of synthesis of prostaglandins. Other mechanisms may also exist.

Ibuprofen has been used to relieve signs and symptoms of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. It is also used to relieve mild to moderate pain like headache, dysmenorrhoea etc.

Daily adult dose for mild to moderate pain with inflammation is 1.2-1.8 gm in 3-4 divided doses and can be increased, if necessary, to a maximum of 2.4 gm in divided doses

Doses in children for pain relieving may be:

1-2 years - 50 mg 3-4 times a day

3-7 years - 100 mg 3-4 times a day

8-12 years - 200 mg 3-4 times a day

Ibuprofen is not recommended for children under 7 kg of weight.

For Juvenile arthritis a child may be given 30-40 mg/kg of weight in 3-4 divided doses.

Adult dose in rheumatoid arthritis and osteoarthritis is 1.23.2 gm daily. Maintenance dose of 0.6-1.2 gm may be sufficient when used for longer period.

Possible side effects

Ibuprofen generally is well tolerated but may cause nausea, vomiting, dyspepsia and diarrhea. It can occasionally cause stomatitis (gastric upset) and gastrointestinal hemorrhage (bleeding). Other side effects include headache, dizziness, nervousness, oedema, skin rash, blurred vision.

Precautions

♦Patients hypersensitive to ibuprofen or other NSAIDs should not use it.

♦Patients with active peptic ulcers should not use it.

♦Alcohol can increase the risk of bleeding.

♦Ibuprofen in high doses can affect platelets and clotting of blood, therefore, it should be avoided by patients with blood clotting problems or those taking warfarin

♦Patients with heart problems may experience swelling in arms, legs or feet.

♦Ibuprofen should be used with caution in patients with impaired liver and/or kidney functions.

♦Ibuprofen can make patient unusually sensitive to sun.

♦Ibuprofen can cause blurred or impaired vision or even color vision. Any patient experiencing this should stop using this medicine and get his vision tested.

Preparations and some trade names

Ibuprofen is usually available in tablet dosage form. There are some suspension preparations also. A combination of ibuprofen and paracetamol is also available in market.

Bren tablets (Kopran) - Ibuprofen 200, 400, 600 mg

Bren suspension (Kopran) - Ibuprofen 100 mg/ 5 ml

Brufen tablets (Knoll) - Ibuprofen 200, 400, 600 mg

Ibugesic tablets (Cipla) - Ibuprofen 200, 400, 600 mg

Ibugesic suspension (Cipla) - Ibuprofen 100 mg/5 ml

Ismelin tablets (Astra-IDL) - Ibuprofen 200, 400, 600 mg Ismelin suspension (Astra-IDL) - Ibuprofen 100 mg/5 ml Tabalon tablets (Aventis) - Ibuprofen 400 mg

Bestophen-1 tablets (BE) - Ibuprofen 400 mg + Paracetamol 325 mg

Brustin tablets (Stancare) - Ibuprofen 400 mg + Paracetamol 325 mg

Calpol Plus tablets (Glaxo-Smithkline) - Ibuprofen 400 mg + Paracetamol 325 mg

Calpol Plus suspension (Glaxo-Smithkline) - Ibuprofen 100 mg + Paracetamol 125 mg

Flexon tablets (Aristo) - Ibuprofen 400 mg + Paracetamol 500 mg

Ibugesic Plus tablets (Cipla) - Ibuprofen 200 mg + Paracetamol 325 mg

Storage

Ibuprofen preparations can be stored at room temperature in a cool and dry place.

INDOMETHACIN

General information

Indomethacin an indole derivative is one of the nonsteroidal anti-inflammatory drugs (NSAIDs). It has analgesic, antiinflammatory and antipyretic activity. However, it relieves only inflammatory or tissue injury related pain. As is the case with other NSAIDs, it should be administered with or after meals. Acid neutralizing antacids are often prescribed along with it. It is readily absorbed from gastrointestinal tract and peak plasma levels are reached in 1-2 hours. It is a schedule H drug and is required to be dispensed only on prescription of a RMP by retail pharmacies.

Action, uses and dosage

Indomethacin has analgesic, anti-inflammatory and antipyretic activity. But it can not be used as a general pain killer as it relives pain only because of inflammation or injury. It is used in relieving symptoms of ankylosing spondylitis, osteoarthritis, gout, rheumatoid arthritis and other musculoskeletal disorders.

For rheumatic disorders, the usual initial dose is 25 mg twice or thrice daily and can be increased to 150 mg daily in divided doses. Sustained release formulations of 75 mg can be taken once a day instead of 25 mg three times a