11

NSAIDsNSAIDs

PROF. DR. SHAH MURADPROF. DR. SHAH MURAD

22

NSAIDs OR (Non-narcotic analgesics or non-NSAIDs OR (Non-narcotic analgesics or non-opioid analgesics)opioid analgesics)

Analgesic Analgesic

Anti-pyretic Anti-pyretic

Anti-inflammatory Anti-inflammatory

Antirheumatic Antirheumatic

Anti-uricosuricAnti-uricosuric

33

differ from opioid analgesics in differ from opioid analgesics in several respectsseveral respects

Effective only in superficial pain of somatic Effective only in superficial pain of somatic origin but not of deep visceral painorigin but not of deep visceral pain

Effective in pain of low to moderate Effective in pain of low to moderate intensity. intensity.

Cause respiratory depression only in very Cause respiratory depression only in very high doses. high doses.

Have no abuse liability. Have no abuse liability.

44

Very common drugs as OTC Very common drugs as OTC salesale

PonstonPonston ParacetamolParacetamol AspirinAspirin DispirinDispirin VorenVoren BrufenBrufen

55

Block cyclo-oxygenase pathway of Block cyclo-oxygenase pathway of arachedonic acid origin in cell arachedonic acid origin in cell membranemembrane

Block lipo-oxygenase pathway of AA Block lipo-oxygenase pathway of AA originorigin

66

Shared toxicities due to Shared toxicities due to inhibition of PG synthesisinhibition of PG synthesis

Gastric mucosal damage Gastric mucosal damage Bleeding due to inhibition of platelet Bleeding due to inhibition of platelet

functionfunction Limitation of renal blood flow: Na+ Limitation of renal blood flow: Na+

and water retentionand water retention Delay/prolongation of laborDelay/prolongation of labor Asthma and anaphylactic reaction in Asthma and anaphylactic reaction in

susceptible individualssusceptible individuals

77

Uses/IndicationsUses/Indications

As analgesic: Headache, toothache, As analgesic: Headache, toothache, myalgia.myalgia.

As antipyretic. Effective in fever of As antipyretic. Effective in fever of any origin.any origin.

Acute rheumatic fever. Dose Acute rheumatic fever. Dose 4-6g/day 4-6g/day

Rheumatoid arthritis. Dose 3-5g/day Rheumatoid arthritis. Dose 3-5g/day OsteoarthritisOsteoarthritis

88

Post myocardial infarction and post Post myocardial infarction and post stroke patients. Aspirin inhibits TXA2 stroke patients. Aspirin inhibits TXA2 synthesis in platelets. synthesis in platelets.

Pregnancy induced hypertension and Pregnancy induced hypertension and pre-eclampsia – imbalance between pre-eclampsia – imbalance between TXA2 and PGI2.TXA2 and PGI2.

Patent ductus arteriosis. Aspirin can Patent ductus arteriosis. Aspirin can bring about closure bring about closure

99

Individual Characteristics Individual Characteristics

Aspirin displaces warfarin, naproxen, Aspirin displaces warfarin, naproxen, phenytoin, sulphonyl ureas, and phenytoin, sulphonyl ureas, and methotrexate from plasma protein methotrexate from plasma protein binding sites; toxicity of these drugs binding sites; toxicity of these drugs may occur. may occur.

Its anti-platelet action increases the Its anti-platelet action increases the risk of bleeding in patients on oral risk of bleeding in patients on oral anti-coagulants.anti-coagulants.

1010

Aspirin inhibits tubular secretion of Aspirin inhibits tubular secretion of uric acid, at low doses and uric acid, at low doses and antagonizes uricosuric action of antagonizes uricosuric action of probenecid. probenecid.

1111

InteractionsInteractions

Aspirin decreases the diuretic action Aspirin decreases the diuretic action of furosemide and thiazides and of furosemide and thiazides and blocks the action of spironolactones.blocks the action of spironolactones.

1212

PharmacokineticsPharmacokinetics

Aspirin is absorbed from stomach Aspirin is absorbed from stomach and intestine. and intestine.

Its poor water solubility is the limiting Its poor water solubility is the limiting factor in its absorption. factor in its absorption.

Microfining the drug and inclusion of Microfining the drug and inclusion of an alkali (solubility is more at higher an alkali (solubility is more at higher pH) enhances absorption. pH) enhances absorption.

1313

However, higher pH also However, higher pH also favours ionization thus favours ionization thus decreasing the diffusible decreasing the diffusible form. (>>>>>>> aspirin is form. (>>>>>>> aspirin is acidic drug so remain acidic drug so remain unionized in acidic medium unionized in acidic medium like in STOMACH >>>>>> so like in STOMACH >>>>>> so >>>>>>> is absorbed more >>>>>>> is absorbed more in stomach than intestine in stomach than intestine >>>>> and so it causes >>>>> and so it causes acidity/gastric ulcer) acidity/gastric ulcer)

1414

MetabolismMetabolism

Aspirin is deacetylated in liver and Aspirin is deacetylated in liver and plasma. plasma.

It is conjugated with glycine and with It is conjugated with glycine and with glucoronic acid.glucoronic acid.

1515

Adverse Effects of Adverse Effects of AspirinAspirin

– Hypersensitivity: Infrequent; urticaria, Hypersensitivity: Infrequent; urticaria, angioedema, anaphylactic reaction.angioedema, anaphylactic reaction.

1616

– Side-effects that occur at analgesic dose Side-effects that occur at analgesic dose (0.3-1.5g/day) are nausea, epigastric (0.3-1.5g/day) are nausea, epigastric distress, increased occult blood loss in distress, increased occult blood loss in the stools, peptic ulceration.the stools, peptic ulceration.

1717

– Anti-inflammatory doses (3-6g/day) Anti-inflammatory doses (3-6g/day) produce the syndrome called ‘salicylism’ produce the syndrome called ‘salicylism’ – dizziness, tinnitus, vertigo, excitement, – dizziness, tinnitus, vertigo, excitement, hyperventilation, electrolyte imbalance. hyperventilation, electrolyte imbalance.

– In children having viral infections In children having viral infections (vericella, influenza), salicylate therapy (vericella, influenza), salicylate therapy may cause ‘Reye’s syndrome’ (hepatic may cause ‘Reye’s syndrome’ (hepatic encephalopathy) encephalopathy)

1818

Acute salicylate poisoningAcute salicylate poisoning

It is more common in children, It is more common in children, manifestations are : manifestations are :

vomiting, dehydration, acidotic breathing, vomiting, dehydration, acidotic breathing, electrolyte imbalance, delirium, electrolyte imbalance, delirium, hallucinations, hyperpyrexia >>> hallucinations, hyperpyrexia >>> convulsions >>> coma >>>>>>>> convulsions >>> coma >>>>>>>> DEATHDEATH

1919

Management of salycylism Management of salycylism

It is symptomatic and supportive. It is symptomatic and supportive. Most important is external cooling Most important is external cooling

I.V fluids with Na+, K+, HCO3-, and I.V fluids with Na+, K+, HCO3-, and glucose.glucose.

Gastric levage.Gastric levage.

Forced alkaline diuresis.Forced alkaline diuresis.

2020

Precautions and Precautions and contraindicationscontraindications

Contraindicated in patients who are Contraindicated in patients who are sensitive to it and in peptic ulcer, sensitive to it and in peptic ulcer, bleeding disorders, in children suffering bleeding disorders, in children suffering from chicken pox or influenza ( risk from chicken pox or influenza ( risk of Reye’s Syndrome)of Reye’s Syndrome)

Aspirin should be avoided in diabetes, Aspirin should be avoided in diabetes, CHFCHF

2121

Aspirin should be stopped one week Aspirin should be stopped one week before elective surgerybefore elective surgery

Given during pregnancy it may be Given during pregnancy it may be responsible for low birth weight babies. responsible for low birth weight babies.

If taken near term, aspirin may cause If taken near term, aspirin may cause prolonged labour, greater blood loss prolonged labour, greater blood loss (post-partum) and premature closure of (post-partum) and premature closure of ductus arteriosis ductus arteriosis

2222

Compare effects, uses, PK and Compare effects, uses, PK and SE ofSE of

Mefanamic acid (ponston)Mefanamic acid (ponston) Phenacetin (paracetamol)Phenacetin (paracetamol) Ibuprofen (brufen)Ibuprofen (brufen) Diclofenac sodium (voren)Diclofenac sodium (voren)

2323

GOUTGOUT

Disease that results from an overload Disease that results from an overload of uric acid in the body. of uric acid in the body.

This overload of uric acid leads to the This overload of uric acid leads to the formation of tiny crystals of urate formation of tiny crystals of urate that deposit in tissues of the body, that deposit in tissues of the body, especially the joints. especially the joints.

2424

When crystals form in the joints it When crystals form in the joints it causes recurring attacks of joint causes recurring attacks of joint inflammation (arthritis). inflammation (arthritis).

Chronic gout can also lead to Chronic gout can also lead to deposits of hard lumps of uric acid in deposits of hard lumps of uric acid in and around the joints and may cause and around the joints and may cause joint destruction, decreased kidney joint destruction, decreased kidney function, and kidney stones.function, and kidney stones.

2525

2626

It is often related to an inherited It is often related to an inherited abnormality in the body's ability to abnormality in the body's ability to process uric acid. process uric acid.

Uric acid is a breakdown product of Uric acid is a breakdown product of purines that are part of many foods we purines that are part of many foods we eat. eat.

2727

An abnormality in handling uric acid An abnormality in handling uric acid can cause attacks of painful arthritis can cause attacks of painful arthritis (gout attack), kidney stones, and (gout attack), kidney stones, and blockage of the kidney-filtering blockage of the kidney-filtering tubules with uric acid crystals, tubules with uric acid crystals, >>>>>>>>> leading to kidney >>>>>>>>> leading to kidney failure. failure.

2828

On the other hand, some people may On the other hand, some people may only develop elevated blood uric acid only develop elevated blood uric acid levels (hyperuricemia) without levels (hyperuricemia) without having arthritis or kidney problems. having arthritis or kidney problems.

2929

Gouty arthritis is typically an Gouty arthritis is typically an extremely painful attack with a rapid extremely painful attack with a rapid onset of joint inflammation. onset of joint inflammation.

The joint inflammation is precipitated The joint inflammation is precipitated by deposits of uric acid crystals in by deposits of uric acid crystals in the joint fluid (synovial fluid) and the joint fluid (synovial fluid) and joint lining (synovial lining). joint lining (synovial lining).

3030

Intense joint inflammation occurs as Intense joint inflammation occurs as white blood cells engulf the uric acid white blood cells engulf the uric acid crystals and chemical messengers of crystals and chemical messengers of inflammation are released, causing inflammation are released, causing >>>>>> >>>>>>

Pain, Heat, and Redness of the joint Pain, Heat, and Redness of the joint tissues.tissues.

3131

Risk factors for gouty Risk factors for gouty arthritis arthritis

an inherited abnormality an inherited abnormality obesity, obesity, excessive weight gain (especially in excessive weight gain (especially in

youth), youth), moderate to heavy alcohol intake, moderate to heavy alcohol intake, high blood pressure, and high blood pressure, and abnormal kidney function abnormal kidney function

3232

Certain drugs, such as thiazide diuretics Certain drugs, such as thiazide diuretics (hydrochlorothiazide) , low-dose aspirin, (hydrochlorothiazide) , low-dose aspirin, niacin, cyclosporine, tuberculosis niacin, cyclosporine, tuberculosis medications (pyrazinamide and medications (pyrazinamide and ethambutol), can also cause elevated ethambutol), can also cause elevated uric acid levels in the blood and lead to uric acid levels in the blood and lead to gout gout

3333

A recent study demonstrated an A recent study demonstrated an increased prevalence of abnormally increased prevalence of abnormally low thyroid hormone levels low thyroid hormone levels (hypothyroidism) in patients with (hypothyroidism) in patients with gout.gout.

3434

Some conditions can Some conditions can precipitate acute attacks of precipitate acute attacks of

gout gout dehydration, dehydration, injury to the joint, injury to the joint, fever, fever, excessive eating, excessive eating, heavy alcohol intake, and heavy alcohol intake, and recent surgery. recent surgery.

3535

Diagnosis Diagnosis

Gout is suspected when a patient Gout is suspected when a patient reports a history of attacks of painful reports a history of attacks of painful arthritis, particularly at the base of arthritis, particularly at the base of the toes. the toes.

3636

Ankles and knees are the next most Ankles and knees are the next most commonly involved joints in gout. commonly involved joints in gout.

Gout usually attacks one joint at a Gout usually attacks one joint at a time, while other arthritis conditions, time, while other arthritis conditions, such as systemic lupus and such as systemic lupus and rheumatoid arthritis, usually attack rheumatoid arthritis, usually attack multiple joints simultaneously.multiple joints simultaneously.

3737

The most reliable test for gout is The most reliable test for gout is finding uric acid crystals in a sample finding uric acid crystals in a sample of the joint fluid obtained by joint of the joint fluid obtained by joint aspiration (arthrocentesis). aspiration (arthrocentesis).

Arthrocentesis is a common Arthrocentesis is a common procedure performed under local procedure performed under local anesthesia. Using sterile technique, anesthesia. Using sterile technique, fluid is withdrawn (aspirated) from fluid is withdrawn (aspirated) from the inflamed joint using a syringe the inflamed joint using a syringe and needle. and needle.

3838

The joint fluid is then analyzed for The joint fluid is then analyzed for uric acid crystals and for infection. uric acid crystals and for infection.

Shiny, needle-like uric acid crystals Shiny, needle-like uric acid crystals are best viewed with a special are best viewed with a special polarizing microscope. polarizing microscope.

3939

The diagnosis of gout can also be The diagnosis of gout can also be made by finding these urate crystals made by finding these urate crystals from material aspirated from tophi from material aspirated from tophi nodules and bursitis fluid.nodules and bursitis fluid.

4040

Sometimes patients with a classic Sometimes patients with a classic history and symptoms of gout can be history and symptoms of gout can be successfully treated and presumed to successfully treated and presumed to have gout without undergoing have gout without undergoing arthrocentesis. arthrocentesis.

4141

However, establishing a firm However, establishing a firm diagnosis is still preferable since other diagnosis is still preferable since other conditions can mimic gout. conditions can mimic gout.

These include another crystal-induced These include another crystal-induced arthritis called pseudogout, psoriatic arthritis called pseudogout, psoriatic arthritis, rheumatoid arthritis, and arthritis, rheumatoid arthritis, and even infection in the joint.even infection in the joint.

4242

X-rays can sometimes be helpful and X-rays can sometimes be helpful and may show tophi-crystal deposits and may show tophi-crystal deposits and bone damage as a result of repeated bone damage as a result of repeated inflammations. inflammations.

4343

ManagementManagement

Change in life styleChange in life style Change in dietChange in diet MedicationMedication SurgerySurgery

4444

There are two key concepts essential to There are two key concepts essential to treating gout. treating gout.

First, it is critical to stop the acute First, it is critical to stop the acute inflammation of joints affected by gouty inflammation of joints affected by gouty arthritis. arthritis.

4545

Second, it is important to address the Second, it is important to address the long-term management of the long-term management of the disease in order to prevent future disease in order to prevent future gouty arthritis attacks and shrink gouty arthritis attacks and shrink gouty tophi crystal deposits.gouty tophi crystal deposits.

4646

The treatment of an acute attack of The treatment of an acute attack of gouty arthritis involves measures gouty arthritis involves measures and medications that reduce and medications that reduce inflammation. inflammation.

Preventing future acute gout attacks Preventing future acute gout attacks is equally as important as treating is equally as important as treating the acute arthritis. the acute arthritis.

4747

Prevention of acute gout involves Prevention of acute gout involves maintaining adequate fluid intake, maintaining adequate fluid intake, weight reduction, dietary changes, weight reduction, dietary changes, reduction in alcohol consumption, reduction in alcohol consumption, and medications to lower the uric and medications to lower the uric acid level in the blood (reduce acid level in the blood (reduce hyperuricemia).hyperuricemia).

4848

Dietary changes can help reduce uric acid Dietary changes can help reduce uric acid levels in the blood. levels in the blood.

Since purine chemicals are converted by Since purine chemicals are converted by the body into uric acid, purine-rich foods the body into uric acid, purine-rich foods are avoided. are avoided.

Examples of foods rich in purines include Examples of foods rich in purines include shellfish and organ meats such as liver, shellfish and organ meats such as liver, brains, kidneys, and sweetbreads brains, kidneys, and sweetbreads

4949

There are three aspects to the There are three aspects to the treatment of gout with medications. treatment of gout with medications.

First, pain relievers such as First, pain relievers such as acetaminophen (paracetamol) or acetaminophen (paracetamol) or other more potent analgesics are other more potent analgesics are used to manage pain. used to manage pain.

5050

DRUGS used in GOUTDRUGS used in GOUT

NSAIDs (aspirin, brufen, probenecid, NSAIDs (aspirin, brufen, probenecid, Naproxin, indocid)Naproxin, indocid)

CorticosteroidsCorticosteroids

ColchicineColchicine

AllopurinolAllopurinol

FebuxostatFebuxostat

5151

Secondly, antiinflammatory agents such Secondly, antiinflammatory agents such as nonsteroidal antiinflammatory drugs as nonsteroidal antiinflammatory drugs (NSAIDS), colchicine, and corticosteroids (NSAIDS), colchicine, and corticosteroids are used to decrease joint inflammation. are used to decrease joint inflammation.

Finally, medications are considered for Finally, medications are considered for managing the chronic underlying managing the chronic underlying metabolic derangement that causes metabolic derangement that causes hyperuricemia and gout. hyperuricemia and gout.

5252

NSAIDsNSAIDs

NSAIDS such as indomethacin (Indocin) NSAIDS such as indomethacin (Indocin) and naproxen (Naprosyn) are effective and naproxen (Naprosyn) are effective antiinflammatory medications for acute antiinflammatory medications for acute gout. gout.

These medications are tapered after the These medications are tapered after the arthritis resolves. arthritis resolves.

5353

Common side effects of NSAIDS include Common side effects of NSAIDS include irritation of the gastrointestinal system, irritation of the gastrointestinal system, ulceration of the stomach and intestines, ulceration of the stomach and intestines, and even intestinal bleeding. and even intestinal bleeding.

Patients who have a history of allergy to Patients who have a history of allergy to aspirin or nasal polyps should avoid aspirin or nasal polyps should avoid NSAIDS because of the risk of an intense NSAIDS because of the risk of an intense allergic (anaphylactic) reaction. allergic (anaphylactic) reaction.

5454

COLCHICINECOLCHICINE

Colchicine for acute gout is Colchicine for acute gout is administered by mouth to reduce administered by mouth to reduce inflammation as well as to inflammation as well as to prevent gouty arthritis attacks prevent gouty arthritis attacks while correcting hyperuricemia while correcting hyperuricemia with medications such as with medications such as allopurinol (Zyloprim) or allopurinol (Zyloprim) or febuxostat (Uloric). febuxostat (Uloric).

5555

For acute attacks, it is given hourly For acute attacks, it is given hourly or every two hours until there is or every two hours until there is significant improvement in pain or significant improvement in pain or the patient develops gastrointestinal the patient develops gastrointestinal side effects such as severe diarrhea. side effects such as severe diarrhea.

5656

For prevention, it is given once or For prevention, it is given once or twice daily. twice daily.

Other common side effects of Other common side effects of colchicine include nausea and colchicine include nausea and vomiting.vomiting.

5757

STEROIDSSTEROIDS

Corticosteroids such as prednisone, Corticosteroids such as prednisone, given in short courses, are powerful given in short courses, are powerful antiinflammatory agents for treating antiinflammatory agents for treating acute gout. acute gout.

They can be administered orally or They can be administered orally or injected directly into the inflamed injected directly into the inflamed joint. joint.

5858

Corticosteroids can be prescribed to Corticosteroids can be prescribed to patients who have accompanying patients who have accompanying kidney, liver, or gastrointestinal kidney, liver, or gastrointestinal problems. problems.

Long-term chronic use of Long-term chronic use of corticosteroids is discouraged corticosteroids is discouraged because of serious long-term side because of serious long-term side effects.effects.

5959

In addition to medications for acute gout In addition to medications for acute gout attacks, other drugs can be taken over attacks, other drugs can be taken over prolonged periods to lower blood uric acid prolonged periods to lower blood uric acid levels. levels.

Lowering blood uric acid levels reduces Lowering blood uric acid levels reduces the risk of recurrent attacks of arthritis, the risk of recurrent attacks of arthritis, kidney stones, and kidney disease, and kidney stones, and kidney disease, and also slowly dissolves hard tophi deposits. also slowly dissolves hard tophi deposits.

6060

Medicines used to lower blood uric Medicines used to lower blood uric acid level work either by increasing acid level work either by increasing the kidney's excretion of uric acid or the kidney's excretion of uric acid or by decreasing the body's production by decreasing the body's production of uric acid from the purines in foods. of uric acid from the purines in foods.

6161

These medicines are generally not These medicines are generally not started until after the inflammation from started until after the inflammation from acute gouty arthritis has subsided acute gouty arthritis has subsided because they can worsen the attack. because they can worsen the attack.

If they are already being taken prior to If they are already being taken prior to the attack, they are continued and only the attack, they are continued and only adjusted after the attack has resolved.adjusted after the attack has resolved.

6262

Probenecid and sulfinpyrazone are Probenecid and sulfinpyrazone are medications that are commonly used medications that are commonly used to decrease uric acid blood levels by to decrease uric acid blood levels by increasing the excretion of uric acid increasing the excretion of uric acid into the urine. into the urine.

6363

Since these drugs can, in rare instances, Since these drugs can, in rare instances, cause kidney stones, they should be cause kidney stones, they should be avoided by those patients with a history of avoided by those patients with a history of kidney stones. kidney stones.

These medications should be taken with These medications should be taken with plenty of fluid so as to promote the rapid plenty of fluid so as to promote the rapid passage of uric acid out of the urinary passage of uric acid out of the urinary system in order to prevent kidney stone system in order to prevent kidney stone formation.formation.

6464

ALLOPURINOLALLOPURINOL

Allopurinol  lowers the blood uric acid Allopurinol  lowers the blood uric acid level by preventing uric acid level by preventing uric acid production. production.

It actually blocks the metabolic It actually blocks the metabolic conversion from purines in foods to uric conversion from purines in foods to uric acid. acid.

6565

This medication is used with caution This medication is used with caution in patients with poor kidney function, in patients with poor kidney function, as they are at a particular risk of as they are at a particular risk of developing side effects, including developing side effects, including severe rash and liver damage.severe rash and liver damage.

6666

FEBUXOSTATFEBUXOSTAT

Febuxostat is used for the chronic Febuxostat is used for the chronic management of hyperuricemia from gout. management of hyperuricemia from gout.

Febuxostat has been shown to be more effective Febuxostat has been shown to be more effective than allopurinol in preventing acute attacks of gouty than allopurinol in preventing acute attacks of gouty arthritis and is effective in shrinking tophi deposits arthritis and is effective in shrinking tophi deposits of uric acid in the tissues such as the fingers, of uric acid in the tissues such as the fingers, elbows, and ears. elbows, and ears.

6767

Because febuxostat is not significantly Because febuxostat is not significantly metabolized by the kidneys, it may have metabolized by the kidneys, it may have advantages over allopurinol in patients advantages over allopurinol in patients with underlying kidney disease. with underlying kidney disease.

While taking febuxostat, patients have While taking febuxostat, patients have uric acid and liver function blood tests uric acid and liver function blood tests monitored regularly.monitored regularly.

6868

HOME REMEDYHOME REMEDY Home remedies which can alleviate the Home remedies which can alleviate the

symptoms of acute gout include resting symptoms of acute gout include resting and elevating the inflamed joint. and elevating the inflamed joint.

Ice-pack applications can be helpful to Ice-pack applications can be helpful to reduce pain and decrease inflammation. reduce pain and decrease inflammation.

6969

Patients should avoid aspirin-Patients should avoid aspirin-containing medications, when containing medications, when possible, because aspirin prevents possible, because aspirin prevents kidney excretion of uric acid.kidney excretion of uric acid.