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Gout Part V

Allopathic drugs and laboratory diagnosis:

Non-prescription Medicines:

Non-steroidal anti-inflammatory drugs (NSAIDs) are medicines that are widely used to relieve pain, reduce inflammation, and bring down a high temperature. They're often used to relieve symptoms of headaches, painful periods, sprains and strains, colds and flu, arthritis, and other causes of long-term pain.

NSAIDs help reduce pain and swelling in the joints during a gout attack. Popular types are ibuprofen and naproxen. If you take NSAIDs in the first 24 hours, it can help shorten the attack. Other ways to reduce the pain are to ice, rest, and raise the joint.Most Common Types of NSAIDs:
(i) Aspirin (Bayer, Bufferin, and Ecotrin, St. Joseph).
(ii) Ibuprofen (Advil, Motrin). Ibuprofen can treat a range of conditions including post-surgical pain and pain from inflammatory diseases, such as ankylosing spondylitis.
(iii) Naproxen (Aleve, Anaprox DS, Naprosyn).
(iv) Celecoxib (Celebrex).

Prescription Medicines:

Your doctor may recommend one of these medicines that you can't get over the counter:

(1) Allopurinol (Aloprim, Zyloprim) reduces uric acid production.
(2) Colchicine (Colcrys, Gloperba, Mitigare) reduces inflammation.
(3) Anakinra (KINERET)
(3) Febuxostat (Uloric) reduces uric acid production.
(4) Indomethacin (Indocin, Tivorbex) is a stronger NSAID pain reliever.
(5) Lesinurad (Zurampic) helps your body get rid of uric acid when you pee.
(6) Pegloticase (Krystexxa) breaks down uric acid.
(7) Probenecid helps the kidneys excrete uric acid from your body.
(8) Steroids (also called corticosteroids) fight inflammation.

(1) Allopurinol (Aloprim, Zyloprim):
Allopurinol is a medicine used to lower levels of uric acid in blood. If you produce too much uric acid or your kidneys do not filter enough out, it can build up and cause tiny, sharp urate crystals to form in and around your joints.Allopurinol is a medicine used to treat gout.
Allopurinol is the most popular medicine for gout.
Allopurinol is a medicine for people who make too much uric acid. It is the most common medicine used to treat chronic gout. Your doctor can tell you if allopurinol is safe for you to take if you have kidney disease.

(2) Colchicine (Colcrys, Gloperba, Mitigare):
It reduces inflammation. Colchicine is used to prevent gout attacks (sudden, severe pain in one or more joints caused by abnormally high levels of a substance called uric acid in the blood) in adults. Colchicine (Colcrys) is also used to relieve the pain of gout attacks when they occur.Colchicine is a medicine for treating inflammation and pain. It can be used to: treat flare-ups (attacks) of gout. prevent increased flare-ups of gout when you first start on a medicine like allopurinol taken to manage your condition long term.To prevent gout attacks during this time, low-dose colchicine is often also prescribed for the first six months. That effectively reduces the risk of those kinds of attacks. But even if one occurs, it's not necessary to stop taking the uric acid reducing drugs.
Due to the risk of dose related serious adverse effects the use of high doses of colchicine to treat acute gout is no longer appropriate, especially in elderly patients, patients with impaired hepatic or renal function, and patients who weigh less than 50kg. Colchicine is an anti-inflammatory drug that is used to treat a variety of conditions, including gout, recurrent pericarditis, and familial Mediterranean fever. Recently, the drug has been shown to potentially reduce the risk of cardiovascular events in those with coronary artery disease.

(3) Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein.

KINERET® (anakinra) is a prescription medicine called an interleukin-1 receptor antagonist (IL-1Ra) used to reduce the signs and symptoms and slow the damage of moderate to severe active rheumatoid arthritis (RA) in people aged 18 years and older when 1 or more other drugs for RA have not worked.

The mechanism of action if Anakinra :
Mechanism of action of anakinra. Both IL-1α and IL-1β act through IL-1 receptor 1 to stimulate the production of inflammatory cytokines and TNFα that lead to the inflammatory cascade. The inflammasome is a complex of distinct proteins which together convert inactive prointerleukin-1β to active IL-1β.
Anakinra an immunosuppressant.
Immunosuppressive therapy (including anakinra) may lead to reactivation of latent tuberculosis or other atypical or opportunistic infections; test patients for latent TB prior to initiation, and treat latent TB infection prior to use.

(4) KRYSTEXXA (kris-Tex-uh): It has been helping patients for more than 10 years and is the first and only medication approved by the FDA to treat gout that has not been controlled by other medicines. Studies show that 1 Intravenous injection treatment every other week for about 6 months is all you may need to take control.

(5) Febuxostat is used to lower hyperuricemia (high uric acid in the blood) in patients with gout who have been treated with allopurinol that did not work well or cannot be treated with allopurinol. This medicine is a xanthine oxidase inhibitor. It works by causing less uric acid to be produced by the body.
Febustat 40 mg is a non steroid oral drug.Tab Febustat is not a steroid medicine. It contains febuxostat, an antigout medicine, which is used for the treatment of gout.
Remember, febuxostat should be taken every day to prevent a gout attack. It can be taken six months to become fully effective. It does not have any effect during a gout attack, although you should continue to take it regularly every day even if this happens.

(6) Indomethacin:
Role of indomethacin in acute pain and inflammation management:
It is commonly prescribed for the relief of acute gouty arthritis pain, but has demonstrated efficacy in the treatment of various other painful conditions. Numerous comparative studies have affirmed the clinical utility of indomethacin relative to other widely used analgesics.
For mild to moderate acute pain: Adults—20 milligrams (mg) three times a day, or 40 mg two or three times a day. Children—Use and dose must be determined by your doctor.Indomethacin is an oral strong painkiller drug.
Indomethacin is approximately 10 times as potent as aspirin.
Indomethacin (Indocin) is a much stronger medication than ibuprofen, which is why it can treat more severe pain.

(7) Lesinurad used in combination with a xanthine oxidase inhibitor to treat hyperuricemia (high levels of uric acid) in people with gout (sudden attacks of redness, swelling, pain, and heat in one or more joints) whose disease is not controlled with their current medication.

Mechanism of action of lesinurad:
Lesinurad inhibits URAT1, a protein that is responsible for reabsorption of uric acid in the kidneys.This leads to increased uric acid excretion with the urine, and consequently lower blood levels. It also inhibits the protein OAT4, which is associated with hyperuricemia caused by diuretic drugs.
Lesinurad is used together with a xanthine oxidase inhibitor (eg, allopurinol, febuxostat) to treat gout. It works to lower uric acid levels in the blood. This medicine is available only with your doctor's prescription.

(8) Pegloticase injection:
Pegloticase injection is used to treat chronic gout in adult patients who have already been treated with other medicines that did not work well. Gout is a condition that is caused by too much uric acid in the blood (hyperuricemia). Pegloticase injection works by causing less uric acid to be produced by the body.
Pegloticase (Intravenous Route)
Pegloticase injection is in a class of medications called Pegylated uric acid specific enzymes. It works by decreasing the amount of uric acid in the body. Pegloticase injection is used to prevent gout attacks but not to treat them once they occur.
The mechanism of action of pegloticase:
Pegloticase is a pegylated, recombinant uricase (urate-oxidase), created by a genetically altered variant of Escherichia coli that exerts its mechanism of action by catalyzing uric acid to the water-soluble purine metabolite allantoin.In clinical trials, pegloticase lowered uric acid levels to as low as 1 mg/dL (or less) within 24 hours. Pegloticase is a drug you take to manage your gout and prevent flares, but it will not treat a gout flare or its symptoms.

(9) Probenecid: Probenecid is used in the treatment of chronic gout or gouty arthritis. These conditions are caused by too much uric acid in the blood. The medicine works by removing the extra uric acid from the body. Probenecid does not cure gout, but after you have been taking it for a few months it will help prevent gout attacks. Probenecid belongs to a class of drugs known as uricosurics. It lowers high levels of uric acid in your body by helping the kidneys to get rid of uric acid. When uric acid levels get too high, crystals can form in the joints, causing gout. Lowering uric acid levels may also help your kidneys.
Probenecid has low risk for cardiac attack than allopurinol .In a large cohort study of 38,888 elderly Medicare patients with gout, use of probenecid appears to be associated with a modest decrease in Myocardial infraction, stroke, and admission for heart failure exacerbation compared to allopurinol.
Probenecid comes in a tablet to take by mouth. It usually is taken two times a day when prescribed for chronic gout or gouty arthritis and four times a day when prescribed with antibiotics to make them more effective.
Probalan is another name for probenecid:Probenecid, also sold under the brand name Probalan, is a medication that increases uric acid excretion in the urine.

(10) Corticosteroid injection: An ultrasound-guided steroid injection can be used to reduce the pain and inflammation present during an acute episode of Gout. A corticosteroid is a powerful anti-inflammatory medication that can be deposited within the affected joint.Gout is also called king of diseases.
Joint inflammation, tenderness and intense joint pain are the first symptoms of gout.Obesity,Diabetes,high blood pressure,drugs of B.P. like beta blockers, genetic
makeup,sex: male or female, excessive exercise damaging body muscles etc are predisposing factors.In conditions like metabolic syndrome, Lead poisoning, Leukaemia , Chemotherapy, stone in kidney, kidney failure etc uric acid level is increased.It is a disabling condition restricting your movement.
Aspirin, disprin, Diuretics and immunosuppressive drugs also increases uric acid in blood.
The Recommended Dietary Allowance (RDA) for protein is a modest 0.8 grams of protein per kilogram of body weight.

*Preventive Measures:
Along with medicine, your doctor may suggest other ways to prevent another attack:
•Exercise and eat a balanced diet to control your weight.
•Drink lots of water.
•Stay away from sugary drinks.
•Avoid excessive alcohol use, especially beer.
•Eat less meat, especially liver and sweetbreads, and seafood.
• Get your protein from foods like low-fat dairy. products like yogurt, cheese and milk.
•These medicine and lifestyle changes can help you get through an attack and prevent other attacks.
A uric acid blood test, also known as a serum uric acid measurement, determines how much uric acid is present in your blood. The test can help determine how well your body produces and removes uric acid. Uric acid is a chemical produced when your body breaks down foods that contain organic compounds called purines.

The importance of estimating serum uric acid:

Uric acid is a useful diagnostic tool as screening for most of purine metabolic disorders. The importance of uric acid measurement in plasma and urine with respect of metabolic disorders is highlighted. Not only gout and renal stones are indications to send blood to the laboratory for uric acid examination.

Collection of blood sample :A uric acid test can be done as a blood test or a urine test. During a blood test, a health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial.
Uric acid as measured in serum by three different uricase (EC 1.7. 3.3) methods (aca, Ektachem, and SMAC) and by the SMAC method with phosphotungstic acid was compared with a candidate Reference Method for uric acid.
(1) Caraway method :
This method is used for estimation of uric acid.
A colorimetric method depends on the reduction of a chromogen such as sodium tungstate by uric acid to produce tungsten blue, a measurable color change.This technique has been commonly employed in automated hospital screening (SMA systems).
Caraway method is analytical method for estimation of uric acid from blood. The most poplular method of this type is the Caraway method, which is based on the oxidation of the uric acid in a protein-free filtrate, with subsequent reduction of phosphotungstic acid (Phosphotugstate) to tungsten blue.

(2) Uricase method, the principle of enzymatic method for uric acid determination:
The principle of the method is that hydrogen peroxide, liberated by the action of uricase and xanthine oxidase on their substrates, is coupled to the production of a coloured product.
Uricase method is widely used to monitor serum uric acid for laboratory diagnosis of gout, kidney function and hyperuricemia-associated diseases. It is easy to quantify uric acid by its distinctive absorbance at the 293 nm or to quantify hydrogen peroxide, one of the uricase products, by peroxidase-coupled analysis.

By this approach, serum uric acid values between 3.5 and 6.8 mg/dL in adult males and postmenopausal women and between 2.6 and 6.0 mg/dL in premenopausal women have been identified as normal in many countries.
normal uric acid level is under 6.8 mg/dL . A high uric acid level (above 6.8 mg/dL) is known as hyperuricemia. This can lead to a disease called gout that causes painful joints that accumulate urate crystals. It can also make your blood and urine too acidic.In Western countries people mostly consume non vegetarian diet hence 6.8 mg% uric acid is setup as maximum limit.But in India people experience symptoms of gout even at level of 5 to 6 mg% of serum uric acid.
If too much uric acid stays in the body, a condition called hyperuricemia will occur. Hyperuricemia can cause crystals of uric acid (or urate) to form. These crystals can settle in the joints and cause gout, a form of arthritis that can be very painful. They can also settle in the kidneys and form kidney stones.
Uric acid stones in kidneys:
A uric acid stone is a type of kidney stone, which is a hard object that is made from chemicals in the urine. After formation, the stone may stay in the kidney or travel down the urinary tract into the ureter.
Uric acid stones can form in people who lose too much fluid because of chronic diarrhea or malabsorption, those who eat a high-protein diet, and those with diabetes or metabolic syndrome. Certain genetic factors also may increase your risk of uric acid stones. Uric acid stones are the most readily dissolvable of all types of urinary stones. By maintaining urinary pH between 6.2-6.8 with the use of sodium acid citrate or uralyt-U and reducing serum uric acid by allopurinol, researchers tried to dissolve 107 stones in 67 patients.

Serum uric acid increases due to certain reasons.
Most of the time, a high uric acid level occurs when your kidneys don't eliminate uric acid efficiently. Things that may cause this slow-down in the removal of uric acid include rich foods, being overweight, having diabetes, taking certain diuretics (sometimes called water pills) and drinking too much alcohol.

X ray, Ultrasonography and CT can be useful for diagnosis.
For laboratory diagnosis of gout the fluid is collected from bone joints and examined microscopically for uric acid crystal.

Information compiled by: Dr. Bhairavsinh Raol