Anti-Gout Drugs, DMARDS, inflammation etc

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DRUGS USED IN GOUT
“DISEASE OF KINGS”

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INTRODUCTION
 Gout results from the precipitation of urate crystals in
the tissues and the subsequent inflammatory
response.
 Acute gout causes a very painful distal mono arthritis,
it can also cause joint destruction, subcutaneous
deposits (tophi) and renal calculi.

 Gout is usually associated with
hyperuricemia.
 Treatment is aimed at relieving the acute
gouty attacks and preventing recurrent gouty
episodes and urate lithiasis.
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1. Natural alkaloids
Colchicine
Demecolchicine
2. NSAID specially used in Gout.
Indomethacin
Naproxen
Sulinidac
3. Corticosteroids
Prednisone
Triamcinolone
Drugs for acute attack

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Drugs For Chronic Gout
1. Drugs which increase the excretion of uric acid
(Uricosuric Agents)
Probenecid
Sulfinpyrazone
2. Drugs which decrease the synthesis of uric acid
(Xanthine oxidase inhibitors))
Allopurinol

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COLCHICINE
Source: -
Alkaloid derived from Colchicum Autumnale (Plant).
Pharmacokinetics: -
Oral absorption is good
PPLs 2 hrs
Metabolism in liver.
80% Metabolites excreted in feces through bile.
20% in urine.

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Colchicine relieves pain in 12-24 hours
Binds to intracellular protein tubulin

Prevents its polymerization into microtubules

Inhibition of mitosis in fast growing cells

Reduction in inflammatory cells
Pharmacodynamics

 Apart from this colchicine inhibits neutrophil
motility and activity it also inhibits the deposition
of urate crystals by changing the Ph.
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Therapeutic Uses
 Acute gouty arthritis.
 Prophylaxis of recurrent episodes of gouty
arthritis.
 Prevention of attacks of acute Mediterranean
fever.
(Familial Mediterranean fever is an inherited condition characterized by recurrent
episodes of painful inflammation in the abdomen, chest, or joints.
These episodes are often accompanied by fever and sometimes a rash or
headache).

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Adverse Effect
 Diarrhea (often) and nausea, vomiting
and abdominal pain on oral administration.
 Rarely it can cause Hepatic necrosis, Acute renal failure, DIC
and seizures
 Hair loss
 BM depression very rarely occur
 Peripheral Neuritis

Overdose is characterized by the following:
•Burning throat pain.
•Hemorrhagic gastroenteritis.
•Extensive vascular damage.
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Rx & Dosage (Prophylactic & for acute
attack)
For Prophylaxis:
 0.6 mg once- thrice a day.
For Termination of an acute attack:
 0.6 mg- 1.2 mg initially followed by 0.6 mg every
2 hours until pain is relieved or nausea and
diarrhea appears.

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ALLOPURINOL (Zyloric)
Chemistry – isomer of hypoxanthine
Pharmacokinetics
80 % absorbed on oral administration
Metabolized by xanthine oxidase
Metabolite Alloxanthine retains the capacity to inhibit xanthine
oxidase (long duration of action – OD dose)
Plasma Half Life = 2 – 3 hrs
Plasma Half Life of Metabolite = 18 - 30 hrs

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Therapeutic Uses
 Hyperuricemia.
 Intercritical period of gout (continued for life).
 Chronic tophaceous gout and gouty nephropathy.
 Use in patients allergic or intolerant to Probenecid &
Sulfinpyrazone.
 Antiprotozoal agent.

What are Tophi ?
 A tophus is a feature of longstanding gout and is the
result of the body's inflammatory response to deposited
MSU monosodium urate monohydrate crystals.
 Tophaceous deposits appear hyperechoic, with an
anechoic rim, and can have a nodular or infiltrative
appearance.
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Adverse Effects
 Hypersensitivity reactions (pruritic maculopapular lesions,
exfoliative dermatitis)
 GIT upsets (N, V, D)
 Peripheral neuritis
 Necrotizing vasculitis
 Depression of BM elements
 Aplastic anemia (rare)
 Cataract formation (rare)

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Precautions: Acute attack of gout.
slow  in dosage.
Interactions
1.  metabolism of mercaptopurine (
dose) & Azothiprine
2. Hypersensitivity if given along with
ampicillin.
3.  metabolism of Probenecid and
oral anticoagulants

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Dosage of Allopurinol
 Initial dose 100mg once daily may be titrated
upto 300 mg/d depending on the response.
 In severe cases 400-600 mg can be given.

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Febuxostat
 The first nonpurine inhibitor of xanthine oxidase
 80 % absorbed after oral administration.
 Reaches peak plasma concentration in 1 hr.
 Dose of 80 mg and 120 mg more effective than
300 mg Allopurinol.
 Adverse effect diarrhea, nausea and headache.

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Probenecid & Sulfinpyrazone
Uricosuric drugs:
Employed to  the body pool of urate in pts with
tophaceous gout or in those with increasingly
frequency gouty attacks, should be avoided in pts
excreting large amounts of uric acid, so as not to
precipitate the formation of uric acid calculi in urinary
tracts.

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Probenecid & Sulfinpyrazone
Pharmacokinetics:
Probenecid is completely reabsorbed by the renal tubules
and is metabolized very slowly.
Sulfinpyrazone or its active hydroxylated derivative in
rapidly excreted by the kidneys so effect after oral
administration is almost as long as that of probenecid.

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MOA of Probenecid & Sulfinpyrazone
At therapeutic doses they block proximal tubular
reabsorption of uric acid increased excretion of uric
acid in the urine  decrease urate pool  relief of
arthritis and remineralization of bone.
However on persistent increase in uric acid excretion renal
stone formation is augmented within urinary tracts.

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Therapeutic Uses
Chronic gout
Probenecid inhibits tubular secretion of penicillin and may be used
to prolong in levels of penicillin.
Adverse Effects
Renal stone formation ( maintain a large urinary volume)
GIT irritation (Sulfinpyrazone)
Allergic dermatitis (Probenecid)
Aplastic anemia (both cause this rarely)
Nephrotic syndrome (Probenecid)

Pegloticase
 Recombinant form of the enzyme urate oxidase or
uricase.
 Acts by converting uric acid  allantoin, water soluble
non-toxic metabolite excretion by kidneys.
 Administration : IV route.
 Adverse effects are infusion related Anaphylaxis.
 Patients should be pre-medicated with antihistamines &
corticosteroids.
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