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PHA321 > Antiuricaemic Drugs > Flashcards

Antiuricaemic Drugs Flashcards

1
Q

Causes of hyperuricaemia

A
  • Excessive intake
  • Increased production
  • Defective excretion
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2
Q

Causes of excessive uric acid production

A

Leukaemia
Rhabdomyolysis
Cytotoxic therapy
Enzyme deficiency HGPRT

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3
Q

Causes of defective uric acid (UA) excretion

A

Glomerulopathy
Tubular pathology
Diuretics
Diabetic ketoacidosis
Starvation ketosis
Reduced tubular secretion
ABCG2 transporter polymorphisim
GLUT9 polymorphism
URAT 1 transporter dysfunction

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4
Q

Uric acid synthesis steps

A

A I I H X U

ATP
IMP
Inosine
Hypoxanthine
Xanthine
Uric acid

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5
Q

Manifestations of hyperuricaemia

A
  • Asymptomatic
  • Gout
  • Nephrolithiasis (kidney stone)
  • Uric acid nephropathy
  • A component of metabolic syndrome
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6
Q

Gout pathology

A

It is a metabolic and inflammatory disorder. The deposition of sodium urate crystals in the synovial membrane causes an activation of the inflammatory cascade.

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7
Q

Gout symptoms

A

It usually presents as a monoarticular arthritis affecting the big toe.
It is characterized by pain and swelling of the affected joint.

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8
Q

Classes of drugs used in treating gout

A
  • Anti-inflammatory drugs
  • Anti-uricaemic drugs
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9
Q

Anti-inflammatory drugs used in gout treatment

A

NSAIDs
Steroids
Colchicine

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10
Q

Classes of urate-lowering drugs

A

Uric acid synthesis inhibitors
Uricosuric drugs
Selective uric acid reabsorption inhibitors
Recombinant urate oxidase

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11
Q

Examples of uric acid synthesis inhibitors

A

Allopurinol
Febuxostat

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12
Q

Examples of uricosuric drugs

A

Probenecid
Benzbromarone
Sulfinpyrazone

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13
Q

Examples of selective uric acid reabsorption inhibitors

A

Lesinuraud

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14
Q

Examples of recombinant urate oxidase

A

Pegloticase
Rasburicase

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15
Q

Colchicine uses

A

The drug is used for the management of acute attacks and to prevent gouty attacks on commencement of anti-uricaemic drugs.

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16
Q

Colchicine MOA

A

It inhibits migration of neutrophils to the affected joint by binding to tubulin. Also prevents activation and degranulation of neutrophils to generate inflammatory cytokines.

17
Q

Colchicine RODA

A

It is given via the oral route

18
Q

Colchicine adverse effects

A

Nausea, vomiting, abdominal pain.

19
Q

Allopurinol MOA

A

It is a xanthine oxidase inhibitor, a hypoxanthine analog that reduces the production of uric acid by competing as substrate for the oxidase enzyme in place of hypoxanthine. It inhibits the last two steps in uric acid biosynthesis, both catalysed by this enzyme. Its metabolite, alloxanthine, has a similar MOA

20
Q

Allopurinol MOA

A

Routes of administration – oral, intravenous

Bioavailability - 49-53%

Onset of action - 2-3 days

Peak plasma time – 0.5 -2 hours

Time to peak effect – 7-14 days

Distribution - protein bound <1%

Volume of distribution – 1.6-2.4 L/kg

Metabolized in the liver – oxypurinol (active), allopurinol riboside

Half –life – Parent drug 1-3 hours
Active metabolites 15-20 hours

21
Q

Adverse effects of allopurinol

A

Gastrointestinal disturbances
Allergic reactions – skin rashes

22
Q

Febuxostat MOA

A

A xanthine oxidase inhibitor, less likely to cause severe hypersensitivity reaction. Does not inhibit other enzymes involved in purine and pyrimidine synthesis.

23
Q

Probenecid MOA

A

Competitively inhibits reabsorption of uric acid in PCT. Contraindicated in uric acid nephrolithiasis.

24
Q

Probenecid side effects

A

GI disturbance
Hypersensitivity reactions

25
Q

Selective uric acid reabsorption inhibitor example and MOA

A

Lesinuraud
Inhibits URAT1 and OAT4

26
Q

Recombinant urate oxidase enzyme examples

A

Pegloticase
Rasburicase

27
Q

Recombinant urate oxidase enzyme MOA

A

Converts urate to allantoin, a soluble form excreted in urine

28
Q

What is the specific use of Pegloticase?

A

Indicated if xanthine oxidase inhibitors fails/contraindicated

29
Q

Rasburicase specific use

A

For prophylaxis and treatment of hyperuricaemia associated with treatment of malignancies.

30
Q

Which drugs are used for uric acid nephropathy in cytotoxic therapy

A

Uric acid synthesis inhibitors

PHA321 (12 decks)

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