Pharmacology ๐Ÿ’Š Flashcards

1
Q

what is the definition of hyperuricemia?

A

Is a plasma uric acid concentration > 6.8mg/dL.

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2
Q

what are the causes of hyperuricemia?

A
  • Underexcretion: 80 % of cases.
  • Over-production: 20 % of cases
  • Both
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3
Q

causes of underexcretion in hyperuricemia

A

decreased secretion or increased reabsorption

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4
Q

causes of overproduction in hyperuricemia

A
  • High purine diet
  • Tumor lysis syndrome
  • Enzymatic defects in purine biosynthesis ( Lesch - Nyhan syndrome) (small % of cases)
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5
Q

what are the medications that increase uric acid levels?

A
  • Loop & thiazide diuretics
  • Low dose aspirin
  • Cyclosporine
  • Niacin
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6
Q

what is the clinical presentation of gout?

A
  • Deposition of urate crystals in joints โ†’an inflammatory process
  • Acute flares (acute attacks) usually present as pain, swelling, tenderness & redness in the affected joints (big toe mainly).
  • Subcutaneous tophi
  • Urate renal stones
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7
Q

lifestyle modification to manage gout

A
  1. Limiting high purine intake (Coffee, tea, meat, egg)
  2. Weight reduction
  3. Stop alcohol
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8
Q

what are anti-gout drugs?

A
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9
Q

what are xanthine oxidase inhibitors?

A
  • Allopurinol
  • Febuxostat
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10
Q

what is the mechanism of action of allopurinol?

A

A purine analog โ†’ competitively inhibit xanthine oxidase โ†’ decrease uric acid production

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11
Q

what causes the long duration of allopurinol?

A

due to conversion to active metabolite, oxypurinol (alloxanthine)

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12
Q

Dose of allopurinol

A

Once /day

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13
Q

what are the uses of allopurinol?

A
  1. Chronic gout
  2. Secondary hyperuricemia to : hematologic malignancies (large amounts of purines are produced, after chemotherapy tumor lysis syndrome) or in renal disease.
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14
Q

what are the side effects of allopurinol?

A
  • Hypersensitivity reactions, Skin rash
  • Precipitation of acute attack of gout at the start of therapy
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15
Q

what causes precipitation of acute attack of gout under intake of allopurinol?

A

mobilization of the deposited uric acid crystals.

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16
Q

how to manage acute attack of gout?

A
  • By the use of anti-inflammatory drugs
17
Q

why should Dose of 6-Mercaptopurine and azathioprine should be decreased when given with allopurinol?

A

because the enzyme used for their metabolism is deficient

18
Q

what are the characteristics of Febuxostat?

A

Comared to allopurinol:

  • A non-purine structure
  • Lower risk for rash and hypersensitivity reactions
  • Lesser degree of renal elimination โ†’ thus requires less adjustment in those with reduced renal function.
  • Greater risk of heart disease or strokeโ†’Febuxostat should be
    used with caution in patients with a history of heart disease or
    stroke
19
Q

what are Uricosuric drugs?

20
Q

what is the mechanism of action of probencid?

A

Biphasic action:

Low doses: โ†“ secretion of uric acid (&other acidic drugs) by the renal PCT.

Therapeutic doses:โ†“ Uric acid reabsorption from renal PCT.

21
Q

what are the therapeutic uses of Probencid?

A
  • Chronic gout.
  • To prolong the half-life of some acidic drugs e.g. penicillins and rifampicin by inhibiting their renal tubular secretion .
22
Q

what are the side effects of Probencid?

A

GIT disturbance, skin rash, rarely anaphylactic reactions & aplastic anemia.

23
Q

Precautions during the use of uricosuric drugs

A
  • Should not be used during acute attack of gout & started 2-3 weeks after the acute attack
  • Maintain large volume of alkaline urine to avoid stone formation.
  • Should be avoided in patients with gouty nephropathy.
24
Q

why shouldnโ€™t probencid be used during acute attack of gout & started 2-3 weeks after the acute attack?

A

because the biphasic action on uric acid excretion during the acute attack may aggravate the condition at initial phase of therapy

25
what are drugs that increase uric acid metabolism?
Rasburicase & Pegloticase
26
what is the mechanism of action of **Rasburicase & Pegloticase**?
- Recombinant form of the uricase enzyme โ†’ converts uric acid to allantoin, a water-soluble nontoxic metabolite โ†’ excreted primarily by the kidneys.
27
when are Rasburicase & Pegloticase used?
Indicated for gout patients who fail treatment with standard therapies
28
method of administration of Rasburicase & Pegloticase
IV infusion/2 weeks (pegloticase)
29
what are adverse effects of Rasburicase & Pegloticase? And how are they managed?
- Infusion-related reactions and anaphylaxis may occur with pegloticase. - **management:** patients should be pretreated with antihistamines and corticosteroids
30
what are NSAIDs used during acute attack of gout?
Indomethacin, ibuprofen, Naproxen
31
what is the mechanism of action of NSAIDs?
- Reversible inhibition of COX enzymes โ†’decreasing synthesis of PGs resulting in decrease inflammation and pain - **Indomethacin** is the NSAID of choice, although all NSAIDs are effective.
32
what NSAID should be avoided during treatment of acute attack of gout?
Donโ€™t use aspirin โ†’ competes with uric acid for excretion.
33
what is the mechanism of action of colchicine?
- It binds to tubulin โ†’ inhibits polymerization of intra-cellular microtubular system and inhibit the motility of leukocyte, phagocytosisโ†’ reduce leukocyte migration and inflammatory functions - It inhibits mitotic spindle and cell division (mitotic block).
34
what are the uses of colchicine?
- Acute attacks of gout - Familial Mediterranean fever (FMF) - liver cirrhosis
35
Dose of colchicine
1.2 mg orally initially followed by 0.6 mg/ 12 hour until the attack resolves.
36
disadvantages of colchicine
slow onset and high toxicityโ†’it is not a first-choice drug in acute gouty arthritis.
37
Side effects of colchicine
**The most common:** - GIT toxicityโ†’Diarrhea (severe), nausea, vomiting & abdominal cramps **The most serious:** - Bone marrow depression (onset in days)โ†’ aplastic anemia and agranulocytosis. **The most rare:** - Alopecia, CV toxicity, Hepatotoxicity.
38
how does colchicine cause diarrhea?
- Colchicine is excreted unchanged in bileโ†’inhibits the continuous renewal of GIT epithelium (mitotic block)โ†’accumulation of toxins and bacterial productsโ†’diarrhea.