Pharmacology 💊 Flashcards
what is the definition of hyperuricemia?
Is a plasma uric acid concentration > 6.8mg/dL.
what are the causes of hyperuricemia?
- Underexcretion: 80 % of cases.
- Over-production: 20 % of cases
- Both
causes of underexcretion in hyperuricemia
decreased secretion or increased reabsorption
causes of overproduction in hyperuricemia
- High purine diet
- Tumor lysis syndrome
- Enzymatic defects in purine biosynthesis ( Lesch - Nyhan syndrome) (small % of cases)
what are the medications that increase uric acid levels?
- Loop & thiazide diuretics
- Low dose aspirin
- Cyclosporine
- Niacin
what is the clinical presentation of gout?
- Deposition of urate crystals in joints →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
lifestyle modification to manage gout
- Limiting high purine intake (Coffee, tea, meat, egg)
- Weight reduction
- Stop alcohol
what are anti-gout drugs?
what are xanthine oxidase inhibitors?
- Allopurinol
- Febuxostat
what is the mechanism of action of allopurinol?
A purine analog → competitively inhibit xanthine oxidase → decrease uric acid production
what causes the long duration of allopurinol?
due to conversion to active metabolite, oxypurinol (alloxanthine)
Dose of allopurinol
Once /day
what are the uses of allopurinol?
- Chronic gout
- Secondary hyperuricemia to : hematologic malignancies (large amounts of purines are produced, after chemotherapy tumor lysis syndrome) or in renal disease.
what are the side effects of allopurinol?
- Hypersensitivity reactions, Skin rash
- Precipitation of acute attack of gout at the start of therapy
what causes precipitation of acute attack of gout under intake of allopurinol?
mobilization of the deposited uric acid crystals.
how to manage acute attack of gout?
- By the use of anti-inflammatory drugs
why should Dose of 6-Mercaptopurine and azathioprine should be decreased when given with allopurinol?
because the enzyme used for their metabolism is deficient
what are the characteristics of Febuxostat?
Comared to allopurinol:
- A non-purine structure
- Lower risk for rash and hypersensitivity reactions
- Lesser degree of renal elimination → thus requires less adjustment in those with reduced renal function.
- Greater risk of heart disease or stroke→Febuxostat should be
used with caution in patients with a history of heart disease or
stroke
what are Uricosuric drugs?
Probencid
what is the mechanism of action of probencid?
Biphasic action:
Low doses: ↓ secretion of uric acid (&other acidic drugs) by the renal PCT.
Therapeutic doses:↓ Uric acid reabsorption from renal PCT.
what are the therapeutic uses of Probencid?
- Chronic gout.
- To prolong the half-life of some acidic drugs e.g. penicillins and rifampicin by inhibiting their renal tubular secretion .
what are the side effects of Probencid?
GIT disturbance, skin rash, rarely anaphylactic reactions & aplastic anemia.
Precautions during the use of uricosuric drugs
- 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.
why shouldn’t probencid be used during acute attack of gout & started 2-3 weeks after the acute attack?
because the biphasic action on uric acid excretion during the acute attack may aggravate the condition at initial phase of therapy
what are drugs that increase uric acid metabolism?
Rasburicase & Pegloticase
what is the mechanism of action of Rasburicase & Pegloticase?
- Recombinant form of the uricase enzyme → converts uric acid to allantoin, a water-soluble nontoxic metabolite → excreted primarily by the kidneys.
when are Rasburicase & Pegloticase used?
Indicated for gout patients who fail treatment with standard therapies
method of administration of Rasburicase & Pegloticase
IV infusion/2 weeks (pegloticase)
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
what are NSAIDs used during acute attack of gout?
Indomethacin, ibuprofen, Naproxen
what is the mechanism of action of NSAIDs?
- Reversible inhibition of COX enzymes →decreasing synthesis of PGs resulting in decrease inflammation and pain
- Indomethacin is the NSAID of choice, although all NSAIDs are effective.
what NSAID should be avoided during treatment of acute attack of gout?
Don’t use aspirin → competes with uric acid for excretion.
what is the mechanism of action of colchicine?
- It binds to tubulin → inhibits polymerization of intra-cellular microtubular system and inhibit the motility of leukocyte, phagocytosis→ reduce leukocyte migration and inflammatory functions
- It inhibits mitotic spindle and cell division (mitotic block).
what are the uses of colchicine?
- Acute attacks of gout
- Familial Mediterranean fever (FMF)
- liver cirrhosis
Dose of colchicine
1.2 mg orally initially followed by 0.6 mg/ 12 hour until the attack resolves.
disadvantages of colchicine
slow onset and high toxicity→it is not a first-choice drug in acute gouty arthritis.
Side effects of colchicine
The most common:
- GIT toxicity→Diarrhea (severe), nausea, vomiting & abdominal cramps
The most serious:
- Bone marrow depression (onset in days)→ aplastic anemia and agranulocytosis.
The most rare:
- Alopecia, CV toxicity, Hepatotoxicity.
how does colchicine cause diarrhea?
- Colchicine is excreted unchanged in bile→inhibits the continuous renewal of GIT epithelium (mitotic block)→accumulation of toxins and bacterial products→diarrhea.
