Gout; OA; RA/ pool/med chem Flashcards
List 2 important transported for Uric acid reabsorption
URAT-1 and GLUT 9
Which part of kidney is important for uric acid reabsorption?
proximal convoluted tube (PCT)
What 2 compounds inhibit uric acid reabsorption?
Probenecid & Benzbromarone
What is the function of Uricase (Pegloticase)?
Convert UA to Allantoin
What is the product of the oxidation of uric acid catalyzed by uricase?
Allantoin
Which form, UA or urate, id predominant at pH 7.4?
urate
Describe the association between gout and uric acid
increase in UA levels –> form insoluble crystals –> increased inflammation –> gout
List 2 XO inhibitors
Allopurinol
Febuxostat
Understand the relationships among Xanthine, Hypoxanthine, uric acid and Allantoin
List 3 uric-acid-lowering therapies
UA synthesis inhibitors
UA reabsorption
UA elimination
What re the primary drugs recommended as first-line treatment for hyperuricemia?
XO inhibitor
What 2 bases in nucleic acid are purine?
Adenine and Guanine
What is the function of Xanthine oxidase?
uric acid synthesis
Uric acid is a weak acid because…
it can release a proton
First-line rate-lowering therapy
Xanthine Oxidase inhibitors
XO inhibitor MOA
inhibit uric acid synthesis
second-line urate lowering inhibitors
Benzbromarone
Probenecid
Pegloticase
Benzbromarone MOA
increase renal urate excretion
Probenecid MOA
increase renal urate excretion
Pegloticase MOA
UA degradation
which XO inhibitor is non-purine-like? Allopurinol or Febuxostat
Febuxostat
Allopurinol is excreted…
by the kidney
Febuxostat is metabolized…
in the liver
How many oxygen atoms are in UA?
3
Which metal atom is the active site of XO?
molybdopterin (MO)
What is NOT a good treatment of hyperuricemia?
inhibiting UA oxidation
Which compound is NOT an XO inhibitor?
-Febuxostat
-Allopurinol
-Oxypurinol
-Allantoin
Allantoin
Which compound is an analogous of hypoxanthine and xanthine?
-febuxostat
-allopurinol
-benzbromarone
-probenacid
Allopurinol
Which medication has multiple significant drug interactions with commonly used drugs like NSAIDs?
Probenecid
Which transporters do Probenecid inhibit?
URAT 1 and GLUT 9
Name the non-selective COX inhibitors
Diclofenac
Flurbiprofen
Ibuprofen
Indomethacin
Naproxen
Nabumetone
T/F
The COX pathway of arachidonate metabolism produces prostaglandins
true
Which COX isoform is induced during inflammation and tends to facilitate the inflammatory response? COX-1 or COX-2
COX-2
Name an NSAID that is ketone prodrug and is metabolized to the acidic active drug?
Nabumetone
biologic DMARDs
- Tumor Necrosis factor Inhibitors -
Etanercept (Enbrel, Erelzi)
Infliximab (Remicade)
Adalimumab (Humira)
Golimumab (Simponi and Simponi ARIA)
Certolizumab pegol (Cimzia)
What do TNF inhibitors (TNFi) block?
both forms of TNF-a
AE of TNF-a-blocking agents
- TNF-a blocking agents increase the risk of bacterial infections and macrophage-dependent infections (including tuberculosis, fungal, and other opportunistic infections) are increased
- associated w/ rick of HBV reactivation
- increase the risk of skin cancers- including melanoma
- Rare cases of leukopenia, neutropenia, thrombocytopenia, and pancytopenia
Rituximab (RTX) MOA
chimeric monoclonal antibody that targets CD20 B-lymphocytes through cell-mediated and complement-dependent cytotoxicity and stimulation of cell apoptosis
Rituximab AE
- assoc with reactivation of Hep B
- about 30% of pts develop rash with the first RTX dose
