Therapeutics Exam 4 Gout Flashcards
What is gout?
An inflammatory process in response to crystallization of monosodium urate (MSU) in articular and non-articular tissues
What uric acid level signals hyperuricemia?
> 6.8 mg/dL
*and symptomatic
What is uric acid?
The main end product in purine degradation
What is allantoin?
Soluble byproduct from uric acid breakdown
-more soluble form of uric acid
What are the 3 main medications that can increase uric acid levels?
Diuretics (thiazides or any)
Cytotoxic drugs (chemo, methotrexate)
Salicylates
What is the presentation of acute gouty arthritis?
Podagra- (first metatarsal joint on foot involved)
Uric acid can deposit elsewhere (fingers, wrists, cartilage, tendons, kidneys)
WBC at what level could signify infection?
> 11,000
What are the complications of acute gouty arthritis?
Tophi (deposits of monosodium urate, form nodules)
Nephrolithiasis (kidney stones)
Gouty nephropathy (kidney disease)
What is the only way to get a definitive gout diagnosis?
Synovial fluid aspiration
-not done much
What are the 3 steps in gout treatment?
-Treat pain and inflammation
-Urate-lowering therapy (ULT) to prevent recurrence
-Anti-inflammatory prophylaxis
What is a possible non-pharm therapy for acute gouty arthritis?
Apply ice to the affected area
What are the 3 options for pharmacologic therapy for acute gout treatment?
NSAIDs
Corticosteroids
Colchicine
What are the NSAIDs that can be used in gout treatment?
Indomethacin
Naproxen
Ibuprofen (not approved but commonly used)
Sulindac
What is the key to NSAID use in gout?
Early initiation
What corticosteroids are used in gout treatment?
PO:
-Methylprednisolone
-Prednisone
IM:
-Triamcinolone
-Methylprednisolone
Intra-articular:
-Triamcinolone
If using an IM or IA corticosteroid, what needs to happen?
Follow up with subsequent anti-inflammatory agent (NSAID or po Corticosteroid)
What are the important considerations with corticosteroid treatment?
Need to taper doses
Limit treatment duration
Increased risk of GI bleed and peptic ulcer disease
Monitor diabetes for increased BG
Avoid intra-articular injections if infection is suspected
What is the MOA of colchicine?
Disrupts cytoskeletal functions
-inhibits B-tubulin polymerization into microtubules
-this prevents migration of neutrophils to sites of inflammation that cause gout symptoms
Colchicine must be administered within how many hours of an acute gout attack?
24 hours
-because otherwise the neutrophils have already reached the site of the gout
What is the dosing of colchicine?
Day 1: 1.2 mg po once, then 0.6mg one hour later
Day 2+: 0.6 mg BID until attack resolves
How do we adjust colchicine dosing for renal impairment?
CrCl >/=30: No adjustment
CrCl < 30: 1.2 mg at onset, then 0.6 mg 1 hour later
*0.6 mg dose is only given once!!!
Only repeat every 2 weeks
Dialysis: A single 0.6 mg dose, only repeat every 2 weeks
What two agents should we try to avoid combining?
NSAIDs
Corticosteroids
What are the abortive gout agents?
NSAIDs
Colchicine
-patients can use the “pill in pocket” method
Who is not a candidate for Urate Lowering Therapy (ULT)?
Asymptomatic hyperuricemia with no prior gout flares or tophi
First gout attack without risk factors
When should urate lowering therapy be administered?
Recommended to wait 2 weeks after acute attack
-can be initiated during an acute attack though
How long are patients on urate lowering therapy?
Indefinitely
What are the 3 types of urate lowering therapy?
1st: Xanthine Oxidase Inhibitors
2nd: Uricosurics
3rd: Uricase Agents
What is the moa of Xanthine Oxidase Inhibitors?
Reduces uric acid by:
-impairing the ability of xanthine oxidase to convert hypoxanthine to xanthine (and therefore to uric acid)
What are the Xanthine Oxidase Inhibitors?
Allopurinol
Febuxostat
What is the dosing of allopurinol?
Initial: 100mg po daily
*Titrate: Every 2-4 weeks in </= 100mg increments prn to achieve uric acid <6
How do we adjust allopurinol dosing in renal impairment?
eGFR</= 60: Initial dose is 50mg daily
What is a concern with allopurinol use?
Allopurinol Hypersensitivity Syndrome
-Stevens-Johnson Syndrome
-Toxic Epidermal Necrolysis
Watch for HLA-B5801 allele
When is Febuxostat used?
When patients cannot tolerate allopurinol
What is the MOA of Uricosurics?
Increase renal clearance of uric acid by inhibiting reabsorption
What are the uricosuric drugs?
*Probenecid
Lesinurad (NOT FDA APPROVED)
When is Probenecid contraindicated?
History of urolithiasis (kidney stones)
What is the MOA of uricase agents?
Recombinant form of urate-oxidase enzyme
-Converts uric acid to more soluble metabolite allantoin
What is the only uricase agent?
Pegloticase
When is Pegloticase used?
SEVERE gout and hyperuricemia
(>/=3 flared in 18 months, >/= 1 tophi, joint damage from gout)
*Note that this is an IV infusion
What is a concern with Pegloticase use?
Anaphylaxis
Infusion reactions
What other medications can be used for gout treatment?
Fenofibrate
-increases hypoxanthine and xanthine clearance
Losartan
-Preferred agent for gout and HTN
When do we use gout prophylaxis?
When initiating Urate Lowering Therapy
How long do we use gout attack prophylaxis?
First 3-6 months of ULT initiation
What agents do we use for prophylaxis?
NSAIDs -lowest effective dose
Prednisone (</= 10 mg/day)
Colchicine (0.6mg daily or BID)
