Gout Flashcards
What is gout and its cause?
- Gout is a type of arthritis caused by a buildup of uric acid (UA) crystals, primarily in the joints
How is UA produced?
- UA is produced as an end-product of purine metabolism
T/F: Purines are present in many foods, and they make up one of the base pairs of DNA
- True
When UA builds up in the blood, the patient can remain __ or the UA can __ in the joints, resulting in a __ gout attack
Fill in the blanks
- Asymptomatic
- Crystallize
- Painful
What are the characteristics of a gout attack?
- Sudden onset
- Typically in one joint
- Most often in metatarsophalangeal joint (MTP, the big toe)
What is used to identify UA crystals in the body?
- A sample of synovial (joint) fluid
- Evaluating UA level in the body
What are the risk factors for gout?
- Male sex
- Obesity
- Excessive alcohol consumption
List drugs that increase UA
- Aspirin, lower doses
- Calcineurin inhibitors (tacrolimus and cyclosporin)
- Diuretics (loops and thiazides)
- Niacin
- Pyrazinamide
- Select chemotherapy (with tumor lysis syndrome)
- Select pancratic enzyme products
T/F: Asymptomatic hyperuricemia is not treated with drugs
- True
The drugs used for acute attacks target __ and __.
Fill in the blanks
- Pain
- Inflammation
Why prophylactic drugs are used?
- Used to lower UA levels with a goal UA level of < 6 mg/dL
Which anti-inflammatory drugs are used to treat acute pain?
- Colchicine
- Steroids (including intra-articular injections)
- NSAIDs (often with a high starting dose)
Once gout has struck, which medications are used to chronically treat to prevent future attacks?
Xanthine oxidase inhibitor (XOI):
* Allopurinol (preferred)
- Febuxostat
- An acute gout flare can occur when an XOI is started, so give initially with colchicine or an NSAID
If XOI didn’t work well and UA remains >6 mg/dL:
* Add on probenecid or lesinurad to daily XOI
- Replace the XOI with IV pegloticase (Krystexxa)
How do you initially treat acute gout attack?
- It should be treated with a single drug, either an NSAID, a systemic steroid or colchicine
- If severe, combination treatment should be initiated. Thiis included colchicine with either an NSAID or an oral steroid
What can be helpful if the gout attack is localized to one or two joints?
- An intra-articular steroid injection which is injected into joint/s
T/F: The ULT treatment should be continued if an acute attack occurs in a patient using ULT
ULT: allopurinol, febuxostat
- True
Colchicine - brand/generic, dosing, CIs, warnings, SEs
Colchicine (Colcrys)
Dosing (Treatment):
* Start within 36 hours of symptom onset
- Wait 12 hours after a treatment dose before resuming prophylaxis dosing
- 1.2 mg PO followed by 0.6 mg in 1hr
- Do not exceed a total of 1.8 mg in 1 hr or 2.4 mg/day
Contraindications:
* Do not use in combination with a P-gp or strong CYP3A4 inhibitor with renal and/or hepatic impairment
Warnings:
* Myelosuppression
- ↑ myopathy risk
Side effects:
* Diarrhea, nausea, myopathy, neuropathy
NSAIDs - medications
- Indomethacin (Indocin)
- Naproxen (Aleve)
- Celecoxib (Celebrex)
Avoid use of NSAIDs in severe __ disease and __ risk.
Fill in the blanks
- Renal
- CVD
Steroids - formulations, SEs
Formulations:
* Steroids are given PO, IM, IV, intra-articular or as ACTH (adrenocorticotropic hormone), which triggers endogenous glucocorticoid secretion
SEs:
* ↑BG,↑BP, ↑ appetite, insomnia
Steroids: medications
- Prednisone/Prednisolone
- Methylprednisolone (Medrol, Solu-Medrol)
T/F: Methylprednisolone should be initiated intra-articularly if 1-2 large joints involved
- True
List colchicine DIs
Fatal toxicity:
CYP3A4 inhibitors or strong P-gp inhibitors
What is the first-line prophylactic treatment for gout?
Chronic ULT
- Initiate if one or more gout attacks are experienced or joint damage or tophi has occured
- Allopurinol, xanthine oxidase inhibitor (XOI) is the first line drug
- XOI stops the production of UA and it should be titrated up slowly to lower UA level of <6 mg/dL
- High risk of allopurinol hypersensitivity reaction: HLA-B * 5801 allele screening
Colchicine, NSAIDs or steroids
* Used as prophylaxis when starting ULT to reduce the risk of attacks
What is the second-line prophylactic treatment for gout?
Probenecid
* Uricosuric that is used when XOIs are contraindicated or not tolerated or can be added when the UA level is not at goal despite maximum doses of XOIs
- It inhibits reabsorption of UA in the proximal tubule of the nephrone and requires adequate renal function to be effective
Lesinurad
* Uricosuric that is taken with the XOI
Pegloticase
* Recombinat uricase enzyme that converts UA to an inactive metabolite that can be easily excreted
- It is reserved for severe, refractory disease
Allopurinol - brand/generic, MOA, warnings, SEs
Allopurinol (Zyloprim, Aloprim)
MOA:
* Decrease uric acid production
Warnings:
* Hypersensitivity reactions (severe rash, including SJS/TEN, DRESS); HLA-B * 5801 testing prior to use if high risk and do not use if positive
- Hepatotoxicity
Side effects:
* Rash, acute gout attacks, nausea
Use with colchicine or an NSAID for the first 3-6 months due to the high rate of gout attacks
Febuxostat - brand/generic, MOA, BW, warnings, SEs
Febuxostat (Uloric)
MOA:
* Decrease UA production
Boxed warnings:
* Use should be limited to those who cannot tolerate allopurinol as there is an increased risk of CV death compared to allopurinol in patients with CV disease
Warnings:
* Hepatotoxicity
* Serious skin reactions (SJS/TEN, DRESS)
Side effects:
* Increased LFTs
Use with colchicine or an NSAID for the first 3-6 months due to the high rate of gout attacks
Uricosurics - MOA, brand/generic
Probenecid
* Increases beta-lactam levels
Lesunurad
* Taken with allopurinol or febuxostat
MOA:
* Inhibit reabsorption of UA in the kidneys, which increases UA excretion
XOI - DIs
- They increase the concentration of mercaptopuriine, the active metabolite of azathioprine
Probenecid - DIs
- ADRs can occur when used with beta-lactams to increase the concentration
Recombinant Uricase - MOA, BWs, CIs
Pegloticase (Krystexxa)
MOA:
* Converts UA to allantoin, which is excreted
Boxed warnings:
* Anaphylactic reactions - premedicate with antihistamines and steroids
Contraindications:
* G6PD deficiency
- Do not use in combination with allopurinol, febuxostat or probenecid (increases risk of anaphylaxis)
Which medication is used to treat tumor lysis syndrome (TLS)?
- Rasburicase (Elitek) - a urate-oxidase enzyme
When is the use of rasburicase contraindicated?
- G6PD deficiency
