Lecture 6 - Gout 1 Flashcards
Hyperuricemia
Elevated Serum Uric Acid
Tophus
Calculus contains sodium rate that develops around fibrous tissues around joins, typically in patients with gout
Podagra
Painful condition of big toe caused by gout
Uricase
enzyme that oxidatively degrade uric acid, thereby catalyzing conversion to soluble allantoin, which is more soluble than uric acid
found in most animals, not in humans
Uricosuric meds
Meds given to increase elim of uric acid
Uric Acid Pathway
Hypoxanthine (Via Xanthine Oxidase ) -> Xanthine (via Xanthine Oxidase) - > Uric Acid (excreted by kindey, metabolized via rate oxidase in animals)
Gets converted to Allantoin in animals
Uric acid comes from?
Metabolism of purines
How is Uric acid eliminated in humans?
Gut and Kidney
Hyperuricemia SUA
> 7mg at 37C for men
> 6mg at 37C for women
Do all patients with hyperuricemia develop acute gout flares?
No
in absence of gout, asymptomatic hyperuricemia does not require treatment
Best description of gout?
Patients with gout will have recurrent acute attacks separated by intercritical periods
Risk Factors for Gout
- Inc age
- Male > female
- injury
- Hyperuricemia** most important
- Fasting
- Recent srugery
- Food/drinks
- Meds
- Medical conditions
- Genetics
Food/Drink risk factors for Gout
Food high in purine = red meat
Foods/drinks w/ high fructose corn syrup = soda
Alcohol
Meds that can cause overproduction
Cytotoxic chemotherapy
Meds that can cause under excretion
Cyclosporine + Tacrolimus
Diuretics (loop/thiazide)
Niacin
Low dose salicylates (< 2g/day)
Medical Condition Risk factors pointed out
Overproduction:
Myeloproliferative disorders
Lymphoproliferative disorders
Underexcretion:
Renal insufficiency
Volume depletion
CVD, common Risk factors
Risk Factors: Genetics
HGPRT deficiency: Leads to more Guanylic acid, leading to more uric acid
PRPP over activity: can increase Hypoxanthien leading to uric acid
Acute Goute Pathophysiology
Uric acid crystals deposit into joint, bringing immune cells that cause them to rupture and perpetuates an inflammatory response
Acute Gout Presentation
12-24hrs after exposure to risk factor
lower extremities
redness, swelling, warmth, extreme pain of the joints
Mot common areas for gout attack
big toe joint = paragraph
can get in knee, finger, wrists elbows
Difference with pseudo gout?
caused by calcium pyrophosphate crystals
can only tell by “tapping joint” looking at fluid after microscope
How to get diagnosis of gout?
Tapping joint and looking at fluid under microscope = gold standard
if cant do that, often do clinical diagnosis
Acute Gout management Treatment
want to rapidly relive symptoms
prevent recurrent attacks
prevent complications associated with chronic deposition of urate crystals
self limiting, can go away on its own but don’t want to do that
** Dont dx ULT in acute attack **
Nonpharm treatment options of Gout
Ice
Rest affected point
Patient education
Pharm treatment options of Gout
Colchicine
NSAIDs
Steroids (systemic/intra-articular)
IL-1 antagonists
FDA approved NSAIDs for gout
Indomethacin (Indocin)
Naproxen (Naprosyn)
Sulidac (Clinoril)
NSAIDs ADR
Inc BP, NA/Water retention, gastritis, GI bleeding
NSAIDs CI
Hx of allergy
HF
Renal Insufficiency
Hx of previous GI
NSAIDs DI
ACE/ARBs Cyclosporine Tacrolimus Tenofovir Lithium Anti-platelet/anticoag Corticosteroids
NSAIDs monitoring efficacy
efficacy, lower pain, reduced number of flairs
NSAIDs monitoring safety
CBC LFTs SCr Fecal occult blood test Black tarry stools BP Edema
Corticosteroids MOA
Synthetic glucocorticoid analog used for anti-inflammatory effects
Corticosteroids ADR
Acute: Hypoglycemia, leukocytosis, fluid retention, impaired wound healing, GI, insomnia, Hypertension
Chronic: HPA axis suppression, osteoporosis
Corticosteroids Precautions
Infection
DM
Peptic ulcer disease
Corticosteroid DI
Strong CYP3A4 inhib
Fluoroquinolone
NSAIDs
anti-hyperglycemic agents
Corticosteroid Pt education
monitor BG if DM
Take w/ food or milk to minimize GI upset
Colchicine MOA
May interferon w/ intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates the activation of IL-1B
Prophylaxis Colchicine Dose
0.6mg or BID for ~6 months
Req renal adjustment in bad renal impairment
adjustment in severe hepatic impairment
Treatment of gout Flair Colchicine Dose
7 days at 1.2mg once, then 0.6mg one hour later
Req renal adjustment in really bad renal impairment
adjustment in severe hepatic impairment
If combo Hepatic/renal impairment can you use Colchicine?
nah
Colchicine Side effects
GI = diarrhea
Blood dyscrasuas
Neuromuscular toxicity
Colchicine CI
Patients w/ renal or hepatic impairment should not use w/ PGP or Strong CYP3A4 inhibitor
Colchicine DI
Strong CYP3A4, PGP inhib
Statins & Fenofibrates
Req dose adjustments if current on meds, or if recently on meds (within last 14 days)
Colchicine Monitoring
Efficacy: signs/symptoms of gout, dec gout flares
Safety: CBC, signs/symptoms, GI
Colchicine Pt education
Appropriate dosing
ADE
Avoid Grapefruit juice
Anakinra Brand
Kineret
Canakinumab brand
Illaris
rilonacept Brand
Arcalyst
Which IL-1 agent only used for prophylaxis?
Rilonacept (Arcalyst)
IL-1 Antagonist SE
injection site reactions
Neutropenia
Hypersensitivity reactions
infectious disease
IL-1 Antagonist CI
Hypersensitivity
IL-1 Antagonist DI
Immunosuppressants
Live vaccines
IL-1 Antagonists monitoring
Neutrophil count
Temp
Signs of infections
IL-1 antagonist Pt education
Report signs of infection Screen for TB avoid live vaccines SE proper injection
IL-1 Antagonists
Anakinra (Kineret)
Canakinumab (Illaris)
Rilonacept (Arcalyst)
Corticosteroids
Prednisone (Deltasone, Prednicort)
Methylprednisolone (Medrol)
Triamcinolone IM (Kenalog)
Triamcinolone acetonide intraarticular
How to select Gout agent for patient?
Patient Preferences Current attack Response to current therapy Comorbid conditions DI Cost of therapy
Acute Gout Med to avoid in CKD
NSAIDs
Cox-2 inhibitor
Colchicine
Acute Gout med to avoid in Liver disease
NSAIDs
Cox-2 inhibitor
Colchicine
Acute Gout med to avoid CHF
NSAIDs
Cox-2 inhibitor
Corticosteroids
Acute Gout med to avoid HTN
NSAIDs
Cox-2 inhibitor
Corticosteroids
Acute Gout med to avoid ASCVD
NSAIDs
Cox-2 inhibitor
Acute Gout med to avoid PUD
NSAIDs
Cox-2 inhibitor
Corticosteroids
Acute Gout med to avoid Diabetes
Corticosteroids
Acute Gout med to avoid Infection/Infection Risk
Corticosteroids
IL-1 antagonists
Acute Gout med to avoid Geriatric Patients
Indomethacin
1st line therapy for Acute Gout
NSAIDs
Colchicine
Glucocorticoids
All preferred over IL-1 antagonists
Low dose Colchicine > High Dose
IL-1 used if pts cant tolerate or take others
1st line therapy for Acute Gout
NSAIDs
Colchicine
Glucocorticoids
All preferred over IL-1 antagonists
Low dose Colchicine > High Dose
IL-1 used if pts cant tolerate or take others
Treatment Goals for chronic Gout?
Maintain SUA of < 6mg/dL
Strongly Recommend to Start ULT
> 1 tophi
Radiographic damage attributable to gout
frequent Gout flares > 2/yrs
Conditionally Recommended to Start ULT
Pts w/ >1 flare but have <2/yr
pts experiencing 1st flare and have > Stage 3 CKD, SUA > 9 or urolithiasis
Patients recommended against Start ULT
pts experiencing 1st flare with exceptions
Asymptomatic hyperuricemia
What to do before starting ULT?
1st initiate prophylactic therapy for mobilization flares
Low dose colchicine
NSAIDs (give with PPI due to length on them ~ 6 month)
Corticosteroids
How long should Prophylactic therapy last for mobilization therapy before ULT?
3-6 months
possible to extend if still experiencing flares
Allopurinol MOA
Xanthine Oxidase inhibitors
Allopurinol Dosing
Start 50 or 100mg daily (depend on renal function), titrate up by 50-100mg every 2-5 weeks until goal of SUA < 6mg/dL
Doses > 300mg often given in divided doses
Max daily Dose = 800mg
When to use 50mg Allopurinol Dose
Stage 4 CKD or higher
when to use 100mg Allopurinol Dose
Everyone, incl blew Stage 4 CKD
