Msk System - Drugs For Gout

Front 1

What is the end product of purine metabolism?

Back 1

Urate/uric acid

Front 2

What are the two main causes of hyperuricemia?

Back 2

Underexcretion (majority
Overproduction

Front 3

What is the definition of gout?

Back 3

Deposition of monosodium urate crystals in tissues.

Front 4

What role do inflammatory mediators play in the formation of gout?

Back 4

When the urate crystals are deposited in the joint, synoviocytes phagocytose the crystals. They then secrete inflammatory mediators whcih attract and activate PMN and macrophages. Drugs active in gout inhibit this phagocytosis and PMN/macrophage activation.

Front 5

What are some general characteristics of gout?

Back 5

Extremely painful inflammatory arthritis.
Typically involves a single joint (50% in first MTP joint), but can also involve multiple joints, bursa, and tendons.
Result of imbalance between uric acid production and renal excretion (hyperuricemia, which does not always lead to gout).
Sudden onset
Intense inflammation
Distal joints
typically in middle-aged males
Can have recurrent episodes
Influenced by diet and other co-morbidities
Can show bony erosions on x-ray
Drugs like thiazides, loop dieuretics, and salicylates can exacerbate hyperuricemia.

Front 6

What are the phases of gout, and waht are their general characteristics?

Back 6

ACUTE gouty arthritis:
precipitation of monosodium urate crystals
Acute inflammatory reponse.

CHRONIC:
Chronic arthritis
joint destruction
tophi
renal calculi and damage (nephrolithiasis and nephropathy)

Front 7

What is the disease course of gout (FIRST ATTACK)?

Back 7

Short duration that resolves in a few days to several weeks
typically involves one joint
subsequent attacks may last several weeks and involve multiple joints.

Front 8

What is the disease course of gout without any prophylaxis after the first attack?

Back 8

asymptomatic periods become shorter (more frequent attacks)
chronic joint symptoms cause permanent erosive joint deformity

Front 9

What are some ways to manage asymptomatic hyperuricemia?

Back 9

Lifestyle modification and risk reduction (diet/alcohol)
Comorbidity management (obesity, hypertension, diabetes, alcoholism, hyperlipidemia therapy)

Front 10

What are the goalsof treatment for gout?

Back 10

reief from acute attacks
prevention of recurrent attacks
prevent/reverse crystal deposits in joints, the urinary tract, the renal interstitium, and tissue/parenchymal organs.

Front 11

What are the ways that treatments will try to help the patient in acute and prevention measures?

Back 11

ACUTE:
inhibit an immune response (Allopurinol)
PREVENTION:
Increase uric acid excretion (Probenecid)

Front 12

What are some characteristics of NSAIDs?

Back 12

First line of therapy for most gout patients
Fast acting
Decrease the inflammatory response
AAA (Analgesic, Antipyretic, Anti-Inflammatory)

Front 13

What is the mechanism of action for NSAIDs?

Back 13

Mainly prohibit prostaglandin synthesis

Front 14

Describe Indomethacin and how it is used in gout PAtients

Back 14

Drug of choice for acute attacks.
Has significant CNS and GI side effects if used long-term.

Front 15

What are some other NSAIDs?

Back 15

Ibuprofen and Naproxen

Front 16

Why should aspirin be avoided in gout patients?

Back 16

In low doses it can cause retention of uric acid, and in high doses it can increase the risk of renal calculi.

Front 17

What are the general characteristics of Colchicine?

Back 17

Slower onset than NSAIDs
Narrow therapeutic index, and can cause bad GI side effects.
Anti-inflammatory
NOT ANALGESIC
Doesnot efect serum uric acid levels, and will not stop destructive aspects of gout

Front 18

What is the mechanism of action of Colchicine in gout patients?

Back 18

Poorly understood.
Binds tubulin and causes an antimitotic effect. Also inhibits leukocyte migration, phagocytosis, and leukotriene B4 formation.

Front 19

What do the different doses of Colchicine do?

Back 19

HIGH DOSE (declining use)
Treatment of acute gouty arthritis
LOW DOSE:
Prevention of recurrent attacks, especially in early stages of anti-hyperuricemia therapy.

Front 20

What are the effects of Colchicine toxicity?

Back 20

Primary toxicity is GI, caused by high doses to treat acute attacks.
Diarrhea, nausea, vomiting, abdominal pain.

Hematological
Bone marrow suppression (agranulocytosis, aplastic anemia, thrombocytopenia)

Myopathy (chronic use)

Front 21

Describe corticosteroids and their use in patients with gout.

Back 21

Anti-inflammatory steroids
Used for acute attacks
intra-articular injections (when one or two joints are affected)
Parenteral use when pt cannot handle NSAIDs or colchicine.
Toxicity can limit chronic use.

Front 22

What are the indications for drug therapy for lowering uric acid levels in gout?

Back 22

Frequent and disabling attacks
clinical/radiographic signs of joint disease
Tophaceous deposits
gout with renal insufficiency
recurrent uric acid stones
No role in managing acute attacks
not recommended for asymptomatic hyperuricemia

Front 23

What are the therapeutic uses of Allopurinol in gout?

Back 23

First choice for the chronic treatment of gout (prevents attacks and prevents development/progression of chronic gouty arthritis)
Prevents stone formation in kidneys
Protects the kidneys from gouty nephropathy
eliminate tophi

Generally well-tolerated
Most commin issue is hypersensitivity (mostly rashes but can be more serious)

Front 24

Why should doses of 6-mercaptopurine and Azathioprine be lowered when giving a patient Allopurinol?

Back 24

Allopurinol is a conpetitive inhibitor of Xanthine Oxidase. Both 6-merca and azathioprine are metabolized by xanthine oxidase, so if it is inhibited, those drugs will build up in the system causing renal damage.

Front 25

Why should you use an NSAID or colchicine before using Allopurinol?

Back 25

Allopurinol will get rid of the uric acid in the blood, causing the tissues to equilibrate and release their stores of uric acid all at once. This can cause an acute attack of gout. Using an NSAID or colchicine before administering allopurinol will prevent this from happening.

Front 26

Under what condition would you use Febuxostat instead of allopurinol?

Back 26

Febuxostat is a xanthine oxidase inhibitor.
May be better for patients with chronic mild-moderate kidney disease, as there is no dose adjustment necessary (allopurinol must have GFR watched and adjust doses accordingly)

Using this may cause an increased risk of CV events.

Front 27

What are the general characteristics of uricosuric agents?

Back 27

Secondline agents for those who are underexcretors (90% of cases, effective in most patients)
Avoid use where stone formation or renal disease may occur
Ineffective in pts with renal impairment
less effective in elderly pts
requires bid or tid dosing

Used in pts resistant to or intolerent of allopurinol.

Front 28

A clinically obese, diabetic 39 year-old male patient presents with an incredibly painful, inflamed big right toe. He says that it is severely painful to even the slightest touch. When asked, the pt says that this is the first time this has happened.

You prescribe him a fast-acting drug that causes analgesia, is anti-inflammatory, and is an antipyretic. What is the mechanism of action for this drug?

Back 28

Mainly inhibits prostaglandin synthesis.

Front 29

A clinically obese, diabetic 39 year-old male patient presents with an incredibly painful, inflamed big right toe. He says that it is severely painful to even the slightest touch. When asked, the pt says that this is the first time this has happened.

The patient asks how he can prevent this from happening again, and you decide to start him on a prophylactic drug to use while he is in the early stages of antihyperuricemia therapy. Which drug would you administer for this purpose?

Back 29

Colchicine.

Front 30

What are the general characteristics of probenecid?

Back 30

Decreases serum uric acid levels
Blocks reabsorption of uric acid
enhances excretion (increases chance of nephrolithiasis)
Not used in pts with renal Dz
frequent but mild side effects
less effective in elderly
2-3x per day dosing (worry about compliance)

Front 31

What are the contraindications for using probenecid?

Back 31

History of kidney stones
existing renal Dz
avoid in pts with high urine uric acid levels due to renal calculi risk
dont use if urinary urates are high
don't use if urine flow is low (Ccl < 50ml/min) or Hx of renal calculi

Front 32

What are some drug-drug intereactions of probenecid?

Back 32

Can interfere with renal excretion of penecillin, cephalosporins, quinolones, loop diuretics, and NSAIDs.
Aspirin can diminish effect.

Front 33

What are some adverse effects of probenecid?

Back 33

Some GI intolerence
Hypersensitivity rash
uric acid stone formation

Can cause an acute attack of gout, so should give NSAID or Colchicine before administering.