Download 4-Gout

GOUT
By
 Prof. Azza El-
 Dr. Osama
Medany
Yousf
OBJECTIVES
 At the end of lectures students should :
 Define gout
 Describe outlines of treatment
 Describe treatment of acute gouty arthritis
 Describe the mechanism of action , clinical uses & side
effects of drugs used in acute attacks
OBJECTIVES ( continue)
 Classify drugs used in chronic treatment
 Define each group of drugs
 Describe the mechanism of action, clinical uses &
side effects & drug interactions for drugs used in
chronic treatment
High blood uric acid level
Acute arthritis
monosodium urate stone in kidney
♂>♀
Familial metabolic disease
Breakdo
wn of
product
of the
body’s
purine
(nucleic
acid)
metaboli
Idiopathic decrease in uric
acid excretion
(75%)
Impaired uric acid
excretion secondary to
thiazide diuretics,
chronic Renal failure
etiology of
raised
uric acid
level
High dietary
purine intake
Increase uric
acid production
due to
increased cell
turn over
(tumors),
increase uric
acid synthesis
What is the treatment for
gout ?
Clinical stages of Gout
1
•Asymptomatic Stage
2
•Acute stage
3
•Intercritical stage
4
•Chronic stage
ASYMPTOMATIC STAGE
 urate levels rise in the blood, but produces no symptoms
ACUTE STAGE
INTERCRITICAL STAGE
 symptom-free intervals between gout
episodes. Most people have a second
attack from six months to two years,
while others are symptom-free for five to
10 years.
CHRONIC STAGE
Broad lines in
treatment of
gout
Nonpharmacologic
pharmacologic
Acute gouty
arthritis
Chronic
gout(long term
treatment)
Non-pharmacologic
Therapy
Control….
Acute gouty
arthritis
NSAIDs
colchicine
corticosteroid
1. NSAIDs
NSAIDs (Selective or non- selective )
 Inhibit pain & inflammation.
 Inhibit urate crystal phagocytosis by decreasing
the migration of granulocytes into the
inflammatory area.
 They are commonly used now for treatment of
acute attack or to prevent recurrent attacks
with other drugs.
 ( Except aspirin & paracetamol)
2. Colchicine
Basyir Bin Kamaruzaman (15)
OVERVIEW
A plant alkaloid
A Selective drug effective only in gouty
arthritis
Has No analgesic effects
MECHANISM OF ACTIONS
Binds to tubulin (microtubular protein )
disrupt cellular function ( migration
of granulocytes to affected area
Inhibits the synthesis and release
of leukotrienes & TNF-α
Blocks cell division by binding to
mitotic spindles
PHARMACOKINETICS
PHAPHARMACOKINETICS
Given orally, followed by rapid absorption
from the GI tract
Reaches peak plasma levels within 2 hours
Excreted unchanged in the faeces & urine.
Should be used with caution in patients with
renal impairment
THERAPEUTIC USES
The anti-inflammatory activity of colchicine is specific for
gout, alleviating the pain within 12 hours
Colchicine is used as prophylaxis to prevent recurrent
attacks in more than 80 percent of patients.
Treatment for Mediterranean Fever
Adverse effects
 Severe diarrhea ( cause of its restriction in
use )
 Chronic use
alopecia, bone marrow depression,
peripheral neuritis, myopathy.
Acute intoxication ( large doses)
 Burning pain in throat
 Bloody diarrhea
 Shock
 Hematuria
 C.N.S. depression
Contraindication
 pregnancy
Precaution
 in hepatic , renal problems
3. Corticosteroids
Chronic gout
(long term
treatment)
1-Inhibition of uric
acid synthesis
2-Increase
excretion of uric
acid
Treatment of Refractory Gout
Mammalian uricase enzyme
Inhibition of uric acid synthesis
Xanthine Oxidase Inhibitors
Mechanism of action
ALLOPURINOL-Pharmacokinetics
 Well absorbed orally (80% )
 Metabolized in the liver to
oxypurinol which is responsible for
most of its urate-lowering effect
 Given once daily.
 Drug & its metabolite excreted
through the kidney.
 Dose adjustment is needed in renal
impairment
Pharmacokinetics
Therapeutic Uses
 Treatment of primary hyperuricemia
 Hyperuricemia secondary to
other conditions such as :
 Impaired renal functions.
 uric acid stones or nephropathy.
 In patients receiving
cancer chemotherapy
ALLOPURINOL
SIDE EFFECTS &
DRUG INTERACTIONS
Side Effects (most common)
exacerbation of
an acute attack of gout
Maculopopular skin rash
nausea, diarrhea
Side Effects (less common)
Body : fever, headache
CVS : vasculitis
Thrombocytopenia
Epistaxis
Drug Interactions
Inhibits metabolism of
oral anticoagulant:
( warfarin )
Potentiates its action
Inhibits metabolism of
anticancer drugs :
(6-mercaptopurine
& azathioprine )
•So ,doses of anticancer
•Must be reduced up to 75%
With ampicillin :
Increases frequency
of skin rash
Febuxostat
 Is a new oral non-purine xanthine oxidase (XO)






inhibitor.
Is structurally different from allopurinol as it lacks
purine ring
Selective and potent inhibitor of XO than
allopurinol
Well absorbed orally ( 84%), given once daily
Can be given with or without food
Metabolized in liver & excreted in urine & feces
No dose adjustment is needed in renal impairment
Continue
 Suitable than allopurinol in patients with impaired
renal function as no dose adjustment is required .
 Used for treatment of chronic hyperuricemia in
gout patients
 Given to patients who do not tolerate allopurinol
Adverse effects
 Recurrent attacks of acute gout during the first few




months of treatment
Increase level of liver enzymes
Nausea, Diarrhea
Headache
Numbness of arm or leg
DRUGS INCREASED EXCRETION OF
URIC ACID
Uricosuric drugs
1- Probenecid
2- Sulfinpyrazone
3- Large doses of aspirin ( more
than 5g )
Mechanism of action of uricosuric drugs
 Block the active transport sites of the
proximal tubules(middle segment )
causing :
reduction of
Uric acid
re-absorption
(uric acid excretion
Clinical uses
 Chronic gout
Warning
 Urine volume should be maintained
at a high level, and urinary pH kept
alkaline .
Adverse effects
 Acute attack of gout
 Risk of uric acid stone
 GIT upset
 Allergic rash
( continue)
 Nephrotic syndrome ( probenecid)
 Aplastic anemia
( rare )
DRUG INTERACTIONS
 Probenecid prolong the action of some
antibiotics as: penicillins
Contraindications
History of urinary tract stones
Impaired renal function
Recent acute gout attack
Administration of low doses of
aspirin
Treatment of Refractory Gout
Mammalian uricase enzyme
Modified mammalian uricase
enzyme
Pegloticase
 Is a modified mammalian uricase
enzyme
 Converts uric acid to allantoin
 Given I.V. Infusion peak decline in
uric acid level within 24-72 hours
Continue
 Used for the treatment of gout in adult patients
refractory to conventional therapy
 Adverse effects
 Infusion reactions
 Anaphylaxis
 Gout flare
 Nephrolithiasis
 Arthralgia, muscle spasm
 Headache
THANK YOU