1. AARTHRITIS AND AANALGESICS

2. GOUTYGOUTY
ARTHRITISARTHRITIS

3. Gouty arthritis
A systemic disease caused by deposition
of uric acid crystals in the joint and body
tissues

4. ETIOLOGY
Primary
 Innate defect of purine metabolism or uric acid
excretion
 HYPERURICEMIA
 Overproduction (10%, >800mg/dL)
 Impaired renal clearance (90%, <600mg/dL)
 HGPRT (Hypoxanthine Guanine
phosphoribosyltransferase) deficiency
 PRPP (Phosphoribosyl – 1 pyrophosphate) excess

5. ETILOGY
Secondary
 Hematological causes
 CRF
 Drug – induced
 ASA and Salicylates (<2g/day)
 Cytotoxic drugs
 Diuretics (except spironolactone)
 Ethambutol and Nicotinic acid
 Cyclosporine, INH, L – dopa
 Ethanol
 Miscellaneous disorders

8. INCIDENCE
Higher in men (95%)
Onset is at 47 y/o
Marked by >7mg/dL serum uric acid
Genetic predisposition (10 – 60%)
Risk factors
 Obesity
 Heavy alcoholics

9. Gouty arthritis
ASSESSMENT FINDINGS
1. Severe pain in the involved joints,
initially the big toe
2. Swelling and inflammation of the joint
3. TOPHI- yellowish-whitish, irregular
deposits in the skin that break open and
reveal a gritty appearance
4. PODAGRA-big toe

10. Gouty arthritis
ASSESSMENT FINDINGS
5. Fever, malaise
6. Body weakness and headache
7. Renal stones

11. Gouty arthritis
DIAGNOSTIC TEST
Elevated levels of uric acid in the blood
(+) monosodium urate crystals
Dramatic response to colchicine

13. INOSINIC
ACID
HYPOXANTHINE
XANTHINE
URIC
ACID
XANTHIN
E
OXIDASE
XANTHIN
E
OXIDASE
ALLANTOIN URATE
OXIDASE
METABOLISM PATHWAYMETABOLISM PATHWAY

14. PATHOPHYSIOLOGY
MONOSODIUM
URATE CRYSTALS
INFLAMMATION
TOPH
ICOMPLICATIONS
•ACUTE TUBULAR OBSTRUCTION
•UROLITHIASIS
•CHRONIC URATE NEPHROPATHY

16. ACUTE GOUTY ARTHRITIS
 Differentials
 Pseudogout (Ca pyrophosphate dihydrate crystals)
 Septic arthritis

17. TREATMENT
 1. Colchicine
 Initiate within 12 – 36 hrs after attack
 DOC for ACUTE attack
 MOA: impairs leukocyte migration and disrupts
urate deposition and subsequent inflammation
- S/E: GI toxicity, BM toxicity

18. THERAPY FOR ACUTE GOUT
COLCHICINE
 PO
 1mg  0.5 q 2hrs  relief/ GIT discomfort
 Total : 8mg
 IV NEVER
GIVEN
IM OR
SQ!

19. 2. Indomethacin
as effective as colchicine but less GI
toxicity
S/E: GI ulcer and bleeding
headache and dizziness (unique)
other NSAIDs are also effective

20. 3. Corticosteroids
- for resistant patients

21. THERAPY FOR ACUTE GOUT
CORTICOSTEROIDS
 Intra – articular injections (Methylprednisolone
acetate)
 Systemic corticosteroid therapy
 C/I NSAIDS, colchicine
 Oral prednisone
 IM corticotropin
 IM Triamcinolone acetonide
 IV methylprednisolone
Taper
dose!

22. Prophylactic Therapy/Chronic
gout
1. Allopurinol (Zyloprim)
- xanthine analog
- xanthine oxidase inhibitor
- major metabolite: oxypurinol
- indicated for patients with renal failure,
leukemias
-S/E: rash, leucopenia, GI toxicity,
acute gouty attack with initiation

23. 2. Uricosurics
- probenecid, sulfinpyrazone
- inh. renal tubular reabsorption of uric acid
- maintain adequate urine flow, alkalinize
urine with NaHCO3
-S/E: GI irritation, rash, acute gout,
renal stones

24. Gout

25. Gout

26. NONDRUG
 Avoid purines!
 Control weight
 Avoid alcohol
Goodbye meat,
organ meats,
seafood, beans,
peas,
asparagus…

27. CHRONIC TOPACEOUS
GOUT
May remain
undetected and
untreated for years
Development of tophi
in pinna of external
ear
Allopurinol and
probenecid

28. OSTEOARTHRITISOSTEOARTHRITIS

29. DEFINITION and ETIOLOGY
OSTEOARTHRITIS (OA)
 “Degenerative Joint Disease”
 Chronic cartilage degeneration
 Most common form of arthritis
 >55 y/o, M = F, F> M if > 55y/o

30. AGING
∀↓ tendon, ligament,
muscle strength
∀↓ chondrocytes
∀↓ proteoglycan
production
AGING
∀↓ tendon, ligament,
muscle strength
∀↓ chondrocytes
∀↓ proteoglycan
production
CHONDROCYTES
∀↓ healing and remodelling
 cartilage matrix
degeneration
∀↓ proteoglycans
CHONDROCYTES
∀↓ healing and remodelling
 cartilage matrix
degeneration
∀↓ proteoglycans
↑ IL – 1 and
Proinflammatory cytokines
↑ IL – 1 and
Proinflammatory cytokines
PAIN
Osteophytes
Synovitis
Bursitis
Tendonitis
PAIN
Osteophytes
Synovitis
Bursitis
Tendonitis

31. RISK FACTORS
Advanced age
Female gender 
Muscle weakness
Obesity
Joint trauma
Heredity
Congenital defects
Repetitive stress

32. SIGNS AND SYMPTOMS
Deep, localized joint pain with rest or
immobility
Lasts < 30 minutes
Mild inflammation
Crepitus upon joint movement

33. DIAGNOSIS
Physical examination
 Joint tenderness, diminished motion range,
crepitus, abnormalities in joint shape
Radiography
 Narrowing of joint space
 (+) Osteophytes

36. TREATMENT
NONDRUG
 Weight reduction
 Aerobic exercises and physical therapy
 Devices
 Avoid prolonged standing, kneeling, and
squatting
 Thermal therapy

37. Pharmacologic:
1. Acetaminophen
- first-line drug for pain in OA
- dose: 325-650 mg 4x daily
S/E: hepatotoxicity
2. NSAIDS

38. 3. Capsaicin
- extract of red peppers
- MOA: release and depletion of substance
P from nerve fibers
-S/E: burning at site of application

39. 4. Glucosamine and chondroitin dietary
supplements
- shown to alleviate pain, slows down loss
of cartilage
5. Corticosteroids
- systemic steroids not recommended
- intraarticular steroids for local
inflammation

40. 6. Hyaluronate injection (Na hyaluronate,
hylan G-F 20)
- reported to decrease pain
7. Narcotic analgesics
- for unresponsive patients and those with
contraindications to acetaminophen or
NSAIDs

41. RHEUMATOIDRHEUMATOID
ARTHRITISARTHRITIS

42. PATHOPHYSIOLOGY
TNF -
a
TNF -
a IL - 1IL - 1
IL - 6IL - 6
GFGF
INFLAMME
D
SYNOVIUM
INFLAMME
D
SYNOVIUM
PANNUSPANNUS
PROTEOLYTIC
ENZYMES
CARTILAGE
DEGRADATION
CARTILAGE
DEGRADATION
BONE
DEMINERALIZATION
BONE
DEMINERALIZATION
OSTEOCLAST
ACTIVATION

44. PROGNOSIS
High RF titer
Elevated ESR
> 20 joints
Early age onset
Extra – articular involvement

46. Rheumatoid arthritis
A type of chronic systemic inflammatory
arthritis and connective tissue disorder
affecting more women (ages 35-45) than
men

47. TREATMENT : NONDRUG
Joint protection
Exercises
Rest
PT and OT
Support groups

48. First-line
1. Methotrexate
- MOA: DHF reductase inhibitor; inhibits
cytokine production and purine synthesis
- relatively rapid onset (2 to 3 weeks)

49. - S/E: GI (stomatitis, nausea, vomiting,
diarrhea),
hematologic (leukopenia,
thrombocytopenia),
pulmonary (fibrosis, pneumonitis),
hepatic (elevated enzymes, cirrhosis)
Teratogenic
leucovorin

50. 2. Leflunomide (Arava)
- inhibits pyrimidine synthesis
- S/E: liver toxicity, teratogenic
3. Hydroxychloroquine
Inhibit NA synthesis
- S/E: diarrhea, blurring of vision, rash
4. Sulfasalazine
- S/E: rash, leukopenia

51. Less frequently used
1. Gold preparations
- aurothioglucose (suspension in oil), gold
sodium thiomalate (aqueous solution)- IM
- auranofin- oral but less effective than IM
Taken up by macrophages,supressing
phagocytosis,then lysosomal activity

52. S/E: GI (nausea, vomiting, diarrhea),
derma (rash, stomatitis), renal (proteinuria),
hematologic (anemia, leukopenia)
dimercaprol

53. 2. Azathioprine
- purine analog converted to 6-
mercaptopurine which inhibits DNA and
RNA synthesis
-S/E: bone marrow suppression,
hepatotoxicity, oncogenic

54. 3. Penicillamine
Analog of AA cysteine
-S/E: rash, metallic taste, hypogeusia
(blunting of taste),stomatitis, proteinuria
4. Cyclosporine
- decreases production of cytokines
- S/E: hypertension, hyperglycemia,
nephrotoxicity, tremor, GI intolerance,
hirsutism, gingival hyperplasia

55. Biologic agents
1. Etanercept (Enbrel)
- TNF receptor; binds to and inactivates TNF
2. Infliximab (Remicade)
- anti-TNF antibody
- combination with MTX is superior than MTX
alone
- S/E: infections

56. 3. Adalimumab (Humira)
- anti-TNF antibody
- S/E: local injection site reaction, infection
4. Anakinra (Kineret)
- IL-1 receptor antagonist

57. Treatment
1.NSAIDS
Analgesic and anti-inflammatory but does
not slow disease progression
2.Disease-modifying anti-rheumatic drugs
(DMARDs)
Started within the first 3 months of
symptom onset

58. SUCCESS is to have made aSUCCESS is to have made a
life breathe easier becauselife breathe easier because
you have livedyou have lived.