3. Introduction
• Gout is a heterogeneous disease characterized
by:-
– Deposition of monosodium urate crystal
– Chronic arthropathy
– Uric acid nephrolithiasis
3
4. • Hyperuricemia may be an
asymptomatic condition with abnormal
urate concentration greater than 7.0
mg/dL for males and >6mg/dl for
females and associated with an
increased risk for gout.
4
5. Epidemiology
• Common in developed countries
• In us 8.3 million people have hyperuricemia
• 3 times more common in mens than womens
5
6. Etiology
• Uric acid is end product in the degradation of
purines
• Excessive accumulation of uric acid leads to
gout
• This excess accumulation may result from
either overproduction or under excretion of
uric acid.
– drugs
– Renal failure
– Dyslipidemia
– Obesity
– Alcohol
– diet
6
7. Pathophysiology
• Purines are degraded into uric acid finally then if there is under
excretion and over production of uric acid there will be
deposition of urate crystals
• Deposition of urate crystals in synovial fluid results in an
inflammatory process involving chemical mediators
(vasodilation, increased vascular permeability, complement
activation, and chemotactic activity)
• Phagocytosis of urate crystals by leukocytes results in rapid
lysis of cells and a discharge of proteolytic enzymes
• Intense joint pain, erythema, warmth, and swelling
7
8. Pathophysiology…
• Uric acid nephrolithiasis occurs in 10% to
25%, Predisposing factors include excessive
urinary excretion of uric acid, acidic urine,
and highly concentrated urine.
• Tophi (urate deposits) at the base of great
toe, helix of the ear, knees, wrists, and
hands.
8
9. Clinical presentation
• Fever, intense pain, erythema, warmth, swelling, and
inflammation of involved joints
• The attack is typically monarticular at first, most
often affecting the first metatarsophalangeal joint
(great toe) and then, in order of frequency, the
insteps, ankles, heels, knees, wrists, fingers, and
elbows.
• The pain usually starts at night.
9
10. • Atypical presentations of gout also occur. For
elderly patients, gout can present as a chronic
poly-articular arthritis that can be confused
with rheumatoid arthritis or osteoarthritis.
10
11. Diagnosis
• Presumptive diagnosis- signs and symptoms, and
response to treatment.
• Definitive diagnosis is accomplished by aspiration
of synovial fluid from the affected joint and
identification of intracellular crystals of
monosodium urate monohydrate in synovial
fluid leukocytes.
11
12. Treatment
goals of treatment
– to terminate the acute attack,
– prevent recurrent attacks of gouty arthritis,
– prevent complications associated with chronic
deposition of urate crystals in tissues, and
– prevent or reverse features commonly associated with
the illness including obesity, elevated triglycerides, and
hypertension. 12
13. Non-Pharmacological
• Weight loss
• Restriction of alcohol intake
• Reduce their intake of foods high in purines
(e.g. Organ meats), increase fluid intake, and
lose weight if obese.
• Joint rest for 1 to 2 days should be encouraged,
and local application of ice
13
14. Pharmacological
• A number of drugs have been used for the
treatment of acute gout,
– Nonsteroidal anti-inflammatory drugs
– Colchicine
– Intra-articular or systemic glucocorticoids
14
15. Nonsteroidal Anti-inflammatory Drugs
• NSAIDs are the mainstay of therapy for acute attacks of gouty
arthritis because of their excellent efficacy and minimal
toxicity with short-term use.
• The most common areas affected include the
gastrointestinal system (gastritis, bleeding, perforation),
kidneys (renal papillary necrosis, reduced creatinine
clearance), cardiovascular system (sodium and fluid
retention, increased blood pressure), and central nervous
system (impaired cognitive function, headache, dizziness).
15
16. Corticosteroids
• Corticosteroids have typically been reserved for treatment
of acute gout flares when contraindications to NSAIDs
exist.
• can be used either systemically or by intraarticular injection.
• Oral corticosteroids are usually administered in doses of
30 to 60 mg of prednisone equivalent for 3 to 5 days.
16
17. Colchicine
• Colchicine is an antimitotic drug that is highly effective at
relieving acute attacks of gout but has the lowest benefit-to-
toxicity ratio of the available pharmacotherapy for gout.
• it should be reserved as a second-line therapy when
NSAIDs or corticosteroids are contraindicated or
ineffective.
17
18. Nephrolithiasis
• management of uric acid nephrolithiasis
includes hydration sufficient to maintain a
urine volume of 2 to 3 L/day, alkalinization of
urine, avoidance of purine-rich foods,
moderation of protein intake
18
19. Prophylactic Therapy
• if the patient had a severe attack of gouty arthritis,
• a complicated course of uric acid nephrolithiasis,
• a substantially elevated serum uric acid level [>10
mg/dL (>595 mol/L)], or
• a 24-hour urinary excretion of uric acid of more
than 1,000 mg (5.95 mmol), then prophylactic
treatment should be instituted immediately after
resolution of the acute episode
19
20. • The following medications can be used:
• Xanthine Oxidase Inhibitors
• Uricosuric Drugs
• Pegloticase
• Miscellaneous Agents
20
23. Definition
• Osteoarthritis (OA) is a common, slowly
progressive disorder affecting primarily the
weight-bearing diarthrodial joints of the
peripheral and axial skeleton.
• Progressive deterioration and loss of articular
cartilage, resulting in osteophyte formation,
pain, limitation of motion, deformity, and
progressive disability.
23
25. epidemiology
• In US 21% in1995 then it became 27% 2005
• As age increase risk of OA increases
• White (9%)more affected than blacks(4%)
• More common in men's before age of 45 but
above 45 years old more common in women's
25
26. Etiology
• Primary (idiopathic) OA, the most common type,
has no known cause.
• localized OA (involving one or two sites) and
• Generalized OA (affecting three or more sites).
• Erosive OA the presence of erosion and marked proliferation
• Secondary OA is associated with a known cause
such as
– Rheumatoid arthritis or another inflammatory
arthritis, trauma, metabolic or endocrine disorders,
and congenital factors.
26
27. Etiology
• Potential risk factors
– Aging
– Obesity
– Repetitive use through work or leisure activities
– Joint trauma
– Heredity
27
28. Pathophysiology
• OA usually begins with damage to articular
cartilage through injury, excess joint loading from
obesity or other reasons, or joint instability or
injury that causes abnormal loading.
• Hypertrophic reparative response-increases the
metabolic activity of chondrocytes, leading to
increased synthesis of matrix constituents
• Increased synthesis of matrix metalloproteinases
(MMPs) 1, 3, 13, and 28, which causes collagen
destruction to occur faster than synthesis, with a
net loss of cartilage.
28
29. Pathophysiology…
• Subchondral bone adjacent to articular
cartilage also undergoes pathologic changes
(new bone formation) that allow progression
of damage to articular cartilage.
• loss of cartilage + new bone formation causes
joint space narrowing , painful, and deformed
joints.
• Local inflammatory changes
• Activation of nociceptive nerve endings within joints
29
31. Clinical presentation
• The prevalence and severity of OA increase
with age.
• Clinical presentation depends on duration and
severity of disease and the number of joints
affected.
• Localized deep, aching pain associated with
the affected joint.
• Early in OA, pain accompanies joint activity
and decreases with rest.
31
32. Clinical presentation…
• Imitation of motion, stiffness, and deformities.
• Joint stiffness typically lasts less than 30
minutes and resolves with motion.
• Warm, swollen, red, and tender joint.
• Physical examination of the affected joints
reveals tenderness, crepitus, and possible
joint enlargement.
32
33. Dx
• Patient history, clinical examination of the affected
joint(s), radiologic findings, and laboratory testing.
• Classification
– For hip OA, a patient must have hip pain and two of the
following: (1) an ESR > 20 mm/hour, (2) radiographic
femoral or acetabular osteophytes, or (3) radiographic
joint space narrowing.
– For knee OA, a patient must have knee pain and
radiographic osteophytes in addition to one or more of the
following: (1) age greater than 50 years, (2) morning
stiffness of 30 minutes’ or less duration, or (3) crepitus on
motion, (4) bony enlargement, (6) bony tenderness, or (7)
palpable joint warmth.
33
34. Treatment
• Goals for the management of OA are to
– (1) educate the patient, caregivers, and relatives
– (2) relieve pain and stiffness
– (3) maintain or improve joint mobility
– (4) limit functional impairment
– (5) maintain or improve quality of life
34
35. Non pharmacologic Rx
• Educate the patient about the extent of the disease,
prognosis, and management approach.
• Dietary counseling and a structured weight-loss
program for overweight patients
• Physical therapy cold treatments and an exercise
program
• to strengthen muscles, improve joint function and motion, and
decrease disability, pain.
• Assistive and orthotic devices such as canes, walkers,
braces, heel cups, and insoles.
• Surgical procedures (e.g., osteotomy, partial or total
arthroplasty, joint fusion)
35
36. Drug therapy
• Drug therapy in OA is targeted at relief of pain.
– Acetaminophen is recommended by the ACR as first-
line drug therapy for pain management of OA
– NSAIDs at prescription strength are often prescribed
for OA if acetaminophen is ineffective, or for patients
with inflammatory OA.
– Topical Therapies (Capsaicin) causes release and
ultimately depletion of substance P from nerve fibers
and relief pain.
– Systemic corticosteroid therapy is not recommended
in OA, given the lack of proven benefit and the well-
known adverse effects with long-term use
36
42. Evaluation of Rx outcome
• Monitor efficacy, by assessing level of pain,
range of motion.
• Monitor adverse effects of medications
• Baseline serum creatinine, hematology
profiles, and serum transaminases with repeat
levels at 6- to 12-month intervals.
42
45. Objectives
• At the end of this lesson, students are expected to
• Explain what is osteoporosis
• List risk factors of osteoporosis
• Describe pathophysiology and clinical presentation of
osteoporosis
• Describe management options to osteoporosis
45
46. Introduction
• Osteoporosis is a bone disorder characterized by low bone
density, impaired bone architecture, and compromised bone
strength that predisposes a person to increased fracture
risk.
• Wrist fractures, hip fractures and fractures of the vertebrae
(bones in the spine) are the most common type of breaks
that affect people with osteoporosis.
46
47. Bone Physiology
• The skeleton comprises two types of bone
:Cortical bone and trabecular bone
• Bone is made of collagen and mineral
components
– Imbalances can impair bone quality and
lead to reduced bone strength.
• Bone remodeling is a dynamic process that
occurs continuously throughout life
47
48. Epidemiology
• Low bone density is estimated to occur in 52% of
white and Asian, 49% of Hispanic, and 35% of
black women age 50 and older.
• Osteoporosis affects 20% of white and Asian,
10% of Hispanic, and 5% of black women age 50
and older.
• Disease prevalence greatly increases with age;
from 4% in women 50 to 59 years of age to 44% to
52% in women 80 years of age and older.
48
49. Risk Factors
• Low bone mineral
density
• Female sex
• Advanced age
• Race/ethnicity
• History of a previous
low-trauma (fragility)
fracture as an adult
• Osteoporotic fracture in a
first-degree relative
(especially parental hip
fracture)
• Low body weight or body
mass index
• Premature menopause
(before 45 years old)
• Medications e.t.c
49
50. Pathophysiology
• depends on sex, age, genetics, and presence
of secondary causes.
Postmenopausal Osteoporosis
• results from enhanced resorption, mainly as a
result of the loss in ovarian hormone
production, specifically estrogen.
• Loss of estrogen also increases calcium
excretion and decreases calcium gut
absorption. The number of remodeling sites
increases, and resorption pits are deeper and
inadequately filled by normal osteoblastic 50
51. Male Osteoporosis
• The etiology of male osteoporosis tends to be
multifactorial with secondary causes and aging
being the most common contributing factors.
• In young and middle-age men, a secondary cause
for bone loss is usually identified, with
hypogonadism being the most common.
Idiopathic osteoporosis can occur.
51
52. Age related osteoporosis
• occurs in seniors, mainly as a result of hormone,
calcium, and vitamin D deficiencies leading to an
accelerated bone turnover rate in combination with
reduced osteoblast bone formation.
• Hip fracture risk rises dramatically in seniors as a
consequence of the cumulative loss of cortical and
trabecular bone and an increased risk for falls.
52
53. Secondary Causes of Osteoporosis
• A secondary cause is identified in more than half
of perimenopausal women, about one third of
postmenopausal women, and more than two thirds
of men.
• The most common secondary cause for
osteoporosis is glucocorticoid therapy
53
54. Clinical presentation
• Frequently asymptomatic
• Pain
• Immobility
• Depression, fear, and low self-esteem from
physical limitations and deformities
• Shortened stature (>1.5-inch [3.81-cm] loss),
kyphosis, or lordosis
• Atraumatic vertebral, hip, wrist, or forearm
fracture
54
55. Treatment
• Non pharmacological
– Diet
– Alcohol, caffeine and cigarette
– Exercise
– Preventing fall
– Vertebroplasty or kyphoplasty
55
58. Bisphosphonates
• mimic pyrophosphate, an endogenous bone resorption
inhibitor.
• Include: alendronate, risedronate, ibandronate,
zoledronic acid, pamidronate, etindronate, pamidronate
• All bisphosphonates become incorporated into bone,
giving them long biologic half-lives of up to 10 years.
• Bisphosphonates consistently provide some of the
higher fracture risk reductions and BMD increases
58
59. • Patients with creatinine clearances less than 30 to 35 mL/min
(0.50–0.58 mL/s), who have serious GI conditions
(abnormalities of the esophagus that delay emptying, such as
stricture or achalasia), or who are pregnant should not take
bisphosphonates.
59
60. Estrogen Agonists/Antagonists
• Raloxifene, a second-generation mixed estrogen
agonist/antagonist (EAA) approved for prevention
and treatment of postmenopausal osteoporosis,
has estrogenic agonist actions in bone but
antagonist actions in breast and uterine tissue.
• decreases vertebral fractures and increases spine
and hip BMD, but to a lesser extent than
bisphosphonates
60
61. Calcitonin
• An endogenous hormone released when serum
calcium level is increased
• efficacy is less robust than the other antiresorptive
therapies, calcitonin is reserved as third-line
treatment.
• Subcutaneous administration with 100 units daily
61
62. Estrogen
• Increases in BMD are less than with bisphosphonates,
denosumab, or teriparatide, but greater than with
raloxifene and calcitonin.
62
63. Anabolic Therapies
Teriparatide
• recombinant product representing the first 34
amino acids in human PTH
• increases bone formation, the bone remodeling
rate, and osteoblast number and activity.
• Both bone mass and architecture are
improved.
63
64. Evaluation of Therapeutic Outcomes
• Assessment of adherence and tolerability of
medication
• Assessment of disease progression
• Assessment of physical examination
• Bone mineral density
• Serum electrolyte (ca ,phosphate)
64
67. introduction
• a chronic, systemic, inflammatory disorder of
unknown etiology that primarily involves joints.
67
68. Epidemiology
• Estimated to have a prevalence of 1% and does not
have any racial predilections
• 3 times more common in women
68
69. Pathophysiology
• RA results from a dysregulation of the humoral and cell-
mediated components of the immune system. Most patients
produce antibodies called rheumatoid factors; these
seropositive patients tend to have a more aggressive course
than patients who are seronegative.
• Chronic inflammation of the synovial tissue lining the joint
capsule results in tissue proliferation (pannus formation).
• Pannus invades cartilage and eventually the bone surface,
producing erosions of bone and cartilage and leading to
joint destruction.
• The end results may be loss of joint space, loss of joint
motion, bony fusion (ankylosis), joint subluxation, tendon
contractures, and chronic deformity.
69
71. Clinical Presentation
• Joint pain and stiffness of more than 6 weeks' duration.
• May also experience fatigue, weakness, low-grade fever,
loss of appetite.
• Muscle pain and afternoon fatigue may also be present.
• Joint deformity is generally seen late in the disease.
• Tenderness with warmth and swelling over affected joints
usually involving hands and feet. Distribution of joint
involvement is frequently symmetrical.
• Rheumatoid nodules may also be present.
71
72. Laboratory Tests
• Rheumatoid factor (RF) detectable in 60% to 70%.
• Elevated erythrocyte sedimentation rate and c-reactive
protein are markers for inflammation.
• Normocytic normochromic anemia is common
72
73. Treatment
Goal
• to improve or maintain functional status, thereby
improving quality of life.
• to achieve complete disease remission,
• To control disease activity and joint pain, and
slowing destructive joint changes.
73
75. Pharmacologic Therapy
• DMARDs (disease modifying antirheumatic drugs) are
a treatment cornerstone.
• commonly used ones include methotrexate,
hydroxychloroquine, sulfasalazine, and leflunomide.
• Combination therapy with two or more DMARDs may
be effective when single- DMARD treatment is
unsuccessful.
75
76. • DMARDs that are less frequently used include
azathioprine, penicillamine, gold salts (including
auranofin), minocycline, cyclosporine, and
cyclophosphamide.
• These agents have either less efficacy or high
toxicity, or both.
76
77. Biologic Agents
• These drugs may be effective when non-biologic
DMARDs fail to achieve adequate responses but
are considerably more expensive to use.
• Biologic agents with disease-modifying activity
include the anti-TNF agents (etanercept,
infliximab, adalimumab) and the interleukin-1
receptor antagonist anakinra
77
78. Nonsteroidal Anti-inflammatory Drugs
• Can be used as adjuvant therapy, because they do
not alter the course of the disease.
• Possess both analgesic and anti-inflammatory
properties and reduce stiffness associated with RA.
• They should seldom be used as monotherapy for
rheumatoid arthritis.
• Cyclooxygenase-2 (COX-2) selective NSAIDs
have a better gastrointestinal (GI) safety profile
and similar efficacy as conventional NSAIDs.
78
79. Corticosteroids
• Oral corticosteroids (e.g., Prednisone, methylprednisolone)
can be used to control pain and synovitis while DMARDs
are taking effect (“bridging therapy”).
• Prednisone doses below 7.5 mg/day (or equivalent) are
well tolerated but are not devoid of the long-term
corticosteroid adverse effects. The lowest dose that
controls symptoms should be used.
• Intra-articular injections of depot forms may be useful
when only a few joints are involved. If effective, injections
may be repeated every 3 months. No one joint should be
injected more than 2 or 3 times per year.
79
80. Evaluation of Therapeutic Outcomes
• Clinical signs of improvement include reduction in joint
swelling, decreased warmth over actively involved joints,
and decreased tenderness to joint palpation.
• Symptom improvement includes reduction in joint pain and
morning stiffness, longer time to onset of afternoon fatigue,
and improvement in ability to perform daily activities.
• Joint radiographs may be of some value in assessing
disease progression.
• Laboratory monitoring is essential for detecting and
preventing adverse drug effects.
• Patients should be questioned about the presence of
symptoms that may be related to adverse drug effects .
80
