Clinical Pharmacy Program

Pharmacotherapy III
2023-2024

Prof Dr Manar A Nader

Musculoskeletal disorder
Disorders-1 1
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Osteoarthritis 2
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 The musculoskeletal system
• The musculoskeletal system includes the bones, joints,
and muscles of the body together with associated
structures such as ligaments and tendons.

• The skeletal system consists of the bones of the skull,

thorax, and vertebral column, which form the axial
skeleton, and the bones of the upper and lower
extremities, which form the appendicular skeleton.
SKELETAL JOINTS:

• Joints, or articulations, are sites where two or

more bones meet to hold the skeleton together
and give it mobility.
• There are two types of joints:
1. Synarthroses, which are immovable joints, and
2. Diarthroses, which are freely movable joints.
• The surfaces of the articulating ends of
bones in diarthrodial joints are covered
with a thin layer of articular cartilage,
and they are enclosed in a fibrous joint
capsule.

• The joint capsule consists of two layers:

an outer fibrous layer and an inner
membrane, the synovium.

• The synovial fluid, which is secreted by

the synovium into the joint capsule, acts
as a lubricant and facilitates movement
of the joint’s articulating surfaces.
 Musculoskeletal Disorders
• The musculoskeletal system which constitutes 70% of the
body is subject to large number of disorders.
• These disorders are the most common causes of severe
long-term pain and physical disability.
Osteoarthritis
Inflammatory arthritis
Rheumatoid arthritis
Osteoporosis
Gout
Back pain
Musculoskeletal trauma
 Osteoarthritis
(Degenerative Joint Disease)
“Osteoarthritis (OA) is a common, slowly progressive
disorder affecting primarily the weight-bearing
diarthrodial joints of the peripheral and axial skeleton.
It is characterized by progressive deterioration and loss
of articular cartilage, resulting in osteophyte
formation, pain, limitation of
motion, deformity, and progressive disability.
Inflammation may or may not be present in the
affected joints.
 Causes of OA
 Primary (idiopathic) OA, the most common type, has no known cause
may be localized OA (involving one or two sites), generalized OA
(affecting three or more sites) or erosive OA indicates 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.
 Osteoarthritis
(Degenerative Joint Disease)
Risk factors include:

Age: People over 50 years of age may be more likely to have OA, as
the risk increases with age.

Joint injury: An injury to the joint area, such as a bone fracture or

a cartilage or ligament tear, may lead to OA.

Overuse: Repetitive use of the same joint, such as through a sport

or an occupation, may lead to OA.

Obesity.

Patients with comorbidities (OA is often comorbid with

cardiovascular disease, diabetes, hypertension, obesity,
depression, and peptic ulcer disease)
 Osteoarthritis
(Degenerative Joint Disease)
Risk factors include:

Musculoskeletal abnormalities: Incorrect alignment of the bones

or joints may increase the OA risk.

Weak muscles: If the muscles cannot support the joints properly,

this can lead to incorrect alignment and OA.

Genetics: People with a close family member with OA are more

likely to develop the condition themselves.

Gender: OA is more likely to affect females than males.

Environmental factors: This includes factors such as level of

physical activity, occupation, diet, sex hormones, and bone density.
Lifestyle factors; modifiable (obesity, Smoking , bone density
Pathophysiology
Pathophysiology
 Pathophysiology

osteophyte

• Articular cartilage becomes yellow & opaque (loss of

proteoglycan & collagen fibers from articular cartilage)
• Joint space narrows, bone spurs (osteophyte)
• Cysts (noninflammatory “enzymatic lysis”)
Mechanisms of pain in OA

mechanisms that lead to chronic pain in OA includes the

contribution of sensitization of nociceptive pathways and other
external factors (ie, psychosocial) in different stages of OA,
neuropathic pain, and the influence of disease phenotypes in the
patterns of pain
Symptoms:
• often affects only one large weight-bearing joint, such as hip, spine,
or knee
• Joint pain that diminished on rest
• morning stiffness, aches during weather changes.
• Crepitus (grating sensation)
• Joint enlargement
• Dislocation
• Deformity
• Limited motion, joint effusion
loss of balance or instability
popping or clicking sounds when a joint moves

• The diagnosis of OA is a clinical one based on characteristic signs and

symptoms described above ●
●Radiography –allows for detection of characteristic features of OA
●Magnetic resonance imaging –MRI can identify OA at earlier stages
of disease before radiographic changes become apparent.
• ●Ultrasonography –s useful for detecting synovial inflammation,
effusion, and osteophytosis. Limitations of ultrasound include that it
is operator-dependent and cannot be used to assess deeper articular
structures and subchondral bone.
 Non-pharmacological therapy
1- Patient education:
• Patients should be fully informed about the etiology of OA, risk
factors (especially the ones that are modifiable and specific to the
patient)
• Patients should be informed of the potential cardiovascular,
gastrointestinal, and other major risks of both nonselective NSAIDs
and selective COX-2 inhibitors
• Self-management education is a complement to traditional patient
education . It aims at teaching patients problem- solving skills and
involves the concept of self-efficacy

2- Local heat— Local application of heat using a heat pack or hot-

water bottle as a self-management strategy may have beneficial short-
term effects on pain in patients with knee OA
 Non-pharmacological therapy
2Rest for several minutes when your pain is at its worst – But don't
rest too long. That can make your muscles weakand your pain worse.

3Lose weight (if you are overweight):Being heavy puts extra

strain on your joints.

4Get some physical therapy and exercise – Having strong muscles

takes some of the strain off of your joints. It can reduce your pain in
the long run, even though it hurts to do at first.
 Non-pharmacological therapy
5- Use shoe inserts, splints, canes, walkers, or any
other devices that help you – These devices can help
keep your joints stable or take weight off them.

6- Psychological interventions: Chronic pain and its impact

on functionality often lead to various levels of psychological
distress which, in turn, has a negative impact on symptoms
• Non-Pharmacological Therapy
6-Transcutaneous electrical nerve stimulation:
• which modulation of the nociceptive stimulus to the brain occurs
through its presynaptic inhibition in the spinal cord dorsal horn

7- Surgery
• surgery is recommended when significant joint-related symptoms
persist despite the use of non-surgical interventions
.
• Surgical treatment is dominated by total knee replacement, and
osteotomy is an alternative for younger patients

• An osteotomy is a
surgical operation whereby a bone is cut to
shorten or lengthen it or to change its
alignment. Osteotomy is one method to relieve
pain of arthritis, especially of the hip and knee.
It is being replaced by joint replacement in the
• Pharmacological Therapy

• Topical NSAIDs

• Topical NSAIDs are preferred rather than oral NSAIDs for

patients with mild OA localized to the knee or with concomitant
hand involvement, given the superficial location of the joints in
these cases.

• Topical NSAIDs are with low risk of gastrointestinal, renal, and

cardiovascular toxicity than oral formulation due to the reduced
systemic absorption

• diclofenac gel or solutions are most commonly used, but the

choice of topical agent may vary according to local availability
and cost.
• Pharmacological Therapy
• Topical capsaicin
• topical capsaicin are recommended for patients with mild OA
localized to the knee or a few other joints in whom other
treatments are ineffective or contraindicated, we suggest.

• Capsaicin derived from hot chili peppers with the potential to

alleviate pain through the down-regulation of the TRPV1
receptor) The transient receptor potential cation channel subfamily V member
1, also known as the capsaicin receptor and the vanilloid receptor 1( activity
on nociceptive sensory neurons and the depletion of
substance P.

• Continued use of capsaicin results in desensitization of

nociceptive fibers and inhibition of pain stimulus transmission.
• Pharmacological Therapy
3- paracetamol
Acetaminophen is recommended by the ACR as first-
line drug therapy for pain management of OA.

The dose is 325 to 650 mg every 4 to 6 hours on a

scheduled basis (maximum dose 4 g/day; maximum 2
g/day if chronic alcohol intake or underlying liver
disease).
• Acetaminophen is usually well tolerated, but
potentially fatal hepatotoxicity
with overdose is well documented.
• Pharmacological Therapy
4-Oral NSAIDs
• NSAIDs at prescription strength are often prescribed for OA
patients after treatment with acetaminophen or topical
NSAIDs proves ineffective, or for patients with inflammatory
OA.

• Analgesic effects begin within 1 to 2 hours, whereas

• antiinflammatory benefits may require 2 to 3 weeks of

continuous therapy.

• All NSAIDs have similar efficacy in reducing pain and

inflammation in OA although individual patient response differs
among NSAIDs.
•
• Pharmacological Therapy
4-Oral NSAIDs
• In patients with risk factors for gastrointestinal toxicity
(eg, advanced age, hypertension, concomitant aspirin
use), we use either:
1 celecoxib
2 A nonselective NSAIDs (Naproxin) with a proton pump
inhibitor (PPI).
3selective COX-2 (coxib) in combination with a PPI in
patients with higher risk of gastrointestinal complications
• Pharmacological Therapy
Choice and use of oral NSAID
The choice of NSAID is based upon a variety of factors including
adverse effect profile, patient comorbidities, cost to patient, and
patient preference regarding frequency of administration.

A- diclofenac 150 mg/day and etoricoxib 60 mg/day are the most

effective NSAID regimens in knee OA

B- In patients suitable for nonselective NSAIDs, we usually initiate

treatment with either naproxen, meloxicam, diclofenac,
or ibuprofen .
• Pharmacological Therapy
5- Pain modulator
a.Duloxetine :

Used in Inadequate response to oral NSAIDs or NSAIDs are

contraindicated

For patients with OA in multiple joints and concomitant

comorbidities that may contraindicate oral NSAIDs and/or those
who have not responded satisfactorily to NSAIDs, we
suggest duloxetine.
• Pharmacological Therapy
5- Pain
modulator
a.Duloxetine :

Sensitization of the central nociceptive processing has been

increasingly recognized as a potential contributor to pain in
OA patients.

The analgesic efficacy of duloxetine has been related to the

modulation of endogenous pain inhibitory pathways through
the selective inhibition of serotonin and norepinephrine
reuptake

b. Also pregabalin and gabapentin show similar efficacy

• Pharmacological Therapy

6- Opioids

Due to the relatively high incidence of side effects, we avoid using

opioids whenever possible, especially in the older adult
population.

we use opioids only in patients with severe pain awaiting joint

replacement (ie, short-term use).

We use it in the lowest dose and duration necessary to control

symptoms and monitor common side effects.
• Pharmacological Therapy
6- Opioids

• Tramadol and tapentadol are centrally acting analgesics act

on mu opioid receptor and monoamine (serotonin and
norepinephrine) reuptake blockade (mixed mechanism).
the most common routes of administration are oral or
transdermal.

• Short-acting Meperidine availability of less toxic and

more effective alternative drugs
• Pharmacological Therapy
7- Intraarticular glucocorticoid injections

• Recommendation are against routine use of intraarticular

glucocorticoid injections for patients with OA having moderate to
severe pain and contraindications to or failure of other treatment
options who are seeking short-term pain relief.

• This procedure, either as a single injection or multiple repetitive

injection (not routinely recommended in our clinical practice).
• Pharmacological Therapy
7- Intraarticular glucocorticoid injections
• 40 mg of triamcinolone or methylprednisolone are the
most commonly used preparation; other formulations
such
as betamethasone can also be used.

• Serial injections (every three months) are discouraged due to

potential negative effects on the progression of cartilage
damage and significantly greater cartilage volume loss in OA
patients

• A few large trials have demonstrated short-term

improvements in pain relief with intraarticular glucocorticoid
for up to six weeks post-injection.
• Pharmacological Therapy
8- nutritional supplements

• Nutritional supplements such as glucosamine, chondroitin,

vitamin D, diacerein, avocado soybean unsaponifiables (ASU),
and fish oil are not routinely recommended due to the lack of
clear evidence demonstrating a clinically important benefit from
these supplements.

• A few supplements such as chondroitin, ASU, and fish oil may

have small effects on symptoms, and patients with mild disease
may benefit more from these therapies.
• Pharmacological Therapy
9- Intraarticular Hyaluronans

The use of any intraarticular hyaluronic acid (HA)

formulation is not widely recommended and not
routinely used in our practice as it is associated with
high costs and potential side effects such as pain flare-
ups and joint infection.
• Pharmacological Therapy
10- Intraarticular Platelet-rich plasma for inducing
regeneration (PRP)
PRP is an autologous mixture of highly concentrated
platelets and associated growth factors and other
bioactive components produced by centrifugal
separation of whole blood that is used in orthopaedic
and sports medicine practices to treat bone, tendon
and ligament injuries.
The growth factors released by PRP have been shown
to promote cell recruitment, proliferation and
angiogenesis resulting in a reduction in the critical
regulators of the inflammatory process and a decrease
in the expression of inflammatory enzymes.
PRP may induce a regenerative response by improving
the metabolic functions of damaged structures
• Pharmacological Therapy
10- Platelet-rich plasma for inducing
regeneration (PRP)
In knee OA, PRP injections aim to stimulate cartilage
repair and offer relief to other osteoarthritic
symptoms, potentially delaying the need for joint
replacement surgery.
PRP injections have shown to influence the entire joint
environment, leading to a short-term clinical
improvement with PRP injections being considered a
safe procedure with more favourable outcomes when
compared to alternative treatments
• Pharmacological Therapy
10- Platelet-rich plasma for inducing
regeneration (PRP)
PRP is relatively easy to use due to its simple and rapid
preparation and the minimally invasive administration
requiring a simple intra-articular injection.
Adverse effects are likely to be reduced due to the
patient’s own protein use and bioactive molecules can
be concentrated to achieve the desired dosage, also
eliminating potential drug interactions