Clinical Pharmacotherapeutic approach of Musculoskeletal System

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4/13/2024
Sreenu Thalla
Associate Professor
Department of Pharmacology
Musculoskeletal System

PEO1 Fundamental knowledge: Develop and demonstrate the depth and breadth of knowledge from the foundational sciences in
core subjects of pharmaceutics, pharmaceutical chemistry, pharmacotherapeutics, social, behavioural, administrative, health
policies and clinical sciences to evaluate the scientific literature, elucidate drug action, identify and solve therapeutic
problems, and advance population health and patient-centered care.
PEO2 Practice and care: Provide patient-centered care as the medication expert and prioritize patients need and
manage patient healthcare needs using human, financial, technological, and physical resources to optimize the
safety and efficacy of medication use systems, graduates will be able to design prevention, intervention, and
educational strategies for individuals and communities to manage chronic disease and improve health and
wellness. Effectively communicate verbally and nonverbally when interacting with an individual, group, or
organization.
PEO3 Lifelong learning and innovation: Demonstrate the ability to set personal and professional goals and priorities,
effectively plan and manage time, and organize work. Identify and analyze emerging issues, products, and
services that may affect public health policy, patient-centered and population-based therapeutic outcomes,
medication use systems, and pharmacy benefits, develop new ideas and approaches to improve quality or
overcome barriers to advance the profession. Engage in innovative activities by using creative thinking to
envision better ways of accomplishing professional goals.
PEO4 Interprofessional collaboration: Collaborate as an integral part of an interprofessional team, inclusive of
patients, caregivers, colleagues, health professionals and members of the community to make patient-centered
pharmacotherapy decisions and care plans; prevent, identify, and resolve drug-related problems; and promote
patient-centered and population-based health and actively participate and engage as a healthcare team member
by demonstrating mutual respect, understanding, and values to meet patient care needs.
PEO5 Traits Improvement and Professionalism: Exhibit behaviours and values consistent with the trust given to the
profession by patients, other healthcare providers, and society. Take responsibility for health outcomes and
make rational and ethical decisions that represent the best interest of the patient and the community. Respect
and actively engage the patient, the community, and other health professionals as well as respect the privacy
and confidentiality of health information.
Programme Educational Objectives (PEO’s)
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Sreenu Thalla, Associate Professor,
4/13/2024

PO1 Comprehensive pharmacy and clinical knowledge: Demonstrate mastery and application of core knowledge and skills in
relation to the evolving pharmaceutical, biomedical, clinical and epidemiological sciences. This includes competency in
areas supporting high quality pharmacy practice (e.g., pharmaceutics, medicinal chemistry, pharmacokinetics,
pharmacodynamics, pharmacology, pathophysiology, pharmacotherapeutics, and pharmaceutical care).
PO2 Patient centered care: Provide patient-centered care to diverse patients using the best available evidence and in
consideration of patients’ circumstances to devise, modify, implement, document and monitor pharmacotherapy care
plans, either independently or as part of healthcare teams.
PO3 Problem solving and decision making: Demonstrate the ability to use observational, analytical and critical thinking skills
to develop, implement and evaluate solutions that solve pharmacotherapy problems and build the ability to take decisions
based on evidenced based practice.
PO4 Social and cultural awareness: Recognize social determinants of health and respect patients’ cultural, social and religious
perspectives to produce safe and appropriate medication use throughout society. Reflect their knowledge, experiences,
values, attitudes, biases and beliefs, to show evidence of being self-aware and life-long learners.
PO5 Professionalism: Exhibit professional ethics, attitudes and behaviors by demonstrating patient advocacy, altruism,
accountability, compassion, integrity and respect for others. Understand, analyze and communicate the value of their
professional roles in society (Ex. Health care professionals, health promoters, educators, managers, employers and
employees).
PO6 Innovation and entrepreneurship: Engage in innovative activities by using creative thinking to envision better ways of
accomplishing professional goals. Utilize the principles of scientific enquiry and critical thinking while solving problems
and making decisions in daily practice. Attain the key ability to start a community pharmacy or chain community
pharmacies with patient care services.
Programme Outcomes (PO’s)
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4/13/2024

PO7 Confidentiality and professional ethics: Practice ethically, maintaining patient confidentiality, responding to
errors in care and professional misconduct (including plagiarism), and understanding principles of ethical
research (including conflicts of interest and obtaining appropriate informed consent). Apply ethical principles
while making decisions and take responsibility for the outcomes associated with decisions.
PO8 Interpersonal and communication skills: Demonstrate effective interpersonal written and verbal skills, adapt to
socioeconomic and cultural factors as well as situational applications. Effectively educate families, patients,
caregivers and other health care professional (HCPs). Function effectively in a team and act in a consultative
position for other members of the health care team, regulatory agencies and policy makers.
PO9 Clinical pharmacist and society: Apply contextual knowledge to assess the societal health care needs and
demonstrate effective planning abilities in order to solve problems related to health care practice. Educate and
aware the patients regarding the aspect of health and prevention of diseases and provide them a cost-effective
drug therapy.
PO10 Environment and sustainability: Understand the impact of professional pharmacy solution in societal and
environmental context and demonstrate the knowledge and need of sustainable development.
PO11 Practice based learning and improvement: Evaluate practice and care, and promote continuous improvement in
one's own patient care and pharmacy services. Demonstrate self-calibration skills and a commitment to the
lifelong learning needed to provide high quality care. Locate, appraise and assimilate evidence from scientific
studies to enhance the quality of care and services. Effectively utilize information, informatics and technology to
optimize learning and patient care.
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4/13/2024

PSO1 To understand various drug distribution methods, know the professional practice management skills in hospital
pharmacies.
PSO2 To provide unbiased and authentic informations to all the stakeholders of health, appreciate practice-based
research methods, and appreciate stores management and inventory control.
PSO3 To prepare personalized therapeutic strategies based on diagnosis, through identification of options, observing
treatment, time-course of clinical and laboratory indices of therapeutic response and adverse effects.
PSO4 To explicate patient care in performing medication history, interpretations of laboratory data, categorizing
potential-medicine related impacts of Pharmacotherapy.
PSO5 To understand the clinical aspects of drug development, such as phases, ethical issues, and roles and
responsibilities of clinical trial personnel and able to design clinical study documents, data management and
safety monitoring in clinical trials.
PSO6 To render the services to the public by providing patient centric effective treatments to curb the therapeutic issues
with the required medicines and explain the effects of the drugs by analyzing the scientific literature for
improving their health and well-being.
Programme Specific Outcomes (PSO’s)
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4/13/2024

CO. 3.3.1
To remember and recall the pathophysiology of selected
diseases and rationale for drug therapy.
CO.3.3.2
To identify various therapeutic approaches for the
management of selected diseases.
CO.3.3.3
To apply the concepts of various drug therapies and identify
the controversies in drug therapy.
CO.3.3.4
To assess the drug therapy by preparing individual
therapeutic plan based on diagnosis.
CO.3.3.5
To evaluate the patient specific parameters relevant in
initiating drug therapy and monitoring therapy.
CO.3.3.6
To create a pharmaceutical care plan, design a list of patient
counselling points on the specific illness.
Course Outcomes (CO’s)
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4/13/2024

Rheumatoid Arthritis
Course Outcome (CO-2)
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• The most common cause of chronic inflammatory joint disease
• Most typical features
a. A symmetrical polyarthritis and tenosynovitis
b. Morning stiffness
c. Elevation of the erythrocyte sedimentation rate (ESR)
d. Appearance of autoantibodies that target immunoglobins in
the serum
• It is a systemic autoimmune disease and changes can be widespread
in a number of tissues of the body
• RA tend to die younger than their peers as a result of the effects of
chronic inflammation on a number of organ systems
• Chief among these is early ischemic heart disease secondary to the
effects of inflammation on the cardiovascular system.
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Epidemiology
• Affects 1 – 3% of the population world wide
• With a peak prevalence between the ages of 30 and 50 years
• Women are affected 3 or 4 times more commonly than men
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Pathology
• RA is a systemic disease but the most characteristic lesions are seen in
the synovium or within rheumatoid nodules.
• The synovium is engorged with new blood vessels and packed full of
inflammatory cells
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Receptor activator of nuclear factor kappa-Β ligand (RANKL)
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Stage 1 – Pre-clinical
• Before RA becomes clinically apparent the immune pathology is
already beginning.
• Raised ESR, C-reactive protein (CRP), and RF may be detectable
years before the first diagnosis.
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• Early changes are
 Vascular congestion with new blood vessel formation
 Proliferation of synoviocytes
 Infiltration of the sub synovial layers by polymorphs,
lymphocytes and plasma cells.
• There is thickening of the capsular structures, villous formation of the
synovium and a cell-rich effusion into the joints and tendon sheath.
Stage 2 – Synovium Course Outcome (CO-2)
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Stage 3 - Destruction
• Persistent inflammation causes joint and tendon destruction.
• Articular cartilage is eroded.
• At the margins of the joint, bone is also eroded by granulation
tissue invasion and osteoclastic resorption.
• Similar changes occur in tendon sheaths, causing tenosynovitis.
• Partial or complete rupture of tendons.
• Swelling of the joints, tendons and bursae.
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Stage 4 – Deformity
• Combination of articular destruction, capsular stretching and
tendon rupture leads to progressive instability and deformity of
the joints.
• The inflammatory process usually continues but the mechanical
and functional effects of joint and tendon disruption now become
vital.
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Clinical Features
• Early feature (synovitis)
 Most commonly affected MCPJ (metacarpophalangeal) and
PIPJ (proximal interphalangeal), wrist, tendon sheaths around
the joints (wrist – feet – knee – shoulder)
 Bilateral symmetrical polysynovitis
 Pain, fusiform swelling, stiffness, loss of mobility
 Constitutional symptom
• Malaise and low grade fever
• Tenosynovitis
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Late feature (DESTRUCTIVE)
• Spread to other joint – wrist, ankle, knee, shoulder (in order of
frequency)
• Morning stiffness (more than 30 min) – improve with activity
• Activity of daily living will be affected – quality of life affected
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More later (DEFORMITY)
I. Pain, deformity, instability, decreased ROM
II. Joint deformity – movement restricted and painful
• Thumb – Z-deformity
• Fingers – Swan neck deformity/ Boutonniere’s deformities, ulnar
deviation
• Wrist – radial and volar displacement
• Elbow – limited extension
• Shoulder - limited abduction
• Knees – swollen, flexion an vulgus
• Toes – clawed
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Mallet Finger
Swan-neck Deformity
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Z-deformity of Thumb
RA -Hands
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Diagnosis
• Mostly clinical
 Bilateral, symmetrical polyarthritis
 Involving proximal joints of hand or feet
 Present for at least 6 weeks
 Confirmed with subcutaneous nodules or periarticular
erosions on x-ray
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Hematological Investigation
• FBC- normocytic hypochromic anaemia (due to abnormal
erythropoiesis from chronic inflammation), WBC
• Inflammatory markers - ESR, CRP elevated (its use as indication of
disease progression monitoring, treatment response)
• Rheumatoid Factor (RF) - anti-IgG auto Ab 80% will have it
• Anti- cyclic citrullinated peptide (CCP) Ab
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For disease monitoring, treatment response
• EARLY STAGE (SYNOVITIS) – Soft tissue swelling, periarticular
osteopenia
• LATER STAGE (DESTRUCTIVE) – Juxta- erosions, narrowing of
joint space
• ADVANCE STAGE (DEFORMITY) – Articular destruction and joint
deformity
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Management
• There is no cure for rheumatoid arthritis
• Aim to delay the progression of the disease, alleviate symptoms,
reduce functional limitation
• Supportive and palliative
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Surgery - Improve quality of life
Synovectomy
• When one or two joints are affected more severely than others, this
procedure is used to reduce the amount of inflammatory tissue by
removing the diseased synovium or lining of the joint.
• It may result in less swelling and pain and the slowing or prevention of
further joint damage
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Arthroscopic Surgery
• Thin tube with a light at the end inserted into the joint through a
small incision.
• It is connected to a closed-circuit television and we can see the
extent of the damage in the joint.
• Tissue samples taken, remove loose cartilage, repair tears, smooth a
rough surface or remove diseased synovial tissue.
• It is most commonly performed on the knee and shoulder
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Osteotomy
• Literally meaning, “to cut bone,” this procedure is used to increase
stability by redistributing the weight on the joint.
• Osteotomy isn’t often used with RA because there are other options
available besides cutting the bones.
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Joint Replacement Surgery or Arthroplasty
• This is the surgical reconstruction or replacement of a joint.
• Successfully used to help people who otherwise might be in a
wheelchair, joint replacement surgery involves the removal of the
joint, resurfacing and relining of the ends of bones and replacing
the joint with a man-made component.
• This procedure is usually recommended for people over 50 or who
have severe disease progression.
• Typically a new joint will last between 20 and 30 years
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Arthrodesis or Fusion
• This procedure fuses two bones together.
• While it limits movement, it does decrease pain and increase
stability of the joints in the ankles, wrists, fingers, toes and spine.
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USUAL DOSES AND MONITORING PARAMETERS FOR ANTIRHEUMATIC DRUGS
Drug Usual Dose Initial Monitoring Tests Maintenance Monitoring
Tests
NSAIDs ___ Scr or BUN, CBC every 2–4 weeks
after starting therapy for 1–2
months; salicylates: serum
salicylate levels if therapeutic
dose and no response
Same as initial plus stool
guaiac
every 6–12 months
Methotrexate Oral or IM: 7.5–15 mg per week Baseline: AST, ALT, ALK-P,
albumin, total bilirubin,
hepatitis B and C studies, CBC
with platelets, Scr
CBC with platelets, AST,
albumin
every 1–2 months
Leflunomide Oral: 100 mg daily for 3 days,
then
10–20 mg daily
Baseline: ALT ALT monthly initially, and
then
periodically when stable
Hydroxychlor
oquine
Oral: 200–300 mg twice daily;
after 1–2 months may increase
to 200 mg once or twice daily
Baseline: color fundus
photography and automated
central perimetric analysis
Ophthalmoscopy every 9–
12
months and Amsler grid at
home
every 2 weeks
Sulfasalazine Oral: 500 mg twice daily, then
increase to 1 g twice daily max
Baseline: CBC with platelets, then
every week for 1 month
Same as initial every 1–2
months
Etanercept 25 mg SC twice weekly or 50 mg
every 7 days
None None
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Drug Usual Dose Initial Monitoring Tests Maintenance Monitoring
Tests
Infliximab 3 mg/kg IV at 0, 2, and 6 weeks,
then every 8 weeks
None None
Adalimumab 40 mg SC every 2 weeks None None
Anakinra 100 mg SC daily None None
Auranofin Oral: 3 mg once or twice daily Baseline: UA, CBC with platelets Same as initial every 1–2
months
Gold
thiomalate
IM: 10-mg test dose, then
weekly
dosing 25–50 mg; after response
may increase dosing interval
Baseline and until stable: UA, CBC
with platelets preinjection
Same as initial every other
dose
Azathioprine Oral: 50–150 mg daily CBC with platelets, AST every 2
weeks for 1–2 months
months
D-
Penicillamine
Oral: 125–250 mg daily, may
increase by 125–250 mg every
1–2 months; max 750 mg/day
Baseline: UA, CBC with platelets,
then every week for 1 month
months, but every 2 weeks
if dose Changes
Cyclophospha
mide
Oral: 1–2 mg/kg per day UA, CBC with platelets every
week for 1 month
Same tests as initial but
every 2–4 weeks
Cyclosporine Oral: 2.5 mg/kg per day Scr, blood pressure every month Same as initial
Corticosteroids Oral, IV, IM, IA, and soft-tissue
injections: variable
Glucose; blood pressure every 3–6
months
Same as initial
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CLINICAL MONITORING OF DRUG THERAPY IN RHEUMATOID ARTHRITIS
Drug Toxicities Requiring
Monitoring
Symptoms to Inquire Abouta
NSAIDs and
salicylates
GI ulceration and
bleeding, renal damage
Blood in stool, black stool, dyspepsia,
nausea/vomiting, weakness, dizziness, abdominal
pain, edema, weight gain, shortness of breath
Corticosteroids Hypertension,
hyperglycemia,
osteoporosis
Blood pressure if available, polyuria, polydipsia,
edema, shortness of breath, visual changes, weight
gain, headaches, broken bones or bone pain
Azathioprine Myelosuppression,
hepatotoxicity,
lymphoproliferative
disorders
Symptoms of myelosuppression (extreme fatigue,
easy bleeding or bruising, infection), jaundice
Gold
(intramuscular or
oral)
Myelosuppression,
proteinuria, rash,
stomatitis
Symptoms of myelosuppression, edema, rash, oral
ulcers, diarrhea
Hydroxychloroqui
ne
Macular damage, rash,
diarrhea
Visual changes including a decrease in night or
peripheral vision, rash, diarrhea
Methotrexate Myelosuppression, hepatic
fibrosis, cirrhosis,
pulmonary infiltrates or
fibrosis, stomatitis, rash
Symptoms of myelosuppression, shortness of
breath, nausea/ vomiting, lymph node swelling,
coughing, mouth sores, diarrhea, jaundice
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Drug Toxicities Requiring Monitoring Symptoms to Inquire Abouta
Leflunomide Hepatitis, GI distress, alopecia Nausea/vomiting, gastritis, diarrhea, hair
loss, jaundice
Penicillamine Myelosuppression, proteinuria,
stomatitis, rash,
dysgeusia
Symptoms of myelosuppression, edema,
rash, diarrhea, altered
taste perception, oral ulcers
Sulfasalazine Myelosuppression, rash Symptoms of myelosuppression,
photosensitivity, rash, nausea/
vomiting
Etanercept,
adalimumab,
Anakinra
Local injection-site reactions,
infection
Symptoms of infection
Infliximab Immune reactions, infection Postinfusion reactions, symptoms of
infection
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• The earliest changes of OA may begin in cartilage.
• The two major components of cartilage are type 2 collagen,
which provides tensile strength, and aggrecan, a proteoglycan.
• OA cartilage is characterized by gradual depletion of aggrecan,
unfurling of the collagen matrix, and loss of type 2 collagen,
which leads to increased vulnerability.
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Physical therapy
• A physical therapist can show you exercises to strengthen the
muscles around your joint, increase your flexibility and reduce
pain.
• Regular gentle exercise that you do on your own, such as
swimming or walking, can be equally effective.
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Occupational therapy
• An occupational therapist can help you discover ways to do
everyday tasks without putting extra stress on your already painful
joint.
• For instance, a toothbrush with a large grip could make brushing
your teeth easier if you have osteoarthritis in your hands.
• A bench in your shower could help relieve the pain of standing if
you have knee osteoarthritis.
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Transcutaneous electrical nerve stimulation (TENS)
• This uses a low-voltage electrical current to relieve pain.
• It provides short-term relief for some people with knee and hip
osteoarthritis.
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Cortisone injections
• Injections of a corticosteroid into
your joint might relieve pain for
a few weeks.
• Your doctor numbs the area
around your joint, then places a
needle into the space within your
joint and injects medication.
• The number of cortisone
injections you can receive each
year is generally limited to three
or four, because the medication
can worsen joint damage over
time.
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Lubrication injections
• Injections of hyaluronic acid might relieve pain by providing some
cushioning in your knee, though some research suggests that these
injections offer no more relief than a placebo.
• Hyaluronic acid is similar to a component normally found in your
joint fluid
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Realigning bones
• If osteoarthritis has damaged one side of your knee more than
the other, an osteotomy might be helpful.
• In a knee osteotomy, a surgeon cuts across the bone either above
or below the knee, and then removes or adds a wedge of bone.
• This shifts your body weight away from the worn-out part of
your knee
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Joint Replacement
• In joint replacement surgery, your surgeon removes your
damaged joint surfaces and replaces them with plastic and metal
parts.
• Surgical risks include infections and blood clots.
• Artificial joints can wear out or come loose and might eventually
need to be replaced.
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Gout
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Treatment Goals
• Gout can be treated without complications.
• Therapeutic goals include
– terminating attacks
– providing control of pain and inflammation
– preventing future attacks
– preventing complications such as renal stones and destructive
arthropathy
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Non- Pharmacologic Treatments
• Immobilization of Joint
• Ice Packs
• Abstinence of Alcohol
– Consumption can increase serum urate levels by increasing uric acid
production.
– When used in excess it can be converted to lactic acid which inhibits uric acid
excretion in the kidney
• Dietary modification
– Low carbohydrates
– Increase in protein and unsaturated fats
– Decrease in dietary purine-meat and seafood.
– Dairy and vegetables do not seem to affect uric acid
• Bing cherries and Vitamin C
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Thank you
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Spondylitis
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