musculoskeletal system Flashcards
What is osteopenia
Reduction in bone mineral content
what is osteoporosis
Reduction in bone mass
What are the main causes of osteoporosis
1) post menopausal oestrogen deficiency
2) Age related bone haemostasis deterioration
3)long term levothyroxine use
4) long term glucocorticoid therapy
5) Myeloma (bone marrow cancer)
what is osteomalacia
softening of bones
Pharmalogical treatment osteoporosis
1)Bisphosphonates
- given if BMD is -2.5 or lower e.g. alendronate, risedronate, zoledronic acid).
- usually paired with calcium and vitamin D (colecafierol).
2) SERMs: e.g. Raloxifene to increase osteoblast activity and reduce osteoclast activity
- low bioavailability but is well distributed
3) Strontium ranelate: Reduces osteoclast activity and increases osteoblast activity.
4) PTH (teriparatide, abaloparatide) : increase bone mass by stimulating increase in number of osteoblasts, and decreasing osteoblast apoptosis.
- They act on PTh-1 receptors and activate adenylyl cyclase, to increase Ca2= levels.
5) monoclonal antibodies (Denosumab): Binds to RANKL to inhibit osteoclast formation.
6) Romosozumab: inhibits sclerostin, causing increase in bone matrix production by osteoclasts.
7) Hormone replacement therapy (HRT)
Non Pharmalogical management to treat osteoporosis
1) Excercise
2) Smoking cessation
3) reducing alcohol intake
4) more calcium (at least 700mg a day) and viatamin D
5) weight loss
non Pharmalogical management for OA
mobility aids
Exercise
weight management
Pharmalogical management for OA
1) Topical nsaids
2) oral nsaids
combo with gastro protective to (e.g. PPI:
omeprazole).
3) intra articular corticosteroid injection
pharmalogical mangement for RA
DMARDs (methotrexate, sulfasalazine).
NSAIDs to control symptoms
also if DMARDs given then, short term bridging treatment with glucocorticoids is also given.
DMARDs can take 2-3 months to be effective.
What is a cDMARD
conventional DMARD
just normal DMARDs like methortrexate etc
examples of biologicla DMARDs used to treat RA
Adalimumab
etanercept
infliximab
certolizumab pegol
golimumab
tocilizumab
abatacept
1) top 5 inhibit activity of tumor necrosis factor alpha, and a pro-inflammatory mediator responsible for damge to joints.
2) Adacept binds to APCs, preventing activation of t lymphocytes, disrupting inflmmatory process.
3) Tocilizumab inhibits interleukin-6 (pro-inflammaootry mediator resposible for joint pain in RA).
what is the suffix for a monoclinal antiboy
mab
methotrexate mechanism of action
prevents the conversion of folic acid to tetrahydrofolate inhibiting DNA synthesis during s phase of cell cycle, and increases t cell apoptosis, causing decrease in immune response.
examples of JAK inhibitors to treat RA
Tofacitinib x2 a day
Baricitinib
upadacitinib
filgotinib
draw backs for pharmalogiccal treatment for RA
increased risk of ifection, due to constant supression or decrease in immune response with DMARDs etc
what is JIA
juvenile idiopathic arthiritis
its RA in kids
DMARD: methotreate
sulfasalzine is avoided in sytemic onset JIA
non Pharmalogical management for RA
exercise: muscle strengthening and joint flexibility
physiotherapy
footwear support
What blood test is done for gout
serum urate levels
pharmalogical mangement for gout
NSAID, colchicine, oral corticosteroid
if nsaids given then PPI also given as a gastro-protective agent.
if gout is severe then allopurinol (anti gout agent) given instead.
mechanism of action of colchicine
disrupts cytoskeletal function by inhibiting B-tubulin polymerisation into microtubules.
anti gout agent general moa: Reduce uric acid production by inhibiting the activity of xanthine oxidase
allopurinol drug class and mechanism of action
xanthine oxidase inhibitor
inhibits xanthine oxidase preventing conversion of hypoxanthine into xanthine into uric acid.
non pharmalogical treatment of gout
- reduce alch intake
- weight loss
- diet (e.g. Mediterranean).
levothyroxine
Drug Class: Thyroid hormone replacement
Indication: Hypothyroidism (underactive thyroid)
Mechanism of Action: Levothyroxine is a synthetic form of thyroxine (T4) that is converted to triiodothyronine (T3) in the body. It increases metabolic activity, growth, and development by replacing the deficient thyroid hormones in hypothyroid patients.
Side Effects:
Common: Palpitations, anxiety, weight loss, heat intolerance, tremors.
Severe: Arrhythmias, chest pain, hyperthyroidism (if dose is too high).
Alendoronate
Drug Class: Bisphosphonate
Indication: Osteoporosis, Paget’s disease of bone
Mechanism of Action: Alendronate inhibits osteoclast-mediated bone resorption, increasing bone mineral density by preventing bone loss and reducing fracture risk.
Side Effects:
Common: Abdominal pain, nausea, heartburn.
Severe: Esophageal ulcers, osteonecrosis of the jaw, atypical femoral fractures
raloxifene
Drug Class: Selective estrogen receptor modulator (SERM)
Indication: Osteoporosis, breast cancer prevention in postmenopausal women
Mechanism of Action: Raloxifene acts as an estrogen agonist on bone, reducing resorption and increasing BMD.
Side Effects:
Common: Hot flashes, leg cramps.
Severe: Deep vein thrombosis (DVT), pulmonary embolism (PE).
strontium ranelate
Drug Class: Bone-forming agent
Indication: Osteoporosis (in postmenopausal women and men)
Mechanism of Action: Strontium ranelate increases bone formation and reduces bone resorption, improving bone strength and reducing fracture risk.
Side Effects:
Common: Nausea, diarrhea.
Severe: Cardiovascular events (e.g., heart attack, stroke), venous thromboembolism.
teriparatide
Drug Class: Parathyroid hormone analog
Indication: Osteoporosis (in high-risk patients)
Mechanism of Action: Teriparatide is a recombinant form of parathyroid hormone (PTH) that stimulates bone formation by activating osteoblasts, enhancing bone density and strength.
Side Effects:
Common: Nausea, dizziness, leg cramps.
Severe: Osteosarcoma (rare), hypercalcemia.
denosumab
Drug Class: Monoclonal antibody
Indication: Osteoporosis, bone metastases, bone loss due to cancer treatment
Mechanism of Action: Denosumab inhibits RANKL (receptor activator of nuclear factor kappa-B ligand), a protein that promotes osteoclast differentiation and activation, thereby reducing bone resorption.
Side Effects:
Common: Back pain, muscle pain, hypocalcemia.
Severe: Osteonecrosis of the jaw, atypical femoral fractures.
romosozumab
Drug Class: Monoclonal antibody
Indication: Osteoporosis (in postmenopausal women at high fracture risk)
Mechanism of Action: Romosozumab inhibits sclerostin, preventing bone formation from being inhbited, thereby stimulating both bone formation and reducing bone resorption.
Side Effects:
Common: Joint pain, headache, back pain.
Severe: Cardiovascular events (e.g., heart attack, stroke)
omeprazole
Drug Class: Proton pump inhibitor (PPI)
Indication: GERD, peptic ulcers, Zollinger-Ellison syndrome
Mechanism of Action: Omeprazole inhibits the proton pump (H+/K+ ATPase) in parietal cells of the stomach, reducing gastric acid production.
Side Effects:
Common: Headache, abdominal pain, nausea.
Severe: Bone fractures, Clostridium difficile infection, kidney disease.
methotrexate
Drug Class: Antimetabolite, Disease-modifying anti-rheumatic drug (DMARD)
Indication: Rheumatoid arthritis, psoriasis, certain cancers
Mechanism of Action: Methotrexate inhibits dihydrofolate reductase, blocking DNA synthesis and cell replication, particularly affecting rapidly dividing cells (e.g., immune cells in rheumatoid arthritis).
Side Effects:
Common: Nausea, mouth sores, fatigue.
Severe: Hepatotoxicity, bone marrow suppression, pulmonary fibrosis
sulfasalazine
Drug Class: Disease-modifying anti-rheumatic drug (DMARD), anti-inflammatory
Indication: Rheumatoid arthritis, inflammatory bowel disease (e.g., ulcerative colitis)
Mechanism of Action: Sulfasalazine is metabolized into sulfapyridine and 5-aminosalicylic acid. It reduces inflammation by inhibiting cyclooxygenase and lipoxygenase pathways.
Side Effects:
Common: Nausea, rash, headache.
Severe: Blood dyscrasias, liver toxicity, hypersensitivity reactions.
adalimumab
Drug Class: Monoclonal antibody, TNF-alpha inhibitor
Indication: Rheumatoid arthritis, Crohn’s disease, psoriasis, ankylosing spondylitis
Mechanism of Action: Adalimumab binds to and neutralizes tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine, reducing inflammation.
Side Effects:
Common: Injection site reactions, headache.
Severe: Increased risk of infections (e.g., tuberculosis), malignancies, hepatotoxicity.
abatacept
Drug Class: Monoclonal antibody, T-cell co-stimulation modulator
Indication: Rheumatoid arthritis, juvenile idiopathic arthritis
Mechanism of Action: Abatacept inhibits T-cell activation by binding to CD80/CD86 on antigen-presenting cells, preventing their interaction with CD28 on T-cells.
Side Effects:
Common: Headache, nasopharyngitis.
Severe: Increased risk of infections, malignancies, infusion reactions.
tofacitinib
Drug Class: Janus kinase (JAK) inhibitor
Indication: Rheumatoid arthritis, psoriatic arthritis, ulcerative colitis
Mechanism of Action: Tofacitinib inhibits Janus kinase enzymes (JAK1, JAK2, JAK3), which are involved in signaling pathways for immune cell activation, reducing inflammation.
Side Effects:
Common: Headache, upper respiratory infections.
Severe: Risk of infections, blood clots, lymphoma, liver enzyme elevations.
colchicine
Drug Class: Anti gout agent
Indication: Gout, familial Mediterranean fever
Mechanism of Action: Colchicine inhibits microtubule polymerization, reducing neutrophil migration and inflammation in affected joints.
Side Effects:
Common: Diarrhea, nausea, vomiting.
Severe: Bone marrow suppression, rhabdomyolysis, liver toxicity.
allopurinol
Drug Class: Xanthine oxidase inhibitor
Indication: Gout, hyperuricemia, prevention of uric acid stones
Mechanism of Action: Allopurinol inhibits xanthine oxidase, the enzyme responsible for converting purines into uric acid, thus lowering uric acid levels.
Side Effects:
Common: Rash, gastrointestinal upset.
Severe: Stevens-Johnson syndrome, liver toxicity, kidney failure.
tocilizumab
Drug Class: Monoclonal antibody, IL-6 receptor antagonist
Indication: Rheumatoid arthritis, cytokine release syndrome, systemic juvenile idiopathic arthritis
Mechanism of Action: Tocilizumab inhibits IL-6 receptors, reducing the inflammatory response mediated by IL-6.
Side Effects:
Common: Upper respiratory infections, headache.
Severe: Liver enzyme elevation, gastrointestinal perforations, serious infections.
