ORTHOPAEDIC PHARMACOLOGY

DRUGS FOR OSTEOPOROSIS

Folowing 5 classes of drugs are used:

1. Bisphosphonates
2. Selective estrogen receptor modulators
3. Calcitonin
4. Denosumab
5. Teriparatide

1. BISPHOSPHONATES:
• Drugs: Alendronate, Ibandronate, Risedronate, Zoledronic acid
• MOA:
I. Increases apoptosis in osteoclasts.
II. Inhibits cholesterol biosynthesis pathway (important for osteoclast function).
• Pharmacokinetics:
I. Oral administration. Poorly absorbs in gut (less than 1% of dose is absorbed
once)
II. Rapidly cleared from plasma after administration, because it binds to
hydroxyapatite in the bone from which they get over a period of hours to years.
III. Eliminates via KIDNEY (avoid in renal impairment)
IV. If patient is unable to tolerate oral bisphophantes. IV ibandronate and Zoledronic
acid can be given.
• Clinical uses:
I. Osteoporosis in post menopausal women
II. Pagets disease
III. Treatment of bone metastases and hypercalcemia of malignancy.
• Adverse effects:
I. Diarrhea
II. Abdominal pain
III. Musculoskeletal pain
IV. Esophagitis and esophageal ulcers (associated with aledronate, risedronate,
ibandronate)
V. Osteonecrosis of jaw – reported in patients taking high IV dose of drug for
hypercalcemia of malignancy.
VI. Atypical fracture - associated with chronic use of drug.
VII. Etidronate is the only bisphosphonate that causes osteomalacia.
2. SELECTIVE ESTROGEN RECEPTOR MODULATORS:
• Drug: Raloxifen
• MOA: this drugs works as estrogen agonist in bone and estrogen antagonist in breast
and endometrial tissue. i.e. increases bone density without increasing the risk of breast
cancer.
• Background physio:
I. low estrogen levels after menopause promotes proliferation and activation of
osteoclasts.i.e. bone density declines.
II. Estrogen may increase the risk of endometrial cancer. If estrogen replacement
therapy is given without progestin in a post menopausal women with intact uterus
III. Estrogen can also cause breast cancer, stroke and venous thromboembolism.
• Used as alternative for postmenopausal women who cannot tolerate bisphosphonates.
• This drug decreases the risk of invasive breast cancer and also reduces levels of LDL (low
density lipoprotein).
• Adverse effects:
1. Hot flashes
2. Leg cramps
3. Risk of venous thromboembolism
3. CALCITONIN:
• Salmon calcitonin is used
• Indicated for osteoporotic women who are atleast 5 year menopausal and not
responding to any other drugs for osteoporosis.
• Uses:
o decreases bone resorption – still less effective than bisphosphonates.
o pain relief – in osteoporotic fracture
• Administration- intranasal and parenteral.
• Resistance develops with long term use. E.g. in paget disease
• Due to resistance issue and malignancy potential. It is used only when other drugs are
not working well with patient.
• Adverse effects:
o Rhinitis and other nasal symptoms- when given intranasaly.
o Increases the risk of malignancy.
4. DONESUMAB:
• It is an antibody; targets receptor activator of nuclear factor kappa-B ligand and inhibits
osteoclast formation and function.
• Administration: via subcutaneous injection, every 6 months.
 • Adverse effects:
o Increased risk of infections
o Dermatological reactions
o Hypocalcemia
o Osteonecrosis of jaw
o Atypical fractures
• Used in osteoporotic women with high risk of fracture and who cannot tolerate other
osteoporosis therapies.
5. Teriparatide:
• Recombinant form of human parathyroid hormone.
• Administration: subcutaneous; daily – to treat osteoporosis.
• MOA: promotes bone formation by stimulating osteoblastic activity.
• Have been reported to produce osteosarcoma in rats.
• Safety and efficacy is not very much pre-defined
• Should be reserved for osteoporotic patients with high risk of fracture and not
responding to other therapies.

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DRUGS FOR OSTEOMEYLITIS

Osteomyelitis: inflammation of bone marrow.

1. Acute osteomyelitis:
I. Hemtogenous:
i. bacterial seeding in blood
ii. more common in children
iii. most common site in children is metaphysis of long bones. And vertebra and pelvis
in adults is most common.
II. Direct inocultaion: either via truama or open fracture.
2. Chrnoic osteomyelitis:
I. Causative factors:
i. Cavity, seqestrum, sinus, foreign body, degree of bone necrosis.
ii. Immunosuppression, nutritional status and diabetes mellitus.
iii. Virulence of organsim
iv. Prosthesis.
II. Complications:
i. Recurrence
ii. Pathological fracturs
iii. Growth disturbace
iv. Amyloid disease
 v. Epidermoid carcinoma of fistula.
III. TB osteomyelitis:
i. The most common site of infection is spine (most common), hip, knee and foot.
ii. Treatment: first 3 months (isoniazid, rifampin,pyrazinamide and ethambutol). Next
9 months (isoniazid and rifampin) pyridoxine is alternative of isoniazid.

CAUSATIVE ORGANISMS:

1. Staph aureus- most common [Floxacillin and fusidic acid. Also MRSA= vancomycin]
2. Staph pyogenes and pneumonia (rarely)
3. H.influenza (gram –ve) - in children [3rd gen cephalosporin]
4. Salmonella: children with sickle cell disease and less than 4 years of age. [3rd gen
cephalosporine, floroquinolone]
5. Trauma- s.aureus, coliform bacilli and pseudomonas aeruginosa → maficillin and
ciprofloxacin.
6. Antipseudomonal, E.coli, kleibbsiella →piperacillin, Ticarcillin, Carbenicillin etc.
7. Nail puncture in atheltic shoe → s.aureus and pseudomonas aeruginosa (ceftazidime or
cefepime and ciprofloxacin)
• Β- lactamase resistant penicillins:methicillin, oxacillin and nafcillin.
• Penillin adverse effects: hypersenstivity reactions, seizures, electrolyte disturbances and
bleeding diathesis.
• 3rd generation cephalosporin: cefotaxime, ceftriaxone and ceftazidime.
o Cross BBB
o Ceftazidime- anti pseudomonal
• th
4 generation cephalosporin: cefepime, cefpirome.
o Broad spectrum (more gram –ve coverage)
o Gram +ve cocci: MRSA and strep pneumonia
• Vancomycin:
o Narrow spectrum (gram+ve specially MRSA)
o MOA: bactericidal; inhibit synthesis of bacterial cell wall phopholipids and peptidoglycan
polymers.
o IM administration
o Adverse effects: fever, chills phlebitis at infusion site. Shock- with rapid infusion. Red
man or red neck syndrome.
• Fusidic acid: narrow spectrum; kills gram +ve
o Used for local infections.
o Adverse effects:
▪ Nausea, vomiting, abdominal pain and diarrheae.
▪ Granulocytopenia, thrombocytopenia
▪ Hepato-toxicity.
• Quinolones:
o Gram +ve, gram –ve,stypical and pseudomonas.
 o Anti pseudomonal- ciprofloxacin/ofloxacin
o Used in children with cystic fibrosis: Levofloxacin, Moxifloxacin.
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DRUGS FOR GOUT
Hyperuricemia causes sodium urate crystal deposition in joints and kidney specially. This leads to
inflammation.i.e. infiltration of granulocytes and phagocytosis of urate crystals.
Etiology:
1. Excessive alcohol consumption
2. Diet rich in purines
3. Kidney disease.

Acute gout:

1. Colchicine
2. NSAIDs
3. Corticosteroids

Chronic gout:

1. xanthane oxidase inhibitors

2. uricouric agents (probencid and febuxostat)
3. uricaase or urate oxidase

prophylaxis for gout in hyperuricemia patients:

1. NSAIDs
2. Colchicine
3. Uricosuric agents- probencid.

Regards - Kuraishi D’22