Role of antibiotics and antiinflammatory

Dr. Harris Tata, M,Kes., SpOT

Musculoskeletal System

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PASIENTS CLINICS /HOSPITAL

DIAGNOSTICPROCESS

THERAPEUTICPROCESS

KNOWLEDGESKILLATTITUDE

ANAMNESTICPHYSIC EXAMIN.SUPPORTING : - laboratory - radiology - electromedic - ect.

DEFINE THE PROBLEMTHERAPEUTIC OBJECT.SELECTING THERPEUT. STRATEGIES - non-pharmacological - pharmacological - surgical

INFORMATION: -RATIONAL(evidence based) -IRRATIONAL(assumption,intuitive, no data)

Antibiotic

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INFEKSI

SISTEM BIOLOGITUBUH MANUSIA

TUMBUH danBERBIAK

SIMPTOM & SIGNPATOLOGIS

VIRUS BAKTERI JAMUR PARASIT

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Infection Musculoskeletal

Osteomyelitis

acute (subacute) chronic

specific (eg TB) non specific(most common)

Skin Infection CellulitisMyositis

Septic Arthritis Etc

Acute Osteomyelitis & Acute ArthritisOrganism

Gram +ve staphylococus aureus strep pyogen strep pneumonie Listeria monocytogenes (rare)

Gram -ve haemophilus influnzae (50% < 4 y) e .coli pseudomonas auroginosa, proteus mirabilis

AntibioticAntibiotic Chemical molecules produced by a microorganism that kills or inhibits the growth of another microorganism

AntibioticSelection of the most appropriate systemic

antibiotic therapy will therefore need to reflect the organism(s) isolated and sensitivity profile ( culture and sensivity test),

Pharmacokinetic factors such as penetration into bone, presence of prosthetic material, vascular supply of the affected limb and the patient’s individual tolerance of the drugs

AntibioticsTreatment of these infections can be difficult,

usually involving a prolonged course of antibiotics, often with surgical intervention.

The selection of antibiotics depends on sensitivity profile, patient tolerance and long-term goals,

Inhibits cell wall synthesisPenicillins,Cephalosporins,Vancomicyn,Bacitracin,AstreonamImipinem.

The CephalosporinsFirs Generation cephalotin, cephapirin,

cephaloridine, cephalexin, cephradine, cefactor, cefadroxyl

Second generation cefoxiitin, cefamandole, cefuroxime, cefotiam, cefmetazole, cefonicid, ceforanide, cefotetan

Third Generation cefotaxime, ceftrizoxine, ceftriaxone, ceftmenoxine, ceftazidine, cefoperazone, moxalactam

Increase in cell membrane permeabilityPolymyxinMystatinAmphotericin

Ribosomal inhibitionBacteriostatic tetracycline, chloramfenicol,

macrolides (erytromycine, clindamycin)Bacteriocidal gentamycin, streptomycin,

tobramycin, amikacin, and neomycin.

Interference with transcription and translation of bacterial DNAQuinolonesRifampin,Metronidazole

Antimetabolite actionSulfonamidDapsoneTrimetoprinPara-aminosalycil acid

Antibiotic classification base on their spectrum activity

No antibiotic is effective against all microbes

Principle antibiotics therapy1. Susceptibility testing2. Drug concentration in blood3. Serum bactericidal titers4. Route of administration5. Monitoring of therapeutic

response6. Clinical failure of

antibiotics therapy

1. Susceptibility testingThe results of susceptibility testing

establish the drug sensitivity of the organism

These results usually predict the MIC of a antibiotics

Choosing of the most effective and the least toxic drug, in time administration2. Drug concentration in the blood

• The measurement of drug concenctration may be appropriate when using antibiotics with low therapeutic index (aminoglycosides & vancomycin)

3. Route of administrationParenteral administration is prefered in

most cases of serious microbacterial infections.

Chloramphenicol, the fluoroquinolones and trimethoprim-sulfamethoxazole may be effective orally.5. Monitoring of therapeutic response

• Therapeutic response should be monitored clinically and microbiologically to detect the development of resistance or superinfection

6. Clinical failure of antimicrobial therapyInadequate clinical or microbial response can result from :laboratory testing error, problems the drug (incorrect choice, poor

tissue penetration, inadeqaute dose)the patient (poor host defense, undrained

abcesses)the pathogen (resistance or superinfection)

Antimicrobial drugs combination indication

1. Emergency situations2. To delay resistance3. Mixed infections4. To achieve synergistic effects

Clinical ApplicationsThe role of antibiotic in orthopedic surgery is

multifoldThey can be used to prevent infection in elective

surgery cases and to treat open fracture and established infection

To prevent or treat infection s most effectively microbiology, pharmacology, toxicity, and cost antibiotics

In general, the least toxic, least expensive, and most effective drug with narrowest spectrum and best penetration should be used

PROFILAKSI dengan ANTIBAKTERIAL

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BEDAH - Bersih; infeksi rate < 2%- Bersih terkontaminasi: < 10% - Terkontaminasi: + 20%- Kotor: + 40%

Inflammatory

Inflammation

Triggered by tissue damage due to infection, heat, wound, etc.

Four Major Symptoms of Inflammation:1. Redness2. Pain3. Heat4. SwellingMay also observe:5. Loss of function

Nyeri inflamasi Pelepasan substansi kimia dan enzim (mediator) yang mempengaruhi aktivitas dan sensitifitas neuron

Akibatnya Kenaikan aktivitas nociceptor Hiperalgesia Edema neurogenik

Vascular Changes in InflammationMediators of blood flow and vascular

permeability changes- vasoactive amines (histamine, serotonin, 5-

hydroxytryptamine)- vasoactive peptides (bradykinin, interleukin 1)- vasoactive lipids (prostaglandins, leukotrienes)

Mediators of leukocyte chemotaxis- leukotriene B4- Eosinophil chemotactic factor of anaphylaxis

The anti-inflammatory Drugs

Vasoactive lipids (prostaglandins, leukotrienes)NSAIDsSAID

Pathway OverviewLinoleic acid

Thromboxane A2 synthase

LipoxygenaseArachidonic acid

Prostaglandin H2 synthase

Prostaglandins (PG) Leukotrienes (LT)

Thromboxanes (TXA)

Anti-inflammatory steroidsGlucocorticoids

NSAIDsaspirin

NSAIDsDazoxiben

NSAIDsBenoxaprofen

Zileuton

Pathway Details

Phospholipase A2(or PLC)

Membrane phospholipids

Cyclooxygenase O2

Arachidonic acid

PGG2

PGH2

PG hydroperoxidase 2GSHGSSG

NSAIDS (aspirin)

Anti-inflammatory steroidsGlucocorticoids

(mediated by lipocortin-Ca2+)

IL-1RIL-1 (inflammation)

PGI2 (PC) PGE2

PGI2 synthase PGE2 synthasePGD2

PGF2a

PGD2 synthase

PGF2synthase

PGH2 synthase LTD4

LTE4

LTB4 LTC4

Glutathione S-transferase

LTA4

TXA2TXA2 synthasePGJ2

Differential Actions of Cyclooxygenases

NSAIDs

COX1Constitutive

COX2InducibleInflammatory

Endothelial integrityVascular patencyGastric mucosal

integrityBronchodilationRenal functionPlatelet function

Inflammation

Unwanted side-effects

Therapeutic anti-inflammatory effects

PGE2PGF2aProteases

PGI2

PGE2TXA2

Housekeeping

Indomethacin , sulindacMeclofenamate, ibuprofencelecoxib, diclofenac, rofecoxib, lumiracoxib, and etoricoxib

AlprostadilMisoprostolmifepristone

Latanoprost

Prostacyclin (PGI2epoprostenol)

Antileukotriene drugs zileuton, zafirlukast, and montelukast

NSAIDs (non-steroidal antipyretic and antiinflammatory drugs)

Most drugs have three major effects:- antipyretic (lowering a raised, not normal temperature) - due to a

decrease in PGE2, which is generated in response to inflammatory proteins and is responsible for elevating the hypothalamic set-point for temperature control

- analgesic (reduction of certain sorts of pain) - decrease PGs generation, relief of headache due to decreased PGs-mediated vasodilatation

- anti-inflammatory (modification of the inflammatory reaction) - decrease in PGE2 and PGI2 »»» less vasodilatation, less oedema

Not all NSAIDs are equally potent in each of these actions.

Classical prototypic compounds include:

1. Salicylates; aspirin, Diflunisal 2. Para-aminophenols; acetaminophen 3. Indoles; indomethacin, sulindac, Tolmetin 4. Aryl propionic acids; ibuprofen, fenoprofen, n

aproxen, ketoprofen 5. Fenamates; mefenamic acid, meclofenamate 6. Pyrazolon derivatives; phenylbutazone, oxyph

enbutazone 7. Oxicams, Piroxicam , Meloxicam 8. Diclovenac, Ketorolac 9. Tolmetin, Nabumetone, Nimesulid 10. COX 2 selective: celecoxib and valdecoxib

Anti-inflammatory steroid

Pathway Details

Phospholipase A2(or PLC)

Membrane phospholipids

Cyclooxygenase O2

Arachidonic acid

PGG2

PGH2

PG hydroperoxidase 2GSHGSSG

NSAIDS (aspirin)

Anti-inflammatory steroidsGlucocorticoids

(mediated by lipocortin-Ca2+)

IL-1RIL-1 (inflammation)

PGI2 (PC) PGE2

PGI2 synthase PGE2 synthasePGD2

PGF2a

PGD2 synthase

PGF2synthase

PGH2 synthase LTD4

LTE4

LTB4 LTC4

Glutathione S-transferase

LTA4

TXA2TXA2 synthasePGJ2

Corticosteroids may regulate gene expression in several ways

Figure 14-3Anti-inflammatory effects of corticosteroids

Clinical uses

NSAID - Three major effects antipyretic, analgesic , antiinflammatory - Responses to these drugs and dose at which they are effective vary considerably from patient to patient - Treatment arthriitis rotator cuff tendinitis, plantar fascitis , tenosynovitis.etc - Indomethasin heterotropic ossification - Side effects gastrointestinal and platelet dysfunction

Clinical uses

COX-2 - New anti-inflamatory drugs , treating patient with out the untoward side effects of gastrointestinal and platelet dysfunction

Corticosteroids - Corticosteroid injections can be administered in an intraarticular, intrabursal and intratendon sheath fashion - Side effect s rupture of tendon or ligament, osteoporosis or AVN

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