Transcript TINJAUAN FARMAKOLOGI OBAT UNTUK SELF MEDICATION

Musculoskeletal System
Role of antibiotics and
antiinflammatory
Dr. Harris Tata, M,Kes., SpOT
CLINICS /
HOSPITAL
PASIENTS
DIAGNOSTIC
PROCESS
ANAMNESTIC
PHYSIC EXAMIN.
SUPPORTING :
- laboratory
- radiology
- electromedic
- ect.
THERAPEUTIC
PROCESS
KNOWLEDGE
SKILL
ATTITUDE
INFORMATION:
-RATIONAL
(evidence based)
-IRRATIONAL
(assumption,intuitive,
no data)
DEFINE THE PROBLEM
THERAPEUTIC OBJECT.
SELECTING THERPEUT.
STRATEGIES
- non-pharmacological
- pharmacological
- surgical
2
Antibiotic
VIRUS
BAKTERI
JAMUR
PARASIT
dll
INFEKSI
SISTEM BIOLOGI
TUBUH MANUSIA
SIMPTOM & SIGN
PATOLOGIS
TUMBUH dan
BERBIAK
4
Infection Musculoskeletal
Skin Infection
Cellulitis
Myositis
Osteomyelitis


Septic Arthritis
Etc


acute (subacute)
chronic
specific (eg TB)
non specific(most common)
Acute Osteomyelitis & Acute Arthritis
Organism

Gram +ve





staphylococus aureus
strep pyogen
strep pneumonie
Listeria monocytogenes (rare)
Gram -ve




haemophilus influnzae (50% < 4 y)
e .coli
pseudomonas auroginosa,
proteus mirabilis
Antibiotic
Antibiotic  Chemical molecules
produced by a microorganism that
kills or inhibits the growth of
another microorganism
Antibiotic
 Selection 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
Antibiotics
 Treatment 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 synthesis
 Penicillins,
 Cephalosporins,
 Vancomicyn,
 Bacitracin,
 Astreonam
 Imipinem.
The Cephalosporins
 Firs 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
permeability
 Polymyxin
 Mystatin
 Amphotericin
Ribosomal inhibition
 Bacteriostatic  tetracycline, chloramfenicol,
macrolides (erytromycine, clindamycin)
 Bacteriocidal  gentamycin, streptomycin,
tobramycin, amikacin, and neomycin.
Interference with transcription and
translation of bacterial DNA
 Quinolones
 Rifampin,
 Metronidazole
Antimetabolite
action
 Sulfonamid
 Dapsone
 Trimetoprin
 Para-aminosalycil
acid
Antibiotic classification base on their
spectrum activity
 No antibiotic is effective against all microbes
Principle antibiotics therapy
1.
Susceptibility testing
2. Drug concentration in blood
3.
Serum bactericidal titers
4. Route of administration
5. Monitoring of therapeutic
response
6. Clinical failure of antibiotics
therapy
1. Susceptibility testing
 The 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 administration
2. 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 administration
 Parenteral 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 therapy
Inadequate 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 situations
2. To delay resistance
3. Mixed infections
4. To achieve synergistic effects
Clinical Applications
 The role of antibiotic in orthopedic surgery is
multifold
 They 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
BEDAH
-Bersih; infeksi rate < 2%
-Bersih terkontaminasi: < 10%
-Terkontaminasi: + 20%
-Kotor: + 40%
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Inflammatory
Inflammation
 Triggered by tissue damage due to infection, heat,
wound, etc.
 Four Major Symptoms of Inflammation:
1. Redness
2. Pain
3. Heat
4. Swelling
May 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 Inflammation
 Mediators of blood flow and vascular permeability
changes
- vasoactive amines (histamine, serotonin, 5hydroxytryptamine)
- 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)
 NSAIDs
 SAID
Pathway Overview
Anti-inflammatory steroids
Glucocorticoids
NSAIDs
aspirin
Linoleic acid
NSAIDs
Benoxaprofen
Zileuton
Arachidonic acid
Lipoxygenase
Prostaglandin H2
synthase
Prostaglandins (PG)
Leukotrienes (LT)
Thromboxane A2
synthase
Thromboxanes (TXA)
NSAIDs
Dazoxiben
Pathway Details
IL-1 (inflammation)
IL-1R
Membrane phospholipids
Anti-inflammatory steroids
Glucocorticoids
(mediated by lipocortin-Ca2+)
Phospholipase A2
(or PLC)
Arachidonic acid
NSAIDS (aspirin)
O2
Cyclooxygenase
PGH2
synthase
PGG2
PG hydroperoxidase
PGJ2
PGD2
PGD2 synthase
PGI2 synthase
PGI2 (PC)
LTAGlutathione
4
Stransferase
LTB4
LTC4
LTD4
2GSH
GSSG
LTE4
TXA2 synthase
PGH2
TXA2
PGF
PGF2
synthase
PGE2 synthase
PGE2
Differential Actions of Cyclooxygenases
Unwanted sideeffects
Constitutive
COX1
NSAIDs
Inducible
Inflammatory
COX2
PGI2
PGE2
TXA2
PGE2
PGF2a
Proteases
Therapeutic antiinflammatory effects
Housekeeping
Endothelial integrity
Vascular patency
Gastric mucosal
integrity
Bronchodilation
Renal function
Platelet function
Inflammation
Indomethacin , sulindac
Meclofenamate,
ibuprofen
celecoxib, diclofenac,
rofecoxib, lumiracoxib,
and
etoricoxib
Prostacyclin (PGI2
epoprostenol)
Alprostadil
Misoprostol
mifepristone
Latanoprost
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:
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1. Salicylates; aspirin, Diflunisal
2. Para-aminophenols; acetaminophen
3. Indoles; indomethacin, sulindac, Tolmetin
4. Aryl propionic acids; ibuprofen, fenoprofen, naproxen,
ketoprofen
5. Fenamates; mefenamic acid, meclofenamate
6. Pyrazolon derivatives; phenylbutazone, oxyphenbutazo
ne
7. Oxicams, Piroxicam , Meloxicam
8. Diclovenac, Ketorolac
9. Tolmetin, Nabumetone, Nimesulid
10. COX 2 selective: celecoxib and valdecoxib
Anti-inflammatory steroid
Pathway Details
IL-1 (inflammation)
IL-1R
Membrane phospholipids
Anti-inflammatory steroids
Glucocorticoids
(mediated by lipocortin-Ca2+)
Phospholipase A2
(or PLC)
Arachidonic acid
NSAIDS (aspirin)
O2
Cyclooxygenase
PGH2
synthase
PGG2
PG hydroperoxidase
PGJ2
PGD2
PGD2 synthase
PGI2 synthase
PGI2 (PC)
LTAGlutathione
4
Stransferase
LTB4
LTC4
LTD4
2GSH
GSSG
LTE4
TXA2 synthase
PGH2
TXA2
PGF
PGF2
synthase
PGE2 synthase
PGE2
Corticosteroids may regulate gene expression in several
ways
Figure
14-3
Anti-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
Terima Kasih