DWITIYANTI,M.Farm.,Apt.

AMINOGLYCOSIDES

MODES OF ANTIBACTERIAL ACTION

 Toxicity (in contrast to antibacterial activity)
depends on a critical plasma concentration and
on that time such a level is exceeded
 Time above such threshold is shorter with
single large dose
 Basis for once-daily dosing protocols
AMINOGLYCOSIDES
PHARMACOKINETICS
 Structurally related amino sugars
attached by glycosidic linkages
 Polar compounds
 Not absorbed orally
AMINOGLYCOSIDES
PHARMACOKINETICS
 Given intramuscularly or intravenously
for systemic effects
 Limited tissue penetration
 Do not readily cross the blood-brain
barrier
AMINOGLYCOSIDES
PHARMACOKINETICS
 Major mode of excretion
 Glomerular filtration
 Plasma levels are affected by changes
in renal function
AMINOGLYCOSIDES
PHARMACOKINETICS
 Excretion is directly proportional to
creatinine clearance
 With normal renal function, elimination
half-life is 2-3 h
AMINOGLYCOSIDES
PHARMACOKINETICS
 Dosage adjustment must be made in
renal insufficiency to avoid toxic accumulation
 Monitoring plasma levels is needed for
safe and effective dosage selection and
adjustment
AMINOGLYCOSIDES
PHARMACOKINETICS
 For traditional dosing regimens
 2 or 3 times daily
 Peak serum levels
 Measured at 30-60 minutes after
administration
 Trough serum levels
 Measured just before the next dose
Mekanisme kerja aminoglikosida
 Difusi melalui kanal air masuk ke dalam rg
periplasmik
 Masuk ke dalam sel
 Aminoglikosida terikat ribosom 30 S.
 Menghambat sintesa protein
 Kerusakan membran sitoplasma.
 Kmatian sel
 Miss reading kode genetik
 Terganggunya sintesis protein
Tabel 1. ANTIBIOTIK AMINOGLIKOSID
Struktur Aminoglikosida
Spektrum aktifitas Aminoglycosida
 Gram positive Aerobs
hampir semua S.aureus and coagulase negative staph
viridans streptococci; enterococcus sp
 Gram negatif Aerobes (tidak streptomycin)
E.coli, K.pneumonia,Proteus sp
pseudomonas aeroginosa
 Mycobacteria
tuberculosis, streptomycin
atypical-streptomycin or amikacin
Indication
 TBC
 Infeksi traktus uranerius kronik
 Vibrio cholerae
Effect
 Ototoksisitas
 Nefrotoksik
 Paralisis neoro muskuler
 alergi
TOXICITY

A. OTOTOXICITY
 Auditory or vestibular damage (or both)
maybe irreversible
 Auditory impairment
- Amikacin and kanamycin
 Vestibular dysfunction
- Gentamicin and tobramycin
TOXICITY

A. OTOTOXICITY
 Risk is proportionate to the plasma
levels
 High if dosage is not modified in renal
dysfunction
 Increased with the use of loop diuretics
 Contraindicated in pregnancy
TOXICITY
B. NEPHROTOXICITY
 Acute tubular necrosis
 Reversible
 Most nephrotoxic
 Gentamicin and tobramycin
TOXICITY
B. NEPHROTOXICITY
 More common in elderly patients
 Patients concurrently receiving
 Amphotericin B
 Cephalosporins
 Vancomycin
AMINOGLYCOSIDES

TOXICITY
C. NEUROMUSCULAR BLOCKADE
 Rare
 Curare-like block may occur at high doses
 Respiratory paralysis
 Reversible
TOXICITY
C. NEUROMUSCULAR BLOCKADE
 Treatment
 Calcium
 Neostigmine
 Ventilatory support
AMINOGLYCOSIDES

TOXICITY
D. SKIN REACTIONS
 Neomycin
 Allergic skin reactions like contact
dermatitis
Makrolida
 Spektrum kerja : bakteriostatik ,terutama gram +
 Golongan makrolida : Eritromisin, Klaritromisin,
Azitromisin.
 Indikasi : Infeksi saluran pernafasan , Pneumonia
mikoplasma, sifilis (triponema polidum)
Diphtheriae, Infeksi klamedia.
 Efeksamping : Gangguan gastrointestinal, ikterus
kolestatik, ototoksisitas (sementara),
Kontraindikasi : gangguan fungsi hati
 Obat pilihan pengganti penisilin.
Makrolida
 Erytromosin secara alamiah macrolide adalah derivat
dari streptomycin erythreus
masalah :
1. labilitas asam
2. spektrum asam
3. kecil intolerans saluran pencernaan
4. eliminasi waktu paruh pendek
makrolida
 Derivat secara struktural termasuk clarithromycin dan
azitromycin :
1. Spektrum aktifitas luas
2. Biovaibilitas lebih baik, penetrasi ke jaringan lebih
baik, waktu paruh lebih panjang
3. Tolerabilitas lebih baik
Struktur Makrolida
 Erytromycin
Struktur Makrolida
 Clarithromycin Azitromycin
Mekanisme Kerja
 Menghambat sintesa protein oleh mengikat 50S
ribosomal subunit secara reversibel
- suppressi dari RNA dependent sintesa protein
 Macrolida secara khusus mempunyai aktifitas
bacteriostatic, tetapi dapat bactericidal bila dalam
konsentrasi tinggi terhadap organisme susceptible.
 Time- dependent activity
Spektrum aktifitas makrolida
 Gram positive aerobes
- erytromycin memberikan aktifitas terbaik.
Clarithro > erytro > azitro

 Gram negative aerobes

- macrolida baru mempunyai aktifitas lebih baik
Azitro > claritho > erythro
FLUOROQUINOLONES
 Grup dari antibiotika sintetik dikembangkan sebagai
respon mengembangkan resistensi
 Obat antibiotika yang tersedia sekarang adalah secara
struktur derivat dari nalidixic acid
Fluorinated quinolones (FQ)
 Memberikan pengobatan mayor yang sdh maju :
1. Spektrum aktifitas yang luas
2. Biovaibilitas baik, penetrasi jaringan, waktu paruh
memanjang
3. Secara keseluruhan aman
Mechanism of Action
 Dual MOA:
1. Inhibition of bacterial DNA Gyrase (Topoisomerase II)
1. Formation of quinolone-DNA-Gyrase complex
2. Induced cleavage of DNA
2. Inhibition of bacterial Topoisomerase IV
1. Mechanism poorly understood

Mechanism of DNA Gyrase

FQ yang tersedia
 FQ lama :
1. Norfloxacin (lexinor, pyrilox,urobacid) –PO
2. Ciprofloxacin (ciproxin, baquinor) –PO, IV

 FQ baru :
1. Levofloxacin (levocin,Cravox,cravit) –PO, IV
2. Gatifloxacin (tequin) – PO, IV
3. Mexifloxacin (avelox) – PO, IV
Ciprofloxacin
 Administration [Usual Dosage]: IV, PO [500 – 750 mg q 8-12h]
 Spectrum: Gram- aerobic rods, and Legionella pneumophila, and other
atypicals. Poor activity against Strep. pneumoniae.
 Indications:
-- Nosocomial pneumonia
-- Intra-abdominal infections
 Anthrax exposure and prophylaxis
 Unique Qualities:
 Binds divalent cations (i.e. Ca & Mg) which decreases absorption
-- Increased effects of warfarin
 ADRs
 arrhythmias
 Nausea, GI upset
 Interstitial nephritis
Levofloxacin
 Brand Name: Levaquin®, Quixin®
 Administration [Usual Dosage]: IV, PO and ophthalmic
[500-750 mg q24h]
 Spectrum: Gram-, Gram+ (S. aureus including MRSA & S.
pneumoniae) and Legionella pneumophila, atypical resp.
pathogens,
Mycobacterium tuberculosis
 Indications:
 Chronic bronchitis and CAP
-- Nosocomial pneumonia
 Intra-abdominal infections
ADRs
 Blood glucose disturbances in DM patients
 Nausea, GI
 Interstitial nephritis
Spektrum aktifitas FQ
 Gram positif
- FQ lama aktifitas terbatas
- FQ baru potensi lebih luas

 Gram Negatif
- semua FQ mempunyai aktifitas sangat baik
Cipro = levo > gati > moxi
WASSALAMU ALAIKUM W.W.