4. Mechanism of Action:
How theyโre transported?
They cross the outer membrane and enter the periplasmic space through
aqueous channels formed porin proteins.These drugs are actively
transported through the cell membrane by an oxygen-dependent process
Mechanism of action?
They irreversibly bind to the 30S ribosomal subunit and inhibit the
protein synthesis by blocking the formation of initiation complex, inhibit
translocation step, misread mRNA
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5. Resistance
๏ต Block the entry into the cell
๏ต Receptor on 30S ribosome deleted from the bacteria
๏ตProduction of transferase enzyme which
inactivate the aminoglycosdie
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6. Pharmakinetics
๏ต Penetrate most of body fluids well except for CSF, they are highly
concentrated in the renal cortex and endolymph of the inner ear
which could account for their nephrotoxicity and ototoxicity
๏ต They must be given IV or IM because they are not absorbed after oral
administration
๏ต Not well GI absorption, polar
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7. Administration
๏ตSingle dose is preferred
1. Concentration-dependent killing
2. Post-antibiotic effect (which can last
for several hours)
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9. Therapeutic Use
๏ต Ecoli, Klebsiella, Pseudomonas aeruginosa & Enterobacter (PEEK)
๏ต They donโt cover the anaerobes because oxidative metabolism is
required for the uptake of these drugs.
๏ต Usually they are coadiministered with B-lactams to extend the
spectrum.
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Streptomycin is very
effective against
enterococcal carditis
in combination with
pencillins
10. Toxicity
๏ต Ototoxicity
Auditory may occur with any aminoglycoside and may be irreversible itโs
more likely with amikacin, ototoxicity is proportional to the plasma level
the toxicity is increased by the use of loop diuretics. It is
contraindicated in pregnancy.
๏ต Nephrotoxicity
Acute tubualr necrosis it is often reversible
๏ต Neuromuscular blockage at high doses (curare-like
effect)
Resulting is respiratory paralysis
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11. Preganncy
๏ต Catigoury Dโ there is a + evidence of human
fetal risk based on advese reaction but
poteinal benfiits may warrant the usuage of
the drug
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12. Clinical use
๏ต Multi-drug resisitant TB
๏ต Aerobic gram โ bacteria
๏ต Always with b-lactum combiniation for
1. Synergism
2. Extend to gram +
3. Bacterocidical in endocarditis
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13. Granulocyte colony-stimulating factor
๏ต Filgrastim (G-CSF) stimulate the production and function of
neutrophils it also mobilize hematopoietic stem cells (ie, increase
their concentration in peripheral blood)
๏ต stimulates proliferation and differentiation of progenitors already
committed to the neutrophil lineage.
๏ต It also activates the phagocytic activity of mature neutrophils and
prolongs their survival in the circulation.
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14. Clinical use
๏ต Used to accelerate the recovery of neutrophils after
๏ง cancer chemotherapy
๏ง aplastic anemia
๏ง congenital and cyclic neutropenia
๏ง Autologous stem cell transplantation
๏ง multiple myeloma
๏ต Given IV/Subcutaneous
๏ต It can cause bone pain
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15. Qโs
๏ต Regarding the mechanism of action of aminoglycosides,
the drugs
a) Are bacteriostatic
b) Bind to 50S ribosome subunit
c) Cause misreading of the codon on the mRNA template
d) Stabilize polysomes
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16. Amphotericin B
๏ต Is used for fungal systemic infections (flucytosin is also used)
Itโs a polyene macrolide which is poorly absorbed (IV)
Mechanism of action: bind to the fungal ergosterol on the cell
membrane and forms pores or channels within the membrane leading to
electrolyte leak out which results in the cell death
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17. Clinical usage
๏ต Candidia, cryptococcus, aspergillas
๏ต For fungal meningitis itโs giver intrathecally
๏ต Topical for occular and bladder infections
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18. Toxicity (Infusion reaction and
cumulative toxicity)
๏ต Infusion reaction
Fever, chills, spasm, headache and vomiting
Usually test by 1 mg IV to know the severity
To ameloirate it
๏ต Slow the infusion rate
๏ต Decrease the daily dose
๏ต Give antihistamin and steroids
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19. Cumulative toxicity
๏ต Renal impairment (renal tubular acidosis, K and
Mg wasting)
๏ต Liver function abnormality
๏ต Anemia due to reduced erythropoitein
(hypochromatic normocytic anemia)
๏ต Seziures after IT therapy
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