Lecture 12: Aminoglycosides, Fluoroquinolones, Macrolides Flashcards
Erdman's Section
What is the Mechanism of Action for the Aminoglycosides?
- Irreversibly bind to 30s [maybe 50s] and decrease protein synthesis & mesread RNA
What are some of the Mechanisms of Resistance for the Aminoglycosides?
- Alteration in AG uptake
- Synthesis of AG modifying enzymes
- Alteration in binding [Rare]
What are the Aminoglycosides that are used?
- Gentamicin, Tobramycin, Amikacin, Streptomycin, Plazomicin
What is the Spectrum of Activity for Gram (+) for the Aminoglycosides?
- NEVER USED ALONE; always low dose with cell wall agents
- Virdian, Entercoccis [G or S], S. Aureus
MAINLY GENTAMICIN USED
Cell Wall Agents = Beta & Vanco
What is the Spectrum of Activity for the Gram (-) for the Aminoglycosides?
- A,P>T>G; NOT S
- PPPEEACKSSS
- Pseudomonas Aeruginosa [Target]
HIGH DOSES with cell wall agents
Cell Wall Agents = Beta & Vanco
What is important to know about Mycobacteria in Aminoglycosides?
- STREPTOMYCIN active aganist it
- Maybe Amikacin too
What is important to know about the Pharmacology of the Aminoglycosides?
- Highly Polar Cations = decreased oral administration
- Vd and ClCr are the main parameters
What in important about Absorption in Aminoglycosides?
- Bad oral = Good Parenteral
- DONT USE IM in critically ill
- IV is Preferred
What is important to know about Distribution in Aminoglycosides?
- In Extracellular Fluids [Ascites, Pericardial, Peritoneal, Pleural…]
- NOT CSF[even with inflammed meninges], sputum, adipose tissue
When discussing Distribution characteristics alter the Vd and Cl?
- IBW should be used when >130% IBW
- Vd is important when calulating a AG dose
- Vdnormal = 0.25; Vddehydration = 0.15-0.20; Vdedema = 0.30-0.35
Vd is HIGHER in neonates and infants
What is important to know about Elimination in Amioglycosides?
- Kidneys; so HIGH urinary conc.
- Half Life = 2.5 - 4h [increase with renal issues]
- Hemodialysis removes 30-50%
What is important to know about the dosing [Traditional & Extended] in Aminoglycosides?
- Trad: 1-2.5 mg/kg/dose [Gram (+)]
- Ext: G/T = 5-7 mg/kg daily & A = 15-25 mg/kg daily [Gram (-)]
What are the Major Clinical used for the Aminoglycosides?
- A, G, T: Good for Gram (-); Pseudomonas Aeruginosa
- G, S: Gram (+); Enterococci, Viridan, Staph
What are some of the Adverse Effects for Aminoglycosides?
- Nephrotoxicity
- Ototoxicity: 8th Cranial damage
prolonged high tough conc., 2w of treatment, renal issue for both
What are the Fluoroquinolones?
- Ciprofloxacin, Ofloxacin, Levofloxacin, Gatifloxacin, Moxifloxacin, Gemifloxacin
What is the mechanism of action for the Fluoroquinolones?
- Inhibition of DNA synthesis by binding to and inhibiting Topoisomerase [Gyrase & IV]
Conc. Dependent Bactericidal Activity
What is the difference between Gyrase and Topo IV?
- Gyrase: blocks replication fork; Gram (-)
- Topo IV: Stops DNA replication Gram (+)
What is the Mechanism of resistance for the Fluoroquinolones>
- Alteration in Binding Site
- Efflux: Enhances the transfer out
- Alteratoin of Permeability: decrease FQ in cell
What are the older and newer repiratory Fluoroquinolones?
- Old: Cipro
- New: Levo, Moxi, Gem [Maybe Dela]
All help with Strep
What is the Spectrum of Activity for the Gram (+) for the Fluoroquinolones?
- Cipro = POOR & Levo, Moxi, Dela = GOOD
- Group/Viridan, PRSP [NOT CIPRO], MSSA, MRSA [ONLY DELA]
Mainly ALL respiratory things
FQs NEVER used in S. Aureus
What is the Spectrum of Activity of the Gram (-) for the Fluoroquinolones?
- HENPECKSSS
- Pseudomonoas Aeruginosa [Cipro>Levo>Dela; NOT Moxi or Gemi] Target
How does the Fluoroquinolones act toward the Atypical Bacteria?
- Extremly active to Legionella
- One of the claim to fames
What are some important things to note about the Pharmacology of Fluoroquinolone?
- Rapid, Conc. Dependent
- AUC/MIC
- Has PAE
AUC/MIC: 30-50 S. Pneumoniae; 100-125 for Gram (-)
What is important to know about the Absorption for the Fluoroquinolones?
- ORALLY absorbed
- Bioavailability: 70-75% for Cipro and >90% for Levo/Moxi
What is important to know about the Distribution fo the Fluoroquinolones?
- Good Tissue Penetration [because of F-]: Prostate, Lung, Bronchial, Sputum, Bone
- High Urine Conc. [NOT Moxi & Gemi]
- Minimal CSF penetration
What is important to know about the Elimination of the Fluoroquinolones?
- Renal [Levo, Oflox, Gati]: Dosage Adjustments are necessary
- Hepatic [Trova, Moxi]
- Renal & Hepatic [Cipro & Dela]
- NONE ARE REMOVED DURING HEMO
What are some of the clinical uses of the Fluoroquinolones?
- CAP: all respiratorys
- Bronchitis/Sinusitis
- HAP
- UTI
- Prostatitis
- Skin Infections
What are some of the adverse effects of the Fluoroquinolones?
- GI, Neurologic
- Hepatotoxic
- OTc Prolongation
- Articular Damage: AVOID IN PREGNANCY/BREAST FEEDING
- Tendonitis
What are some of the drug interactions for the Fluoroquinolones?
- Divalent and Trivalent cations: Impair ANY absorption
- Warfarin
What is the differences in the chemical structures between Erythromycin, Azithromycin, and Clarithromycin?
- Clarith: Methoxy group on C-6
- Azithro: 15-membered ring with an Azalide
How does the structural difference between Clarithromycin and Azithromycin have advantages over Erythromycin?
- They will improve oral bioavailability, antibacterial activity, tissue penetration, prolong half life
What are the Macrolides that are used?
- Erythromycin, Clarithromycin, Azithromycin
What is the mechanism of action for the Macrolides?
- Binds to 50s during synthesis and suppresses bacterial growth
What is the Mechansim of resistacne for the Macrolides?
- Efflux Pumps: Low level resistances
- Alteration of Binding: High Level of resistance AND others that bind to 50s
- Cross reactivity among MACs
Time Dependent & Bacteriostatic
What is the Spectrum of Activity of the Gram (+) for the Macrolides?
- C>E>A [Clarith is da best]
- Group/Viridan Strep, PSSP, MSSA, Bacillus, Corynebacterium
What is the Spectrum of Activity of the Gram (-) for the Macrolides?
- A>C>E [Azith is da best; NOT enterbacteriacea
- H. Influenzae, M. Catarrhalis, Neisseria
What is the Spectrum of Activity for the Other Organism for Macrolides?
- Legionella & Mycoplasma [Azith & Clarith]
What is important to know about the Absorption of the Macrolides?
- Eryth: Bioavailability 15-45%; Some have EC so they get absorbed
- Clarith: Stable in GI
- Azith: Stable in GI
What is important to know about the Distribution of the Macrolides?
- Tissues and Cells [Except the CSF]
What is important to know about the Elimination of the Macrolides?
- Eryth: From Bile; Half Life = 1.4h; NO dosage adjustment
- Clarith: From Urine; Half Life = 3-7h; Dosage adjustment when CrCl < 30
- Azith: From Bile; Half Llife = 68h
What are some of the main clinical uses for the Macrolides?
- Repiratory Tract Infection [CAP, H. Flu, Strep Pneumo]
- STI [1g of Azith for Chalmydia]
- Mycobacterium avium Complex Infections [MACs for MAC]
What are some of the Adverse Reactions for the Macrolides?
- GI [MOST COMMON; cant take with food to help]
- Thrombophlebitis
- QT Prolongation
What are some of the drug interaction for the Macrolides?
- Eryth & Clarith inhibit P450, increases conc of the follow:
- Theophylline, Carbamazepine, valproate, Cyclosporine, Digoxin, Phenytoin, Warfarin
