Antibiotics Macrolides/Fluoroquinolones Danita Dee Narciso Pharm D - PowerPoint PPT Presentation

UH Hilo School of Nursing NURS 203 General Pharmacology Antibiotics Macrolides/Fluoroquinolones Danita Dee Narciso Pharm D 1

2 Objectives  Become familiar with antibiotics that are commonly used and recognize areas of potential practical conflicts  Recognize antibiotics that have interactions with other medications or illnesses  Learn how to monitor for and adjust for changes in drug levels due to interactions with antibiotics

3 Macrolides – derived naturally from Steptomyces

4 Macrolides  Bactericidal vs. bacteriostatic  MOA  Inhibits RNA synthesis by binding to 50s subunit  Time dependent killing  The bacteria’s defense  Methylation mutation of bacterial RNA  Production of drug inactivating enzymes  Efflux pumps/decreased membrane permeability

5 Erythromycin  Spectrum similar to PCN  Gram positive organisms  But also atypical bacteria  Drug of choice for corynebacterial infections  Respiratory  Neonatal  Ocular  Genital chlamydial  Community acquired pneumonia (CAP)  Dosed Q 6 hours due to short half life  Not first line  Group A streptococci and pneumococci organisms  Inhibits CYP 3A4 enzymes & ADRs

6 Clarithromycin  Spectrum almost identical to erythromycin  Increased Mycobacterium avium activity and Gram negatives  Longer half life  BID dosing  Lower incidence of ADRs when compared to erythromycin  Inhibits CYP 3A4 enzymes

7 Azithromycin  Spectrum  More closely related to that of clarithromycin  Increased activity over H influenzae but decreased over Gram positives  Pharmacokinetic differences  Distribution  Half-life  Does not inhibit CYP enzymes

8 Macrolide - Kinetics  Absorption  Acid sensitive, delayed by food  Distribution  Most tissues  CSF  Metabolism  Liver  Kidney as metabolite and parent compound – clarithromycin  Excreted in feces and urine

9 Adverse drug reactions  GI disturbances – up to 33%  Nausea, diarrhea, vomiting, dyspepsia  Dermatologic  Rash  Fever  QTc prolongation  Cholestatic hepatitis - rare  Ototoxicity – high dose erythromycin  Bad taste – Clarithromycin

10 Drug-drug interactions  Statins (L.A.S)  Carbamazepine  Warfarin (R)  CCBs  Buspirone  Methadone and oxycodone  Cyclosporine  PDE5 inhibitors  Benzodiazepines (not the L.O.T)

11 Allergy  Normal hypersensitivity reaction symptoms  Erythromycin  Cholestatic hepatitis  Telithromycin  Ketolide  Can be used in macrolide resistant strains

12 Fluoroquinolones – synthetic antibiotics

13 Fluoroquinolones  Bactericidal vs. bacteriostatic  MOA  Inhibit DNA gyrase and topoisomerase IV  Concentration dependent killing  The bacteria’s defense (Resistance)  Point mutations  Membrane permeability  Acetyltransferase  Efflux pumps

14 First generation  Nalidixic acid & norfloxacin  Not active against Gram positive bacteria  Poor oral absorption and tissue penetration  May still be useful for:  UTIs – E.coli, Proteus, Shigella, Enterobacter, Klebsiella

15 Second generation  Ciprofloxacin & ofloxacin  Gram negative coverage  Even pseudomonas  Limited Gram positive coverage  Limited atypical coverage  Used for:  UTI, skin & soft tissue inf, bacterial diarrhea, bone, joint, intra-abdominal, and respiratory infections  Resistance

16 Third generation  Levofloxacin & gemifloxacin (Respiratory Fluoroquinolones)  Less active against Gram negative  Greater Gram positive coverage  Including some MRSA stands  Used for:  UTI, skin & soft tissue inf, bacterial diarrhea, bone, joint, intra-abdominal, and respiratory infections  Upper and lower respiratory tract – increased Gram positive

17 Fourth generation  Moifloxacin  Even greater Gram positive coverage  Less coverage against pseudomonas and enterobacter  May also be considered a “Respiratory Fluoroquinolone”  Used for:  UTI, skin & soft tissue inf, bacterial diarrhea, bone, joint, intra-abdominal, and respiratory infections  Upper and lower respiratory tract – increased Gram positive

18 Fluoroquinolone - Kinetics  Absorption  Well absorbed  Impaired by antacids  Distribution  Body fluids and tissues  Half lives 3-10 hours  Metabolism  Kidney – most  Liver - moxifloxacin  Excretion  Urine  Feces and biliary excretion – moxifloxacin

19 Adverse drug reactions  GI disturbances – 5%  Nausea, diarrhea, vomiting, & dyspepsia  Headache  CNS  Agitation, anxiety, seizure, confusion, insomnia, dizziness, panic attack, paranoia, hallucinations, and toxic psychosis  Peripheral neuropathy – rare  Irreversible  Hepatotoxicity – hepatic failure, cholestatic hepatitis (levo, cipro, moxi)  Cardiovascular  Prolong QTc interval (moxifloxacin > ciprofloxacin)

20 Notable  Dermatologic  Severe hypersensitivity reactions  Some of the older generations will cause photo toxicity  A dermatologic reaction to a fluoroquinolone can make a patient more sensitive to more severe adverse drug reactions.

21 Fluoroquinolones  Black Box Warning  Increased likelihood of tendon rupture  Most at risk  60 years of age or greater  Also taking systemic corticosteroids  Transplant patients (kidney, heart, or lungs)  Stop immediately if pain, swelling, inflammation or rupture

22 Drug-drug interactions  Antacids or supplements  Ca, Fe, Mg, Al, Zn  CYP1A2 inhibition  Ciprofloxacin  Caffeine, theophylline, cyclosporine, warfarin, duloxetine, clozapine  NSAIDs  Benzodiazepine-dependent patients  Withdrawal  Super infection  MRSA, C diff

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