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

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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

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Macrolides – derived naturally from Steptomyces

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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

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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

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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

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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

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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

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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

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Drug-drug interactions

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

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Allergy

 Normal hypersensitivity reaction symptoms  Erythromycin

 Cholestatic hepatitis

 Telithromycin

 Ketolide  Can be used in macrolide resistant strains

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Fluoroquinolones – synthetic

antibiotics

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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

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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

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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

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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

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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

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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

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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)

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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.

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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

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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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Questions

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