Term
|
Definition
1. Erythromycin
2. Clarithromycin
3. Azithromycin |
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Term
| What is the MOA of macrolides? |
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Definition
| 1. Bind reversibly to 50S of the bacterial ribosomal subunit, inhibiting translocation of the growing peptide chain and therefore inhibiting protein synthesis |
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Term
| Are macrolides bacteriocidal or static? |
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Definition
Static
(May be cidal for atypicals bc all bacteria needs ribosomes to make proteins) |
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Term
| What are the mechanism of resistance? |
|
Definition
1. Induction of efflux pumps (mrsA, mefA, mefB)
2. Methylase enzyme (ermA, ermB, ermC)
3. Esterase enzyme (hydrolyzes the lactone ring, esp erythromycin) or Phosphorylase enzyme for all macrolides
4. Chromosomal mutation of 50S ribsome (seen in gram pos bacteria) |
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Term
| If resistance develops, are all macrolides useless? |
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Definition
| Yes, if resistance develops to a given macrolide, the bacteria will be resistant to ALL macrolides |
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Term
| Resistance is more commonly seen in what type of organisms? |
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Definition
| Resistance to macrolides is more common in PCN-resistant organisms |
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Term
| What can't macrolides be used in? |
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Definition
| Macrolides can't be used to treat UTI's bc of low concentrations present in the urine but may treat tissue specific UTI and STDs |
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Term
| Which macrolide is available IV? |
|
Definition
| Erythromycin, Azithromycin |
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Term
| What are the half lives of the macrolides? |
|
Definition
1. Erythromycin: 1-1.5 hr
2. Clarithromycin: 3-7 hrs
3. Azithromycin: 40-60 hrs |
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Term
| What are the potential for interactions? |
|
Definition
1. Erythromycin - high
2. Clarithromycin - high
3. Azithromycin - low |
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Term
| Which macrolide is affected by food? |
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Definition
|
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Term
| What are the FDA Pregnancy Category? |
|
Definition
1. Erythromycin - B
2. Clarithromycin - C
3. Azithromycin - B |
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Term
| What organism is erythromycin isolated from? |
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Definition
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Term
| What is the spectrum of erythromycin? |
|
Definition
THINK Gram Positive cocci and bacilli
- Mainly staph, strep, corynebacterium diphtheriae, clostridium perfringens
- Also C. trachomatis, E. histolytica, L. monocytogenes, B. burgdorferi, M. pneumoniae, T. pallidum, U. urealyticum
- Agonist of motilin R in the GI tract may be used to promote GI motility |
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Term
| Describe the bioavailability of erythromycin. |
|
Definition
Erythromycin has low absorption and acid stability - by taking on an empty stomach, can decrease residual time in the stomach and allow for increase absorption in the upper small intestine
- Most PO forms are enteric coated tablets or granules to reduce acid degradation
- Various salt forms make erythromycin more acid-stable and increase absorption |
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Term
| What are the IV forms of erythromycin? |
|
Definition
1. Lactobionate
2. Glyceptate |
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Term
| Describe the distribution of erythromycin into tissues. |
|
Definition
Decent distribution into tissues:
- Levels in prostate can be 1/3 higher than blood
- Little to no CSF distribution
- Low conc in middle ear fluid
- Drug levels in breast milk are 50% of blood and will cross the placenta in low amounts |
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Term
| What does erythromycin have DDI with? |
|
Definition
| Since it is a CYP3A4 substrate and inhibitor, basically DDI with every drug involving CYP3A4 |
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|
Term
| How is erythromycin excreted? |
|
Definition
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Term
| What are the SE of erythromycin? |
|
Definition
1. GI intolerance
2. Jaundice and hepatotoxicity
3. Rash
4. Interstitial nephritis
5. Dose-related ototoxicity
6. Prolonged QT interval |
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|
Term
| What is the dosing of erythromycin? |
|
Definition
| 0.5-1 gram IV q6hr over 60 min (may cause phlebitis so ice may help) and increased risk of torsades de pointes (infuse at less than 15 mg/min) |
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Term
|
Definition
1. It is a combination of 200 erythromycin and 600 sulfisoxazole per 5 mL)
- Not given if under 2 yo
- Given TID or QID for 10 days |
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Term
| What is the maximum dose of erythromycin? |
|
Definition
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Term
| What is the brand name of Clarithromycin? |
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Definition
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Term
| What is the spectrum of Clarithromycin? |
|
Definition
Basically the same as erythromycin but more activity against gram pos (H. influenza, M. catarrhalis, CAP-causing atypicals, and MAC.
- Also can be used to treat mycobactrium leprae, toxoplasmosis and cryptosporidium plasmodium |
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Term
| When is Clarithromycin used? |
|
Definition
| For CAP, COPD exacerbations, bronchitis, tonsilitis, OM, STDs, MAC (only as combo with ethambutol +/- rifampin), H. pylori |
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Term
| What is the bioavailability of clarithromycin? |
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Definition
| - Improved absorption as compared to erythromycin (regular release without regards to meals, XL given with food to increase absorption) |
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Term
| How effective is the active metabolite of clarithromycin? |
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Definition
| Active metabolite (14-hydroxyclarithromycin) has 2x the activity of the parent against H. influenza but has 4-7x less activity against MAC |
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Term
| Describe the distribution of clarithromycin. |
|
Definition
Extensive tissue distribution.
- High conc in lung tissue and alveolar macrophages
- Conc in middle ear are 50% higher than in blood |
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Term
| Do you need to dose adjust for clarithromycin? |
|
Definition
| Yes if severe renal impairment |
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|
Term
| What are the SE of clarithromycin? |
|
Definition
1. Fewer GI ADRs in adults
2. Rare cases of rash, hepatic dysfunction, CNS changes, QT prolongation, interstitial nephritis |
|
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Term
|
Definition
Biaxin 500mg BID or Biaxin XL 1000 mg QD
(Max: 1g/day, decrease dose by 50% if CrCl<30 mL/min) |
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|
Term
| What is the brand name of azithromycin? |
|
Definition
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Term
| How is azithromycin different from erythromycin? |
|
Definition
| N substituted into lactone ring improving acid degradation resistance |
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Term
| What is the spectrum of activity of azithromycin? |
|
Definition
| Less gram (+) coverage as compared to erythromycin, increased gram (-) and atypical coverage, MAC coverage (similar to clarithromycin), toxoplasmosis, crptosporidium |
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Term
| When do you see azithromycin used? |
|
Definition
| Peds, PCN allergic patients, STDs, MAC, pulmonary |
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Term
| How should you take Azithromycin? |
|
Definition
| Take on an empty stomach for better absorption but if there are GI problems, then take it with food |
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Term
| When taking azithromycin, what should be avoided? |
|
Definition
| Avoid Mg and Al containing products within 2-4 hrs of admin |
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|
Term
| Describe the distribution of azithromycin |
|
Definition
| HUGE distribution in tissue as azithromycin is rapidly taken up by macrophages and fibroblasts (does not enter CSF) |
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Term
| What are the DDI of azithromycin? |
|
Definition
| Limited CYP interactions, thus better for HIV patients |
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Term
| What are the SE of azithromycin? |
|
Definition
1. GI effects typically less than erythro/clarithromycin (D/N/V)
2. GI SE are noted with higher doses Tri-Pak and Z-max
3. Rare LFT increases and hepatitis in post marketing surveillance
4. Ototoxicity is rare but does occur |
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Term
| What is the dosing for CAP for azithromycin? |
|
Definition
| Z Pak 500 mg day 1, 250mg QD days 2-5 |
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Term
| How do you treat bronchitis or less serious CAP with azithromycin? |
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Definition
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Term
| How do you treat sinusitis, mild-moderate bronchitis, & STDs with azithromycin? |
|
Definition
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Term
| How do you treat MAC and toxo with azithromycin? |
|
Definition
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