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35 Cards in this Set
- Front
- Back
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First member of the macrolide class
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Erythromycin
(others in class also end in -mycin) |
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What is the mechanism of action for macrolides?
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- inhibit bacterial protein synthesis by binding to 50S ribosomal subunit
- act at the peptide translocation center (in the subunit) and block elongation of the peptide - typically gram + organisms |
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Macrolides: static or cidal?
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Bacteriostatic!
- The bacteria will go back to doing their replication thing when macrolides go away |
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Three names of specific macrolides
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- erythromycin
- clarithromycin - azithromycin |
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What is the mechanism of resistance for MLSb?
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- the organism will make methylase that acts at the site on the 50s ribosome where the drugs want to bind
- Macrolide, Lincosamide, Streptogramin affected (MLSb) - prevents binding of the drug and good resistance results |
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Why should you not administer clindamycin and macrolides together?
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- they both bind to (basically) the same site on the 50s ribosome so if they are given together there will be competition for binding at that site
- will get decreased efficacy of drugs |
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Describe M resistance (to macrolides)
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- via expression of mefA gene, bugs are able to increase EFFLUX of macrolides out of the cell
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How is erythromycin able to induce resistance to other macrolides and clindamycin?
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- erythromycin induces expression of the methylase gene that encodes the enzyme that will bind to the site where these drugs try to attach
- when erythromycin binds to the 50s subunit of the ribosome there is a conformational change in mRNA which allows for the methylase start site to be available for translation - Resistance is PERSISTANT! |
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Absorption of macrolides
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oral (with varying bioavailability)
- erythromycin needs to be coated, though, to avoid destruction in stomach |
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Distribution of macrolides
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extensive in tissues and fluids
NOT CSF |
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What has the half life of azithromycin allowed for in dosing considerations?
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azithromycin has a half life of greater than 40 hours so you can do short dosing
- think of a Z pack (2 pills, then 1 pill next 4 days) |
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Excretion of macrolides
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bile
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Adverse effects of macrolides
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- GI irritation (mostly for erythromycin)
- transient deafness (when renally / hepatically impaired) - hypersensitivity reactions |
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What hypersensitivity reaction should you consider when giving a patient erythromycin estolate?
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- Cholestatic Hepatitis
(actually you wouldn't consider anything since this drug isn't for sale in the US anymore.... so probably don't use it) |
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What drug interactions must you consider when administering erythromycin?
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- P450!!!!!!!!!
- erythro can decrease P450 metabolism of other drugs like carbamezepine and cyclosporine - if patient is on terfenadine; the levels can actually rise and cause fatal cardiac arrhythmia |
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Describe the interaction between terfenadine and erythromycin
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- terfenadine requires p450 for activation
- when given with erythromycin; p450 inhibited - terfenadine levels rise - can lead to fatal cardiac arrhythmias (don't have to worry about this too much anymore.... allegra works as active terfenadine and doesn't require p450 metabolism) |
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Clinical uses of macrolides
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- atypical pneumonias (mycoplasma, chlamydia, legionella)
- STDs (chlamydia) - gram + cocci (if pts allergic to penicillin, strep infection) - mycobacterium avium (with clarithro and azithro) Use this drug for infections where you need to get across cell membranes and get to the intracellular stuff |
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What is the mechanism of action for tetracyclines?
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- tetracyclines will inhibit bacterial protein synthesis
- binds to 30S subunit - inhibits binding of aatRNAs - it is bacteriostatic - when first introduced had broad spectrum activity |
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What is the difference in the mechanism of action for tetracyclines and tigecycline?
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Tigecycline (a tetracycline) will still bind to the 30S subunit, but it binds stronger than the other tetracyclines
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What are the main mechanisms of resistance to tetracyclines?
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- increased efflux of drug from bug
- decreased active transport / penetration of drug into bug - protection proteins can bind to the ribosome and keep the drug from binding |
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Why is tigecycline not as susceptible to resistance?
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- decreased affinity for efflux pumps (because of structure change)
- long group allows for tighter binding to ribosome; can out compete protection proteins |
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Absorption of tetracyclines
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the oral absorption is variable and is impaired by cations
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Distribution of tetracyclines
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the volume of distribution can actually be greater than body water (indicating sequestration, probably in the liver)
low concentrations in the CSF |
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metabolism of tetracyclines
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in liver
variable half life: 6-16 hours |
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excretion of tetracyclines
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mostly renal, some hepatic
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If a patient is experiencing renal problems (maybe renal failure), which two tetracyclines would you want to prescribe and why?
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- doxycycline and minocycline
- because they are eliminated hepatically rather than renally |
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How is tigecycline absorbed?
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IV ONLY!!!!
(no oral absorption) |
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Distrubution of tigecycline
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well distrubuted
also has a large volume of distribution (Greater than body water) and will achieve high concentrations in respiratory tissues |
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metabolism of tigecycline
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little bit in liver
has a LONG half life that increases with multiple dosing (t1/2 = 27 hours +) |
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excretion of tigecycline
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bile, renal, some hepatic
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Clinical uses of tetracyclines
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- not so great at broad spectrum activity anymore because of resistance =(
Can use for: - lyme disease - chlamydia - acne |
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clinical uses of tigecycline
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- complicated skin or intra-abdominal infections
- used for drug-resistant bugs ONLY USE TIGECYCLINE FOR RESISTANT INFECTIONS NOT SENSITIVE TO OTHER DRUGS!!! - can be used for MRSA, E. faecium, E. coli |
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adverse effects of tigecycline
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- GI
- hypertension, CNS, hematologic - rare pancreatitis and hepatotoxicity |
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adverse effects of tetracyclines
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- GI irritation
- has effect on calcifying tissues (because it can bind to divalent cations) bone growth, tooth discoloration - hepatic / nephro toxicity - superinfections are common CI: pregnant or nursing women, kids under 8 |
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contraindications for tetracyclines
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- pregnant, nursing women
- kids under 8 (because of effects on calcifying tissues) |
