Protein Synthesis Inhibitors Flashcards by Uche PM

When a drug blocks a reaction that is vital to both

the microbe and host but has greater impact on the microbe, this is referred to as _

Selective toxicity

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When the small ribosomal subunit and the first tRNA

arriving at the start codon of the mRNA, this described _

Initiation

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What is the common ribosome subunit shared by both bacterial and mammalian species that accounts for a lot of toxicity when treating with antibiotics?

70S ribosome (mitochondrial)

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What are the 3 tetracyclines provided as examples? What is their mechanisms of action? What ribosome subunit do they target?

Tetracycline
Doxycycline
Minocycline
- Bind the 30s ribosome, prevent binding of tRNA to A site

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The selective toxicity associated with the tetracyclines results from its effects on _

70S mitochondrial ribosomes

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Tetracyclines have [broad/narrow] spectrum, are more active against gram [positive/negative] and are bacteriostatic/bacteriocidal

Very broad
Positive
Bacteriostatic

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What are the 3 mechanisms by which resistance develops with the tetracyclines?

Decreased intracell. levels (e.g. increased efflux)
Enzymatic inactivation of drug
Protein expression that protects target ribosomes

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What is the route of administration of the tetracyclines?

Oral admin

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What are 2 conditions that decrease the absorption of tetracyclines?

Divalent / trivalent cations (e.g. dairy)

Increased stomach pH

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Tetracyclines have a wide distribution area. In addition to liver, spleen and bone marrow, what 3 notable areas do they accumulate in?

Bone
Dentin
Enamel of unerupted teeth

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Tetracyclines do/don’t penetrate the CNS

Tetracyclines do/don’t penetrate the placenta

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Most tetracyclines are cleared by the _ (organ). What is the 2 exceptions? How are they cleared?

Kidneys
Docycline - feces
Minocycline - liver - feces

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What are 2 major uses for the teracyclines?

Lyme disease

Acne

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What are 5 side effects associated with the tetracyclines?

GI irritation (pseudomembranous colitis)
Photosensitivity
Hepatotoxicity
Renal Toxicity 
Vestibular disturbance

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Why shouldn’t tetracyclines be given to pregnant women or children under 8?

Discolors teeth in children

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What bacteriocidal antibiotics should not be used in combination with the tetracyclines? Why?

Penicillins

Tetracycline alters the bacteriocidal effects of the penicillins

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What are 3 known drug interactions of the tetracyclines?

Digoxin
Oral anticoagulants (warfarin)
Oral hypoglycemics

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How is tigecycline related to tetracycline? What is its mechanism of action?

An analogue of tetracycline

Also binds the 30S ribosome, but with higher affinity

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What are 2 uses of tigecycline?

Tetracycline resistant bugs

Hershey isolate of MRSA

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What is the major aminoglycoside provided as an example? What is its mechanism of action

Gentamycin

Irreversibly binds the 30S ribosome subunit

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The aminoglycosides are [ bacteriostatic / bacteriocidal ] ?

Bacteriocidal

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What is the antibacterial spectrum of the aminoglycosides? i.e. Gram what is targeted?

Mainly gram - aerobes

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When combined with aminoglycosides, what to antibiotics act synergistically against S. aureus and S. epidermis?

Penicillin

Vancomycin

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What are 3 mechanisms by which resistance occurs against aminoglycosides?

Mutant ribosome
Decreased uptake / increased efflux
Enzymatic inactivation of drug

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What is the major way by which the aminoglycosides are administered?

IM or IV

The aminoglycosides are not well distributed to the cells, eyes or CNS. What is one area it accumulates, one of which is associated with major toxicity? How is it cleared?

Inner ear *** Renal cortex Cleared by kidneys

There are 3 major toxicities associated with the aminoglycosides. They are_

Ototoxicity Vestibular toxicity (vertigo) Renal toxicity

What is a major factor limiting the use of spreptomycin? When it is used, what is it use for?

High resistance | Mycobacterial infections

What is the major use for gentamycin? When not used IV/IM, what is another way to use this drug?

Severe gram negative infections | Topically, for burns, wounds, skin lesions

Tobramycin in similar to which aminoglycoside? It is slightly more active against what organism? What is its use in cystic fibrosis?

Gentamycin Pseudomonas P. aeruginosa respiratory tract infections in cystic fibrosis

Amikacin is a semisynthetic, less toxic derivative of _. It us used to treat bugs resistant to _ and _, as well as used to treat what major disease?

Kanamycin Tobramycin and gentamycin Tuberculosis

What aminoglycoside no longer used in the US is similar to gent/tobramycin and less suceptible to enzymatic degradation?

Netilmicin

A topical aminoglycoside that is limited to topical use because of widespread resistance is _

Neomycin / kanamycin

Spectinomycin in not an aminoglycoside, but rather it is a _. It works by _. It is [ bacteriostatic/bacteriocidal ]

Aminocyclitol Binding the 30S subunit of the ribosome Bacteriostatic

Regarding its spectrum, spectinomycin works against _

Mostly gram - but also some gram + bacteria

What are 2 major uses of spectinomycin? How is it administered?

MRSA and antibiotic resistant gonorrhea | IM administration

What are the 4 examples of macrolide antibiotics provided?

Azithromycin Clarithromycin Erythromycin Troleandomycin

What is the mechanism by which the macrolide antibiotics work? Are they bactriocidal / static?

Reversibly bind the 50S ribosome subunit. | Bacteriostatic

What are 3 drug (classes) that should not be used with macrolide antibiotics? Why?

Streptogramins Clindamycin Chloramphenicol Site of action very close to each other, competitively inhibit each ther

Regarding spectrum, what is the target of the macrolide antibiotics?

Narrow, accumulate more in the gram + bacteria

How dp erythromycin, clarithromycin and azithromycin compare in their activity against anaerobes?

clarithromycin and azithromycin are more effective than erythromycin against anaerobes

What are the 3 mechanisms by which resistance develops to macrolide antibiotics?

Efflux pumps Modified bacterial ribosome (methylase) Drug hydrolysis by esterases

True or false, cross resistance is a problem for macrolide antibiotics?

True

Majority of the macrolides are stable in acid environmets. Which of the macrolide antibiotics is unstable in acid environments? How is this countered?

Erythromycin | Admin. orally in stearate and estolate form (tablets)

Generally, macrolides have poor penetration of the CNS. Which macrolide is able to penetrate abcesses and placenta?

Erythromycin

How are erythromycin and clarithromycin excreted?

erythromycin- in bile clarithromycin- metabolized by liver, secreted by kidney

What are 3 main uses for macrolide antibiotics?

- Alternative to penicillin for allergic patients - Respiratory infections by atypical microbes (legionella) - Common bacterial infections like acne

What are 2 major toxicities associated with macrolide antibiotics?

GI disturbances | Hepatotoxicity (allergic type cholestatic hepatitis)

How are theophilline, warfarin, carbemazepine, astemizole and protease inhibitors related to macrolide antibiotics? Which macrolide is the exception?

Macrolides inhibit CYP3A4, potentiating the effect of these drugs Azithromycin is exception, structurally dissimilar

What is the example of a ketolide provided? What macrolide is it related to? What is the mechanism?

Telithromycin Semisynthetic deriv. of erythromycin Binds the 50 S ribosome in 2 places (blocks protein synthesis)

How is telithromycin administered? What enzyme metabolizes it? Under what conditions should adjustments be made to the dose?

Oral admin CYP3A4 50% Renal insufficiency

What do S. aureus and S. pyogenes have to express to be resistant to telithromycin?

MLS-B

What are 3 main uses of telithromycin?

Community acquired RTIs (pneumonia) Acute bacterial sinusitis Chronic bronchitis

What are 3 common side effecrs associated with telithromycin? What are 3 less common side effects associated with telithromycin?

diarrhea, nausea, abdominal pain | visual effects, blurred vision, difficulty focusing

What group of patients should not use telithromycin? What are 2 drugs that are known to interact with telithromycin?

Myesthenia gravis patients | Cisapride and simvastatin

What is the mechanism of action of chloramphenicol? is it bacteriostatic or bacteriocidal? What is its spetrum?

Reversibly binds 50S ribosome Bacteriostatic Wide - Most anaerobes, most gram -

What is the major means by which resistance develops to chloramphenicol?

Acetyltransferases modifying the drug

How is chloramphenicol administered? Which does it cross, CNS or placenta? Where is it metabolized? How is it excreted?

Oral or parenteral Crosses both Metabolized in liver, excreted in urine

What is a major consideration for the use of chloramphenicol? What drug does it replace (i.e. used only when this drug cannot be used)?

Major toxicity | Tetracycline

What are 4 major toxicities associated with chloramphenicol?

Aplastic anemia Hematological toxicities Hypersensitivity Gray baby syndrome

What is the drug associated with gray baby syndrome? What causes this syndrome?

Chloramphenicol Inadequate levels of liver glucuronyl transferase=> can’t metabolize the drug

Streptogramins are composed of what 2 drugs? How do each of these drugs act individually? Combined?

Quinupristin/dalfopristin Quin - Binds 50S ribosome Dal - Binds near by Each bacteriostatic, combined bacteriocidal (synergy)

What are 2 major uses of streptogramins?

MRSA | Vanco resistant gram positive infections

What are 2 associated adverse effects of streptogramins?

Pain and phlebitis at IV site | Interaction with CYP enzymes (affects other drugs)

Resistance to strpetogramins occurs to each component drug. What are the mechanisms? (2 each)

``` Quin - Methylases to 50S rib (erm) - lactonases (vgb) Dal Acetyltransferases (vat/sat) Efflux pumps (vga/vgb) ```

What is the example of the oxazolidinones provided? What is the mechanism of action? How is it administered?

Linezolid bind novel site in 23S ribosomal RNA of the 50S ribosomal subunit Oral Drug

Is linezolid bactriostatic / bacteriocidal? What is it used to treat (3)? What is an advantage it has associated with other protein synthesis inhibitors?

Bacteriostatic MRSA, VREf and multidrug resistant strep. pneumoniae No cross resistance (different mechanism)

What is the example of the lincosamide provided? What is its mechanism?

Clindamycin Binds exclusively to the 50S subunit of bacterial ribosomes

What is the major group of bacteria targeted by clindamycin? Is it bacteriocidal or bacteriostatic?

Majority of gram + bacteria | Mainly bacteriostatic, some bacteriocidal activity

What is the major mechanism by which resistance to clindamycin develops?

Ribosomal methylase (ermA, ermB and ermC)

How is clindamycin administered? It has a wide distribution area includin bone. Where is not not able to accumulate in high concentrations? How is it metabolized? How is it excreted?

Oral or parenteral CNS Liver metabolism Urine and bile excretion

What are 4 uses of clindamycin?

Abcesses Osteomyelitis MRSA (other group A strep. infections) RTIs caused by anaerobes

What are 4 adverse effects assoc. with clindamycin?

Pseudomembranous colitis (C. dificile) Diarrhea Skin rash Stevens-Johnson syndrome

How is muciprocin administered? What is it used for? What is its mechanism? How does resistance develop?

``` Topically administered Used to treat impetigo from MRSA or Group A strep inhibits isoleucyl tRNA synthetase Resistance is rare ```