Antibacterials 4 Flashcards
Route of administration of vancomycin:
slow IV infusion
Adverse effects of Vancomcyin
- Red man/red neck syndrome which is a infusion related flushing over the face so just need to slow the infusion rate (not allergenic)
- ototoxicity
- nephrotoxicity
What is the clinical use of daptomycin
Created because bacteria became resistant to vancomycin → used tot rest resistant gram positive organisms include VRE and VRSA
Daptomycin cannot be used to treat ____________
Pneumonia; surfactant inactivates it
Mechanism of action of daptomycin
Unique: binds to cell membrane via Calcium dependent insertion of lipid tail → depolarization → K efflux → cell death
Unique mechanism allows for ↓ resistance against daptomycin
Adverse effects of daptomycin
Constipation, nausea, headache, insomnia
Also causes ↑ creatine phosphokinases which makes them at higher risk for myopathies
It is recommended to discontinue coadminstiation of _________ when taking daptomycin
Statins (due to ↑ creatine phosphokinases)
What is bacitracin used to treat and is there risk of resistance?
Gram positive organisms;
No cross resistance due to having a unique mechanism
Acts at late stage of cell wall synthesis
What is an adverse effect of bacitracin ?
Marked nephrotoxicity so must be given topically
Mechanism of action of fosfomycin and what kind of bacteria is it used against
Inhibits enolpyruvate transferase in the early stage of cell wall synthesis
Gram positive and gram negative
What condition is fosfomycin used to treat
Uncomplicated lower UTI’s
Protein synthesis inhibitors are mostly bacterio_________ and they target the bacterial ribosome _____S.
Static;
70S ( mammalian are 80S)
Drugs that are in the class of tetracyclines (3)
Doxycycline, minocycline, tetracycline
Mechanism of action of tetracycline and
Enter via passive diffusion and energy dependent transport which is unique to bacterial inner cytoplasmic membrane
Bind reversibly to 30S subunit of the ribosome and prevents attached of tRNA
Tetracyclines bind to ________
30S subunit of the ribosome
Tetracyclines are especially effective in treating conditions caused by __________ organisms
Intracellular organisms
What are the 3 main mechanisms of tetracycline resistance (plasmid encoded)
- impaired influx or ↑ efflux by active (plasmid encoded) protein pump
- production of proteins that interfere with binding to the ribosome
- enzymatic inactivation
What are the conditions that tetracyclines are used to treat
- most common: severe acne and rosacea
- empiric therapy of community acquired pneumonia (outpatients)
- atypical pneuma (mycoplasma, chlamydia and legionella)
- treat syphillis patients who are allergic to penicillin for
________ decreases the GI absorption of tetracyclines
Calcium and other divalent and trivalent cations which will chelate the tetracyclines
What type of things should patients who are taking tetracyline avoid?
Milk/diary (calcium)
Antacids (magnesium)
____________ is a tetracycline that is lipid soluble and is preferred by parenteral administration
Doxycycline
_________ is a tetracyline that is used for STD’s and prostatitis
Doxycycline
Where can tetracyclines concentrate?
Liver, kidneys, spleen, and skin
Tetracyclines are primary excreted in the urine except for _______ which is excreted primarily by _______
Doxycycline; bile
What are some adverse effects of tetracycline
- Gastric effects/ super infections
- discoloration and hypoplasia of teeth (calcium)
- stunning of growth (teratogenic in pregnancy and should not be given to kids under 8 years old)
- photosensitization
- dizziness, vertigo (esp with doxycline and minocycline)
Example of a glycylcycline drug and what is important about this family of drugs
Tigecycline
Similar to tetracyclines but with less resistance
Route of administration of glycylcyclines
IV
Primary route of elimination of glycylcyclines
Biliary/fecal
What are the aminoglycoside drugs (5)
Amikacin Gentamicin Tobramycin Streptomycin Neomycin
Aminoglycoside s are bateri______
Bactericidal;
Associated with serious toxicities
Which class of protein synthesis inhibitors are bactericidal?
Aminoglycosides
What is the difference between concentration dependent killing and time dependent killing of antibiotics
Concentration dependent: the amount of organisms that are killed is based on how high the peak concentration is
Time dependent: the amount of organisms killed is dependent on how long the drug concentration stayed above the MIC
Unique pharmacodynamic features of amnioglycosides that allow it to be only given once daily
Post antibiotic effect + concentration dependent killing
What is the mechanism of action of aminoglycosides
- passive diffuses across membranes of gram NEGATIVE
- actively transported (O2 dependent) across cytoplasmic membrane
- covalently binds to 30S subunit and causes irreversible inhibition of the initiation complex → misreading of mRNA and blockade of translocation
What are some of the consequences of the irreversible inhibition of the initiation complex in aminoglycoside
Misreading of mRNA and blockade of translocation
Aminoglycosides are most active against _______ bacteria
Aerobic gram negative
3 principle mechanisms of aminoglycoside resistance
- Plasmid associated synthesis of enzymes that modify and inactivate drugs by: acetylation, phosphorylation and adenylation
- ↓ accumulation of the drug
- mutation can alter or delete the receptor protein on the 30S subunit
_____________ (an aminoglycoside) is used for bowel surgery and hepatic encephalopathy
Neomycin
What is aminoglycosides used to treat
Used mostly in combination
- empiric therapy for serious infections such as septicemia, nocosomial RTI, complicated UTI’s, endocarditis, etc
Once the organism is identified, aminoglycosides are usually discontinued to favor less toxic drugs
Aminoglycosides are given ______ except for _______
Parenteral; neomycin which is given topically
High levels of aminoglycosides are seen in _____ and _____
Renal cortex and inner ear
Adverse effects of aminoglycosides
- ototoxicity
- nephrotoxicity
- neuromuscular blockade in patients who have neuromuscular conditions such as Myasthenia
In what conditions are aminoglycosides contraindicated with
Myasthenia gravis (and other similarly conditions) and pregnancy
What drugs are used to treat hepatic encephalopathy and explain why
- oral neomycin
- lactulose
- oral vancomycin
- oral metronidazole
- rifaximin
Drugs that are poorly metabolized in the gut are used to treat this and the encephalopathy is due to the ↑ NH4 (ammonia)
Mechanism of action of how lactulose treats hepatic encephalopathy
Acidified the gut lumen which favors NH4 → NH3 and thus plasma ammonia concentrations are ↓
When lactulose is degraded by the intestinal bacteria, lactic acid is produced
Effects of lactulose
- treat hepatic encephalopathy
- prebiotic: suppression of urase producing organisms
- osmotically active laxative
Macrolide family drugs: ( 4)
Erythromycin
Clarithromycin
Azithromycin
Telithromycin
Macrolide are bacterio________ and are mainly used to treat gram ______ bacteria
Bacteriostatic; gram positive
mechanism of action of macrolide
Reversibly binds 23S rRNA of the 50S subunit and blocks translocation
3 Mechanisms of resistance for macrolides
- reduced membrane permeability or active efflux
- production of esterase that hydrolyze drugs (by enterobacteriase)
- modification of ribosomal binding site by either mutation or methylation
Macrolide drugs that have complete cross resistance:
3
Erythromycin, azithromycin, clarithromycin
Macrolides are most active against gram _________ bacteria
Positive
Clinical applications for Macrolides
- community acquired pneumonia outpatient (combine with β lactam for inpatients)
- atypcial pneumonia
- upper respiratory tract and soft tissue infection
_________ is the drug of choice for whooping cough
Erythromycin
Macrolides is a common substitute for someone with ______ allergy
Pencillin
Compare the pharmacokinetics of the macrolide drugs
Clarithromycin, azithromycin and telithromycin have improved oral absorption, longer half life, ↑ bioavailability, and broader spectrum than erythromycin
__________, __________, and _________ are CYP 450 ___________ .
Erythromycin, clarithromycin, telithromycin
Inhibitors
_________ is a macrolide drug that does NOT inhibit CYP 450
Azithromycin
Contraindications for macrolides:
- statins (macrolides inhibit CYP 450)
- do not use telithromycin for minor illnesses because it can cause fatal hepatotoxicity
