Antibacterials - Protein Synthesis Inhibitors Flashcards
What are the primary modes of use of aminoglycosides?
IV, IM, and Topical - Not Oral
What is a unique process of function of aminoglycosides?
Transported into the cell
binds to ribosomes causing multiple types of dysfunction: -stops initiation
-premature release
-mRNA misreading
What is the post-antibiotic effect?
Aminoglycosides stay within the bacteria causing effects long after the blood concentration levels decrease.
–Concentration Dependent Killing– Peak Levels
What kind of organisms are aminoglycosides used to treat?
Aerobic Gram Negative organisms
Such as E.Coli and Pseudomonas
–Severe Infections Only–
What are the three aminoglycosides commonly used?
Gentamicin
Tobramycin
Amikacin - used when resistant to the other two
What are side effects of using aminoglycosides?
Very Narrow therapeutic window. Nephrotoxicity. Ototoxicity - irreversible.
–Only used for severe infections due to side effects–
What is the common mode of resistance to aminoglycosides and why is Amikacin resistant?
Most common mode of resistance is modification of the drug once inside of the bacteria inactivating them.
However, Amikacin is resistant to that type of modification of the others, used if resistant to them.
What other class of antibiotics are used with Aminoglycosides to increase effectiveness against gram positive bacteria?
B-Lactams increase the penetration of Aminoglycosides. Synergistic effects.
How does the class of Tetracyclines work as an antibacterial?
They bind the 30S subunit of bacteria preventing the binding of tRNA. Bacteriostatic
What kind of bacteria are tetracyclines typically used for?
They have a broad spectrum, but due to lots of resistance use has been limited to Unusual infections as first line. -Rocky Mountain Spotted Fever -Lyme Disease -Chlamydia + Uncommon bacteria Alternate for Syphilis and Gonorrhea
What should you be aware of when taking tetracyclines?
All tetracyclines bind divalent cations, causing decreased absorbance and effectiveness.
Do not take Calcium supplements with tetracyclines.
What are unique side effects of tetracyclines?
Photosensative Rash
Discolor teeth in young children
Can cause C.Diff and Candida in GI
What is the most common type of resistance to tetracyclines?
Efflux Pumps that reduce the concentration inside the bacteria. If resistant to one kind of tetracycline, then resistant to all of them.
What are the two most common tetracyclines currently?
Doxycyline and Minocycline
Calcium binding: Doxycycline < Minocycline
What drug has a similar mechanism to tetracyclines, but is not in the class of tetracyclines?
Tigecycline - also binds additional sites in ribosome
If a patient is allergic to tetracyclines how susceptible are they do Tigecycline allergy?
There is no cross reactivity between tetracyclines and Tigecycline
What are the common types of uses for Tigecycline?
IV use Only
Skin Infections Complicated intra-abdominal infections Community acquired pneumonia Most Gram Positive and Negative --Does not work for pseudomonas--
What are side effects of Tigecycline?
SImilar to Tetracycline, even Calcium binding.
However, increased risk of death from serious allerigies.
–LAST LINE OF DEFENSE–
What antibacterial interferes with peptide bond formation on the 50S subunit?
Chloramphenicol
What are common uses for Chloramphenicol?
They are used as a back up for bacterial meningitis and brain abscesses.
What is Chloramphenicol not commonly used today?
Due to very serious side effects.
- Aplastic Anemia (irreversibly inhibits bone marrow)
- Grey Babe Syndrome due to build up in fetus
- Optic Neuritis and blindness
- -Very Serious Infections only–
What drugs are included in the class of Macrolids?
Erythromycin, Azithromycin, and Clarithromycin
What class of drugs bind to the 50S subunit preventing the translocation of the ribosome?
Macrolids - Erythromycin, Azithromycin, and Clarithromycin
What kind of bacterial infections does Erythromycin usually work best for?
Gram Positive Bacteria - Strep
Also used for unusual bacteria - Lyme, Rocky, Legionella, Bordella
What is a concerning side effect of Erythromycin?
Nausea and Vomiting (20-40%)
Inhibits CYP3A - many drug interactions
Increased risk for Arrhythmias and Cardiac Arrest
What drug has a wider spectrum and longer half life compared to Erythromycin?
Clarithromycin
What is a common risk associated with Macrolids and which has the least risk?
Increases risk of Arrhythmias and Cardiac Arrest.
Azithromycin has a lower risk, compared to the others.
Which macrolid is used for mycobacteria and H.pylori infections?
Clarithromycin
What antibacterial is used most commonly for outpatient respiratory tract infections?
Azithromycin
Why is Azithromycin more effective at respiratory infections?
Azithromycin concentrates in lung tissue when blood concentration decreases below, allowing more effectiveness at killing respiratory infections.
What is the recommended treatment for gonorrhea by the FDA?
To use two drugs for treatment to limit resistance.
Ceftriaxone + Azithromycin or Doxycyline
What has a similar mechanism of Macrolids, but is not in the same class?
Clindamycin - binds 50S subunit blocking translocation
What kind of organisms is Clindamycin effective against?
Gram Positive - Strep and Staph (Community MRSA)
Also used against flesh eating bacteria, to limit toxin production
What is a major side effect of Clindamycin?
Causes GI irritation and more than usual rate of development of C.Diff
Hepatotoxicty
Why are antifolates effective against bacteria?
Bacteria must produce their own folates, but humans get them from their diet.
What antibacterial prevents the interaction of the 50S and 30S ribosome subunits?
Linezolid
What kind of bacteria and infections does Linezolid primarily work against?
Gram Positive - Multi-Resistant Bacteria
Complicated Skin infections - MRSA + VRE
Pneumonia - Step/Staph
When is Linezolid contraindicated in a patient?
If a patient is currently taking anti-depressants, since Linezolid is a nonspecific MAO inhibitor.
What is a uncommon side effect the patients on Linezolid must be monitored for?
Bone Marrow Suppression
At what step do Sulfonamides inhibit folate synthesis?
Inhibite dihydropterate synthase - An Early step in the process due to the antibacterial being an analog.
What drug is Sulfamethoxazole usually paired with for antibacterial use?
Trimethoprim - Synergistic inhibiting two spots in folate synthesis for better effectiveness.
What drug is typically used topically for skin infections in burn patients?
Silver Sulfadiazine
What are common side effects of Sulfonamides?
Photosensative rashes,
GI effects – C. Diff
Renal - Crystalluria
MANY DRUG INTERACTIONS
What antibacterial inhibits late synthesis of folate?
Trimethoprim
What drug is typically combined with Trimethoprim and what new quality does it acquire?
Trimethoprim + Sulfamethoxazole = Bactericidal
What is the abbreviation used for the Sulfonamide drug combination?
TMP / SMX - Allowed on Exam
What is the most common use of TMP/SMX?
First choice in uncomplicated UTIs
URI and Ear infections
Also used for less common bacteriums: Pneumocystisis, Shigella, and Salmonella
What are common side effects of TMP/SMX?
n/v/d, rash, and bone marrow suppression - can onset significantly after treatment by the drug.
