30s binders Flashcards
What are the bacterial ribosomal subunits? Mammalian?
Bacterial: 50s, 30s
Mammalian: 60s/40s
What are the two 30s binders
Aminoglycosides
Tetracyclines
Describe aminoglycosides
Basic polycations
Polar organic bases
Are aminoglycosides static or cidal
Cidal
What do aminoglycosides target
Gram neg AEROBIC infections
Aminoglcyosides (7)
TANG - KPS Tobramycin Amikacin Neomycin Gentamycin
Kanamycin
Paromomycin
Streptomycin
How do aminoglycosides permeate bacteria?
- Passive diffusion
2. Active transport (oxygen dependent – which is why only aerobic bacteria are susceptible)
What are the only protein syntethsis inhibitors that are bactericidal? Why?
Aminoglycosides because they cause irreversible non-functional proteins
Do aminoglycosides have post-antibiotic effect
Yes
Can aminoglycosides be given at long intervals
Yes
T/F - you can give aminoglycosides in a single dose
True
T/F - gentamycin can be used against anerobic bacteria
FALSE - NO ANEROBES!
Gentamycin CAN be used against gram + but there are better options available
How does environmental pH affect antibacterial activity of aminoglycosides
Alkaline pH —> increases antimicrobial activity
Acidic pH and Ca, Mg cations —> reduced antimicrobial activity
T/F - oral absorption of aminoglcyosides is good
False - poor, best to give parenteral
T/F - parenteral absorption aminoglycosides is good
True - 100% bioavailability IM/SC
T/F - aminoglycosides have high concentrations in brain, CSF…
False- diffusion across cell membrane is low due to poor lipid solubility
T/F aminoglycosides have long withdrawal period
True - slow depletion from tissues
T/F - lean, cachetic animals have increased aminoglycoside distribution
True - reduced protein. Can lead to toxicity
Where can aminoglycosides bind to, causing issues
Proximal tubule and cochlear tissue in inner ear
T/F - aminoglcyosides are excreted as active drug
TRUE - no biotransformation
What kind of toxicity (if any) can aminoglycosides have
Nephrotoxic due to drug sequestration in PT of kidney
Your patient has renal insufficiency. Are aminoglycosides safe?
Not really - adjust dose and give with lots of water to avoid nephrotoxicity
Adverse effects aminoglycosides (3)
- Nephrotoxicity: binds to basolateral membrane of PT. TUBULAR NECROSIS
- Ototoxicity: irreversible. Auditory (dogs), Vestibular (cats)
- Neuromuscular : crurare like (non-depolarizing). Rapid IV bolus = respiratory arrest
Resistance to aminoglycosides (3)
- Enzymatic inactivation
- Ribosomal alterations
- Reduced permeability
Efficacy predictor aminogycosides
Type 1
Which aminoglycoside has broadest spectrum
Amikacin
Which aminoglycosdie is not effective against Pseudomonas
Gentamycin
Which aminoglycoside is effective against pseudomonas mediated respiratory tract infections
Tobramycin
Which aminoglycoside can be absorbed orally and is added to feed/water
Apramycin
What formulation are tetracyclines given in? Why?
Hydrochloride formulation
To stabilize proteins (denature easily)
Natural tetracyclines
COT
Chlortetracycline
Oxytetraclyine
Tetraclycine
Semi-synthetic tetracylines
Minocycline
Doxyclyine
MOA tetracyclines
Reversibly binds to 30s ribosomal subunit
Blocks the binding of aminoacyl-tRNA to acceptor cycle on mRNA-ribosomal complex
Inhibits addition of new AAs to peptide chain
T/F - tetracyclines are broad spectrum
True - highly broad spectrum
T/F - all tetracyclines are effective against pseudomonas
False
Which tetracycline is drug of choice for Chlamydia psittaci in birds
Doxycycline
Which tetracycline is drug of choice for Rickettsia
Oxytetracycline
A horse has equine monocytic ehrlichiosis. Which drug is effecive?
Oxytetracycline
A dog has a resistant strain of Staph aureus. Can you treat with tetracyclines?
Yes - minocycline
Heartworm infected dogs should be given which tetracyline? Give four reasons why
Doxycycline
- Sterilizes female worms
- Prevents spread of infection via mosquitos
- Improves efficacy of heartworm adulticide
- Reduces inflammation and risk of adverse reactions to Melarsomine
Which tetracycline has complete absorption when given orally
Doxy
T/F - tetracyclines have good oral absorption
True - can be variable
T/F - horses and ruminants should be given tetracyclines with caution as may impair GIT microflora
TRUE!
What do tetracyclines form complexes with after oral absorption
Divalent and trivalent calcium ions – form chelation complexes
Which tetracycline has good parenteral absorption
Oxytetracycline
Which tetracycline is given as opthalmic ointment
Oxytetracyline
Which tetracylines have prolonged half-life? Why?
Doxy
Minocycline
80-90% plasma protein binding
Which tetracyclines are most lipid soluble?
Minocycline
Doxy
Which tetracyclines would be used for a menigeal infection?
Minocycline
Doxy
Because they are most lipid soluble - can penetrate brain, CSF
What is a negative side effect of chelate complexes formed by tetracyclines
They can deposit at active site of ossification in bone and developing teeth of young animals
Which tetracyclines are metabolized
Mino and Doxy - oxidation in the liver
How are most tetracyclines excreted
Urine and feces
T/F tetracylines undergo enterohepatic circulation
True
Which is tetracyline is drug of choice for patients with impaired renal function
Doxycycline – excreted in bile/feces
General adverse effects of tetracyclines
GIT disturbances
Hepatoxicity
Photoxicity (sits under dermis)
Renal damage
Tooth mottling
Inhibited growth of long bones in young animals
Hypersensitivity and drug fever in cats
What is adverse effect of tetracycline in cats
Esophageal lesions
Rapid IV inject of tetracycline can cause what? How can you prevent this
Chelating of calcium –> reduced Ca for heart contraction and collapse
Prevent by diffusing with saline
IV injection of tetracyline can cause what in dogs
Anaphylactic shock
What can doxy cause in horses
Fatal cardiac arrhythmias
What can oxytetracyline cause in horses
Enteritis - alters commensal microflora
Tetracyline bacterial resistance (3)
Impair drug permeation
Tetracycline efflux
Ribosomal alteration
Efficacy predictor of tetracyclines
Type III - time dependent killing with moderate persistent effects
