Inhibitors of Protein Synthesis Flashcards
What are the Tetracyclines
Doxycycline
Minocycline
Tetracycline
What is the Glycylcycline
Tigecycline
What are the Aminoglycosides
Gentamycin Neomycin Amikacin Tobramycin Streptomycin Netilmicin
What are the Macrolides
Erythromycin
Clarithromycin
Azithromycin
Telithromycin
What are the Misc Protein Synthesis Inhibitors
Chloramphenicol
Clindamycin
Linezolid
Fidaxomicin
What are the Streptogramins
Quinupristin
Dafopristin
Which bind 30S
Aminogycosides
Tetracyclines
Glycylcyclines
Which inhibit 50S
Chloramphenicol Clindamycin Macrolides Linezolid Streptogramins
Most common treatment of severe acne and rosacea
Tetracyclines
Don’t take with milk/antacids
Tetracyclines
Teratogenic
Tetracyclines (D)
Tigecycline
Aminoglycosides (D)
Discoloration and hyperplasia of teeth
Tetracyclins
Main AE is photosensitivity
Tetracyclins
Last resort for MDR b/c increased risk of mortality
Tigecycline
DOC empiric Tx infective endocarditis
Gentamycin
with Vanco or PCN
DOC plague
Streptomycin
Adjunct for hepatic encephalopathy
Oral Neomycin
Action of Oral Neomycin in hepatic encephalopathy
Reduce NH3 formation by gut bacteria
Only useful against aerobes
Aminogycosides
Main Aminoglycoside AE
Nephrotoxicity (ATN)
Ototoxicity
Good choice for Pts with PCN allergy
Macrolides
Empiric Tx community acuired PNA and pseudomonas
Macrolides
DOC pertussis
Erythromycin
What is contraindicated to give with Macrolides
Statins
Due to P450 inhibition
Which Macrolide doesn’t inhibit P450
Azithromycin
What is the Macrolide effect on the heart
QT prolongation
What is the effect of Chloramphenicol on the bone
BM toxicity leading to reversible or aplastic anemia
Gray Baby Syndrome
Chloramphenicol
Cyanosis due to drug accumulation
What can you give for G+ anaerobes like bacteriodes
Cindamycin
Alternative Tx of PCP
Clindamycin with Primaquine
Can cause C. diff colitis
Clindamycin
Which organism is intrinsically resistant to Streptogramins
E. faecalis
Can penetrate macrophages and PMNs
Streptogramins
Inhibits 3A4
Streptogramins
Normally static but cidal against C. perfringes
Linezolid
Good for MDR G+, MRSA, VRE
Linezolid
Linezolid AE
Reversible myelosupression
Optic and peripheral neuropathy
Lactic acidosis
No cross resistance
Linezolid
Can give for C. diff after Metro and Vanco
Fidaxomicin
Inhibits RNAP
Fidaxomicin
100% f orally
Linezolid
What can you give to syphilis patients allergic to PCN
Tetracyclins
DOC Tetracyclins
Chlamydia, M. pneumoniae
Lyme disease w/o CNS, joints
Rickettsia
Cholera, Anthrax prophylaxis
Where is Tetracycline used as a combination therapy
H. pylori
Malaria prophylaxi
Plague, Tularemia, Brucellosis
Lipid soluble, IV for STIs and prostatitis
Doxycyclin
Reduce meningococcal carrier state
Minocycline
Where are Tetracyclines excreted
Urine Except Doxycycline (bile)
Where to Tetracyclines concentrate
Kidney
Spleen
Skin
Liver
Stunting of growth
Tetracyclines
Other Tetracycline AE
Photosensitivity
Renal dysfunction
Hepatotoxicity
Dizziness/Vertigo
Mechanisms of Tetracycline Resistance
Increase efflux, decrease influx
Interfering with ribosome binding
Enzymatic inactivation
Military personnel taking Drug X for malaria prophylaxis and develops photosensitivity
Doxycyxline
What can expired Tetracycines cause
Fanconi’s Syndrome
Defective reabsorption in PCT
Broad spectrum use against MDR
Tigecycline
Given for complicated skin, soft-tissue and intra-abdominal infections
Tigecycline
DOC Hepatic encephalopathy
Lactulose
Tigecycline elimination
Bile/Fecal
Susceptible to Proteus and Pseudomonas efflux pumps
Tigecycline
Irreversible 30S inhibition
Aminoglycosides
Oral/Topical Aminoglycoside
Neomycin
Contraindicated in Myasthenia
Aminoglycosides (NMJ blockade)
Why are Aminoglycosides only good for Aerobes
O2 dependent transport into G-
Aminoglycoside excretion
Renal
Aminoglycoside Resistance mechanisms
Plasmid to modify/inactivate
Decreased accumulation
Altered/deleted receptor on 30S
How does Lactulose cause osmotic diarrhea
Acidify gut lumen trapping NH4+
Good for URTs
Macrolides
Bacteriostatic but cidal at high concentrations
Macrolides
What can Macrolides have cross-reactivity with
Clincamycin
Chloramphenicol
Can cause hepatotoxicity, MG exacerbation and visual disturbances
Telithromycin
Macrolide with worst oral absorption and f
Erythromycin
Macrolide with greatest tissue penetration
Azithroycin
Telithromycin
Additional Macrolide AE
GI effects (Inhibit motilin) Cholestatic hepatitis
Macrolide Resistance
Decrease influx, Increase efflux
Esterase hydrolyzes
Methylate binding site
Actual uses of Chloramphenicol
VRE
Topical eye infections
Inhibits 3A4 and 2C9
Chloramphenicol
Chloramphenicol Resistance
Acetyltransferase inactivates
Altered permeability
What organisms can Chloramphenicol act on
Rickettsia Anaerobes N. meningitidis H. influenzae Salmonella Bacteriodes
Toxoplasmosis Tx
Clindamycin with Pyrimethamine
Endocarditis prophylaxis for PCN allergy
Clindamycin
Most G- aerobes and enterococci are intrinsically resistant
Clindamycin
Can penetrate abscesses and bone
Clindamycin
Clindamycin AE
GI irritation
Skin rash
Neutropenia
Impaired liver
What does Clindamycin cross react with
Macrolides
Clindamycin resistance
Mutate receptor
Enzymatic inactivation
Actually used to treat MDR and works on G+ cocci
Streptogramins
Always given in combination
Quinupristin
Dalfopristin
Long Post-ABx effect
Streptogramins
Streptogramin AE
Venous irritation Arthralgia Myalgia GI HA/pain
Works on most G+ and TB
Linezolid (not actually given for TB)
How does Linezolid work
Inhibit formation of 70S by binding 23S of 50S
Weak reversible inhibitor of MAO
Linezolid
Linezolid Resistance
Decreased binding
Especially works on Clostridia
Fidaxomicin
Almost no systemic absorption so Oral
Fidaxomicin
May not be safe/effective <18
Fidaxomicin
Prevent C. diff recurrence
Fidaxomicin