Abx targeting DNA & RNA synthesis/replication Flashcards
1
Q
Rifamycins
A
- bind to RNA polymerase = prevent mRNA elongation
- rifampin (PO, IV, cyp 450 inducer!!!!!! will clear the drug faster) , rifaputin (less DDI), rifapentine(longer half life), rifaxamin (only for travelers diarrhea, poor absorption)
- used in combination with other drugs due to bacterial rapidly gaining resistance
- tx: (GRAM -, cocci and coccobacillus) My New Strange Friend
- Mycobacterium
- Neiserria meningitidis
- Staph
- H.flu
- prophylaxis of Neisseria and H.flu
- SEs:
- N/V/D: MOSTLY GI
- hepatitis
- rashes
- orange-red discoloration of tears, urine, and other body fluids
2
Q
Aminoglycosides coverage, resistance, meds, and SEs
A
-
Excellent against Gram negative
- enterobacter, pseudomonas, mycobacterium tuberculosis, or mycobacterium avium complex (MAC)
-
synergistic effects to affect gram positive
- need to break down cell wall
- Streptomycin: IV
- Gentamycin: IV
- Tobramycin : IV, no activity against enterococcus
- Amikacin: IV, no activity against enterococcus
- Neomycin: topical eye cream, ointment, eye drops– not for systemic use
- only PO use: bowel prep or hepatic encephalopathy
- SEs: ototoxicity –irreversible hearing loss
- vestibular toxicity: balance problems
- nephrotoxicity
- penetrate the proximal renal tubules
- nephrotoxicity
- test for toxicity with creatinine tests, check trough level of meds
- vestibular toxicity: balance problems
3
Q
Macrolides and Ketolides general function
A
- bind reversibly to the 50S subunit→ inhibit peptidyltransferase
- prevent formation of peptide bonds
- bulky structure
- sometimes prevents penetration
- effflux
- resistance is a class effect
- Spectrum:
- G+: strep, staph
- G-: Neisseria, Hflu, Bordetella, pertussis
- Atypicals: chlamydia, mycoplasma, legionella, rickettsia, mycobacterium, spirochetes
- Meds: Erythromycin PO and IV
- azithromycin PO and IV
- Clarithromycin PO
- Fidaxomicin PO
- Telithromycin PO
4
Q
Tetracyclines and Glycyclines Action and Resistant Modes
A
- Bind to 30s subunit, prevent binding of tRNA
- blocks tRNA
- Resistant modes:
- efflux pumps
- mutation of the ribosome
- prevents TCN from binding
5
Q
Tetracyclines Spectrum, drugs, and SEs
A
- Spectrum:
- Strep pneumo, staph aureus (MRSA)
- H.flu, and Neisseria
- Atypical: Rickettsia, Chlamydia, Mycoplasma, Borrelia, Treponema
- Meds: Doxycycline: PO IV
- Minocycline PO IV
- Omadacycline PO IV
- Tetracycline PO
- Sarecycline PO
6
Q
Aminoglycoside MOA and Resistant Modes
A
- MOA:
- AG = positive and binds to negative membrane charge
- they create holes for the AG to move into but require 0xygen by the bacterial transporter to get actively transported inside
- leads to poor anaerobe coverage
- binds to 30S⇒ causes mismatch of tRNA
- Resistant modes:
- efflux
- enzymes get modified so that aminoglycosides cannot bind to ribosomes
- random mutation of ribosomes → AGs can’t bind
- Resistance is NOT classwide
7
Q
Ketolides
A
- tighter binding to 50S subunit (preventing peptidyltransferase from forming peptide bonds between amino acid)
- more resistance to efflux
-
for respiratory infections:
- Covers:
- strep, staph, Hflu, pertussis, Atypical: chlamydia, mycoplasma, and legionella
- Covers:
-
SEs:
- erythromycin: N/V/D, GI, phlebitis
- QT prolongation
- erythromycin and clarithromycin: = inhibit CYP3A4
- blurred vision, diplopia, difficulty focusing
- severe liver damage
8
Q
Glycycline
A
- binds to 30S prevents tRNA binding and thus prevents protein synthesis
- Resistant modes:
- efflux pumps
-
Tigecycline
- glycyl amide group: prevents recognition of the efflux pumps
- Improved sensitivity to TCN resistant bacteria
- spectrum:
- G+: Strep, Staph (MRSA), enterococci (including VRE)
- G-: H.flu, Neisseria, Enterobacteriacea
- anaerobes: B. fragilis, and many others
- Mycoplasma
9
Q
Chloramphenicol
A
- bind to 50S to block formation of peptide bonds
- Resistant modes:
- prevent binding to target
- efflux pumps
- only IV in the US
- Spectrum:
- strep, H.flu, Neisseria, Salmonella, Shigella
- Anaerobes: B fragillis, and others
- Atypical: Mycoplasma, Chlamydia, Rickettsia
- SEs:
- Reversible bone marrow suppression
- irreversible aplastic anemia
-
gray baby syndrome
- accumulation of unmetabolized chloramphenicol
10
Q
Clindamycin
A
- Binds to 50S and inhibits protein synthesis
- MOA similar to macrolides
- **most gram negative are intrinscially resistant to clindamycin because the outermembrane resists penetration**
- **bacteria resistant to macrolides are also resistant to clindamycin**
- Spectrum:
- G+: strep, staph (MSSA & CA-MRSA)
- Anaerobes: B. fragillis, clostridium (NOT C. diff), and most others
- Toxicity:
- induces C.diff colitis
- diarrhea
- rashes
11
Q
Streptogramin
A
- 2 different macrocyclic compounds that work synergistically
-
bind to 50S subunit and prevent protein synthesis
- binding site is same one as macrolides and clindamycin
- bugs that are resistant to macrolides and clindamycin will also be resistant to streptogramin
-
bind to 50S subunit and prevent protein synthesis
- COVERS G+ only
- Resistances modes:
- efflux pumps
- mutation in 50s subunit
- enzymatic inactivation
- CYP450 inhibitor
- Toxicity:
- phlebitis (should only be given via central line)
- arthralgias
- hyperbilirubinemia
12
Q
Linezolid
A
- completely synthetic
-
binds to 50s and prevents 30s from associating
- no ribosome formation
- Resistant mode:
- mutation of ribosomes
- efflux pumps
- Spectrum: G+ : strep, staph (MRSA and VRE)
- SEs:
- NVD
- thrombocytopenia
- anemia, leukopenia
- not to be given with MAO inhibitors
- can be given with SSRIs BUT→ can cause serotonin syndrome
13
Q
Nitrofurantoin
A
-
MOA: inhibits translation
- concreates in urine but poor levels in blood
- tx: acute cystitis
- spectrum: staph and enterococcus
- SEs:
- N/V
- rash, interstitial pneumonitis, hepatitis, hemolytic anemia, and neuropathy
-
contraindicated in patients with poor renal function
- Crcl < 60ml/min
- ineffective in pts Crcl<40ml/min
14
Q
Sulfa Drugs MOA and different meds
A
- Abx that target DNA and Replication
- target folic acid synthesis
- sulfamethoxazole (SMX) mimics PABA and competitively inhibits DHT synthetase (Dapsone also works here)
- Trimethoprim (TMP) revents formation of dihydrofolate reductase
- risk of resistance is less
- TMP/SMX = given both IV and PO
- Dapsone: PO
- Sulfisoxaole/erythromycin (Pediazole): PO
- toxoplasmosis
15
Q
Sulfa Drugs Spectrum and Toxicity
A
- Spectrum: G+: staph strep, Listeria
- not helpful for enterococcus
- G-: H.flu enterobacteriaceae
- anaerobes and atypicals tend to be resistant to Septra
- Dapsone: txs mycobacterium leprae
- SEs:
- GI effects
- fever
- rash/Steven Johnson Syndrome
- leukopenia
- thrombocytopenia
- hepatitis
- hyperkalemia
