Antibacterial Agents Flashcards
What are the B-lactams?
Are they -cidal or -static?
What is their mechanism?
Penecillins
Cephalosporins
Carbapenems
Aztreonam
-cidal
Bind to PBP and inhibit transpeptidation
So, inhibit an enzyme
SE of penicillins
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Penicillin G
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Narrow spectrum: G+
Natural penicillin
Route: IV or IM–hydrolyzed w/ stomach acid
Given w/ procaine to slow release
Destroyed by B lactamase
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Penicillin V
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Narrow spectrum: G+
Route: Oral
Natural penicillin
Absorption unpredictable
Destroyed by B lactamase
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
B lactamase resistant penicillins
Name and spectrum
Nafcillin
Oxacillin
Cloxacillin**
Dicloxacillin**
Methicillin
“Nafcillin and -oxacillin”s
NAFcillin=Not AFfected by penicillinase
- Oxacillin’s=Ox is resistant to penicillinase*
- Methicillin too but not in use anymore*
Narrow spectrum
Nafcillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
B-lactamase resistant
Narrow spectrum: G+
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
NAFcillin=Not AFfected by penicillinase
“-oxacillin”s
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
B-lactamase resistant
Narrow spectrum: G+
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
OXacillin=OX is strong animal, resistant to penicillinase
Methicillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
B-lactamase resistant
Narrow spectrum: G+
Does not readily enter CNS
Do not use anymore-too toxic
Broad or extended spectrum penicillins
Amoxicillin
Ampicillin
Ticarcillin
Piperacillin
Mezlocillin
Carbenicillin
TAMPAC
Amoxicillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Broad spectrum
Route: Oral
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- B lactam ring may inh. GABAergic neurons
Ampicillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Broad spectrum
Does not readily enter CNS
SE:
- Rash in pts who have mononucleosis +other viral inf.
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Ticarcillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Broad spectrum
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Piperacillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Broad spectrum
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Mezlocillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Broad spectrum
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Carbenicillin
Tx: Antibacterial
Mech: Bind to PBP→inh. transpeptidation
inhibit an enzyme
Broad spectrum
Does not readily enter CNS
SE:
- Allergic rxns→anaphylactic shock
- High IV doses→seizures
- B lactam ring may inh. GABAergic neurons
Sulbactam
Mech: Bind to and inh. B lactamase
Non antibiotic B-lactam ring compounds
Clavulanic acid
Mech: Bind to and inh. B lactamase
Non antibiotic B-lactam ring compounds
Augmentin
Amoxicillin+clavulanic acid
Timentin
Ticarcillin and clavulanic acid
Unasyn
Ampicillin and sulbactam
What’s the difference b/w each generation of cephalosporins?
Succeeding generation has:
- more G- activity (broader spectrum)
- More res. to B lactamase
Cephalosporins
cef or ceph
SE:
- Allergic cross activity w/ penicillin sensitive pts
- Possibility of superinfection
Carbapenems
Tx: Antibacterial–mixed infections
Penicillin analog
Small penicillinase resistant B lactam
Spectrum: Very broad
Route: IV
SE:
- Can enter CNS→Seizures
Imipenem
Tx: Antibacterial–mixed infections
Class: Carbapenem
Penicillin analog
Small penicillinase resistant B lactam
Spectrum: Very broad-Better against G+
Route: IV
SE:
- Can enter CNS→Seizures
- Metabolized in kidney to nephrotoxic product
- Given w/ cilastatin which inh. enzyme that produces toxic product
Meropenem
Tx: Antibacterial–mixed infections
Class: Carbapenem
Penicillin analog
Small penicillinase resistant B lactam
Spectrum: Very broad-Better against G-
Route: IV
SE:
- Can enter CNS→Seizures
Cilastatin
Given w/ impenem
Prevents nephrotoxic product by inh. enzyme
Aztreonam
Antibacterial
Class: Monobactam
Route: IV or IM
Not affected by lactamases
Spectrum: Aerobic G- organisms
Not cross reactive w/ allergic pts
SE:
- Seizures
Vancomycin
Antibacterial
Class: Non B lactam CW inhibitors
Mech: Binds to dialanine residue on CW and prevents cross linking
Use: Severe infection in which B lactams can’t be used
Primary alt. to penicillins for staph infections.
Spectrum: G+
Route: IV–unless target in gut (pseudomembranous colitis)
SE:
- Nephrotoxicity
- Ototoxicity
- If given rapidly via IV→histamine release→Redman or red neck syndrome
- Flushing
- Rash
- Itching
Resistance:
- Target changed
- Dialanine changed to lactic acid
Dr. Van Ron
Dialanine Residue. Vancomycin. Redman. Ototox. Nephrotox
“-vancin”s
Televancin
Dalbavancin
Antibacterial
Class: Non B lactam CW inhibitors
Lipoglycopeptide
Mech: Binds to dialanine residue on CW and prevents cross linking + disrupt bacterial CM
SE:
- Nephrotoxicity
- Fetal damage
- Metallic taste
Bacitracin
Antibacterial
Class: Non B lactam CW inhibitors
Polypeptide
Mech: Inh. recycling of bactoprenol carrier
Spectrum: G+
Route: Topically–very toxic
SE:
- Nephrotoxicity–if not given topically
Fosfomycin
Antibacterial
Class: Non B lactam CW inhibitors
Mech: Blocks synth of NAM
Spectrum: Aerobic G-
Use: Uncomplicated UTI
SE:
- Diarrhea–killing bacteria in gut
Cycloserine
Antibacterial
Class: Non B lactam CW inhibitors
Mech: Inh. incorporation of alanine into NAM
Enzyme inhibitor
Used against mycobacterium TB
SE:
- CNS
- Sedation
- Tremor
- Psychosis
- Cyclo- gives you psycho-*
- Go to war in NAM, when you come back you have PTSd*
- Psychosis*
- Tremors*
- Sedation*
Erythromycin
Antibacterial
Class: Macrolides-inhibit protein synth
-static
Mech: Reversibly binds to 50s subunit and inh. translocation of mRNA
Inh binding of tRNA to P site
Spectrum: G+
SE:
- GI upset, nausea, and heartburn
- Increase in GI activity b/c activates motilin
- Inh P450
- Liver damage
- Arrythmias
macROlides like erythROmycin inh. transLOcation
Motility
Arrythmia
Cholestatic hepatitis (liver tox)
Restricts P450
Ototoxicity
Clarithromycin
Antibacterial
Class: Macrolides-inhibit protein synth** **
Oral stability
vs. Helicobacter Pylori
* macROlides like erythROmycin inh. transLOcation*
Motility
Arrythmia
Cholestatic hepatitis (liver tox)
Restricts P450
Oral stability/Ototoxicity
Azithromycin
Antibacterial
Class: Macrolides-inhibit protein synth** **
Longer T1/2 (3 days)
macROlides like erythROmycin inh. transLOcation
Motility
Arrythmia
Cholestatic hepatitis (liver tox)
Restricts P450
Ototoxicity
Telithromycin
Antibacterial
Class: Macrolides-inhibit protein synth** **
Same sites as erythromycin (50s) but induces less resistance b/c not readily transported out of bacterial cell
SE:
- GI upset, nausea, and heartburn
- Increase in GI activity b/c activates motilin
- Inh P450
- Liver damage-_SEVERE liver toxicity_
- Arrythmias
-
Block cholinergic receptor
- Worsen myasthenia gravis
- Inh long ciliary ganglion→Decrease visual accomodation
macROlides like erythROmycin inh. transLOcation
Motility/ Myasthenia gravis worsens
Arrythmia
Cholestatic hepatitis (liver tox)
Restricts P450
Ocular inh./Ototoxicity
Streptomycin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
Spectrum: Aerobic G-
Must be absorbed by active transport
SE:
- Ototoxicity
- Hearing and balance affected
- hearing loss may be permanent
- Nephrotoxic
- Most common cause of drug induced renal failure
- Used very widely
- High doses
- Neuromuscular blockade
- Decrease in ACh+ ACh receptors on mm
- Fetal damage
- Preg cat. D
- Neuromuscular blockade
- Strippers fornicate*
- Strep. FORNICAT*
Fetal damage
Ototox.
Renal tox
Negative (G-)
Irr. bind 30s
Cidal
*ACh block *
tRNA can’t bind to mRNA
- *
Aminoglycoside antibacterial agents
Names and mech
Streptomycin
Gentamycin
Tobramycin
Neomycin
Amikacin
Kanamycin
Netilmicin
_Kan_ye’s Cobra _A_rose _Gent_ly as _N_aughty _Nat_alie Stripped
_Kan_amycin _Tobra_mycin _A_mikacin _Gent_amycin _N_eomycin _Netil_mycin _Strept_omycin
Mech: Irr bind to 30s subunit
Can inh. or alter tRNA binding along mRNA including initiation site
Irr. mRNA misreading=bactericidal
Gentamycin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
**Use: **Ointment for eye
Tobramycin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
Neomycin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
Route: Topical or oral
**SE: **Very nephrotoxic–so only topically or orally
Amikacin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
Kanamycin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
Netilmicin
Antibacterial
Class: Aminoglycosides-inhibit protein synth** **
-cidal
Mech: Irr. binds to 30s subunit
Inh. or alter tRNA binding along mRNA including initiation site
DROPPED in the US
Tetracycline
Tx:
- Rickettsia
- Spirochetes (lyme disease)
- Helicobacter
- Legionella
Mech: Reversibly bind to 30s.
Inhibits the binding of tRNA to the A site
-static
SE
- Deposited in Ca storage sites-bones/teeth-esp fetus or child
- Binds to cations, esp Ca, also Fe and Al.
- Preg risk D
- Renal and hepatic toxicity
- Degrades to toxins–don’t use after expiration date
Other cyclines vs tetracycline
Less likely to bind Ca+
Chloramphenicol
Antibacterial agent
Mech: inh. peptidyl transferase
SE:
- Inh. P450
- Can cause aplastic anemia
- Hemolytic anemia too (said this in the review)
- Gray baby syndrome
- Metabolized by a phase II enzyme that is not active in newborns.
- Can’t metabolize it→baby turns blue and circulatory system inhibited
Clindamycin
Antibacterial agent–lincosamide
Mech: like erythromycin-inh. translocation
SE: Severe superinf. w/ C. dificile
Targets:
- Severe anaerobic infections (penetrating gut wound)
- Dental prophylaxis in pts w/ heart valve problems
Lincomycin
Antibacterial agent–lincosamide
Mech: like erythromycin-inh. translocation
SE: Severe superinf. w/ C. dificile
Targets:
- Severe anaerobic infections (penetrating gut wound)
- Dental prophylaxis in pts w/ heart valve problems
-pristin
Quinupristin (A+P site)
Dalfopristin (P site)
Mech: Inh. A and P sites
Always used together–synergistic
SE: Muscle pain
Spectrum: G+
-zolid
Linezolid
Tedizolid
Mech: Inh. binding of fmet (start codon) tRNA to P site
Prevents initiation of protein synth.
SE
- Anemia
- Pseudomembranous colitis
- Will happen w/ any powerful AB b/c of C. dificile
Daptomycin
Antibacterial agent–lipopeptide
Mech: Forms pores in bacterial CM
Targets: Aerobic G+ (staph, strep)
Skin and soft tissue inf. or severe blood inf w/ S. aureus
SE:
- Muscle pain and weakness
- careful w/ statins
- Eosinophilic pneumonia
Fidaxomycin
Antibacterial agent
Mech: Inh. C. dificile RNA pol
Orally–Not systemically absorbed
Target: C. dificile
-floxacin
Antibacterial agent
Mech:
- Inh topoisomerase II (DNA gyrase)
- Inh topoisomerase IV
No effect on mammalian topoisomerase
SE:
- May damage developing cartilage
- Not for children or pregnant women
- Tendonitis–achilles tendon rupture
- Phototoxicity (drug in skin responds to sunlight)
- May worsen myasthenia gravis
- Peripheral neuropathy (said it in review along w/ retinal detachment)
Spectrum: Broad–G+,G-, Acid fast
Sulfisoxazole
PABA*→folic acid→DHFA**→THFA
*→=Dihydropterate synthetase
**→DHFR
Mech: Reversible inh. dihydropterate synthetase
For UTIs
SE:
- Allergic whole body rash (Stevens Johnson syndrome)
- Hemolytic anemia in G6PDH deficient pts
- Megaloblastic anemia
Sulfa drugs have sulf or sul
Trimethoprim
Antibacterial agent
Mech: Inh. DHFR (like methotrexate)
Specific for bact. enzyme
*Used in conj. w/ sulfamethoxazole *
SE:
- Megaloblastic anemia
- Can be avoided w/ leucovorin
Targets:
- G- bacteria
- UTIs
- Concentrates in acidic prostate and vaginal tissue
Metronidazole
Mech: Prodrug-converted to a free radical active molecule by obligate anaerobic bacteria
Route: IV for severe anaerobic bacterial inf.
Use: Protozoal inf:
- Trichoma (STD)
- Giardia (from water)
SE:
- Seizures
- Peripheral neuropathy
Nitrofurantoin
Mech: Reduced by bacteria to a highly reactive molecule
Concentrates in urine
Use: UTI
SE:
- Cough
- Chest pain
- Brown urine
Polymixin B
Antibacterial agent
Mech: Binds to negatively charged sites on LPS of G- bact
→to memb. permeability
Route: Topical
SE: (all reversible)
- Nephrotoxic
- Neurotoxic
- Neuromuscular blockade
- Ataxia
- Perioral paresthesia
- Poly mixes in her PANNNN*
- Polymixin B. Perioral paresthesia. Ataxia. Neurotoxic. Nephrotoxic. Neuromuscular blockade. binds to Negatively charged sites on LPS*
Gramicidin
Antibacterial agent
Mixture of 3 diff peptide AB
Mech: forms pores in bacterial CM
Route: topical
NEVER give IV–toxic
Spectrum: G+
Retapamulin
Antibacterial agent
Mech: inh. peptidyl transferase
Route: Topical
Use: skin staph or strep inf.
Mupirocin
Mech: Binds to bacterial isoleucyl tRNA synthetase
Route: Topical
Use: Staph inf.
Neosporin
Neomycin+ polymixin +gramcidin
Polysporin
polymixin+ bacitracin
Polytrim
Trimethoprim+ polymixin
Terak
oxytetracycline+ polymixin
Isoniazid
Antimycobacterial agent
Mech: Produces inh. of multiply mycobacterial enzymes
Inh CW synth
Prodrug
Cidal, but static for dormant cells
Used alone for prophylaxis–in combo for active tx
Metabolized by acetylation–slow acetylators affected
SE:
- Increase excretion of vit B6→pyroxidase deficiency→niacin deficiency
- Pellegra
- Peripheral neuropathy
- Optic neuritis
- Hepatotoxicity
Isoniazid is IHOPPIN
Inh. mycobacterial enz.
- Hepatotox.
- O**ptic neuritis.
*Peripheral neuropathy + Pellegra. *
Prodrug + Prophylaxis
Increase excretion of vit B6→→
Niacin def.
Rifampin
Antimycobacterial agent
Antibacterial agent
Mech: Inh DNA dep. RNA polymerase
-cidal
SE:
- Hepatic toxicity
- Red color in all body fluids
- Induces P450–very strong
- Can metabolize BC!
Rifampin=red
Will metabolize BC (induce P450) so the sperm will LIVEr
Pyrazinamide
Antimycobacterial agent
Mech: Inh FA synth
Prodrug converted in macrophase where TB lives
SE:
- Gout
- Hepatitis
Ethambutol
Antimycobacterial agent
Mech: Inh arabinosyl transferase
Necessary for CW synth
SE:
- Optic neuritis
- Impaired red/green discrimination
- Decreased vision
Bedaquiline
Antimycobacterial agent
Mech: inh. mycobacterial ATP synthetase
Always used w/ 3 other anti-TB drugs
SE:
- Arrythmias
- Increase incidence of death
*You’re in your bed MASTurbating your erection (arrection) *
_Bed_aquiline. Mycobacterial Atp SyntheTase. Arrythmia.
Dapsone
Antimycobacterial agent
Related to sulfonamides
Mech: Reversible inh. dihydropterate synthetase
Use: For mycobacterium leprae (leprosy
Antimycoplasma agents
NO CELL WALL!
So use non CW inhibitors:
Erythromycin
Tetracycline
