Antibiotics Flashcards
Cidal
Kill target organism. No not need host defense to make it work. Concentration dependent
Static
stop growth and replication. rely on pts immune system to work. Time dependent
Bacteria have this, we do not
a cell wall! This is key to drug targeting.
Penicillins, how do they work?
Cell wall inhibitors. Degrade the peptidoglycan wall of the pathogen. Penicillins are Cidal and Bind to PBP to inhibit the cross-linking of peptidoglycan units. They only work on actively proliferating cells!
PCN Gram activity
Good G+, little G- because they cannot penetrate the outer membrane of G-
PCN side effects
anaphlaxis- rare but when it happens it is severe. 10% of pts allergic to PCN will also react to cephalosporin, but its ok to give ceph if all they have get with PCN is a rash. 100% of its with mono will develop a PCN rash.
PCN preg category
B
PCN G
Natural penicillin, came from a mold. It is semi bulk, cannot get through porins. It is IV only, and is the DRUG OF CHOICE FOR SYPHILIS!
PCN V
Natural penicillin, only orally active. Cannot fit through porins, is semi-bulky.
Antistaphylococcal PCN
these are resistant to penicillinase. These are used for treating Methicillin sensitive S. Aureus (MSSA). Can penetrate the CNS only if there is active inflammation there. So this is a narrow- spectrum drug.
Aminopenicillin drugs
ampicillin, ampicillin/sulbactam, amoxicillin, amoxicillin/clavulanic acid
Aminopenicillin gram activity
G+ and a little G- (more than PCN because these are smaller and can fit through more porins)
Aminopencillin use
WHEN GIVEN WITH BETA-LACTAMASE INHIBITORS can be used fro MSSA.
Ampicillin use
IV for meningitis
Amoxicillin use
its absorbed better than ampicillin. Used for almost everything.
B-lactamases
kill the b-lactam ring of the antibiotic. these are acquired by bacteria through plasmid transfer/conjugation –> antibiotic resistance.
B-lactamase inhibitors
keep b-lactameses busy and away from the antibiotics. Must be given with smaller sized abx whose bulkiness does not protect them from b-lactamases.
antipseudomonal drugs
piperacillin, ticarcillin, carbenicillin. Piperacillin is most Potent.
antipseudomonal gram activity
Improved G- activity, decreased G+ activity
when do you use an antipseudomonal?
treats P. aeruginosa (green skin infection!) and will treat MSSA if combined with a beta-lactamase inhibitor. Used empirically to create hospital acquired infections (nosocomial)
pereracillin/tazobactam
an antipseudomonal + b-lactamse inhibitor to treat MSSA
monobactams- how do they work?
cell wall inhibitors
Aztreonam
a monobactam that can be given even if a pt is allergic to penicillins!
monobactam gram activity
only G- rods
Aztreonam pregnancy category
B
Cephalosporins, how do they work?
Cell wall inhibitors. Cidal. Have the same mechanism as PCN. They are resistant to pencillinases, but there are now cephalosporinases….
1st generation cephalosporin drugs
Cephalexin and cefazolin
1st generation cephalosporin activity
good G+ and MSSA coverage. PEK G- coverage. No anaerobic coverage
PEK G-
P. mirablis
E. coli
K. pneumo
2nd generation cephalosporin drugs
cefuroxime, cefaclor, cefoxitin, cefotetan
2nd gen cephalosporin activity
Good G+ and MSSA coverage. HENPEK G- coverage. IV will cover B. fragilis (an anaerobe)..
HENPEK G-
H. flu
Enterobacter aerogenes
Neisseria
P. mirablis
E. coli
K. pneumo
cefotetan side effects
a disulfiram-like reaction and bleeding disorder
3rd generation cephalospirin drugs
cefdinir, ceftriaxone, ceftazidime
3rd gen ceph activity
variable G+, good G-. will cover p.aeruginosa, but resistance is becoming an issue. will also cover lyme disease
ceftriaxone
used to treat goborrhea. Not renally eliminated. good bone and BBB penetration.
4th generation cephalosporin drugs
cefepime
cefepime activity
Good G+ and G-, MSS and P.aeruginosa. it is consistently useful in enterobacter and serratia.
5th generation cephalosporin drug
ceftaroline
5th generation cephalosporin activity
Good G+, MSSA, S. pneumo. Similar to vanco+ ceftriaxone efficacy.
Vancomycin, how does it work?
Cidal. Inhibits cell wall construction by preventing glycosylatyion (prevents glycan units)
Vancomycin activity
good G+ and MRSA. treats c.diff when given orally (2nd line tx).
Vanco side effect
red man syndrome can happen when you give it infusion too rapidly. this is from a histamine release.
Vancomycin pregnancy category
C
Tetracyclines, how do they work?
They are protein synthesis inhibitors (remember that human ribosomes are similar to bacterial ribosomes). They reversibly bind to the 30S ribosomal subunit, inhibiting protein synthesis of the bacteria. They are Static.
Tetracycline drugs
tetracycline, doxycycline, minocycline
Tetracycline activity
G+, G-, some atypical, some anaerobes.
When would you use tetracycline drugs?
Known for treatment of rikettsial diseases like Lyme and Rocky mountain spotted fever. Also common in acne tx.
tetracycline pregnancy category
D
Tetracycline side effects
GI upset, growth issues, tooth discoloration and enamel dysplasia and sun sensitivity.
Macrolides, how do they work?
Static. protein synthesis inhibitor, bind irreversibily to the 50S subunit on the bacterial ribosome.
Macrolide activity
Good G+ and atypical coverage
Macrolide drugs
erythromycin, azithromycin, clarithromcin. (Erythromycin is poorly absorbed)
When would you use azithromycin?
chlamydia, and walking pneumonia (DOC)
Macrolide drug side effects
N/V/D, QT prolongation –> arrhythmia
Clindamycin, how does it work?
Protein sythesis inhibitor that has the same mechanism of action as Macrolide drugs. It can be static or cidal, depending on the organism.
Clindamycin activity
G+ and anaerobes
Clindamycin pregnancy category
B
Most likely abx to result in c.diff
Clindamycin
Aminoglycosides, how do they work?
Protein synthesis inhibitors. Cidal. Bind to 30S ribosomal subunit irreversibly. Used in conjunction with b-lactams or vancomycin.
Aminoglycoside drugs
gentamycin, tobramycin, amikacin
Aminoglycoside activity
Only tx aerobic G+/-
Aminoglycoside pregnancy category
C/D
Aminoglycoside side effects
ototoxicity and nephrotoxicity.
Fluoroquinolones, how do they work?
DNA replication inhibitors. All interfere with topoisomerases. Gen 1 and 2 work better on TOPO II, Gen 3 and 4 work better on TOPO IV.
TOPO II
A DNA gyrase, nicks the strand, allows uncoiling, then re-seals.
TOPO IV
cuts 2 strands instead of 1, releasing the daughter strand as well.
Fluoroquinolone first gen
Nalidixic acid –> quinolone.
Fluoroquinolone 2nd gen drug
Ciprofloxacin
Ciprofloxacin activity
It has atypical coverage, G+ cocci, and G-rods
3rd generation Fluoroquinolone drug
levofloxacin
Levofloxacin activity
atypicals, G+ cocci, G-rods, and activity against s.pneumo. Its a respiratory Fluoroquinolone.
4th gen Fluoroquinolone drug
Moxifloxacin
Moxifloxacin activity
atypicals, G+ cocci, G-rods, and activity against s.pneumo. Addition of anaerobe activity. Its a respiratory Fluoroquinolone. The only one excreted in bile, all others are renally excreted.
Fluoroquinolone activity, general
All have good gut activity and in general are good for UTI.
General Fluoroquinolone precautions/side effects
N/V/D, Drug interactions (its a cytochrome inhibitor), headache, dizziness, QT prolongation (Moxi>levo> cipro), photosensitivity, tendon rupture in elderly. Not recommended in kids, unless its a complicated UTI or CHF pt with p.aeruginosa infection.
Sulfonamides, how do they work
Static. Interfere with folic acid synthesis, which is needed for bacterial DNA synthesis. These are often COMBINED with trimethoprim or pyrimethamine, which block a step downstream in bacterial folate synthesis. THis provides synergism of drug activity.
When would you use a sulfonamide?
to treat MRSA. To treat prophylactively for PCP (opportunistic pneumonia). To treat a UTI caused by e.coli.
Sulfonamide drug
sulfamethaxazole/trimethoprim–> bactrim
Sulfonamide side effects
crystalluria, rashes, kericterus of newborn. Don’t give if pt has a known G6PD deficiency. Watch out for drug interactions, it easily displaces other protein bound drugs.
Sulfonamide pregnancy category
B. If mom is near delivery it is a D because of Kericterus in newborn.
Metronidazole, how does it work?
Cidal. Treats anaerobes and protozoa.
When would you use Metronidazole?
used in vaginal yeast infection.s First line of treatment for C.diff.
Metronidazole side effects
Disulfiram-like reaction, no EtOH while taking.
Metronidazole pregnancy category
B
Nitrofurantoin, how does it work?
Cidal. It is metabolized really fast and renal excreted, so only gets to function in the lower UTI.
When would you use nitrofurantoin?
For a lower UTI. CrCl needs to be > 60 ml/min, otherwise can get toxicity.
Antifungals, general
keep in mind that these are hard to kill without harming the host because we are both eukaryotes. The thing we do target on these is their chitin cell wall.
Amphotericin B
An anti fungal that inserts itself into the fungal membrane, creating leaky pores. Can be static or cidal.
When would you use amphotericin b?
in a life-threatening systemic fungal infection. It is broad spectrum, but is toxic and renal damage is common –> renal failure.
Ketoconazole
its a fungistatic, it inhibits the fungus’s CYP450 enzymes, which prevents them from making ergosterol.
When would you use ketoconazole?
its used topically. Its not that good, because it lacks specificity for fungi vs. humans.
ketoconazole pregnancy category
C when taken orally
amphotericin B pregnancy category
B
Fluconazole
its a fungistatic, has the same MOA as ketoconazole, but it is better because it is more selective for the fungi. Unlike Itraconazole, you do not need an acidic environment for it to work.
Fluconazole pregnancy category
C
Itraconazole
Fungistatic, same MOA as ketoconazole but has better selectivity. You need a high stomach acid in order for it to be absorbed.
Itraconazole side effects
Has a BLACK BOX warning for QT prolongation –> arryhtmias –> CHF
Itraconazole pregnancy category
C
Voriconazole
an anti fungal that is better than amphotericin b for aspergillosis. Drug interactions with this are common. Pts can have auditory and visual hallucinations if trough levels are too high
Voriconazole pregnancy category
D
Posaconazole
an anti fungal used in prevention of candida and aspergillus infections in immunocompromised patients.
Posaconazole pregnancy category
C
terbinafine
an anti fungal that is used topically, especially for nail infections.
Griseofulvin
an antifungal, used for topical infections. Need to take with a Greasy fatty meal in order for it to be absorbed. Usually takes 6-12 months of tx.
