Antimicrobial Pharmacology Flashcards
What bugs does amoxicillin / ampicillin cover?
HELPS
-> remember we have extended gram negative and anaerobe coverage (especially with beta lactam inhibitors paired)
Hemophilus, H. pylori E. coli / Enterococcus Listeria Proteus mirabilis - UTI's Salmonella / Shigella
+ Lyme disease (robin of Ixodes)
How do nafcillin and ampicillin differ with regards to resistance?
Ampicillin - still penicillinase sensitive, just wider spectrum. Needs to be combined with a Beta-lactamase inhibitor to retain activity
Nafcillin - Penicillinase resistant, narrower spectrum. Works by having a bulky R group which is not cleaved by penicillinases, but MRSA is still resistant due to altered penicillin-binding protein.
What drug is used for prophylaxis in patients at high risk for endocarditis undergoing surgical (i.e. cystoscopy) or dental procedures?
Amoxicillin - think of the guy’s teeth getting punched out in sketchy.
Are piperacillin / ticarcillin susceptible to beta-lactamases? What are they good for?
YES! They are in the amoxicillin / ampicillin sketch.
However, they are the pipers in the tiger suit charming mona lisa, in gas masks.
They are good against P. aeruginosa and anaerobes, but they MUST be paired with a Beta-lactam inhibitor (i.e. tazobactam / sulbactam)
What is the main use for 1st generation cephalosporins? And name a few.
Surgical prophylaxis + PEK UTIs -> proteus, E. coli, Klebsiella. More gram + coverage than other cephalosporins.
Think of General “Lex” flexing and his fez
Cephalexin, Cefazolin
What is the main use for 2nd generation cephalosporins? And name a few.
Cefotetan (tea), Cefoxitin (general fox), cefuroxime (furious)
HENS - Hemophilus, Enterobacter, Neisseria, Serratia
Pretty low yield overall
What is the main use for 3rd generation cephalosporins and name a few.
Great CNS penetration -> Ceftriaxone, cefotaxime (used in neonates so no biliary sludging), cefpodixime
Used for treatment of common meningitis, and better gram negative coverage than 1st two generations: Neisseria, Hemophilus, and Streptococcus pneumoniae.
What 3rd generation cephalosporin is most useful for nosocomial pneumonia?
If you have to cover for Pseudomonas -> Ceftazidime - general Taz’s wife is Mona Lisa.
Ceph TAZ for pseudomone-AZZ
What is usage of the 4th generation cephalosporin and what is it called?
Called Cefepime (general prime) -> know that it is broad spectrum and also next to the Mona Lisa poster -> covers Pseudomonas
Also wearing meningitis helmet -> good coverage for meningitis.
What is the usage of the 5th generation cephalosporin and what is it called? Does it have Pseudomonas coverage?
Think of General Tara knocking over the emperor -> only cephalosporin to have MRSA coverage
NO Pseudomonas coverage -> not next to the poster.
What are the mechanisms of resistance to cephalosporins?
- Altered PBPs
2. Extended spectrum beta lactamases - (they are generally resistant to normal beta lactamases due to side changes)
What is the only monobactam and what is its spectrum of activity? Why is it notably useful?
Aerobic gram negatives only -> think of the bellows. Mona Lisa stands by and is covered by this drug.
Notably useful because it has no side chain -> no cross-reactivity with penicillin. Think of the penicillin pencil sticking out of the robot, who is still being treated.
What is imipenem always administered with and why?
Also given with cilastin, an inhibitor of dehydropeptidase 1, which is a renal tubular enzyme which normally breaks down imipenem.
What is the primary clinical use of carbapenems in general and what is the side effect of concern?
Used broad spectrum for all types of infections, especially against organsms making extended-spectrum beta-lactamases (think of rainbow beta-lactamase guys crawling over the wall). -> ESBLs
Side effect of concern - seizures, especially imipenem. Also cause Rash and GI distress (think of robot getting covered in poop / poopy rash)
What is the mechanism of Vancomycin / why is does it work where beta-lactams don’t?
Does not bind to PBPs, instead binds directly to what PBPs are binding, the D-ala-D-ala motif.
-> beta-lactamases and altered PBPs will have NO effect, since vancomycin doesn’t interact with this.
Resistance mechanism is just switching to D-ala-D-lac
Why is vancomycin added to meningitis regimens?
To cover penicillin-resistant Strept pneumo. (i.e. altered PBPs).
What are the side effects of vancomycin?
Nephrotoxicity - renally excreted so be careful
Ototoxicity - broken ear
Thrombophlebitis - vines coming up
Red man syndrome
DRESS syndrome may also occur
What is the mechanism of resistance to tetracycles?
Think of the efflux bike pump. Can also modify the 30S ribosome
How are tetracyclines eliminated, and why are expired ones an issue?
Eliminated fecally, so safe to use in renal failure -> think of the colonic poop tube in the back.
Expired ones are hella problematic cuz they can cause Fanconi syndrome (proximal absorption defect, including a Type II RTA).
What are the side effects of macrolides?
Increased GI motility
Prolonged QT
Cholestatic hepatitis (failure to excrete bowel, think of the Gi soldier’s yellow face)
CYP inhibition
What is the most commonly tested indication for Clindamycin?
Aspiration pneumonia -> since it has good coverage against gram positives of the mouth, as well as anaerobes
What is a common treatment regimen for severe polymicrobial infections of the female genital tract (i.e. endometritis)?
Clindamycin + gentamicin -> think of the karate lady doing Pec fly’s with the ovaries while having psi’s in her pockets
Give four other indications for clindamycin than aspiration pneumonia and female GU infections.
Trainer with MRSA tattoo holding pie:
- MRSA
- Group A strept
Guy who has falling and perforated his pants:
3. Clostridium perfringens
Plants all around the front:
4. Gardnerella vaginosis (Metronidazole can also be used)
What are the indications for chloramphenicol?
Used to treat meningitis in developing countries (kid with helmet hitting ball)
Also used to treat Rickettsia ricketsii infection of pregnant mothers (doxycycline contraindicated in pregnancy)
What are the side effects of chloramphenicol?
- Dose-dependent anemia - deflated RBCs
- Aplastic anemia - gray bone
- Gray baby syndrome
What is gray baby syndrome?
Gray baby syndrome - hypothermia, flaccidity gray color, and shock since infants have low UDP-glucuronyltransferase activity needed to properly inactivate the drug
What is the activity / usage of Linezolid?
Gram + infections, especially MRSA and vancomycin-resistant enterococcus
What are the side effects of linezolid?
- Peripheral neuropathy - glove and stocking of crime investigator
- Optic neuropathy - snapped camera cord
- Thrombocytopenia most commonly, even pancytopenia
- Serotonin syndrome - weak MAOI
What is the general indication of aminoglycosides? Mechanism of action? What are they used with?
severe AEROBIC gram NEGATIVE infections (sepsis).
Usually combined with a cell wall active drug (esp. beta lactams or vancomycin) to enhance penetration. They are then uptaken thru the cell membrane in an oxygen-dependent transport method
They are 30S ribosome bacterioCIDAL (think of the assassin killing the dude).
What two luminal aminoglycoside agents are used for bowel prep before surgery or treating intraintestinal parasites? (Aminoglycosides have poor oral absorption and are usually given IV)
Neomycin - think of neo at the ditch
Paromomycin - i guess it’s not actually paramycin lol
What aminoglycosides are generally used against pseudomonas?
TAG
Tobramycin
Amikacin
Gentamicin -> this one is used for a lot of gram negative septicemia
What is the role of aminoglycosides in treating enterococcus infection?
Often used to treat enterococcus endocarditis -> good activity against this gram positive bug with the help of vancomycin.
What are the mechanisms of resistance against aminoglycosides?
- Bacterial acetylation enzymes, or other transferase enzymes i.e. phosphorylation, adenylation - think of the enterococcus throwing shurikens at the tobramycin cobra
- Porin mutation -> which brings the aminoglycosides into the cell
- Modification of ribosome binding sites
What are the adverse effects of aminoglycosides?
- Nephrotoxicity - Acute Tubular Necrosis - Killing is max concentration dependent so try to keep the troughs low
- Ototoxicity / Vestibulotoxicity
- Neuromuscular blockade - contraindicated in myasthenia gravis due to severe weakness
- Teratogenicity - deafness in the newborn - tarantula on gong
What drug can be used as a monotherapy against latent TB?
ISOniazid - think of the lone ranger next to the sleeping guy.
What is the mechanism of action of isoniazid (INH)? How is it activated / how do you get resistance to it?
Inhibits synthesis of mycolic acids (think of the fuchsia cacti on the horizon)
It is a prodrug converted by Kat-G (Catalase-peroxidase in mycobacterium, think of the tiger leaping at the isolated ranger in sketchy)
-> resistance is via downregulation of KatG
What patients are at greatest risk for toxicity from isoniazid? How does it interact with other drug levels?
Slow acetylators - metabolism occurs in liver initially by N-acetyltranferase
It is a CYP inhibitor (while rifampin is a CYP inducer)
What are the most common adverse effects of isoniazid therapy?
INH
Injures
Nerves - peripheral neuropathy due to increased B6 wasting -> give with pyridoxine
Hepatocytes - hepatitis is common adverse effect, must monitor liver function tests -> think of the cow liver spot (all RIPE drugs) and LFT flag held up by slow acetylator
Also causes drug-induced lupus -> wolf next to lone ranger
MUDPILES - metabolic acidosis