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antimicrobials: side effects & resistance
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158
Art History
Pre-School
02/10/2012

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Term
generation of penicillins that are lactamase-resistant
Definition
2nd gen (methicillin, nafcillin, oxacillin)
Term
use penicillinase inhibitors with this generation of penicillins
Definition
3rd gen (ampicillin, amoxicillin)

Ex: clavulanic acid, sulbactam, tazobactam
Term
Penicillins that are "antipseudomonal"
Definition
4th gen (ticarcillin)
Term
major SE of 3rd gen penicillins
Definition
C.diff colitis (ampicillin, amoxicillin)
Term
SE of methicillin
Definition
interstitial nephritis
Term
name the beta lactamase inhibitors (3)
Definition
clavulanic acid, sulbactam, tazobactam
Term
exception to the "ph" rule for cephalosporins
Definition
cefazolin (only 1st gen to not have a "ph" in it)
Term
3rd gen cephalosporin that is too lipid soluble (and thus too protein bound) to cross BBB
Definition
cefoperazone
Term
prophylaxis for gonorrhea
Definition
ceftriaxone
Term
always safe in meningitis treatment
Definition
3rd gen cephalosporin (esp ceftriaxone); exception is cefoperazone
Term
cephalosporin used for pseudomonas
Definition
ceftazidime (3rd gen)
Term
cephalosporins with disulfiram-like effect
Definition
those w/ methylthiotetrazole group (e.g. cefamandole, cefoperazone)
Term
what type of penicillin allergy contraindicates the use of cephalosporins?
Definition
anaphylaxis (but not rash)
Term
Name monobactams
Definition
aztreonam
Term
name carbapenems
Definition
- imipenem (remember, always with cilastatin)

- meropenem
Term
action of cilastatin
Definition
renal dihydropeptidase 1 inhibitor: prevents imipenem (a carbapenem) from too quick of a degradation & renal excretion
Term
Which is used in pts w/ G(-) infection, with a penicillin allergy, and a decreased GFR?
Definition
Aztreonam (monobactam): used when there is a penicillin allergy, and aminoglycosides can't be used because of decreased renal function

Is a possible Tx for pseudomonas
Term
MOA of aztreonam (a monobactam)
Definition
similar to penicillins: binds to PBP3 & is resistant to beta lactams
Term
a penicillin-like drug that is synergistic with aminoglycosides
Definition
imipenem/cilastatin
Term
red man syndrome
Definition
vancomycin (administered too fast)
Term
red man syndrome prevention
Definition
slow infusion & antihistamines
Term
T/F for side effects of Vanco:

Ototoxicity
Hepatotoxicity
Nephrotoxicity
Thrombophlebitis
Myalgias
Tendonitis
Osteomalacia
Chills/fever
Definition
T- Ototoxicity
F- Hepatotoxicity
T- Nephrotoxicity
T- Thrombophlebitis
F- Myalgias
F- Tendonitis
F- Osteomalacia
T- Chills/fever
Term
mechanism of resistance to vanco
Definition
change D-ala D-ala to D-ala D-lac
Term
protein synthesis inhibitor that is bacteriocidal
Definition
Aminoglycosides
Term
Use these protein synthesis inhibitor in combination w/ beta lactams & aztreonam
Definition
aminoglycosides
Term
aminoglycoside used in bowel surgery
Definition
neomycin (b.c. it's poorly absorbed)
Term
protein synthesis inhibitors that are chelators of divalent cations?

What is the implication of this?
Definition
Tetracyclines (can't give with meals)

(as a side-note, fluoroquinolones are also mild chelators, and cannot be coadministered w/ antacids)
Term
PSI that shouldn't be used when expired?
Definition
Tetracyclines, they cause Fanconi's syndrome (proximal tubule dysfunction, mechanism unknown)
Term
PSI for MRSA
Definition
Linezolid
Term
Tetracycline used in renal failure? why?
Definition
doxycycline; because it is completely fecally eliminated
Term
Resistance to macrolides
Definition
methylation of binding site on 30S (23S rRNA)
Term
Tx for atypical pneumonias

list the atypical pneumonias (3)
Definition
Macrolides

chlamydia pneumoniae, mycoplasma pneumoniae, legionella pneumoniae
Term
Pro-kinetic antibiotics
Definition
Macrolides
Term
increase QT interval
Definition
Macrolides
Term
PSI that decreases P450
Definition
macrolides
Term
cholestasis (cholestatic hepatitis)
Definition
macrolides
Term
PSI with Eosinophilia & skin rash
Definition
macrolides
Term
Gray baby syndrome
Definition
Chloramphenicol (from insufficient glucuronyl transferase in neonates)
Term
PSI causing anemia & aplastic anemia from bone marrow supression?
Definition
Chloramphenicol
Term
reserved for severe salmonella & bacterial meningitis in beta-lactam sensitive patients
Definition
chloramphenicol
Term
what is the spectrum of chloramphenicol?
Definition
very wide (but limited b.c. of side effects)
Term
what is the resistance for chloramphenicol?

What is it carried on?
Definition
acetyl transferase that inactivates the drug

plasmid
Term
mechanism of resistance for tetracycline
Definition
pumps
Term
contraindicated in pregnancy because it decreases bone growth
Definition
tetracyclines (remember, they are chelators)
Term
Tooth enamel dysplasia
Definition
tetracyclines (chelators)
Term
Fanconi's syndrome when expired
Definition
Tetracyclines
Term
Hepato & vestibular toxicities; mechanism of resistance is increased transport pumps. PSI
Definition
tetracycline
Term
#1 reason for noncompliance noncompliance with macrolides
Definition
GI distress (remember it is pro-kinetic)
Term
PSI that will increase coumadin concentrations
Definition
macrolides (p450 inhibitor)
Term
spectrum of clindamycin
Definition
narrow: anaerobic infections (ABC) such as those caused by aspirational pneumonia
Term
most important side effect of clindamycin
Definition
C. diff colitis
Term
mechanism of resistance of clindamycin
Definition
methylation of 30S (same as macrolides)
Term
How is aminoglycoside resistance carried?
Definition
Plasmid-mediated (group transferases)
Term
ethacrynic acid and aminoglycosides share this side effect
Definition
ototoxicity (all loop diuretics)
Term
This side effect is a major problem when aminoglycosides are combined with cephalosporins
Definition
nephrotoxicity
Term
PSI that causes MAO inhibition & thrombocytopenia
Definition
Oxazolidinones (e.g. linezolid)
Term
Use of oxazolidinones
Definition
VRSA (e.g. Linezolid, a PSI)
Term
MOA of sulfonamides (what else shares this?)
Definition
inhibits dihydropteroate synthase

p-aminosalicylic acid (PAS) and pyramethamine (an antiprotozoal for P.falciparum & toxo)
Term
3 mechanisms of resistance to sulfonamides
Definition
1) altered dihydropteroate synthase
2) decreased uptake
3) increased PABA synthesis
Term
hemolytic anemia in G6PD def. Kernicterus in newborns b.c. it displaces unconjugated bilirubin from albumin.
Definition
Sulfonamides
Term
Tubulointerstitial nephritis from this folate inhibiting drug
Definition
sulfonamide
Term
MOA of trimethoprim
Definition
inhibits dihydrofolate reductase
Term
why is TMP good for UTIs?
Definition
b.c. it is excreted unchanged into the urine
Term
Drug causing: megaloblastic anemia, leukopenia, granulocytopenia.

Hint: it is an antibacterial, it isn't a penicillin or PSI
Definition
Trimethoprim
Term
what is the common denominator for these drugs:
Furosemide, clelcoxib, probenecid, acetazolamide
Definition
they are all sulfa drugs (that don't have "thio" or "sulf" in the name
Term
are fluoroquinolones bacteriocidal or bacteriostatic?
Definition
bacteriocidal
Term
don't take this antibiotic with antacids (not tetracycline)
Definition
fluoroquinolones (weak divalent cation chelator)
Term
Drug that causes tendonitis & tendon rupture in adults?

(what do you get in kids?)
Definition
Fluoroquinolones

Myalgias & leg cramps

These drugs are contraindicated in preganancy because of the connective tissue issues
Term
2 mechanism of resistance for fluoroquinolones
Definition
1) chromosomal mutation in DNA gyrase
2) efflux pumps
Term
T/F: metronidazole is bacteriostatic?
Definition
False, bacteriocidal
Term
Protozoal infections that you use metronidazole for?
Definition
Trichomonas vaginalis
Giardia lamblia
Entameoba histolitica
Term
what anaerobe can't you use metronidazole on?
Definition
actinomyces (good for the others, though)
Term
BMT therapy
Definition
Bismuth, metronidazole, tetracycline (or amoxicillin)

used for elimination of H.pylori (the cheaper drug regimin). The other regimin is Omeprazole, amoxicillin, and clarithromycin.
Term
H pylori eradication protocols?
Definition
BMT

Amoxicillin, Clarithromycin, Omeprazole

usually no longer than 14 days
Term
MOA of polymyxin
Definition
pokes holes in bacteria (cationic detergent; used in thayer martin media to eliminate G(-) rods)
Term
Use polymyxin for?
Definition
very resistant pseudomonas
Term
polymyxin toxicities?
Definition
neurotoxicity & acute tubular necrosis
Term
Possible drugs used for Tx of TB (5)
Definition
RIPE & streptomycin

rifampin, INH, ethambutol, pyrazinamide
Term
prophylaxis of TB
Definition
INH
Term
prophylaxis of MAC
Definition
azithromycin
Term
drugs used for Tx of M.leprae (3)
Definition
Dapsone, rifampin, clofazimine
Term
MOA of clofazimine
Definition
1) binds guanines --> inhibits prolif
2) increase PLA2 in bacteria --> toxic damage
Term
mycobacteria drug w/ SE of: skin problems & discolorations & eosinophilic enteritis
Definition
clofazimine (leprae drug)
Term
drug w/ SE of red-green color blindness
Definition
Term
which drugs in RIPE treatment have hepatotoxicity?
Definition
"IPE" (INH, pyrazinamide, ethambutol)
Term
MOA of ethambutol
Definition
blocks arabinosyl transferase --> decreased carbohydrate polymerization in mycobacterium cell wall
Term
where is pyrazinamide active?
Definition
in the phagosomes (it is stable at low pH); this is why it's a good TB drug, because it is active where the TB are held
Term
MOA of isoniazid
Definition
decreased synthesis of mycolic acid
Term
is INH a prodrug?
Definition
yes, it needs activation by bacterial catalase-peroxidase
Term
INH SE (3)
Definition
Neurological
Hepatic
Lupus
Term
4 R's of rifampin
Definition
RNA polymerase inhibitor (DNA-dep RNA polymerase)
Revs up the microsomal P450 (inducer)
Red-orange body fluids
Rapid resistance if used alone
Term
What drug does rifampin delay resistance to in Tx of leprosy?
Definition
dapsone
Term
prophylaxis of meningococcal
Definition
rifampin
Term
prophylaxis of H.influenza group B
Definition
rifampin
Term
SE of rifampin (3)
Definition
minor hepatotoxicity (not as much as the "IPE" part)
orange body fluids
P450 inducer
Term
does amphotericin B cross BBB?
Definition
no, must give intrathecally for meningitis
Term
Mechanism of resistance to amphotericin B
Definition
resistance is uncommon:
- altered or decreased amount of ergosterol
Term
What is special about amphotericin B nephrotoxicity?
Definition
cumulative over lifetime (give fluids during administration to minimize damage)
Term
Drug with "Shake and bake" symptoms from cytokine storm
Definition
Amphotericin B (fever & chills)
Term
antifungal that can decrease EPO
Definition
amphotericin B

(this causes anemia)
Term
name SE of amphotericin B (5)
Definition
-"Shake & bake" (fever & chills)
- Nephrotoxicity (cumulative)
- reduced EPO --> anemia
- Arrythmias
- IV phlebitis (amphoterrible)
Term
MOA of flucytosine
Definition
5FU-like: inhibits S-phase by preventing thiamine synthesis
Term
SE of flucytosine (3)
Definition
- N/V & diarrhea
- Bone marrow suppression
- Alopecia
Term
flucytosine is usually used in combination with what drug?
Definition
amphotericin B
Term
MOA of -azoles
Definition
prevents P450 conversion of lanosterol --> ergosterol
Term
which azole can cross BBB and be used for crytococcus meningitis (AIDS)
Definition
fluconazole
Term
mechanism of resistance of -azoles and flucytosine
Definition
decreased sensitivity of target enzymes to drug
Term
-azole used for hypercortisolism
Definition
ketoconazole (gynecomastia is a SE)
Term
SE of -azoles (5)
(one is rare)
Definition
- gynecomastia
- Fever, chills
- GI upset: vomiting, diarrhea
- skin rash
-rare liver toxicity
Term
inhibits synthesis of B-1,2 glycan
Definition
echinocandin/caspofugin (antifungal)
Term
used for invasive aspergillus
Definition
echinocandin/caspofugin
Term
Systemic antifungals used for systemic fungal diseases
Definition
-Ampho B (no CNS penetration)
- Flucytosine (narrow spectrum: candida & crypto; used in combination of Ampho B)
- Azoles
- Echinocandin/caspofugin (invasive aspergillosis)
Term
disrupts microtubules in fungi
Definition
griseofulvin
Term
accumulates in keratin (esp nails)
Definition
griseofulvin
Term
SE of griseofulvin (3)
Definition
- Disulfiram like
- Confusion & vertigo
- induces P450
(also Carcinogenic & teratogenic)
Term
is griseofulvin teratogenic?
Definition
yes
Term
Inhibits squalene epoxidase
Definition
Terbinafine (used for onchomycosis)
Term
Drugs used for superficial infections (3 systemic; 1 topical)
Definition
Systemic:
- griseofulvin
- terbinafin
- -azoles

Topical:
- Nystatin
Term
SE of nystatin (2)
Definition
- contact dermatitis
- steven johnson syndrome
Term
MOA of nystatin?
Definition
same as ampho B (resistance is same, too)
Term
MOA of pyramethamine
Definition
inhibits protozoal DHF reductase (same as TMP)

(best for P.falciparum &
DOC when used in combo w/ sulfadiazine for Toxo)
Term
MOA of suramin
Definition
unknown (?messes up protozoal energy metabolism)

(DOC for T.brucei rhodensiense when there is no CNS involvement)
Term
MOA of melarsoprol
Definition
inhibits sulfhydryl groups in parasite enzymes

(DOC for T.brucei if there is CNS involvement)
Term
MOA of nifurtimox
Definition
ROS production

(Tx for T.cruzei)
Term
MOA of Sodium stibogluconate
Definition
inhibits protozoal PFK --> inhibits glycolysis

(Tx for leishmaniasis)
Term
MOA of chloroquine
Definition
Blocks heme-polymerase --> toxic hemoglobin breakdown products damage/kill plasmodium

(DOC for falciparum & malaria; add primaquin for ovale & vivax b.c. primaquin needed to eliminate exoerythrocytic infection)
Term
MOA of mefloquine
Definition
unknown

used as prophylaxis for chloroquine resistant malarias
Term
MOA of quinine
Definition
unknown

Used as TREATMENT for chloroquine resistant malarias
Term
antimalarial with SE of:
Gi distress, pruritis, headache, dizziness, hemlysis, ocular dysfunction
Definition
Chloroquine, hydroxychloroquine
Term
anitmalarial w/ SE of:
NVD, dizziness, syncope, extrasystoles, CNS effects (rare)
Definition
mefloquine
Term
antimalarial with these SE:
GI distress, headache, dizziness, neutropenia, hemolysis
Definition
Primaquin
Term
antimalarial w/ these SE:
GI distress, cinchonism, CNS effects, hemolysis, hepatotoxicity
Definition
Quinine
Term
describe cinchonism
Definition
- flushed, sweaty
- tinnitis
- lichenoid reaction
- vertigo
- NVD
Term
avoid this antimalarial in psoriasis
Definition
chloroquine
Term
avoid this antimalarial in seizures, psyche disorders, & CV conduction defects
Definition
mefloquine (can cause syncope/extrasystoles)
Term
avoid this antimalarial in pregnancy, G6PD def, and autoimmune disorders
Definition
Primaquine
Term
avoid this antimalarial in pregnancy
Definition
quinine
Term
MOA of amatadine
Definition
viral penetration/uncoating (M2 protein on influenza A)
Term
which antiviral can be used as a Tx for parkinsons?
Definition
Amantidine (because it induces release of dopamine from nerve terminals)
Term
antiviral that causes ataxia, dizziness, & slurred speach?
Definition
amantadine
Term
Mechanism of resistance to amantadine
Definition
mutated M2 protein on influenza A (~90% are resistant, so it is only used for prophylaxis)
Term
Amantidine without the CNS effects
Definition
Rimantidine
Term
Two antivirals that inhibit viral neuraminidase
Definition
Oseltamivir, Zanamivir

(Tx for influenza A & B)
Term
antiviral that is a competetive inhibitor for IMP dehydrogenase
Definition
ribavirin

(used in chronic HepC & RSV)
Term
Ribavirin SE
Definition
- Hemolytic anemia
- Severe teratogen (makes since since it's a purine analog)


(used in chronic HepC & RSV)
Term
non-HIV tx, antiviral Guanosine analogs
Definition
Acyclovir & Gancyclovir
Term
Activation of Acyclovir
Definition
phosphorylated by HSV/VZV thymidine kinase

(guanosine analog goes on to inhibit viral DNA polymerase by chain termination)
Term
MOA of gancyclovir
Definition
phosphorylated (activated) by CMV viral kinase or HSV/VZV thymidine kinase --> guanosine analog inhibits viral DNA pol
Term
SE of acyclovir
Definition
NONE
Term
SE of gancyclovir
Definition
- leukopenia, neutropenia, thrombocytopenia

- renal toxicity
Term
mechanism of resistance to acyclovir & gancyclovir
Definition
- Acyclovir: lack of viral thymidine kinase (never gets activated)

- Gancyclovir: mutated CMV DNA pol or lack of viral thymidine kinase
Term
Foscarnet toxicity
Definition
renal
Term
MOA of foscarnet
Definition
viral DNA pol inhibitor: binds to pyrophosphate-binding site

this drug, unlike acyclovir/gancyclovir does not require activation
Term
mechanism of resistance of foscarnet
Definition
mutated DNA pol
Term
Metronidazole SE (2)
Definition
- metallic taste
- disulfiram like
Term
MOA of Artemether & Artesunate
Definition
blocks P.falciparum ER ATPase
Term
2 drugs that block P.falciparum ER ATPase
Definition
Artemether & Artesunate
Term
drugs that can cause G6PD def pts to hemolyze? (3)
Definition
Sulfonamides
INH
quinine derivatives (esp primaquin)
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