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283 Cards in this Set
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selective toxicity?
|
injury of invading organisms without injury to the host
|
|
concentration-dependent killing?
|
the more the drug concentration exceeds the MIC, the greater the rate of killing;
Cmax/MIC or AUC/MIC |
|
examples of drugs with concentration-dependent killing?
|
fluroquinolones
aminoglycosides |
|
time-dependent killing?
|
rate of killing is dependent on the length of time the drug concentration remains above the MIC
|
|
example of drug with time-dependent killing?
|
β-lactams
|
|
MIC?
|
minimum inhibitory concentration
|
|
post-antibiotic effect?
|
bacteria do not immediately resume growth once the antibacterial concentration drops below the MIC
|
|
bacteria susceptibility to PAE?
|
most antibiotics for Gm(+)
only fluoroquinolones and aminoglycosides fro Gm(-) |
|
superinfection and examples?
|
secondary infection caused by antibiotic;
oral or vaginal candidiasis; pseudomembranous colitis (c. difficile) |
|
intrinsic resistance?
|
absence of drug target
inability of drug to penetrate to site of action |
|
acquired drug resistance?
|
antibiotics help select for drug resistant organisms but do not cause drug resistance
|
|
how do organisms acquire resistance?
|
random mutations
transduction transformation conjugation |
|
major concern with conjugation?
|
transfer of plasmids that code for multiple drug resistance
|
|
transformation?
|
acquisition of genetic material from environment coding for drug resistance by competent bacteria
|
|
two major competent pathogens?
|
s. pneumoniae
n. meningitides |
|
biomechanical mechanisms of drug resistance?
|
decreased intracellular concentration
inactivation decreased affinity |
|
why not use antibiotics together if their effect is additive?
|
not enhance very much but introduces possibilities of more side effects, etc
|
|
synergistic combinations?
|
cell wall synthesis inhibitors + aminoglycosides;
trimethoprim-sulfamethoxazole; quinupristin/dalfopristin; amphotericin B + flucytosine |
|
breakpoint?
|
drug concentration that determines if an organism is susceptible or resistant
|
|
when use combination antibacterial therapy?
|
mixed infections
delay emergence of resistance synergism unknown etiology |
|
crosslinking of peptidoglycan occurs via which amino acids?
|
glycine and D-alanyl-D-alanine
|
|
mechanism of β lactams?
|
act on growing bacteria by binding to and irreversibly inactivating several penicillin binding proteins (PBPs);
activate a group of bacterial enzymes, autolysins, causing degradation of the cell wall |
|
transpeptidase?
|
enzyme responsible for crosslinking the linear glycopeptide strands of the cell wall
|
|
end consequence on bacteria treated with β lactams?
|
bactericidal
time-dependent killing weakened cell wall lysis |
|
β lactamase?
|
multiple families of enzymes that hydrolyze β lactam ring to carboxylic acids without antibacterial activity
|
|
β lactamase in Gm(+)?
|
coded by plasmid
most commonly penicillinases secreted |
|
β lactamase in Gm(-)?
|
coded by genetic elements on chromosome or a plasmid;
can be constitutively expressed or be inducible; broad spectrum that hydrolyze several different substrates; localized to periplasmic space |
|
resistance to β lactams?
|
β lactamase
decreased pore size [Gm(-)] altered PBPs |
|
MRSA and MDRSP method of resistance to β lactams?
|
altered PBPs that have either very low or no affinity for β lactam drugs
|
|
all penicillins are derived from?
|
6-aminopenicillanic acid
|
|
disadvantages of pharmacokinetics of penicillin?
|
destroyed by acid content in stomach;
actively secreted from kidney tubules by anion transport system |
|
use of probenecid with penicillin?
|
prolongs duration by blocking its active transport in the proximal tubule
|
|
repository forms of penicillin G and benefit?
|
procaine and benzathine salts are administered IM into large muscle mass and slowly absorbed
|
|
means of prolonging duration of action of penicillin?
|
simultaneous administration of probenecid;
repository forms (procaine and benzathine salts) |
|
deficiencies of penicillin?
|
low oral bioavailability
β lactamase inactivation narrow therapeutic spectrum |
|
natural penicillins?
|
penicillin G
penicillin V |
|
penicillin V?
|
form resistant to acid so more reliable absorption
|
|
pencillinase-resistant penicillins?
|
methicillin
oxacillin cloxacillin dicloxacillin nafcillin |
|
use of nafcillin?
|
chiefly excreted in the bile so useful for renal failure patients to treat penicillinase-producing staphlococci
|
|
amino or extended spectrum penicillins?
|
ampicillin
bacampicillin amoxicillin |
|
ampicillin effective against?
|
e. coli
h. influenzae salmonella shigella some proteus species |
|
amoxicillin advantage?
|
given po as has good stability and is better absorbed than ampicillin;
not used for shigellosis |
|
antipseudomonal penicillins?
|
carbenicillin
ticarcillin piperacillin |
|
antipseudomonal penicillin spectrum?
|
enhanced activity against:
pseudomonas enterobacter indole (+) proteus klebsiella |
|
β lactamase inhibitors?
|
clavulanic acid
sulbactam tazobactam |
|
mechanism of clavulanic acid, sulbactam, and tazobactam?
|
irreversibly inactivate some β lactamases
|
|
penicillin plus β lactamase inhibitor combinations available?
|
amoxicillin/clavulanic acid
ampicillin/sulbactam piperacillin/tazobactam ticarcillin/clavulanic acid |
|
characteristics of hypersensitivity reactions to penicillins?
|
cross-sensitivity;
more often = delayed allergic reaction (maculopapular eruptions, fever, or both); less common, more serious = immediate mediated by IgE |
|
adverse effects of penicillins?
|
hypersensitivity
serum sickness hemolytic anemia allergic interstitial nephritis convulsions at high doses |
|
carbenicillin and ticarcillin adverse effects?
|
bind ADP receptor on platelets leading to impaired aggregation and coagulation;
electrolyte disturbances |
|
which drugs may cause impaired platelet aggregation or electrolyte disturbances?
|
carbenicillin
ticarcillin |
|
ampicillin and amoxicillin adverse reaction?
|
rash that is not immune mediated;
100% incidence in mono patients |
|
cause rash that is not immune mediated?
|
ampicillin
amoxicillin |
|
cephalosporins general mechanism and characteristics?
|
bactericidal;
inhibit cell wall synthesis similarly to penicillins and are similarly resisted; intrinsically resistant to Gm(+) penicillinase |
|
cephalosporin susceptibility to β lactamases?
|
intrinsic resistance to Gm(+) penicillinase;
hydrolyzed by cephalosporinase and broad spectrum β lactamases |
|
trends as proceed from 1st to 4th generation cephalosporins?
|
increased flux across outer membrane of Gm(-);
increase stability toward Gm(-) β lactamases |
|
how does penicillin penetrate cerebrospinal fluid?
|
normally poor penetration
meningeal inflammation allows accumulation in CFS |
|
cephalosporins penetration of bbb?
|
most 1st and 2nd generation do not penetrate even when inflammation is present
|
|
1st generation cephalosporins?
|
cephalexin
cefazolin |
|
activity of 1st generation cephalosporins?
|
active against:
Gm(+) cocci e. coli k. pneumoniae p. mirabilis ineffective against: enterococci MRSA listeria penicillin-resistant streptococci |
|
2nd generation cephalosporins?
|
cefuroxime
cefaclor |
|
spectrum of cefuroxime and cefaclor (2nd)?
|
e. coli
klebsiella proteus h. influenzae moraxella catarrhalis |
|
cefotetan?
|
cephamyin
more resistant to β lactamases similar spectrum as 2nd gen added activity against b. fragilis |
|
which has added activity against bacteroides fragilis?
|
cefotetan
|
|
3rd generation cephalosporins?
|
cefotaxime
ceftazidime ceftriaxone |
|
spectrum of cefotaxime, ceftazidime, and ceftriaxone?
|
expanded Gm(-) specturm and some CNS penetration;
enterobacteriaceae; pseudomonas; serratia; n. gonarrhoeae; s. aureus; strep. pyogenes |
|
4th generation cephalosporins?
|
cefepime
|
|
spectrum of cefepime?
|
similar to 3rd but more resistance to some β lactamases
|
|
adverse effects of cephalosporins?
|
hypersensitivity
renal damage local tissue reactions interfere with vitamin K metabolism disulfuram like reaction |
|
cephalosporin causing a serum sickness-like reaction in children?
|
cefaclor
|
|
pseudocholelithiasis as adverse effect?
|
ceftriaxone
|
|
contraindication for cephalosporins?
|
individuals who have experienced an immediate-type or other serious allergic reaction to penicillin
|
|
carbapenems?
|
imipenem
meropenem ertapenem |
|
widest spectrum of activity of any β lactam?
|
imipenem
held in reserve for resistant infections |
|
what is imipenem combined with and why?
|
cilistatin to prevent the metabolic inactivation of imipenem by enzyme dehydropeptidase
|
|
adverse reactions of imipenem?
|
allergic (some cross sensitivity with penicillins and cephalosporins);
seizures |
|
difference between imipenem and meropenem or ertapenem?
|
meropenem and ertapenem are resistant to metabolism by dehydropeptidase
|
|
aztreonam class and spectrum?
|
monobactam;
Gm(-); excellent stability to β lactamase; main use is treatment of nosocomial Gm(-) pathogens |
|
vancomycin class and mechanism?
|
glycopeptide antibiotic
binds terminal D-alanyl-D-alanine to inhibit transglycosylase preventing further elongation of peptidoglycan chain and cross-linking |
|
resistance to vancomycin?
|
substitution of a D-lactic acid for the terminal D-alanine
|
|
'redman' or 'red neck syndrome'?
|
flushing of upper body caused by rapid infusion of vancomycin;
vancomycin-induced release of histamine from mast cells |
|
vancomycin spectrum?
|
narrow Gm(+) antibiotic:
MRSA antibiotic-induced enterocolitis streptococcal endocarditis (+ cephalosporin) MDRSP |
|
adverse effects of vancomycin?
|
redman or red neck syndrome
nephrotoxicity ototoxicity |
|
other miscellaneous inhibitors of cell wall synthesis?
|
bacitracin
cycloserine fosfomycin teicoplanin |
|
which not approved in us due to treatment failure?
|
teicoplanin
|
|
bacitracin?
|
peptide antibiotic
used topically due to extreme nephrotoxicity |
|
macrolides?
|
erythromycin
clarithromycin azithromycin |
|
resistance to macrolides?
|
efflux pump
mutation of ribosomal binding site methylation of binding site (cross resistance) |
|
macrolide mechanism?
|
protein synthesis inhibitor that binds the 50S ribosome;
generally considered bacteriostatic |
|
erythromycin pharmacokinetics?
|
destroyed in stomach;
concentrated in liver and excreted in bile; metabolized by P450; potent inhibitor of CYP3A4 |
|
problems with erythromycin?
|
narrow antibacterial spectrum
instability in acid severe abdominal cramping in some inhibition of CYP3A4 |
|
clarithromycin?
|
broader spectrum than erythromycin;
less likely to produce gi upset; inhibits P450 |
|
azithromycin?
|
macrolide;
higher tissue concentrations; expanded spectrum from erythromycin |
|
adverse effects of erythromycin?
|
cholestatic hepatitis;
epigastric distress |
|
ketolide mechanism and consequence?
|
binds domains II and V of 23S rRNA;
poor ligand for efflux pump; binding to domain II is sufficient for inhibition of protein synthesis |
|
telithromycin?
|
ketolide;
treatment of community acquired pneumonia |
|
telithromycin adverse effects?
|
acute hepatic failure and severe liver injury;
not to be used in patients with myasthenia gravis |
|
lincosamide mechanism?
|
similar to macrolides
|
|
clindamycin spectrum?
|
lincosamide:
many Gm(+) community acquired MRSA highly active vs b. fragilis |
|
which antibiotic has affinity for osseus tissue?
|
clindamycin
|
|
adverse effects of clindamycin?
|
most frequently associated with pseudomembranous colitis
|
|
most frequently associated with pseudomembranous colitis?
|
clindamycin
|
|
quinupristin/dalfopristin?
|
streptogramin (synercid is combo):
50S ribosome protein synthesis inhibitors; synergistic because bind at different sites that are unrelated |
|
which compounds have to cross resistance with other agents that inhibit 50S ribosome?
|
quinupristin
dalfopristin linezolid |
|
quinupristin/dalfopristin spectrum?
|
Gm(+)
used for nosocomial infections or those that do not respond to other agents |
|
streptogramins adverse effects?
|
metabolized by CYP3A4
venous problems at infusion site arthralgia myalgia |
|
linezolid?
|
oxazolidinone:
50S ribosome inhibitor Gm(+) spectrum enterococci |
|
linezolid pharmacokinetics?
|
nearly 100% bioavailability
does not inhibit or induce P450 |
|
linezolid adverse effects?
|
myelosuppression
peripheral neuropathy nonspecific monoamine oxidase inhibition |
|
which possesses nonspecific monoamine oxidase inhibition?
|
linezolid
|
|
chloramphenicol?
|
nitrobenzene:
50S ribosome inhibitor use is restricted to when no other antibacterial is effective |
|
resistance chloramphenicol?
|
due to acetylation that converts to inactive metabolite
|
|
chloramphenicol pharmacokinetics?
|
rapidly absorbed and widely distributed;
conjugated by glucuronosyl transferase |
|
adverse effects of chloramphenicol?
|
aplastic anemia
blood dyscrasias gray-baby or gray syndrome |
|
aplastic anemia and chloramphenicol?
|
not dose related;
symptoms can start as long as 6 months after use; not reversible |
|
blood dyscrasias and chloramphenicol?
|
dose dependent;
reversible |
|
gray syndrome?
|
chloramphenicol caused:
cyanosis respiratory irregularities vasomotor collapse abdominal distention loose green stools ashen-gray color (cannot adequately conjugate the drug to eliminate it) |
|
tetracyclines mechanism?
|
30S ribosome inhibitor;
bacteriostatic; inhibit both eukaryotic and prokaryotic cells |
|
why are tetracyclines somewhat selective for bacteria?
|
susceptible organisms have an active transport system
|
|
resistance to tetracyclines?
|
pump that removes drugs from cells
|
|
tetracyclines?
|
tetracycline
minocycline doxycycline |
|
why has use of tetracyclines declined?
|
increasing bacterial resistance
newer, more effective antibiotics |
|
similarities/differences between the tetracyclines?
|
similar structures
similar antibacterial spectrum difference is drug half life |
|
why is doxycycline preferred over other tetracyclines?
|
long half life
nearly complete absorption high tissue concentrations excretion in feces (does not accumulate when compromised renal function) |
|
use of tetracyclines?
|
rickettsiae
chlamydiae mycoplasmas h. pylori plasmodia amebas |
|
adverse effects of tetracyclines?
|
hypersensitivity with cross sensitization;
phototoxic reaction; hepatic dysfunction; tooth discoloration and depressed bone growth in children |
|
minocycline adverse effects?
|
vertigo and dizziness
hyperpigmentation due to iron complexes in skin |
|
tetracyclines drug interactions?
|
antacids, milk, or multivitamins inhibit absorption of tetracyclines
|
|
tigecycline?
|
glycylcycline: similar to tetracyclines
|
|
resistance to tigecycline?
|
not affected by common mechanisms;
unaffected by tetracycline efflux pumps; exception is efflux pump in pseudomonas); no cross-resistance with other classes |
|
tigecycline spectrum?
|
activity against variety of multidrug-resistant pathogens
|
|
adverse effects of tigecycline?
|
high occurrence of nausea and vomiting (1/3)
|
|
aminoglycoside mechanism?
|
bactericidal inhibitors via interference with initiation, cause misreading, produced decreased or abnormal proteins;
taken up by bacteria in energy-dependent oxygen-dependent process |
|
resistance to aminoglycosides?
|
metabolism by bacteria to inactive species
|
|
aminoglycoside specificity for bacteria vs host?
|
large, low lipid solubility, and high polycationic charge allow for poor penetration except to specialized cells (renal tubular, hair cells);
bacteria have an uptake pump |
|
aminoglycosides?
|
gentamicin
tobramycin amikacin kanamycin streptomycin neomycin |
|
three aminoglycosides most important for treating systemic infections due to Gm(-) enteric bacteria?
|
gentamicin
tobramycin amikacin |
|
kanamycin use?
|
bowel sterilization prior to surgery
|
|
streptomycin use?
|
treatment of TB
|
|
neomycin use?
|
topically or in irrigation solutions
|
|
aminoglycosides dosing?
|
narrow ti
once daily limits side effects requires adjustment for kidney function dose based on lean body mass |
|
adverse effects of aminoglycosides?
|
ototoxicity
nephrotoxicity neuromuscular blockade |
|
fluoroquinolone mechanism?
|
inhibit bacterial DNA gyrase Gm(-) and topoisomerase IV Gm(+)
|
|
resistance to fluoroquinolones?
|
mutation of gyrA
mutation of gyrB (low level) active efflux (cross resistance) |
|
where do fluoroquinolones accumulate and why might this be beneficial?
|
prostate, kidney, neutrophils, macrophages;
in prostate is good to prevent reseeding following treatment for UTI |
|
fluoroquinolones?
|
ciprofloxacin
levofloxacin gatifloxacin moxifloxacin |
|
fluoroquinolone black box warning?
|
tendon rupture following vigorous exercise
|
|
adverse effects of fluoroquinolones?
|
gi disturbance
rash headache vertigo excitement visual disturbances tendon rupture not in children to due to possible damage of cartilage |
|
rifamycins?
|
rifampin
rifabutin |
|
rifampin mechanism?
|
inhibits DNA dep RNA polymerase
|
|
resistance to rifampin?
|
develops rapidly when used as a single agent
|
|
use of rifampin?
|
TB
in combo carriers of n. meningitidis |
|
rifampin drug interactions?
|
potent inducer of CYP3A4
|
|
sulfonamide selectivity?
|
consequence of fact that source of folic acid is different for humans and bacteria;
humans require dietary folic acid while many bacteria synthesize it de novo |
|
sulfonamide mechanism?
|
structural PABA analog and act as competitive inhibitor of dihydropteroate synthetase
|
|
resistance to sulfonamides?
|
increased PABA synthesis
altered dihydropteroate synthetase utilize exogenous folic acid |
|
sulfonamides pharmacokinetics?
|
oral absorption
renal elimination metabolized by acetylation |
|
sulfonamides?
|
sulfisoxazole
sulfamethoxazole sulfacetamide silver sulfadiazine sulfasalazine |
|
sulfisoxazole and sulfamethoxazole use?
|
UTIs
|
|
sulfacetamide use?
|
ophthalmic infection
topical application |
|
silver sulfadiazine use?
|
prevent colonization of burns by bacteria
|
|
adverse effects of sulfonamides?
|
mild rash to steven johnsons
drug fever blood dyscrasias eosinophilia crystalluria hepatitis kernicterus in newborns |
|
can cause kernicterus?
|
sulfonamides
|
|
trimethoprim mechanism and specificity?
|
inhibits dihydrofolate reductase;
greater affinity for bacterial enzyme vs mammalian enzyme |
|
trimethoprim + sulfamethoxazole?
|
sequential inhibition of formation of tetrahydrofolate;
synergistic making it bactericidal vs bacteriostatic; bronchitis; otitis media; PCP |
|
adverse effects of trimethoprim?
|
potential to interfere with folate metabolism in malnourish individuals
|
|
characteristic of urinary tract antiseptic effects?
|
no systemic activity
exert effects entirely in urinary tract |
|
why is there no systemic activity with urinary tract antiseptics?
|
rapid elimination
high protein binding requirement for low pH to be effective |
|
urinary tract antiseptics?
|
nitrofurantoin
methenamine fosfomycin |
|
nitrofurantoin and its adverse effects?
|
urinary tract antiseptic
gi disturbances headache acute allergic pulmonary (chills, cough, pulmonary infiltrations) chronic pulmonary fibrosis |
|
why is fosfomycin useful for urinary tract infections?
|
distributed to bladder, prostate, etc
|
|
drugs that act at the bacterial cytoplasmic membrane?
|
daptomycin
colistin colistimethate polymyxin B |
|
daptomycin mechanism?
|
binds cell membrane of Gm(+) cells in Ca-dependent process that disrupts the membrane potential
|
|
daptomycin has activity against?
|
growing or resting bacteria
biofilms MRSA VRSA VRE |
|
polymyxins?
|
colistin
colistimethate polymyxin B |
|
polymyxin mechanism?
|
surface-active amphipathic agents;
penetrate cell membranes, interact with phospholipids, disrupt the membranes of Gm(-) aerobic bacilli; bactericidal in concentration-dep manner; have post-antibiotic effect |
|
use of polymyxins?
|
fell into disuse due to nephrotoxicity;
used as last resort against some Gm(-) organisms |
|
metronidazole?
|
reduced to free radical by bacteria ultimately damaging bacterial DNA
|
|
metronidazole use?
|
antiprotozoal
anaerobic bacteria c. difficile esp |
|
metronidazole adverse effects?
|
headache
metallic taste disulfuram like reaction when consuming alcohol |
|
spectinomycin?
|
alternative drug to n. gonnorhea including penicillinase-producing strains in patient allergic to other drugs;
not active against t. pallidum |
|
major TB drugs?
|
isoniazid
rifampin ethambutol streptomycin pyrazinamide |
|
treatment of TB?
|
multiple drugs with separate MOAs to decrease chance of resistant organisms developing
|
|
isoniazid mechanism?
|
inhibits synthesis of mycolic acids;
bactericidal for growing; bacteriostatic for resting; requires a catalase/peroxidase enzyme for activation |
|
isoniazid elimination?
|
primarily acetylation - consequence of polymorphisms
|
|
consequence of slow acetylator taking isoniazid?
|
no effect on efficacy
more prone to peripheral neuropathy |
|
mechanism of peripheral neuropathy with slow acetylators?
|
increased excretion of pyridoxine caused by isoniazid;
can be diminished by supplementing diet with pyridoxine |
|
isoniazid side effects?
|
peripheral neuropathy (slow acetylators);
isoniazid-induced hepatitis |
|
primary agent for treatment of TB and only drug approved for prophylaxis?
|
isoniazid
|
|
rifampin mechanism?
|
inhibits transcription by inactivating DNA dep RNA polymerase
|
|
second most important drug in TB treatment?
|
rifampin
|
|
adverse effects of rifampin?
|
minor cutaneous, gi, or hepatic reactions;
potent inducer of CYP3A4 |
|
ethambutol?
|
major drug used for TB
|
|
ethambutol adverse effects?
|
uni or bilateral ocular toxicity
hyperuricemia, may precipitate gout |
|
characteristics of uni or bilateral ocular toxicity and associated drug?
|
ethambutol dose related, reversible
gradual loss in visual acuity decrease in visual fields loss of red/green color discrimination |
|
streptomycin use and disadvantages?
|
major TB drug
must be injected ototoxic nephrotoxic |
|
dapsone use and mechanism?
|
treatment of leprosy
inhibition of folic acid synthesis |
|
clofazimine use and mechanism?
|
treatment of leprosy
interfere with replication of bacterial DNA |
|
drugs used to treat leprosy?
|
dapsone
clofazimine rifampin |
|
polyenes?
|
nystatin
amphotericin B |
|
polyenes mechanism?
|
bind to sterols, especially erogsterol, to alter membrane permeability
|
|
nystatin use?
|
localized fungal infections
too toxic to be used systemically |
|
gold standard for drugs to treat serious systemic fungal infections?
|
amphotericin B
|
|
pharmacokinetics of amphotericin B?
|
poor gi absorption, given iv
half-life of 15 days stored in tissues, slowly excreted in urine |
|
amphotericin B adverse effects?
|
anaphylaxis
fever chills headache gi disturbances decreased renal function (80% of patients) |
|
renal function and amphotericin B?
|
decreased in 80% and typically does not fully recover after therapy is completed
|
|
classes of antifungals?
|
polyene
fluorinated pyrimidine azole allyamine echinocandin |
|
flucytosine mechanism?
|
fluorinated pyrimidine;
taken up by fungus-specific enzyme cytosine permease; converted by cytosine deaminase to 5-fluorouracil; causes RNA miscoding and inhibits DNA synthesis |
|
use of flucytosine and why?
|
synergistic with amphotericin B;
rapid resistance as single agent |
|
flucytosine adverse effects?
|
potentially lethal bone marrow depression;
gi upset; rash; hepatic dysfunction |
|
bone marrow depression and flucytosine?
|
gut bacteria convert to active 5-fluoruracil and body uses
|
|
azole mechanism?
|
inhibit fungal P450, lanosterol 14α-demethylase, required for conversion of lanosterol to erogsterol leading to depletion of ergosterol and failure of cytoplasmic membrane;
inhibit mammalian P450s to some degree |
|
resistance mechanisms to azoles?
|
alterations to target binding site
increased target expression induction of efflux pumps |
|
azoles?
|
ketoconazole
itraconazole fluconazole voriconazole |
|
ketoconazole adverse effects?
|
gynecomastia
menstrual irregularities drug interactions need acidic pH for absorption |
|
greatest ability to inhibit mammalian P450s?
|
ketoconazole
|
|
distribution of itraconazole?
|
extensive in lipophilc tissues
accumulates in the stratum corneus |
|
most potent of azoles?
|
itraconazole
|
|
fluconazole pharmacokinetics?
|
over 90% oral bioavailability;
widely distributed into body tissues and fluids; urine and skin concentrations = 10x plasma; distributes well into CSF; elimination primarily renal |
|
used successfully of invasive fungal infections, including aspergillosis in children refractory or intolerant of conventional antifungal therapy?
|
voriconazole
|
|
terbinafine mechanism?
|
potent noncompetitive inhibitor of fungal squalene epoxidase (early step in ergosterol synthesis)
|
|
terbinafine + amphotericin B?
|
additive or synergistic interactions vs aspergillus
|
|
terbinafine + itraconazole or voriconazole?
|
potent syngergistic interactions against aspergillus
|
|
terbinafine + fluconazole?
|
additive to synergistic interaction
|
|
caspofungin?
|
echinocandin
inhibits synthesis of β-1,3-D-diglucans (essential component of fungal cell wall); approved for invasive aspergillosis in patients that don't respond to other antifungals |
|
griseofulvin?
|
miscellaneous antifungal
|
|
amantadine and rimantadine mechanism?
|
inhibits viral uncoating or disassembly of virion during endocytosis;
inhibit ion channel function of the M2 protein |
|
use of amantadine and rimantaine?
|
prophylaxis during influenza A virus epidemics
|
|
amantadine adverse effects?
|
confusion
hallucination seizure coma |
|
antiviral agents for respiratory viruses?
|
amantadine
rimantadine oseltamivir zanamivir ribavirin |
|
neuraminidase inhibitors?
|
oseltamivir
zanamivir |
|
oseltamivir and zanamivir mechanism of action?
|
inhibit neuroaminidase (normally removes the sialic acid residues from surface to prevent clumping);
cause clumping of virions making then noninfectious; active against influenza A and B |
|
major difference between oseltamivir and zanamivir?
|
zanamivir is administered by inhalation;
oseltamivir is taken orally |
|
ribavirin mechanism?
|
guanosine analogue;
rapidly phosphorylated to compete with guanosine triphosphate-dependent 5'-capping of influenza viral mRNA |
|
use of ribavirin?
|
influenza viruses
RSV parainfluenza viruses adenoviruses hepatitis C (+ INF-a) |
|
acyclovir mechanism?
|
synthetic purine nucleoside analog;
phosphorylated by viral thymidine kinase; competitive inhibitor of viral DNA polymerase; incorporation leads to premature chain termination |
|
loss of thymidine kinase activity by a virus causes resistance to what antivirals?
|
acyclovir
valacyclovir famciclovir ganciclovir |
|
acyclovir use?
|
iv for serious HSV and VZV infections
|
|
valacyclovir?
|
L-valine isomer of acyclovir;
metabolized to acyclovir |
|
acyclovir adverse effects?
|
headache
rash gi disturbances crystalline nephropathy |
|
spectrum of acyclovir?
|
HSV1, HSV2 > VZV > CMV
|
|
famciclovir mechanism?
|
inhibits viral DNA polymerase
NO chain termination |
|
ganciclovir activity?
|
similar to acyclovir but enhanced activity against CMV;
inhibitor and substrate for viral DNA polymerase |
|
ganciclovir adverse effects?
|
granulocytopenia
thrombocytopenia |
|
ganciclovir is approved to treat?
|
CMV retinitis, colitis, and esophagitis in AIDS patients;
prevent and treat CMV disease in transplant patients |
|
cidofovir?
|
alternative to ganciclovir or to treat ganciclovir resistant CMV
|
|
trifluridine use?
|
topic (HSV keratoconjunctivitis)
too toxic for systemic use as causes strand breakage when incorporated into viral or mammalian DNA |
|
foscarnet mechanism?
|
binds phosphate binding site of viral DNA or RNA polymerase and HIV reverse transcriptase and inhibits the enzyme
|
|
foscarnet use?
|
resistant CMV retinitis and acyclovir-resistant HSV and VZV;
last resort due to high nephrotoxicity |
|
what does HAART stand for?
|
Highly
Active Anti Retroviral Therapy |
|
purpose of HAART?
|
HIV rapidly becomes resistant when single drug is used;
survivorship is inversely related to circulating level of HIV RNA in the blood; survivorship is positively correlated with CD4 count |
|
goals of HAART?
|
reduce blood levels of HIV RNA to undetectable levels (<50 copies RNA/mL blood);
maintain the CD4 count |
|
classes of drugs used to treat HIV?
|
nucleoside/nucleotide reverse transcriptase inhibitors (nRTI);
non-nucleoside reverse transcriptase inhibitors (nnRTI); HIV protease inhibitors (PI); fusion inhibitor; entry inhibitor; integrase inhibitor |
|
nRTIs mechanism?
|
require intracellular phosphorylation;
competitive inhibitors of normal nucleoside triphosphates for HIV reverse transcriptase; are incorporated and act as chain terminators; lack ribose 3'-hydroxyl group |
|
nRTIs?
|
zidovudine
stavudine lamivudine zalcitabine emtricitabine tenofovir didanosine abacavir |
|
nRTIs adverse effects?
|
lactic acidosis
hepatic steatosis peripheral neuropathy myopathy lipoatrophy (inhibit mitochondrial DNA polymerase-g and causing mitochondrial dysfunction) |
|
nnRTIs mechanism?
|
no intracellular metabolism necessary;
allosteric binding in noncompetitive fashion near active site of reverse transcriptase to lock the enzyme to an inactive state |
|
nnRTIs?
|
efavirenz
nevirapine |
|
nnRTIs adverse effects?
|
cross-resistance is common;
rash that sometimes can be very severe; metabolized by CYP3A4 |
|
protease inhibitor mechanism?
|
bind to active site of the enzyme
|
|
protease inhibitors?
|
atazanavir
fosamprenavir darunavir lopinavir squinavir |
|
ritonavir?
|
protease inhibitor booster;
very potent inhibitor of P450 that metabolizes the PIs |
|
protease inhibitor adverse effects?
|
gi intolerance
increase aminotransferase activity increased bleeding in hemophiliacs hyperglycemia new onset or worsening diabetes insulin resistance fat wasting and redistribution metabolized by P450 |
|
drug to be avoided with protease inhibitors and why?
|
rifampin due to CYP3A4 inducing action - decreases effectiveness of the protease inhibitors
|
|
which HIV drugs are used for those that have failed therapy?
|
fusion inhibitor (enfuvirtide)
entry inhibitor (maraviroc) integrase inhibitor (raltegravir) |
|
enfuvirtide?
|
fusion inhibitor
binds gp41 preventing fusion |
|
maraviroc?
|
entry inhibitor
binds CCR5 (coreceptor) |
|
which strains of HIV are resistant to maraviroc?
|
those that use CXCR4 as coreceptor
|
|
raltegravir?
|
integrase inhibitor
prevents insertion of HIV DNA into human genome |
|
what form is malaria in when it is in the salivary gland of the mosquito?
|
sporozoite
|
|
life cycle of malaria in human?
|
sporozoite injected --> invade liver and form an exoerythrocytic or hepatic schizont --> release merozoites by rupturing --> invade erythrocytes to form erythrocytic schizonts --> rupture to release merozoites --> etc
|
|
which forms of plasmodium can also remain dormant in liver and what are the dormant form called?
|
p. vivax and p. ovale
hypnozoites later reactivated |
|
p. falciparum?
|
most severe form
frequently drug resistant |
|
drug of choice for erythrocytic stage of malaria?
|
chloroquine
|
|
drug of choice for erythrocytic stage of malaria resistant to chloroquine?
|
mefloquine
|
|
for cure of malaria due to p. vivax or p. ovale?
|
primaquine to treat hepatic stage
|
|
quinine adverse effects?
|
cinchonism: tinnitus, headache, nausea, visual distrubances
|
|
antimalarials?
|
chloroquine
mefloquine quinine primaquine pyrimethamine + sulfadoxine atovaquone/proguanil |
|
fansidar?
|
pyrimethamine + sulfadoxine
|
|
malarone?
|
atovaquone/proguanil
|
|
atovaquone mechanism?
|
disrupts the mitochondrial electric transport
|
|
proguanil mechanism?
|
inhibitor of plasmodial dihydrofolate reductase
|
|
other antiprotozoals?
|
metronidazole
idoquinol diloxanide furoate pentamidine |