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381 Cards in this Set

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Which classes of antibiotic are bactericidal?
bacitracin
beta-lactams
isoniazid
metronidazole
polymyxins
pyrazinamide
quinolones
rifampin
Which classes of antibiotics are bacteriostatic?
chloramphenicol
clindamycin
ethambutol
macrolides
nitrofurantoin
novobiocin
tetracyclines
sulfonamides
bacteriostatic agents CCEMeNNTS them in their tracks
Which antibiotics have excellent CNS penetrating ability?
chloramphenicol
metronidazole
rifampin
sulfonamides
Which antibiotics only penetrate the CNS with inflammed meninges?
penicillins
3rd-gen cephalosporins
Which antibiotics are very poor at penetrating the CNS?
aminoglycosides
clindamycin
vancomycin
Which antibiotics can get into the prostate?
macrolides
trimethoprim
ciprofloxacin (fluoroquinolone)
doxycycline (tetracycline)
Many Try but few Can Do it
Which antibiotics require dosage reduction with renal insufficiency?
aminoglycosides
vancomycin
tetracyclines (except doxycycline)
polymyxins
most cephalosporins (except cefoperaxone)
imipenem
Which drugs do not require dosage adjustments with renal insufficiency?
macrolides
ceftriaxone
chloramphenicol
metronidazole
clindamycin
cefoperazone
Which antibiotics cause ototoxicity?
aminoglycosides
vancomycin
erythromycin
clarithromycin
minocycline
Which antibiotics cause phototoxicity?
tetracyclines
quinolones
sulfonamides
azithromycin
Which antibiotics cause phlebitis?
naficillin
oxacillin
cephalothin
cephapirin
cefepime
vancomycin
erythromycin
tetracyclines
clindamycin
Which antibiotics are contraindicated during pregnancy?
aminoglycosides
erythromycin
clarithromycin
quinolones
tetracyclines
sulfonamides
Administering Erythromycin Causes Queer Teratogenic Syndromes
Which antibiotics cause hemolysis with G-6-P dehydrogenase deficiency?
tetracyclines
sulfonamides
quinolones
nitrofurantoin
azithromycin
trimethoprim
beta-lactam drugs
penicillins
cephalosporins
carbapenems
monobactams
inhibitors of beta-lactamase
What is the mechanism of action for penicillins?
covalently binds transpeptidase, preventing cross-linking of peptidoglycan

requires bacteria cell-wall synthesis (growing bacteria)

bactericidal
PBP 1
penicillin binding protein 1

involved in cross linking of peptidoglycan

inhibition causes rapid lysis

(most important site of action of beta-lactam drugs)
PBP 2
involved in maintaining the "rod" shape

inhibition causes ovoid shape and slow lysis
PBP 3
involved in septum formation

low beta-lactam concentration -> filaments

high beta-lactam concentration -> lysis
autolysins
normal component of bacteria
may be required for growth of cell wall or for cells to divide

absence or alteration may prevent penicillins from killing bacteria
What are the mechanisms of resistance to beta-lactam drugs?
1) beta-lactamase
2) reduced permeability of outer membrane
3) altered PBP
4) non-multiplying organisms
5) unknown mechanisms
Which is more readily absorbed orally?

Pen V or Pen G
Penicillin V - ~2/3 absorbed

(Pen G ~1/3 absorbed)
Do penicillins cross the BBB?
Yes; most do when the meninges are inflammed
What is probenecid?
a weak acid that competes with other WA for transport (has almost no pharmacologic activity)

increases the half-life of penecillins

reduces renal clearance of acyclovir and cidofovir
Can a patient allergic to penicillin use cephalosporins?
Yes, under most circumstances

<5% cross-allergenicity (probably closer to 2%)
What is the Jarisch-Herxheimer Reaction?
occurs only in patients with syphillis

release of bacterial toxins when they die

symptoms: chill, fever, muscle and joint pain with the 1st dose

(continue therapy)
How is amoxicillin administered?
PO
How is ampicillin administered?
IV
Which penicillins are penicillinase resistant?
methicillin (no longer on market)
nafcillin
dicloxacillin
Which penicillins are effective against pseudomonas?
ticarcillin
pipercillin
What is procaine penicillin G?
ester of pen G

procane is a local anesthetic that slows down the rate of absorption -> increased half-life

blood levels not very high

(good for prophylaxis)
What is benzathine penicillin G?
similar to procaine pen G, but get longer half-life and lower blood levels

(good for prophylaxis)
What is the mechanism of action for cephalosporins?
covalently binds transpeptidase, preventing cross-linking of peptidoglycan

requires bacteria cell-wall synthesis (growing bacteria)

bactericidal
Which is more stable to hydrolysis?

penicillins or cephalosporins
cephalosporins
What are the adverse effects of cephalosporins?
nephrotoxicity

low when used alone, but slightly higher than penicillins

slightly more toxic when used w/ aminoglycosides (synergistic toxic effect)
Which cephalosporins cause bleeding disorders?
cephalosporins with MTT side chain
(cefotetan, cefamandole, cefoperazone, cefametazole)

these compete w/ vit. K in the liver and reduces synthesis of clotting factors -> bleeding

(pts. on these drugs are usually given vit. K)
Which cephalosporins have a disulfiram-like reaction?
cephalosporins w/ MTT side chain

interferes w metabolism of ethanol (acetylaldehyde dehydrogenase), causing an unplesant reaction to ethanol
Which causes more superinfections?

penicillins or cephalosporins
cephalosporins, b/c they have a broader spectrum
Which 1st-gen cephalosporin is administered orally?
cephalexin
Which 1st-gen cephalosporin is administered parenterally?
cefazolin
Which 2nd-gen cephalosporin is administered orally?
cefaclor
cefprozil
Which 2nd-gen cephalosporin is administered parenterally?
cefoxitin
cefuroxime
cefotetan
Which 3rd-gen cephalosporin is administered orally?
cefixime
Which 3rd-gen cephalosporin is administered parenterally?
cefotaxime
ceftriaxome
ceftazidime
cefoperazone
Which generation of cephalosporins are most active against gram-positives?
1st generation
Which generation of cephalosporins are most susceptible to beta-lactamases?
1st-generation
Which generation of cephalosporins have the worst penetration into the CSF?
1st generation
Which generation of cephalosporins have the shortest half-lives?
1st generation
Which generation of cephalosporins have the least activity against gram-positives?
3rd generation

(not 4th; 4th has good gram-positive and gram-negitive activity)
What are the advantages of 4th-generation cephalosporins?
good activity against gram-positives and gram-negatives

very stable to beta-lactamases

less induction of resistance in hospital colonizing gram negative organisms?
Which cephalosporin is the best penetrator of the CSF?
ceftriaxone
Which cephalosporin has the longest half-life?
ceftriaxone
Which cephalosporins require no adjustment in renally impaired patients?
ceftriaxone
cefoperazone
Which cephalosporin is the most active against pseudomonas?
ceftazidime
cefoperaxone
Which cephalosporin causes "biliary sludging?"
cefoperazone

b/c it attains high levels in the bile -> slows down the ability of the liver to secrete bile
What is the parent compound of carbapenems?
thienamycin

(unstable)
What is the mechanism of action for carbapenems?
binds to transpeptidase -> preventing crosslinking of peptidoglycan

especially binds to PBP 2 ("rod shape")
Which drug has the broadest antimicrobial spectrum of any antibiotic currently available?
imipenem (carbapenem)

good penetration of gram-neg cell membrane
high affinity for PBPs
stable to most types of beta-lactamases
Why does imipenem induce microorganisms to produce beta-lactamases?
b/c it is very stable to them
How is imipenem administered?
IV
What is dehydropeptidase I?
normal enzyme in the brush border of the proximal tubules of the kidney

hydrolyzes imipenem, but not other beta-lactams
Why is imipenem always administered with cilastatin?
prevent hydrolysis of imipenem by dehydropeptidase I in kidneys

in animal studies, large doses of imipenem alone was more toxic than with cilastatin
What are the adverse effects of imipenems?
1) convulsions - 3%. Not recommended for pts. w/ meningitis

2) superinfections - b/c very broad spectrum (however, lower rate than expected b/c almost never reaches GI)

3) seizures

4) nephrotoxicity
What part of the body does imipenem almost never reach?
GI tract

b/c administered IV and excreted renally
What is the difference between imipenem and meropenem?
1) not hydrolyzed by dehydropeptidase I -> no need for cilastatin

2) less likely to cause seizures

3) less likely to cause convulsions -> can be used to treat meningitis
Can imipenems be used to treat meningitis?
no

b/c it can cause convulsions (~3%)
What are the inhibitors of beta-lactamases?
clavulanic acid
sulbactam
tazobactam
Which beta-lactam has only one ring?
aztreonam (monobactam)
Which organisms is aztreonam effective against?
gram-negative aerobes only

no activity against gram-positive or anerobic bacteria

(gram-positive PBP intrinsically do not bind aztreonam)
Can aztreonam be used in patients that are allergic to penicillin and/or cephalosporin?
yes

no cross-allergenicity, even though allergic reactions w/ beta-lactams occur due to the beta-lactam ring
What are aztreonams used for?
gram-negative aerobic infections

used as a safer alternative to aminoglycosides (similar spectrum, but safer)

used as a substitute for penicillins and cephalosporins in patients allergic to these (no cross allergenicity)
How is bacitracin administered?
topical only

too toxic
What is the mechanism of action for vancomycin?
inhibitor of cell wall synthesis

binds terminal D-ala-D-ala -> blocks crosslinking of peptidoglycan

activates autolysins
What is the mechanism of action for bacitracin?
inhibits the dephosphorylation of bactoprenol -> inhibiting transport of precursors out of the cell
What is vancomycin used for?
gram-positives (no gram-negative activity)

DOC for MRSA

pseudomembranous colitis (C. difficle) - not DOC anymore
What was vancomycin originally developed for?
as a substitute for penicillin

no cross-allergenicity
How is vancomycin administered?
IV

PO if needed for GI tract (not destroyed by acid, not absorbed orally)
How is vancomycin excreted?
glomerular filtration only

no tubular secretion b/c it is not a WA

(half-life markedly prolonged in renal failure)
What are the adverse effects of vancomycin?
ototoxicity - damage to CNVIII

Red-man Syndrome - w/ rapid IV infusion

nephrotoxicity - increases in combination w/ aminoglycoside
Which drug causes the Red-man Syndrome?
vancomycin - with rapid IV infusion
(due to displacement of histamines w/o degranulation)
How is Red-man syndrome prevented?
slow down IV infusion

and/or

administer anti-histamine
What are the components of streptogramin?
quinupristin and dalfopristin

30:70 combination (b/c individually, they are only bacteriostatic)
What is the mechanism of action for streptogramins?
inhibits bacterial protein synthesis

the 2 components bind to separate sites on 50S

quinupristin - inhibits synthesis of tRNA and blocks addition of new amino acids to nascent peptide

dalfopristin - inhibits peptidyl transferase -> blocks peptide bond formation
What is streptogamin used for?
mainly used for infections caused by vancomycin-resistant strains

used when pt. can't tolerate adverse effects of vancomycin (ex: renally impaired pt.)
Which bacteria is streptogamin active against?
gram-positives

MRSA
What are the adverse effects of streptogramins?
pain, inflammation, phlebitis at site of infusion (~75%)

arthralgia
myalgia
Why is resistance to streptogramin unlikely?
b/c mechanism is due to synergistic combination of 2 drugs with different sites of action
What is linezolid active against?
bacteriostatic against staphlococci and enterococci

bactericidal against streptococci

active against large # of gram-positives - MRSA, enterococcus feacium, enterococcus faecalis
What is the mechanism of action for linezolid?
inhibits bacterial protein synthesis by binding to 50S

binding site is near the interface w/ 30S -> prevents formation of 70S initiation complex (unique mechanism = no cross allergenicity)

same binding site as chloramphenicol and erythromycin -> competition for binding

(however, linezolid does not inhibit peptidyl transferase or the translation reaction)
What do linezolid, chloramphenicol, and erythromycin have in common?
they all bind to the same 50S binding site -> inhibiting protein synthesis

however, linezolid does not inhibit peptidyl transferase or the translation reaction

(linezolid prevents the formation of 70S)
Aminoglycosides rely on what mechanism to get inside cells?
active transport

(thus inactive against anaerobes)
Why are aminoglycosides inactive against anaerobes?
b/c it relys on active transport to get inside cells, which is an oxygen-dependent process
What is the mechanism of action for aminoglycosides?
irreversibly binds 30S which...


blocks initiation of 70S complex

miscodes peptide chain

blocks translocation of peptide
Why are aminoglycosides bactericidal?
it has high affinity for 30S of bacterial ribosomes (irreversible binding)

it is rapidly taken up through the membrane
What antibiotics are aminoglycosides synergystic with?
cell-wall inhibitors

theory: disruption of cell wall allows more aminoglycosides to enter the cell
Are aminoglycosides susceptible to beta-lactamases?
no

it is not a beta-lactam drug
What are aminoglycosides used for?
gram-negative, aerobic infections

mainly used for pseudomonas

gram-positives - enterococci and strep. viridans (in combination w/ a penicillin or vancomycin, esp. for endocarditis)
Which antibiotics have a concentration-dependent effect?
aminoglycoside - bactericidal activity increases with increased concentration

quinolones

chloramphenicol
If aminoglycosides are active against gram-positives, why are they not used to treat gram-positive infections?
b/c there are many other drugs that are active against gram-positives and are safer
How do microorganisms resist the effects of aminoglycosides?
1) decreased ribosomal binding to drug

2) decreased transport of drug into the cell

3) elaboration of drug-metabolizing enzymes (main mechanism)-- ie. acetylation, adenlyation, phosphorylation
Which antibiotic exhibits "one-way" cross-resistance?
aminoglycosides

order of increasing cross-resistance
streptomycin
kanamycin
gentamicin
tobramycin
amikacin

(resistance to gentamicin = resistance to kanamycin and streptomycin, but not to tobramycin or amikacin)
How are aminoglycosides administered?
PO - steralize GI (no oral absorption)
IV - most common route
IM - peak serum levels in 30-60 mins
intrathecal - polar, so doesn't cross BBB
topical
Where are aminoglycosides mainly distributed in the body?
inner ear (5-10x plasma)
kidneys (50-90x plasma)

due to specific transport mechanisms

very polar, so small Vd - some distribution to tissues, low deposition in fat
What are the adverse effects of aminoglycosides?
ototoxicity - vestibular and cochlear
initial loss of high frequency sounds
vertigo greater with streptomycin and gentamycin

nephrotoxicity - 50-90x plasma level
neomycin>>gentamicin>>tobramycin=amikacin
(half-life prolonged with decreased renal function)

neuromuscular blockade - esp. if pt. has myasthenia gravis, hypocalcemia, other nuromuscular blocking agents
(curare-like effect)
How are aminoglycosides excreted?
glomerular filtration (no tubular secretion)

parallels creatinine clearance (CrCl decreases by half, half-life of a.g. increases by 2x)

(drug is not metabolized - unchanged)
Why are aminoglycosides usually administered via "once-daily-dosing?"
1) concentration-dependent activity

2) long post-antibiotic effect

3) active transport of a.g. into cells of renal tubules and inner ear is a saturable process

4) at large doses, a.g. causes down-regulation of active transport into bacterial cells

5) nephrotoxicity and ototoxicity are correlated w/ trough levels of a.g.

6) toxicity less with once-daily dosing b/c of reduced accumulation in inner ear and kidneys
What drugs are used to treat endocarditis?
combination of streptomycin (aminoglycoside) and vancomycin
Why does the loading dose of aminoglycoside have to be decreased for obese patients?
b/c aminoglycosides are very polar (small Vd), and thus are not distributed in fat
Which is the most widely used aminoglycoside?
gentamicin
When is kanamycin used?
used as a 2nd or 3rd line drug in TB

(not used much else)
Which aminoglycoside has the broadest spectrum?
amikacin
Which aminoglycoside has the least cross-resistance?
amikacin
Which aminoglycoside is limited to topical use and oral administration to steralize the gut?
neomycin
Which aminoglycoside is used for TB and endocarditis?
streptomycin
Which drugs cannot be combined with aminoglycosides due to chemical reaction?
antipseudomonal penicillins (ticarcillin, piperacillin)
Which class of drugs cannot be combined with ticarcillin/piperacillin due to chemical reaction?
aminoglycosides
Why are aminoglycosides preferentially used even though aztreonam has a similar spectrum of activity and is safer?
b/c of synergystic effect of a.g. w/ penicillins or cephalosporins

(no synergism b/w aztreonam and penicillin or cephalosporin)
What is the mechanism of tetracyclines?
binds to 30S to block binding of aminoacyl tRNA to mRNA
Which antibiotics blocks aminoacyl tRNA binding to mRNA?
tetracyclines
What is the mechanism of resistance against tetracyclines?
1) decreased binding to ribosomes

2) inactivation of enzymes

3) decreased accumulation - increased efflux/pumping out drug (major mechanism)

4) cross resistance - resistance to one tetracycline = resistance to all
What are the drawbacks of using tetracyclines?
chelates cations (Ca, Mg, Fe) -> thus, not good taken w/ certain foods/vitamins
(binds to teeth and bones -> not used in pregnant women and children)

also, increase pH -> increase chelation,
thus not good to use tetracyclines w/ antacids
What is the number 1 cause of drug-induced renal failure?
aminoglycosides
Where is tetracycline distributed in the body?
1) teeth and bones - chelates Ca, interferes w/ development of bones (not used in pts. <8 y.o.)

2) prostate (doxycycline)

3) tears and saliva (minocycline)
Which tetracycline is most lipid soluble?
doxycycline
Which tetracycline is least lipid soluble?
tetracycline
Which tetracycline has the greatest oral absorption?
doxycycline
Which tetracycline has the lowest oral absorption?
tetracycline
Which tetracycline has the longest half-life?
doxycycline
Which tetracycline has the shortest half-life?
tetracycline
Which tetracycline has the greatest renal excretion?
tetracycline
Which tetracycline has the least renal excretion?
doxycycline
What are the adverse effects of tetracyclines?
1) GI irritation - diarrhea, superinfections (broad spectrum, high concentration in kidneys)

2) espohageal ulceration (if gets stuck in esophagus)

3) hepatotoxicity (pregnant women w/ polynephritis)

4) phototoxicity (drug deposits in skin -> free radicals w/ UV light)

5) nephrotoxicity

6) deposition in teeth and bones

7) vestibular toxicity (minocycline)
What drug is Fanconi's Sydrome associated with?
tetracyclines

breakdown product of tetracyclines in acid
(used to be a problem when citric acid was used as a preservative)
What tetracycline is not used as an antibiotic?
demeclocycline

an anti-diuretic

used to treat SIADH
What tetracycline is used to treat SIADH?
dimeclocycline
What is dimeclocycline used for?
used as an anti-diuretic to treat SIADH
Why does tetracycline turn teeth black?
chelates with Ca in teeth

breakdown product of tetracycline is black, and deposits permanently in the teeth
Which tetracycline is associated with vestibular toxicity?
minocycline
Which antibiotic has the highest incidence of superinfections?
tetracyclines (10-20%)
What are tetracyclines used for?
gram-positives, gram-negatives, aerobes, anaerobes, non-bacterial microorganisms

DOC for rickettsial infections
DOC for chlamydial infections

used for gonorrhea and syphillis when beta-lactams cannot be used

used for lower respiratory tract infections

used for plague, tularemia, brucellosis

used to treat acne
Which is the most preferred tetracycline?
doxycycline

better absorbed
longer half-life
better tissue levels
less GI disturbance
non-renal and non-hepatic
How does tetracycline affect enterohepatic recirculation?
kills bacteria that contain beta-glucronidase -> prevents regeneration of drug -> excretion -> lower blood levels

(drugs that depend on enterohepatic recirculation, such as oral antibiotics, will become ineffective as concentration in the blood decreases)
How do tetracyclines prevent acne?
1) inhibits bacterial lipase -> no free fatty acid -> no irritation

2) kills bacteria directly
Why is doxycycline no longer used for traveller's diarrhea?
b/c of high incidence of phototoxicity
What is the mechanism of action for chloramphenicol?
blocks peptidyl transferase at 50S
Which antibiotic blocks peptidyl transferase at 50S?
chloramphenicol
dalfopristin
What is the resistance mechanism of chloramphenicol?
acetylation

chloramphenicol acetyl transferase (CAT)
Which antibiotic concentrates best in the CNS?
chloramphenicol

b/c it is highly lipid soluable -> readily penetrates the BBB
How is cloramphenicol metabolized?
90% glucuronidation (phase II)

8% unchanged

2% deacetylation/dehalogenation
Which drug is associated with Gray Baby Syndrome?
chloramphenicol - caused by dosing neonates the same as adults per kg weight

(glucuronidation absent in neonates)
(renal function reduced in neonates)
What are the adverse effects of chloraphenicol?
1) Gray Baby Syndrome

2) bone marrow depression

3) aplastic anemia - appears weeks to months after stopping drug
Which drug is associated with aplastic anemia?
chloramphenicol
What is the alternative for treating RMSF?
chloramphenicol

(usually treat RMSF w/ tetracyclines)
What is the mechanism of action for macrolides?
binds at 50S to blocks translocation of peptide
Which antibiotics do macrolides compete with?
delfopristin (part of streptogramin)
chloramphenicol
How are the macrolides selectively toxic?
Can't get through mitochondrial membrane -> can only affect bacterial ribosomes
What drugs are part of the macrolides?
erythromycin
azithromycin
clarithromycin
Why are macrolides mainly used for gram-positive infections?
gram-positive organisms absorb macrolide 100x better than gram-negatives
Which macrolide has the best bioavailability?
clarithromycin
What are the macrolides used for?
mainly treating gram-positives

legionella, mycoplasma, chlamydia, some mycobacteria
What are the resistance mechanisms against macrolides?
1) decreased intracellular concentration (increased efflux)

2) hydrolysis by esterases

3) decreased binding
What are the adverse effects of erythromycin?
1) cholestatic hepatitis (erythromycin setolate)

2) GI irritation - epigastric pain, nausea, diarrhea -> problems w/ compliance

3) hearing loss (usually w/ IV) - uncommon

4) inhibition of CYP450 (causes arrhythmias when combined w/ terfenadine [antihistamine]; causes seizures and arrhythmias when combined w/ theophylline [asthma medication])
What are macrolides used for?
alternative for penicilln-resistant patients (similar spectrum to pen G)

used to treat mycoplasma, chlamydia, legionella
How are azithromycin and clarithromycin different from erythromycin?
better absorption
higher tissue concentrations
less GI upset
extended spectrum (MAC and H. influenzae)
fewer drug interations (b/c doesn't inhibit CYP450 enzymes)

H. pylori (peptic ulcers) - clarithromycin

uncomplictated chlamydial infections - azithromycin

very expensive compared to erythromycin
What is the mechanism of action for clindamycin?
binds 50S
How is clindamycin excreted?
primarily biliary excretion

(no dosage adjustments required in renal failure)
What are the adverse effects of clindamycin?
pseudomembranous colitis

(highest incidence of all antibiotics, though amoxicillin causes more b/c of its frequency of use)
Which antibiotic has the highest incidence of pseudomembranous colitis?
clindamycin
Which antibiotic causes the most pseudomembranous colitis?
amoxicillin
What is clindamycin used for?
used for gram-positive infections in pts. allergic to penicillin

anaerobic infections (esp. B fragilis), except in endocarditis and CNS infections

no effect in gram-negatives
Does clindamycin penetrate the CNS?
no
What is the mechanism of action for metronidazole?
reduction of nitro group by MO -> reactive metabolite -> interacts w/ DNA

(selective toxicity b/c mammalian cells to not convert to active form)
Which antibiotic is active against anaerobes?
clindamycin

metronidazole
reductive metabolite (active form) cannot be formed in aerobic environment
What is metronidazole used for?
anaerobic bacterial infections

DOC for pseudomembranous colitis (C. difficile)

also used for protoza and H. pylori (stomach ulcers)
Which antibiotics turns the urine brown?
metronidazole
nitrofurantoin
Does metronidazole penetrate the CNS?
yes
What are the adverse effects of metronidazole?
most common - GI disturbances

most severe - CNS and peripheral neuropathies

disulfiram-like reaction
Why is metronidazole contraindicated during pregnancy?
because mechanism of action disrupts DNA (possible mutagen?, carcinogen?)

can possibly cause birth defects, esp. during 1st trimester

however, no evidence in human and animal studies
Which antibiotics exhibit a disulfuram-like reaction?
cephalosporins w/ MTT side chain

metronidazole
What is the mechanism of action for rifampin?
binds to the beta-subunit of bacterial DNA-dependent RNA polymerase -> blocks initiation of RNA synthesis
What are the drawbacks of rifampin?
rapid emergence of resistance -> always used in combination w/ other antibiotics

not reliable by itself

hepatotoxicity, red body fluids
What are the primary drugs used for treating TB?
isoniazid
rifampin
streptomycin
ethambutol
pyrazinamide
What is p-glycoprotein?
MDR protein that pumps drugs out of the cell
What is the mechanism of action for isoniazid?
interferes w/ mycolic acids
inhibits cell wall synthesis of mycobacteria

(no activity against gram-positives or gram-negatives)
Which antibiotic is associated with causing SLE?
isoniazid - rare
What antibiotic is associated with causing SLE-like symptoms?
dapsone
What are the adverse effects of isoniazid?
1) peripheral neuritis - due to loss of B6
(INH binds B6 -> inteferes w/ formation of pyridoxal phosphate)

2) hepatotoxicity - major problem

3) SLE
What are the adverse effects of rifampin?
1) hepatotoxicity - not synergystic with INH

2) induction of CYP450 enzymes - interferes w/ oral contraceptives by increasing metabolism of drug
(induces CYP450 mechanisms more than any other drug)

3) discoloration of body fluids - turns body fluids red (due to large Vd)
What is the mechanism of action for ethambutol?
inhibition of arabinosyl transferase -> decreases incorporation of arabinose and interferes w/ cell wall synthesis of mycobacteria
What are the adverse effects of ethambutol?
optic neuritis
loss of green color vision
What antibiotic is causes loss of green color vision?
ethambutol
What is the mechanism of action of pyrazinamide?
unknown

Brenner: acts by lowering pH
What are the adverse effects pyrazinamide?
hepatoxicity - not to extent of INH

hyperuricemia - increase in plasma uric acid levels -> gout
When is isoniazid used alone?
prophylaxis for TB

(otherwise always used in combination with another drug)
Which anti-TB drugs causes liver toxicity?
isoniazid
rifampin
pyrazinamide - to a lesser extent
Which anti-TB drugs causes ototoxicity?
streptomycin (aminoglycosides cause ototoxicity)
Which anti-TB drugs causes hyperuricemia?
pyrazinamide
(reason why pyrazinamide causes gout)
Which anti-TB drugs causes visual toxicity?
ethambutol
What is the precursor of sulfonamides?
prontosil
What is the mechanism of action for sulfonamides?
structural analogs of PABA

competitive inhibitor of dihydropteroate synthetase
Why don't the sulfonamides affect mammalian cells?
mammalian cells can't synthesize DHFA
(don't contain dihydropteroate synthetase)

MO synthesizes DHFA, which is inhibited by sulfonamides
What are the resistance mechanisms for sulfonamides?
1) increased production of dihydropteroate synthetase

2) alteration of dihydropteroate synthetase so that it's less sensitive to binding and inhibition by sulfonamides

3) decreased penetration of sulfonamides into cells

4) increase PABA
How does procaine (local anestetic) reduce the competitiveness of sulfonamides?
procaine is metabolized to PABA -> increasing the concentration of PABA which decreases comptitiveness of sulfonamides
What are the adverse effects of sulfonamides?
1) crystallurea - w/ high concentrations

2) hypersensitivity rxns - urticaria, photosensitization, serum-sickness, Stevens-Johnson syndrome (destroys mucus membranes, GI tract)

3) cross-sensitivity - allergic to one, allergic to all

4) hemolytic anemia - in pts. w/ G-6-P dehydronase deficiency

5) kernicterus (in neonates) - displacement of bilirubin -> gets into CNS

(pts w/ aids have a high incidence of adverse effects)
Which antibiotic is associated with Stevens-Johnson syndrome?
sulfonamides
What antibiotic is associated with kernicterus?
sulfonamides
Which sulfonamide is least likely to cause crystallurea?
sulfisoxazole
What is the advantage of triple sulfas compared to other sulfonamides?
reduced crystallurea due to solubility of each agent being independent of the others
(thus, can have increased concentrations of drug w/ less crystallurea)
What are sulfonamides used for?
used for UTI
nocardiosis, chancroid - DOC sulfasoxazole
Sulfamethoxazole is often combined with what drug?
trimethoprim
How is mafenide administered?
topical only

absorbed from burned skin
How is silver sulfadiazine administered?
topical only
What is the adverse effect of mafenide?
1) pain on application

2) skin rashes

3) metabolic acidosis - inhibition of carbonic anhydrase
What is the adverse effect of silver sulfadiazine?
skin rashes, however lower than mafenide
Does an increase in PABA decrease the activity of silver sulfadiazine?
no

different mechanism from other sulfonamides

silver is the active compound (known to have antibacterial activity)
What is the mechanism of action for trimethoprim/sulfamethoxazole (AKA co-trimoxazole)?
trimethoprim is a structural analog of DHFA -> inhibits DHFR

sulfamethoxazole is a sulfonamide (inhibits dihydropteroate synthetase)

double-sequential blockade (synergistic)
How is trimethoprim selective for bacteria?
concentration needed to inhibit mammalian DHFR in much greater than in bacteria (~60000x)
What ratio has the maximum synergistic effect for sulfamethoxazole:trimethoprim?
20:1

however, dose is 5:1 (400mg:80mg)
What are the adverse effects of trimethoprim?
1) folic acid deficiency (SMZ)

2) anemia (TMP) - treat w/ folinic acid
What is used to treat anema caused by trimethoprim?
folinic acid

bypasses blockade -> reverses anemia

doesn't affect activity or TMP b/c MO can't transport it (mammalian cells can)
What group of people develop allergy to sulfonamides?
AIDS patients (60-90%)
What is trimethoprim:sulfamethoxazole used for?
used for UTI, resistant infections, pneumocystitis carinii pneumonia

no anaerobic coverage
What drug is used to prevent pneumocystis carinii pneumonia in AIDS patients?
trimethoprim/sulfamethoxazole (co-trimoxazole)
What is the mechanism of action for sulfones?
structural analogs of PABA

act as antimetabolites in the synthesis of folic acid
What is dapsone used for?
DOC for leprosy
What is the drug of choice for treating leprosy?
dapsone
What are the adverse effects of dapsone?
1) nonhemolytic anemia - common

2) acute hemolytic anemia - less frequent

3) SLE-like symptoms

4) erythema nodosum

5) peripheral neuropathy
What is the precursor for the fluoroquinolones?
nalidixic acid
What is the mechanism of action for fluoroquinolones?
binds to A-subunit of DNA gyrase -> interfers with supercoiling and inhibits DNA synthesis
How are the fluoroquinolones selective for bacteria?
mammalian topoisomerases are inhibited at a much higher concentration than bacterial topoisomerases
Which antibiotics are selective based on the differences of MIC between bacterial and mammalian cells?
trimethoprim
fluoroquinolones

methotrexate (anti-cancer)
What are fluoroquinolones used for?
gram-positive, gram-negative

pesudomonas (PO)

resistant infections - due to unique mechanism

prophalaxis for traveller's diarrhea - replaced tetracyclines, but still causes phototoxicity

UTI, prostatitis

(active against some MRSA strains, but not reliable)
What are the drawbacks of fluoroquinolones?
chelates divalent and trivalent cations

normal amount in the diet is not a problem

use of supplements, antacids, vitamins can decrease absorption
What are the adverse effects of fluoroquinolones?
1) GI irritation - nausea, vomiting, diarrhea

2) CNS - seizures, headache, dizziness, visual disturbances, hallucinations

3) cartilage eroson - evidence from animal studies (not recommended for <18 y.o.)

4) tendinitis w/ occasional rupture of Achilles tendon

5) inhibition of CYP450 system
What antibiotic is associated with seizures in patients consuming large quantities of caffeine?
fluoroquinolones
What are the quinolones used for?
UTIs

achieves theraputic levels only in the urine
What is the mechanism of action for quinolones?
binds to A-subunit of DNA gyrase -> interfers with supercoiling and inhibits DNA synthesis
What is the mechanism of action for nitrofurantoin?
reductive metabolite that causes DNA damage
What is nitrofurantoin used for?
UTIs

achieves pharmacological effect only in the urine
What are the adverse effects of nitrofurantoin?
1) GI disturbances

2) hemolytic anemia in pts. w/ G-6-PDH deficiency

3) pulmonary rxns

(nitrofurantoin inhibits the activity of nalidixic acid - don't combine)
What drug cannot be combined with nitrofurantoin?
nalidixic acid
What drug cannot be combined with nalidixic acid?
nitrofurantoin
What is the mechanism of action for methenamine?
hydrolyzed under acidic conditions -> releases ammonia and formaldehyde

formaldehyde is bactericidal

urea-splitting bacteria (proteus) are resistant
(increase ammonia -> increase pH -> decreases hydrolyzation of methenamine -> inactivates drug)
What class of antibiotics cannot be combined with methenamine?
sulfonamides - mutual antagonism
Which antibiotic cannot be combined with sulfonamides?
methenamine
What are the adverse effects of methenamines?
1) painful urination due to formaldehyde

2) contraindicated in pts. w/ hepatic insufficiency -> leads to CNS problems
(compromised liver -> decreased clearance of ammonia -> ammonia levels build up)
What are the inhibitors of p-glycoprotein?
Ca-channel blockers
quinidine
phenothiazine
What is the mechanism of action for nitrogen-mustards?
covalently binds N7 on guanine -> cross-links same or differenf DNA strands
Why is cis platinum not a true alkylating agent?
b/c it contains no carbons
(not an organic conpound)
What is the mechanism of action for 6-mercaptopurine?
interferes w/ purine metabolism -> disrupts DNA synthesis
What is the mechanism of action for cis-platinum?
covalently cross-links DNA
What is hypoxanthine-guanine phosphoribosyltransferase (HGPTR)?
enzyme involved in purine metabolism

also converts 6-mercaptopurine to active form
What is the mechanism of 5-fluorouracil?
interferes w/ pyrimidine metabolism

inhibits thymidylate synthesase -> interferes w/ production of DNA

incorporated into RNA -> dysfunctional RNA
What is the mechanism of action for methotrexate?
interferes w/ folic acid metabolism

inhibits mammalian DHFR -> inhibits production of FH2 and subsequently FH4
(no FH4, no cofactors for DNA synthesis)
What antibiotics inhibit DHFR?
trimethoprim - inhibits MO DHFR
methotrexate - inhibits mammalian DHFR
What is the difference b/w trimethoprim and methotrexate?
trimethoprim binds MO DHFR
MTX binds mammalian DHFR
How do trimethoprims and methotrexates stay in the cell for a long period of time?
forms polyglutamates
What is the mechanism of action for antracyclines?
intercalate b/w adjoining nucleotide pairs of DNA

inhibits topoisomerase
disrupts cell membrane function
produces free radicals -> toxicity
Doxyrubicin and daunorubicin are what class of drugs?
anthracyclines

antibiotics used to treat cancer
broad spectrum for many different cancers
What is the mechanism of action for dactinomycin?
binds DNA -> breakup of chain
What is the mechanism of action for bleomycin?
causes chain scission and frangmentation of DNA
What is the mechanism of action for mitomycin?
forms product that alkylates DNA
What is the mechanism of action for vinca alkaloids?
binds to tubulin of microtubules in mitotic spindls and arrests mitosis at metaphase
Vinblastine and vincristine are what type of drugs?
vinca alkaloids (from plants)

used to treat cancer

binds mictotubules -> arresting mitosis
What is the mechanism of action for paclitaxel?
stimulates microtubule formation (blocks disassembly of microtubules) -> arrests cell in mitosis
What is the mechanism of action for L-asparaginase?
hydrolyzes asparagine

asparagine is a requirement for some cancer cells (destruction of asparagine in blood -> kills certain cancer cells)

(normal cells synthesize asparagine)
What drugs are cell-cycle specific anti-metabolites used to treat cancer?
5-fluorouracil
mercaptopurine
methotrexate
What drugs are cell-cycle mitotic inhibitors used to treat cancer?
vincristine
vinblastine
paclitaxel
What drugs are cell-cycle non-specific alkylating agents used to treat cancer?
mechlorethamine
cyclophosphamide
cisplatin (cis-platinum)
Whic is more effective in low-growth fraction tumors?

CCS or CCNS
CCNS b/c acts on both dividing and non-dividing cells
Which drug is better used on high-growth fraction tumors?

CCs or CCNS
CCS b/c they are less toxic
(larger doses/longer duration possible)

they only work on dividing cells
What are the adverse effects of anti-cancer drugs?
1) acute toxicity - nausea, vomiting (due to chemoreceptor trigger zone)

2) delayed toxicity - bone marrow suppression*, ulceration, alopecia (hair loss), interference w/ reproductive systems (birth defects)
*bone marrow suppression -> immunosuppression (main problem)

3) hyperuricemia - elevated uric acid levels -> gout or gouty nephrothapy

4) pulmonary fibrosis (esp. bleomycin, busulfan)

5)hepatotoxicity (esp. cyclophosphamide) -> hemorrhagic cyctitis

6) nephrotoxicity (esp. MTX, cisplain)
What anti-cancer drugs are associated with causing pulmonary fibrosis?
bleomycin
busulfan
What anti-cancer drug is associated with hepatotoxicity leading to hemorrhagic cystitis?
cyclophosphamide

caused by acrolein accumulation

(mesna inactivates acrolein and reduces toxicity)
What is mesna used for?
treating hemorrhagic cystitis caused by cyclophosphamide (caused by acrolein accumulation)

(inactivates acrolein and reduces toxicity)
What is mannitol and sodium thiosulfate used for?
treating nephrotoxicity caused by cisplatin

mannitol (diuretic) -> dilutes urine

sodium thiosulfate -> directly inactivates cisplatin
What is leucovorin rescue?
treat pt. w/ very high levels of MTX

administer leucovorin, citrovorum, or folinic acid (antidote to MTX) before delayed toxicity begins

works primary b/c toxicity for MTX is delayed, and cancer cells don't transport in antidote as well as normal cell
What is allopurinol used for?
inhibitor of xanthine oxidase

used for prolonging the half-life of 6-mercaptopurine by inhibiting metabolism of drug

also decreases uric acid levels by inhibiting normal metabolism of purines, preventing gouty nephropathy

(however, also decreases body's ability to inactivate 6-MP -> must reduse dose by 50-75%)
Which anti-cancer drugs have reduced bone marrow suppression?
vincristine
cisplatin
bleomycin
L-asparagine
hormones
What is the major dose-limiting toxicity of vincristine?
neurotoxicity
What is the major dose-limiting toxicity of cisplatin?
nephrotoxicity
What is the major dose-limiting toxicity of bleomycin?
pulmonary toxicity
What is the major dose-limiting toxicity of L-asparginase?
allergic rxns

(b/c originally isolated from guinea pig serum)
What is the major problem with anti-cancer drugs?
potent immunosuppressants
Which drug has the longest post-antibiotic effect?
aminoglycosides (3-6 hours)
Which antibiotic exhibits a curare-like effect?
aminoglycosides
What is the DOC for B. fragilis?
clindamycin
What nucleoside analogs are used against HIV?
zidovudine
didanosine
zalcitabine
stavudine
lamivudine
abacavir
What NNTRIs are used against HIV?
nevirapine
delavirdine
efavirenz
What protease inhibitors are used against HIV?
saquinavir
indinavir
ritonavir
nelfinavir
amprenavir
lopinavir
What fusion inhibitor is used against HIV?
enfuvirtide
What drugs are used against CMV?
ganciclovir
foscarnet
cidofovir
fomivirsen
What drugs are used against hepatitis?
interferon alpha-2a
interferon alpha-2b
What drugs are used against herpes simplex?
acyclovir
famciclovir
valcyclovir
vidarabine
idoxuridine
trifluridine
foscarnet
docosanol
What drugs are used against influenza A?
amantadine
rimantadine
zanamivir
oseltamivir
What drugs are used against RSV?
ribavirin
What drugs are used against VZV?
acyclovir
valcyclovir
famciclovir
foscarnet
What is the mechanism of action for zidovudine?
analog of deoxythymidine

phosphorylated by cellular kinases ->
AZTTP (which has greater affinity for RT than human DNA pol.)

inhibitor of HIV RT
What is the bioavailability of AZT?
65%
What is the half-life of AZT?
1 hour
What is the distribution of AZT?
brain
liver
muscle
placenta
How is AZT excreted?
mostly in urine
What are the adverse effects of AZT?
granulocytopeina
anemia
headache
nausea
insomnia
What is AZT used for?
improve of quality of life

reduce incidence of opportunistic infections

reduce transmission of HIV to offspring (given 14-34th week of gestation)
When is didanosine used?
in patients unresponive/intolerant to zidovudine
What is the mechanism of action for didanosine?
analog of inosine

phosphorylated by cellular kinases -> termination of DNA synthesis

inhibitor of HIV RT
What are the adverse effects of didanosine?
abdominal cramps
diarrhea
peripheral neuropathy
acute pancreatitis
hepatic failure
Who should not be taking didanosine?
pts. w/ history of pancreatitis or alcoholism
What is the mechanism of action for zalcitabine?
inhibitor of HIV RT
What are the adverse effects of zalcitabine?
rash
stomatitis
fever
peripheral neuropathy
pancreatitis
When is zalcitabine used?
for pts. refractory to or intolerant of zidovudine
What is the mechanism of action for stavudine?
nucleoside analog

inhibitor of HIV RT
What is the bioavailability of stavudine?
80%
What are the adverse effects of stavudine?
peripheral sensory
neuropathy
pancreatitis
What is the mechanism of action for lamivudine?
nucleoside-analog inhibitor of HIT RT
When is lamivudine used?
for pts. who have failed or are intolerant to approved drugs
What are the benefits of combining zidovudine and lamivudine?
suppresses HIV resistance to zidovudine
decreases viral load
increases CD4 cell counts
What is the bioavailability of abacavir?
95%
What are the adverse effects of abacavir?
hypersensitivity
fever
nausea
vomiting
What is the mechanism of reaction for abacavir?
nucleoside analog

inhibits HIV RT
What are the adverse effects of protease inhibitors for HIV therapy?
inhibits of metabolism of other drugs that use CYP3A4 isozyme

GI intolerance

nephrotoxicity (indinavir)

paresthesia

taste perversion

elevated triglycerides (ritonavir)

diarrhea (nelfinavir)
Do the protease inhibitors for HIV penetrate the CNS?
no
Which protease inhibitor for HIV has the lowest bioavailability?
saquinavir (4%)
Which protease inhibitor for HIV has the greatest bioavailability?
ritonavir (80%)
What is the mechanism of action for nevirapine?
NNRTI of HIV-1

binds directly to RT and blocks activity by disrupting the catalytic site

does not compete with template or nucleoside triphosphate

(does not inhibit HIV-2 RT and eukaryotic DNA pol.)
What are the adverse effects of nevirapine?
severe rash - when occurs -> discontinue therapy

hepatitis
What is the bioavailability of nevirapine?
90%
What are the adverse effects of delavirdine?
rash
What are the adverse effects of efavirenz?
rash
dizziness
What is the mechanism of action for enfuvirtide?
inhibition of the fusion of HIV-1 w/ CD4+ cells

binds to the 1st heptan-repeat (HR1) in the gp41 subunit of the viral envelope glycoprotein and prevents the conformational changes required for the fusion of viral and cellular membranes
What is the structure of enfuvirtide?
CH3CO-tyr-thr-ser-leu-ile-his-ser-leu-ile-glu-glu-ser-gln-asn-gln-gln-glu-lys-asn-glu-gln-glu-leu-leu-glu-leu-asp-lys-trp-ala-ser-leu-trp-asn-trp-phe-NH2

THIS WILL PROBABLY BE ON THE TEST!!!
How is enfuvirtide administered?
IM 2x daily

give each injection at a site different from the preceding injection site and only where there is no current injection site rxn from an earlier dose

(do not inject into moles, scar tissue, bruises, navel)
What are the adverse effects of enfuvirtide?
pain at injection site
erythema
induration
nodules
cysts

high incidence of bacterial pneumonia

(does not affect CYP450)
Which anti-HIV drug is associated with high incidences of bacterial pneumonia?
enfuvirtide
What is the DOC for HIV infection in adults?
2 nucleosides + 1 protease inhibitor
2 nucleosides + 1 non-nucleoside

alternatives
2 nucleosides
1 nucleoside + 1 protease inhibitor
2 protease inhibitors +/- nucleoside or non-nucleoside
1 protease inhibitor + 1 nucleoside + 1 non-nucleoside
What does HAART therapy usually include?
1 nucleoside analog
1 protease inhibitor

plus either
another nucleoside analog
or
non-nucleoside RT inhibitor
What is acyclovir active against?
HSV-1
HSV-2
VZV
What is the half-life of acyclovir?
3.5 hours
What is the bioavailability of acyclovir?
15-20%
What drug reduces the renal clearance of acyclovir?
probenecid
What is valacyclovir used for?
treatment of VZV in immunocompetent adults

also effective against henital herpes
What is the bioavailabilitiy of valacyclovir?
50%
What is the difference between acyclovir and valacyclovir?
valacyclovir is a prodrug of acyclovir and is more rapidly absorbed

valacyclovir is hydrolyzed to acyclovir in the intestinal wall and liver
What is the mechanism of action for acyclovir?
guanosine analog

activated by viral thymidine kinase

inhibits herpes virus DNA by interfering w/ the action of viral DNA polymerase
What is the mechanism of action for ganciclovir?
guanosine analog

inhibits herpes virus DNA by interfering w/ the action of viral DNA polymerase

100x more active against CMV than acyclovir
What are the adverse effects of gancyclovir?
bone marrow suppression

neutropenia (40%)

headache, psychosis, convulsions, coma (5%)
What drugs are used for the treatment of CMV retinitis?
ganciclovir
cidofovir
fomivirsen
What is the mechanism of action for cidofovir?
nucleotide analog

pre-phosphorylated -> does not depend on phosphorylation by CMV enzyme

taken up by CMV DNA pol. -> early chain termination
What is the mechanism of fomivirsen?
antisense drug

complimentary to mRNA sequence for the major immediate-early transcriptional region of CMV

inhibits CMV replication

(active against resistant strains to ganciclovir, foscarnet, cidofovir)
What are the adverse effects of fomivirsen?
iritis
vitritis
cataracts
increased intraocular pressure (15-20%)
vision changes
What is the mechanism of action for vidarabine?
analog of adenosine

inhibits viral DNA pol. -> early chain termination
(mammalian DNA pol. inhibited to lesser extent)
Why is a large administration volume required for vidarabine?
b/c of poor solubility
What are the adverse effects of vidarabine?
nausea
vomiting
diarrhea
hallucinations
psychoses
ataxia
tremor
pain syndrome
dizziness
bone marrow suppression
What is vidarabine used for?
HSV
VZV

(replaced by acyclovir, which is more effective and less toxic)

used topically for superficial keratitis caused by HSV
What is the mechanism of action for idoxuridine?
thymidine analog

incorporated into both viral and mammalian DNA -> DNA susceptable to breakage
What is idoxuridine used for?
HSV infections of cornea

(not effective against genital herpes)
What are the adverse effects of idoxuridine?
irritation
pain
pruritus
inflammation or edema of eyelids
photophobia

(not used systemically since it causes hepatic injury and is teratogenic and mutagenic)
What is the mechanism of action for trifluridine?
thymidine analog

incorporated into viral DNA -> early chain termination
What is trifluridine used for?
HSV-1 and 2 (including thymidine kinase deficient strains)

CMV

vaccinia

adenovirus

used to treat keratoconjunctivitis caused by HSV-1 and 2
What are the adverse effects of trifluridine?
discomfort
irritation
edema
What is docosanol used for?
topical treatment of recurrent oral-facial herpes simplex episodes
What is the mechanism of action for docosonal?
inhibits fusion b/w the plasma membrane and viral envelope, blocking viral entry
What are the adverse effects for docosanol?
headache
What are the anti-herpes agents?
acyclovir/valcyclovir/famciclovir
ganciclovir
cidofovir
fomivirsen
virdarabine
idoxuridine
trifluridine
docosanol
What is the mechanism of action for ribavirin?
phosphorylated to RMP by adenosine kinase

RMP inhibits IMP dehydrogenase -> decreasing guanine levels

RMP converted to RTP -> inhibits viral RNA polymerase

RTP inhibits GTP-dependent enzymes required for "capping" of viral mRNA
Where does ribavirin accumlulate?
RBCs

half-life 40 days in RBCs
What are the adverse effects of ribavirin?
anemia due to hemolysis

increased bilirubin, iron, uric acid levels in plasma

teratogenic
What viruses is ribavirin active against?
myxoviruses, paramyxoviruses, arenaviruses, bunyviruss, retroviruses, herpes viruses, adenoviruses, pox viruses, Lassa fever

(wide range of RNA and DNA viruses)
What is the mechanism of action for amantadine?
not fully known

blocks late stage in assembly of influenza A virus

acts to buffer pH of endosomes -> blocks fusion of virus envelope w/ endosome membrane

blocks viral M2 protein -> blocks acidification of endosome -> blocks fusion
What are the adverse effects of amantadine?
nervousness
confusion
hallucinations
seizure
coma
insomnia
GI upsets
dry mouth
pupillary dilation
What is amatadine used for?
treatment of influenza A (not B)
reduce severity and duration of influenza

useful in treatment of Parkinsonism
What is the mechanism of action for zanamivir?
neuraminidase inhibitor for influenza A and B -> prevent the release of progeny virons
What is the mechanism of action for oseltamivir?
neuraminidase inhibitor for influenza A and B -> prevent the release of progeny virons
What is the bioavailability of zanamivir?
<5%
What is the bioavailability of oseltamivir?
80%
What are the adverse effects of zanamivir/oseltamivir?
diarrhea
nausea
headache
nasal and throat discomfort (zanamivir)
bronchospasm - pts. w/ asthma
What is the mechanism of foscarnet?
inhibits viral DNA pol., RNA pol., and HIV RT by interacting w/ pyrophosphate binding site
What are the adverse effects of foscarnet?
reduced renal function
malaise
nausea
vomiting
fatigue
anemia
What is foscarnet used for?
herpesviruses
CMV
HIV

(strains of HSV resistant to acyclovir and gancyclovir are sensitive to foscarnet)
What is the mechanism of action for interferons?
INFs bind to cell surface receptors -> induces 2'-5' oligoadenylates -> activates latent ribonuclease that degrades

major effect: inhibition of viral protein translation
What are the adverse affects of interferons?
chills, headaches, myalgias, nauesa, vomiting (INF-aplha)

bone marrow suppression

fatigue, anorexia (long-term Tx)

reduces activity of CYP450 system

development of antibodies against INF
What are interferons used for?
hairy-cell leukemia
Kaposi's sarcoma
condylomata acuminata (genital warts)
hepatitis B and C