Glossary of Pharm Exam 1 EVMS

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Which classes of antibiotic are bactericidal?
Which classes of antibiotics are bacteriostatic?
Which antibiotics have excellent CNS penetrating ability?
Which antibiotics only penetrate the CNS with inflammed meninges?
3rd-gen cephalosporins
Which antibiotics are very poor at penetrating the CNS?
Which antibiotics can get into the prostate?
ciprofloxacin (fluoroquinolone)
doxycycline (tetracycline)
Which antibiotics require dosage reduction with renal insufficiency?
tetracyclines (except doxycycline)
most cephalosporins (except cefoperaxone)
Which drugs do not require dosage adjustments with renal insufficiency?
Which antibiotics cause ototoxicity?
Which antibiotics cause phototoxicity?
Which antibiotics cause phlebitis?
Which antibiotics are contraindicated during pregnancy?
Which antibiotics cause hemolysis with G-6-P dehydrogenase deficiency?
beta-lactam drugs
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)

penicillin binding protein 1

involved in cross linking of peptidoglycan

inhibition causes rapid lysis

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

inhibition causes ovoid shape and slow lysis
involved in septum formation

low beta-lactam concentration -> filaments

high beta-lactam concentration -> lysis
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?
How is ampicillin administered?
Which penicillins are penicillinase resistant?
methicillin (no longer on market)
Which penicillins are effective against pseudomonas?
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)

Which is more stable to hydrolysis?

penicillins or cephalosporins
What are the adverse effects of cephalosporins?

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?
Which 1st-gen cephalosporin is administered parenterally?
Which 2nd-gen cephalosporin is administered orally?
Which 2nd-gen cephalosporin is administered parenterally?
Which 3rd-gen cephalosporin is administered orally?
Which 3rd-gen cephalosporin is administered parenterally?
Which generation of cephalosporins are most active against gram-positives?
1st generation
Which generation of cephalosporins are most susceptible to beta-lactamases?
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?
Which cephalosporin has the longest half-life?
Which cephalosporins require no adjustment in renally impaired patients?
Which cephalosporin is the most active against pseudomonas?
Which cephalosporin causes "biliary sludging?"

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?

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?
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?

b/c it can cause convulsions (~3%)
What are the inhibitors of beta-lactamases?
clavulanic acid
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?

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)


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?

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


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?

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

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?

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


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?

order of increasing cross-resistance

(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
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
(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?
When is kanamycin used?
used as a 2nd or 3rd line drug in TB

(not used much else)
Which aminoglycoside has the broadest spectrum?
Which aminoglycoside has the least cross-resistance?
Which aminoglycoside is limited to topical use and oral administration to steralize the gut?
Which aminoglycoside is used for TB and endocarditis?
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?
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?
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?
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?
Which tetracycline is least lipid soluble?
Which tetracycline has the greatest oral absorption?
Which tetracycline has the lowest oral absorption?
Which tetracycline has the longest half-life?
Which tetracycline has the shortest half-life?
Which tetracycline has the greatest renal excretion?
Which tetracycline has the least renal excretion?
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?

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?

an anti-diuretic

used to treat SIADH
What tetracycline is used to treat SIADH?
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?
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?

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?
What is the resistance mechanism of chloramphenicol?

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

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?
What is the alternative for treating RMSF?

(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)
How are the macrolides selectively toxic?
Can't get through mitochondrial membrane -> can only affect bacterial ribosomes
What drugs are part of the macrolides?
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?
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?
Which antibiotic causes the most pseudomembranous colitis?
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?
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?

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?
Does metronidazole penetrate the CNS?
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

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?
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?
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?
What is the mechanism of action of pyrazinamide?

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?
pyrazinamide - to a lesser extent
Which anti-TB drugs causes ototoxicity?
streptomycin (aminoglycosides cause ototoxicity)
Which anti-TB drugs causes hyperuricemia?
(reason why pyrazinamide causes gout)
Which anti-TB drugs causes visual toxicity?
What is the precursor of sulfonamides?
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?
What antibiotic is associated with kernicterus?
Which sulfonamide is least likely to cause crystallurea?
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?
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?

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?

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?
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?

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?
What are the quinolones used for?

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?

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?
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?
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
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

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