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983 Cards in this Set

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What are the 3 groups of chemotherapeutic agents?
antiparasitics, antimicrobials, and antineoplastics
What are the 3 groups of antimicrobials?
antibacterials, antifungals, and antivirals
What is the definition of chemotherapeutic agents?
drugs used to eradicate pathogenic bacterial organisms
What are the two ways to produce antibacterials?
antibiotic: produced by other microbes

synthetic: synthesized in laboratory
What is selective toxicity?
ability of the chemotherapeutic agent to inhibit the function of an invading organism or cancer cell with little effect on the host or normal cell
What was used in Africa to clean teeth and what did the active ingredient prevent?
diospyros twig prevented gingivitis
What was used in Egypt to dress wounds and what was the active ingredient?
honey, hydrogen peroxide
What was used for GI infections in China?
Cha-tiao-qi
What was used to dress wounds in Serbia and what is the active ingredient?
old bread, penicillins
Who figured out in the 1860s that diseases were caused by bacteria and not spells?
Louis Pasteur
What is antibiosis?
the growth of one microbe can be inhibited by another (Pasteur named it)
What was the red azo dye found in 1932 that was found to have antibacterial activity and was the first antibiotic used clinically?
prontosil
What drug class is a derivative of prontosil?
sulfonamides
Who studied staphylococcus aureus and found that its growth could be inhibited by the penicillium mold and when was it first used clinically?
Alexander Fleming in 1928, penicillin used in 1943
Who isolated streptomycin and when?
Selman Waksman and Albert Schatz in 1944
What (-cidal or -static) would you use if the host has no immune system function?
bactericidal
What are some facts about bactericidal drugs?
kills organism, number of organisms falls rapidly after drug exposure, activation of host immune system is NOT required
What is the MOA of bactericidal drugs?
block an essential function of organism
What are 2 examples of bactericidal drugs?
penicillins and aminoglycosides
What are some facts about bacteriostatic drugs?
inhibit growth of organism, number of organisms remains relatively constant, activation of host immune system IS required
What is the MOA of bacteriostatic drugs?
blocks function needed for growth but not survival
What are 2 examples of bacteriostatic drugs?
tetracyclines and macrolides
What are narrow spectrum drugs?
antimicrobial agents that are effective against a single organism or a limited group of pathogens
When do you use narrow spectrum drugs?
when the pathogen has been identified
What are broad spectrum drugs?
antimicrobial agents that are active against a wide range of pathogens
When do you use broad spectrum drugs?
when the pathogen is not identified
What are extended spectrum drugs?
antimicrobial agents that possess an intermediate range of activity
What are the 5 major classes of antibiotics?
cell wall synthesis inhibitors
protein synthesis inhibitors
antifolates
fluoroquinolones
miscellaneous antibiotics
Does the plasma membrane contain penicillin-binding proteins?
yes
What is step 1 in peptidoglycan synthesis of cell wall synthesis inhibitors?
muramic acid is acticated by the addition of UDP and then a 5 amino acid peptide is added to the complex
What is step 2 in peptidoglycan synthesis of cell wall synthesis inhibitors?
the UDP-muramic acid-5aa complex binds to bactoprenol and N-acetyl glucosamine is then added to this complex
What moves subunits to the outside of the wall in peptidoglycan synthesis?
bactoprenol
What is the peptidoglycan building block?
muramic acid + 5aa + N-acetyl glucosamine
What happens to bactoprenol after it translocates the peptidoglycan building block to the outside of the cell?
it is recycled to the inside of the cell for later use
What is step 3 in peptidoglycan synthesis of cell wall synthesis inhibitors?
the 5aa peptide is cross-linked to the neighboring peptidoglycan and the amino acid in the 5th position is lost during crosslink
What is the MOA of cell wall inhibitors?
block the activity of several enzymes that are involved in the complex process of building the peptidoglycan wall
Why do cell wall inhibitors work?
the cell wall is constantly being rebuilt
What does an unstable cell wall cause?
bacterial cell lysis (cell dies)
Are cell wall inhibitors bactericidal or bacteriostatic?
bactericidal b/c bacteria dies without the cell wall
In what group do B-Lactam drugs fall?
cell wall synthesis inhibitors
What do B-lactam drugs bind to?
a diverse group of bacterial enzymes known as penicillin binding proteins (PBPs)
Where are PBPs anchored and what are they responsible for?
anchored to the cytoplasmic membrane and are responsible for the assembly and maintenance of the cell wall
What are 2 groups of B-lactam drugs?
penicillins and cephalosporins
Do bacteria all have the same PBPs?
no, they have different types that express different affinities for the B-lactam
Why do protein synthesis inhibitors work?
b/c prokaryotes and eukaryotes have different ribosomes and the drugs selectively target ribosomes in prokaryotes
What are the ribosomes in prokaryotes and eukaryotes?
P: 30S and 50S

E: 40S and 60S
What are the steps in elongation of polypeptide chains in bacterial protein synthesis of protein synthesis inhibitors?
1. binding of aminoacyl tRNA to the A-site on the ribosome complex
2. formation of a peptide bond on the 50S ribosome
3. translocation to the P-site
How do protein synthesis inhibitors work?
inhibit various steps in bacterial protein synthesis
Is continuous bacterial protein synthesis required for survival?
no, b/c bacteria can enter a vegetative state and most protein synthesis inhibitors are bacteriostatic
What are 2 groups of protein synthesis inhibitors?
aminoglycosides and tetracyclines
What is the exception to the "most protein synthesis inhibitors are bacteriostatic"?
aminoglycosides are bactericidal
What are antifolates?
agents that prevent the production of folic acid
_____ acid is required for synthesis of DNA?
folic
How do prokaryotes and eukaryotes get the folic acid they need?
P: synthesize folic acid

E: must acquire folic acid from the diet
What are 2 groups of antifolates?
sulfonamides and dihydrofolate reductase inhibitors
What do quinolones do?
inhibit bacterial DNA topoisomerase which inhibits DNA synthesis
What are 2 groups of quinolones?
levofloxacin and ciprofloxacin
What is bacterial drug resistance?
the ability of a microorganism to withstand the effects of an antibacterial agent (innate and acquired)
What is innate resistance?
natural, drug target does not exist or is not susceptible to the antimicrobial agent (there is either no target or the antibiotic does not fit the target)
What is acquired resistance?
organism gains a factor which allows it to withstand the effects of an antibacterial agent (mutated gene product becomes insensitive to a particular antibiotic)
What are resistance factors?
genes that confer resistance to a particular antibiotic (kicks drug out of cell)
What is the chromosomal mech by which altered genes and Rf are acquired?
genes in bacterial chromosome acquires mutation
What is transferable acquired resistance?
plasmids are acquired from other organisms (conjugation) and bacteriophage (infection)
What is enzymatic drug inactication mech?
bacterial enzymes inactivates the antimicrobial agent
What inactivates penicillins?
B-lactamases (cleave the B-lactam ring of B-lactam antibiotics)
What inactivates aminoglycosides?
bacterial acetylases, adenylases, and phosphorylases
What is the mech of reduced affinity for drug target?
DNA mutations often cause structural changes in bacterial proteins targeted by the antimicrobial agent (decreases the affinity of teh antibiotic for the antibiotic target)
What is the mech for decreased accumulation of drug?
increased drug exit (efflux) or decreased drug uptake into bacteria
What mediates increased efflux?
membrane proteins that transport the antibiotics out of the bacteria
What mediates decreased uptake?
porins, membrane proteins through which some antibiotics enter bacteria
What is a common mechanism of resistance for cell wall synthesis inhibitors, DNA gyrase inhibitors, and RNA polymerase inhibitors?
reduced affinity for drug target
What is a common mechanism for resistance to fluoroquinolones and tetracyclines?
decreased accumulation of drug
What is a common mechanism for resistance to sulfonamides (bacteria used pre-formed folic acid from host diet)?
alteration of metabolic pathway
What is the mechanism of alterateion of metabolic pathway?
bacteria develop a metabolic pathway that bypasses the intended antibiotic target
When do you use multiple antibiotics?
to treat serious infections (different mechanisms of action) then bacteria has to develop resistance to more than 1 drug target for resistance to develop
What is definitive drug therapy?
drug selected based upon the identification of the organism and known drug susceptibility of the organism (generally not initial approach if infection is serious)
What is empiric drug therapy?
drug selected based upon the knowledge of the most common causative agents for a particular type of infection
What drugs do you avoid in pregnancy due to accumulation in teeth and bones?
tetracyclines
What are host factors to take into account with empiric drug therapy?
immunodeficiency, kidney/liver function, pregnancy, and age
Does the place where the infection was acquired matter?
yes, hospital is probably more resistant
What are 2 mechanical predisposing factors?
indwelling catheters and respirators
What is prophylactic drug therapy?
administered to a pt before a bacterial infection exists to protect individuals exposed to highly infectious organisms, to prevent infections in individuals with other medical conditions, to prevent infection related to surgical problems
What is drug combination therapy?
ideal antibacterial therapy utilizes multiple narrow spectrum agents, helps prevent development of resistance
What is an antagonistic response?
the combined effect is less than the effect of the drug alone?
What is an additive effect?
the combined effect is equal to the sum of the individual drug effects
What is a synergistic effect?
the combined effect is greater than the sum of the individual drug effects (this is the desired effect when antimicrobial agents are used in combination)
What is indifferent effect?
the combined effect is similar to the greatest effect produced by the individual drug alone
What are some Gram Positive bacteria?
streptococcus
staphylococcus
enterococcus
corynebacterium
nocardia
mycobacterium
bacillus
listeria
anaerobes
What are some Gram Negative bacteria?
moraxella
neisseria
enterobacteriaceae
campylobacteriaceae
helicobacteriaceae
psudomonadaceae
francisella
How is the antimicrobial activity of a drug characterized?
in terms of its bactericidal or bacteriostatic effect
What is a bactericidal drug?
a drug that kills sensitive organisms so that the number of viable organisms falls rapidly after exposure to the drug
What is a bacteriostatic drug?
drug that inhibits the growth of bacteria but does not kill them
What is MIC?
minimal inhibitory concentration: lowest conc. of a drug that inhibits bacterial growth
What is PAE effect?
postantibiotic effect: evidence of a persistent effect on bacterial growth after an antibacterial drug is removed from a bacterial culture
What can organisms be classified as having on the basis of MIC?
susceptibility, intermediate sensitivity, and resistance to drug
In general, the peak serum conc. of a drug should be ___ to ____ times greater than the MIC in order for a pathogen to susceptible to a drug.
4-10
What are pharmacokinetic properties of antibiotics that influence their selection?
oral bioavailability, peak serum conc, distribution to particular sites of infection, routes of elimination, and elimination half-life
Tissue concentrations of a drug are often _____ than the plasma concentrations?
lower
What antibiotics penetrate the blood-CSF barrier when the meninges are inflamed?
penicillin G (aminoglycosides DO NOT)
What disease is ALWAYS treated with more than one drug?
TB
Laboratory tests used to determine microbial sensitivity to drugs include the ____ ____ ____ (Kirby-Bauer test) and the ___ ____ test.
disk diffusion method and broth dilution test
What test determine MIC?
broth dilution test
What is the most common mechanism of transferable resistance?
bacterial conjugation and exchange of plasmids containing R factors
When is combo drug therapy used?
for tx of mixed infections, empiric tx of serious infections, and prevention of antibiotic resistance
What 2 structures do both gram (+) and gram (-) organisms have?
cytoplasmic membrane and cell wall
Where is the cytoplasmic membrane and what does it contain?
it is located next to the cytoplasm of bacteria containing various types of transport proteins and enzymes needed to build the cell wall (PBPs)
Which organsims have a thicker cell wall?
gram positive
Which organisms have porins?
gram negative
What does the cell wall primarily consist of?
peptidoglycans (repeating disaccharide units of N-acetylglucosamine and N-acetylmuramic acid)
What does muramic acid contain?
a pentapeptide that terminates in Ala-Ala
What is required to be intact for bacterial survival?
cell wall
What are agents that disrupt the bacterial cell wall?
bactericidal
Do cell wall inhibitors work best in rapidly dividing bacteria or in slowly dividing?
rapidly (combo of bactericidal and bacteriostatic will make -cidal work less efficiently b/c the -static slows division of bacteria)
Which organisms have outer membranes?
gram negative
What does the outer membrane contain?
species specific lipopolysaccharides (LPS) and protein channels (porins)
What do porins allow for?
the passage of ions and small hydrophilic molecules and antibiotics (mutations in them can lead to antibiotic resistance)
What do B-lactam antibiotics bind to?
a diverse group of bacterial enzymes known as penicillin-binding proteins (PBPs)
Where are PBPs anchored and what are they responsible for?
anchored to the cytoplasmic membrane and responsible for assembly and maintenance of the cell wall
What are some B-lactam antibiotics?
penicillins, B-lactamase inhibitors, cephalosporins, monobactam, and carbapenems
What are the 3 groups of penicillins?
narrow spectrum, penicillinase resistant penicillins, and extended spectrum
What are 2 narrow spectrum penicillins?
penicillin G and penicillin V
What are 3 penicillinase-resistant penicillins?
methacillin, dicloxacillin, and nafcillin
What are 4 extended spectrum penicillins?
ampicillin, amoxicillin, piperacillin, and ticarcillin
What is the chemsitry of penicillins?
beta-lactam ring fused to a thiazolidine ring with an R-group that is unique for each drug (the "house")
What is the MOA of penicillins?
inhibit bacteria cell wall synthesis interfering w/ the integrity of the wall causing cell death
Are penicillins bactericidal or bacteriostatic?
bactericidal
How is the route of admin determined for penicillins?
by the acid stability of the drug
How are acid-stable penicillins admin and what are some drugs?
oral admin: amoxicillin, dicloxacillin, and penicillin V
How are acid labile penicillins admin and waht are some drugs?
parenterally: piperacillin, ticarcillin, nafcillin, and penicillin G
Which penicillins are admin IM?
procaine (PenG): slow release, fast acting

benzathine (PenG): slow release, lasts several weeks
How are penicillins distributed in the body?
widely distributed to organs and tissues except the CNS (can go to CNS when meninges are inflamed-used in meningitis)
How are penicillins eliminated?
most are rapidly excreted by renal excretion except ampicillin (biliary and renal) and nafcillin (biliary)
What can be given with penicillin that competes with organic transporters and slows the excretion of penicillin?
probenicid
What are the 3 mech of resistance of penicillins?
inactivation of drug by B-lactamase, reduced affinity of antibiotic for the PBP, and reduced drug entry into bacteria
Describe inactivation of penicillins by B-lactamase.
B-lactamase cleaves the amide bond in the B-lactam ring resulting in inactivation of the drug (expressed from a plasmid or chormosome and expression can be constitutive or induced by drug)
Describe reduced affinity of penicillins for the PBP.
mutation in PBP changes the drug binding affinity
Describe reduced penicillin entry into bacteria.
many gram negative organisms express porins in the outer membrane which prevent the entry of drug
How do B-lactam antibiotics work?
inhibit cell wall synthesis by inhibiting PBP acticity
What are penicillins G/V active for?
mostly gram positive organisms, anaerobes, and spirochetes
What is penicillin G/V the DOC for?
streptococcal infections, enterococcal endocarditis (+ aminoglycosides), treponema pallidum (syphilis), neiserria meningitidis, sterptobacillis moniliformis (rat bite fever), anaerobes (NOT B. fragilus!!)
What are some other susceptible organsisms for penicillin G/V?
actinomycetes (Corynebacterium diptheria) and Borrelia burgdorferi (lyme disease)
What organisms are resistant to penicillin G/V?
staphylococci (COMPLETELY RESISTANT)
gonococci
some pneumococci
most gram neg
What are adverse effects of penicillins G/V?
allergy and seizures (at high doses and decreased renal function)
What drug is the most common cause of drug-induced sensitivity reactions?
penicillins G/V (degrades to penicilloic acid and other compounds and binds to cellular proteins and elicits antibody formation)
What other drug should you avoid if patient is SEVERELY allergic to penicillin?
cephalosporins
What are 9 clinical uses of penicillins G/V?
streptococcal infections
meningitis
pharyngitis
endocarditis
syphillis
lyme disease
anthrax (PCN is not DOC anymore)
gas gangrene
actinomycosis
What are 3 penicillinase-resistant penicillins?
dicloxacillin (oral), nafcillin (parenteral) and methicillin
What is the chemistry of penicillinase-resistant penicillins?
large bulky R-group to prevent cleavage of the b-lactam ring
What is the activity of penicillinase-resistant penicillins?
developed to treat penicillinase producing staph (penicillinase is a type of b-lactamase) and they are generally not active against other penicillinase producing organisms
What diseases can penicillinase-resistant penicillins be used for?
serious staph infections (MSSA) like endocarditis, osteomyelitis, and skin & soft tissue infections
What is resistant to penicillinase-resistant penicillins?
methicillin resistant staphylococcus aureus (MRSA)
What is MRSA due to?
reduced affinity for drug target PBP and is also resistant to cephalosporins
What is the clinical use of penicillinase-resistant penicillins?
staphylococcal infections
What are most staphylococcus and epidermidis?
methicillin resistant
Are hospital acquired MRSA worse?
yes b/c they are resistant to additional antibiotic classes
How do you treat MRSA?
vancomycin for severe b/c it inhibits cell wall synthesis but is not a B-lactam, use clindamycin, trimethoprim-sulfamethoxazole, and doxycycline for moderate
What are 2 subgroups of extended spectrum penicillins?
aminopenicillins (amoxicillin and ampicillin) and pseudomonal penicillins (pipericillin and ticarcillin)
How is amoxicillin admin and excreted?
admin: oral

excreted: renally
How is ampicillin admin and excreted?
admin: parenteral

excreted: renal and biliary
How is pipericillin admin?
parenteral
How is ticarcillin admin?
parenteral
What is the activity of extended spectrum penicillins?
penicillin coverage + additional G(-) bacilli, inactivated by b-lactamase
What are aminopenicillins the DOC for?
enterococcal endocarditis (+ gentamycin)
listeria monocytogenes (+ gentamycin)
proteus mirabilis
What are extended spectrum penicillins also useful for?
infections caused by diseases that penicillin treats + HELP

H. influenza
E. coli
Listeria monocytogenes
Proteus mirabilis
M. catarrhalis
K. pneumonia
What are some clinical uses for aminopenicillins?
URI, UTI, meningitis, endocarditis, and GI infections
What are aminopenicillins resistant to?
b-lactamase
What are adverse effects of aminopenicillins?
similar to penicillin + non-allergic skin rashes (particularly w/ mono) and psuedomembranous colitis
What are 3 important drug combos for aminopenicillins?
amoxicillin + clavulanate = augmentin
ampicillin + sulbactam = unasyn
ampicillin + aminoglycosides
Why does ampicillin + aminoglycosides work?
ampicillin is a cel wall synthesis inhibitor and aminoglycosides are protein synthesis inhibiors, both are bactericidal, the cell wall is weakened allowing aminoglycosides to enter the bacteria
What is the activity of antipseudomonals?
coverage of aminopenicillins + additional enterobacteriacea, inactivated by b-lactamase
What is antipseudomonals the DOC for?
psuedomonas aeruginosa (w/ aminoglycosides)
What are other G(-) organisms that antipseudomonals work for?
serratia, citrobacter, klebsiella, and B. FRAGILUS!!
What are antipseudomonals resistant to?
bacterial b-lactamases
What are the adverse effects of antipseudomonals?
similar to penicillin + bleeding and precipitation when mixed directly with aminoglycosides
What are the clinical uses of antipseudomonals?
pseudomonal and other G(-) infections
What are 2 important drug combos of antipseudomonals?
pipericillin + tazobactam = zosyn
ticarcillin + clavulanate = timentin
What do B-lactamase inhibitors do?
block the activity of bacterial B-lactamases by binding irreversibly to B-lactamase and serve as suicide substrates for bacterial B-lactamase with little or no antimicrobial activity alone
What are teh 2 peptide antibiotics that target the bacterial cytoplasmic membrane?
daptomycin and polymyxin
What does inhibition of PBP prevent?
cross-linking of peptidoglycan
What 2 drugs inhibit cell wall peptidoglycan synthesis by blocking specific steps in the formation of the disaccharide precursor, murNAc-GlcNAc?
bacitracin and fosfomycin
What are semisynthetic penicillins produced from?
6-aminopenicillanic acid, a building block obtained by removing the R group of a natural penicillin
How are B-lactamases (BLM) classified?
functional or biochemical classification and molecular classification (based on aa sequences)
What are functional group 1 BLMs?
enzymes that hydrolyze cephalosporins and correspond to molecular class C
What are group 2 BLMs?
enzymes that correspond to molecular classes A and D and includes penicillinases, cephalosporinases and carapenemases
What is the only BLM class that is inhibited by claculanic acid, sulbactam, or tazobactam?
class A
What are group 3 BLMs?
metallo (zinc) enzymes that correspond to molecular class B (hydrolyze most penicillins cepahalosporins, and carbapenems)--not inhibited by clavulanate
What will B-lactamase inhibitors act like in combo with a penicillin antibiotic?
a suicide inhibitor of these BLM enzymes serving as a surrogate substrate for them
What are 4 combinations of B-lactamase inhibitors w/ antibotics?
clavulanate + amoxicillin = aumentin
clavulanate + ticarcillin = timentin
sulbactam + ampicillin = unasyn
tazobactam + pipericillin = zosyn
What are 3 first generation (G1) cephalosporins?
cefazolin, cephalexin, and cefadroxil
What are 3 second generation (G2) cephalosporins?
cefprozil, cefotetan, and cefuroximide
What are 3 third generation (C3) cephalosporins?
ceftriaxone, cefixime, and cefdinir
What is 1 fourth generation (C4) cephalosporin?
cefepime
What is the largest and most widely used antibiotic class?
cephalosporins
What do G1 acta against?
g(+) cocci and a limited number of g(-) bacilli
What do G2-G4 act against?
increasing activity against g(-) bacilli, decreasing activity against g(+)
What is the general chemistry of cephalosporins?
semi-synthetic, derived from organism isolated from a sewage outlet, B-lactam ring + dihydrothiazine ring
What is the MOA of cephalosporins?
cell wall synthesis inhibitor
Are cephalosporins bacteriostatic or bactericidal?
-cidal b/c bacteria cannot survive w/ holes in cell wall
How are cephalosporins admin?
oral or parenteral and are well-distributed
How are cephalosporins eliminated?
most by renal tubular excretion except ceftriaxone (biliary) and ceftazimide, cephalexin (glomerular and tubular secretion)
What are cephalosporins NOT active against?
listeria, enterococci, or MRSA
What is the resistance of cephalosporins?
PBP affinity, B-lactamase (more resistant than PCN), porins
What are adverse effects of cephalosporins?
little toxicity, some hypersensitivity rxns, some cross sensitivity to PCN (avoid in pts w/ severly allergic to PCN), platelet dysfunction and bleeding, superinfections
What is a superinfection?
normal bacterial flora is inhibited allowing growth of other organisms (particularly drug resistant organsims), normal flora protects host from other organisms, extended use of antibiotics inc chances of developing superinfections
What is the activity of G1 ceph?
mostly g(+) organisms, few g(-) organisms, sensitive to B-lactamases
Do G1 ceph penetrate CNS?
NO--not even w/ inflammation
G1 ceph are _____ to BLA but less than ____.
sensitive, PCN
What is cefazolin the DOC for?
surgical prophylaxis
What organsims are susceptible to G1 ceph?
similar to PCN + KEP'M

Klebsiella
E. coli
Proteus
Methicillin-sensitive S. aureus (MSSA)
What are G1 cephalosporins inactive against?
L. monocytogenes
P. aeruginosa
Enterococci
B. fragilis
MRSA
What is the clinical use of G1 ceph?
Klebsiella infections
Streptococcal and Staphylococcal infections
Empiric tx of infections
Surgical prophylaxis (cefazolin)
What is the activity of G2 cephalosporins?
similar to G1 ceph, less active against some g(+), covers more g(-) organisms
What is G2 ceph a DOC for?
moraxella (cefuroxime)
What are some susceptible organisms to G2 ceph?
gonococci
meningococcal
H. influenzae (cefuroxime)
aerobic and anaerobic g(-) bacilli
What are G2 ceph NOT active against?
MRSA
enterococci
P. aeruginosa
listeria
What is a clinical use of G2 ceph?
URI
What are adverse effects of G2 ceph?
cefotetan has MTT side chain that can cause bleeding (Vit K antagonist), disulfiram-like rxns can also be produced (makes you sick w/ EtOH)
Do G3 ceph penetrate CNS?
yes, good when inflamed
How are G3 ceph excreted?
renal tubular mostly, some biliary
What is the activity of G3 ceph?
less active against g(+) than G2 and wider range of g(-)
What are G3 the DOC for?
E. coli
Klebsiella
N. gonorrhoeae
Salmonella
N. meningitis
What is the spectrum for G3 ceph?
G2 + ESPN

E. coli
Salmonella
P. aeruginosa
N. meningitis
What are 4 clinical uses of G3 ceph?
meningitis, pneumonia, urogenital (gonorrhea), and GI infections
Does G4 ceph have good CNS penetration?
yes
How are G4 ceph excreted?
renal tubular
What is the activity of G4 ceph?
less g(+) than G3, more g(-), more resistance to B-lactamases, last resort tx ffor infections resistant to G1-G3
What is G4 ceph the DOC for?
E. coli
What are G4 ceph not active against?
Listeria
Enterococci
MRSA
What are other susceptible orgs to G4 ceph?
Psuedomonas
Enterobacteriacea
Penicillin-resistant streptococci
What is a monobactam?
aztreonam
What is the MOA of monobactams?
cell wall synthesis inhibitor
How are monobactams admin?
parenterally
What is the distribution and elimination of monobactams?
well distributed and metabolized prior to renal excretion
Are monobactams -static or -cidal?
bactericidal
What is the activity of monobactams?
g(-) ONLY, relatively resistant to B-lactamases, good for PCN allergic pts
What are monobactams not active for?
g(+) and anaerobes
What are susceptible orgs for monobactams?
psuedomonas and serratia
What are adverse effects of monobactams?
hypersensitivty rxns in some, rarely shows cross-sensitivity to PCN and ceph
What are 3 carbapenems?
imipenem, meropenem, and ertapenem
What is the MOA of carbapenems?
cell wall synthesis inhibitors
What is the activity of carbapenems?
most broad spectrum of all B-lactams, covers ALL g(-), g(+), and anaerobes, resistant to most b-lactamases, last resort antibiotic
How are carbapenems distributed and excreted?
distributed well, and penetrate CNS w/out inflammation and excreted in renal tubule
What are carbapenems the DOC for?
enterobacter
serratia
acinetobacter
psuedomonas
What are carbapenems not active for?
MRSA and C. difficile
What are some adverse effects of carbapenems?
superinfections, seizures, some cross sensitivity to PCN and other B-lactams
What is the resistance of carbapenems?
porin mutations
What is a good drug combo of carbapenems?
imapenem + dehydropeptidase inhibitor
What is the chemistry of vancomycin?
glycoprotein
What is the MOA of vancomycin?
cell wall synthesis inhibitor (step 2), bind to nascent peptidoglycan pentapeptide and prevents addition to the existing cell wall
What is the absorption/distribution of vancomycin?
poorly absorbed from the gut, well distributed to most body fluids and tissues parenterally, some CNS penetration if meninges inflamed
How is vancomycin excreted?
glomerular filtration
What is the activity of vancomycin?
mostly g(+) orgs and is used as a last resort drug
What is vancomycin the DOC for?
MRSA
What is the spectrum of vancomycin?
staph infections
enterococcal endocarditis
streptococcal
C. difficile
What is the resistance of vancomycin?
dec affinity for bacterial target
What are adverse effects of vancomycin?
nephrotoxicity, ototoxicity
What are 3 good drug combos with vancomycin for vancomycin resistant enterococci (VRE)?
+ gentamicin OR
+ streptomycin
What is bacitracin derived from?
bacillus subtilis
What is the MOA of bacitracin?
inhibits cell wall peptidoglycan synthesis (step 2) and blocks regeneration of bactroprenol phosphate (BP)
What is the activity of bacitracin?
G(+) cocci and topical tx of minor skin and ocular infections
What is the antimicrobial spectrum of bacitracin?
streptococci
staphylococci
enterococci
What are adverse effects of bacitracin?
nephrotoxic, not used systemically
What is bacitracin often combined w/?
neomycin and/or polymyxin in ointment and creams
What is the chemistry of fosfomycin?
structurally similar to phosphoenol pyruvate
What is the MOA of fosfomycin?
irreversibly inhibits the enzyme enolpyruvate transferase and blocks the addition of phosphoenoyl pyruvate to UDP-GlcNAc (prevents synthesis of UDP-MurNAc)
What is the admin/distribution/excretion of fosfomycin?
oral
distributed to kidneys, bladder wall, prostate, and seminal vesicles
excreted renally
What is fosfomycin primarily used for?
UTI
What is the specturm of fosfomycin?
enterobacteriacea (E. coli, Citrobacter, Klebsiella, Proteus, Serratia)
What is the resistance of fosfomycin?
dec drug influx
What is an adverse effect of fosfomycin?
diarrhea
What do you use to treat E. coli?
ampicillin
What do you use to treat pseudomonas infections?
G3 ceph
What do you use to treat B. fragilus?
G2 ceph
What are drugs that inhibit bacterial cell wall synthesis?
B-lactam antibiotics, vancomycin, bacitracin, and fosfomycin
What are the B-lactam antibiotics?
penicillins, cephalosporins, monobactams, and carbapenems
How do B-lactams work?
inhibit the transpeptidase reaction that cross-links the peptidoglycan component of the cell wall
What is admin in combo w/ a B-lactam antibiotic to prevent degradation of the antibiotic by bacteria?
B-lactamase inhibitor
What are narrow-spectrum PCN active against?
gram-positive cocci and spirochetes
What are penicillinase resistant penicillins used to treat?
staphylococccal infections
What penicillins are active against various gram-negative bacilli?
extended-spectrum
Acid-stable PCN can be given ____ whereas acid-labile drus must be given _____.
PO, parenterally
How are most PCN eliminated?
renal tubular secretion (inhibited by probenecid)
The activity against gram-negative orgs _______ from G1-G4.
increases
What ceph can be used as a single-dose to treat gonorrhea?
ceftriaxone
What are the 3 steps in elongation of polypeptide chains?
1. binding of aminoacyl tRNA to the A-site on the ribosome complex
2. formation of a peptide bond on the 50S ribosome
3. translocation to the P-site
what are three 30S inhibitors?
aminoglycosides (-cidal)
tetracyclines (-static)
spectinomycin (-static)
What are four 50S inhibitors?
macrolides (-static)
clindamycin (-static)
chloramphenicol (-static)
quinpristin-dalfopristin (static/cidal)
What are the aminoglycosides?
Tobramycin
Amikacin
Neomycin
Gentamicin
Streptomycin
What is the activity of aminoglycosides?
g(-) orgs, few g(+)
What are aminoglycosides NOT effective agaisnt?
anaerobes (cannot enter the cells)
What is the MOA of aminoglycosides?
binds primarily to 30S subunit and causes misreading of the genetic code (wrong aa is added to the protein chain)
Why are aminoglycosides bactericidal?
b/c the ribosomal binding is irreversible
What is the chemistry of aminoglycosides?
composed of amino sugars, amino groups are basic and becoem extensively protonated and ionized in body fluids
How are aminoglycosides admin?
parenteral for systemic, oral for GI, topical for skin, mucous membrane, and ocular tissues
Why are aminoglycosides often used in combo w/ B-lactam antibiotic?
inc bacteria permeability and inc coverage of G(+) orgs
How are aminoglycosides absorbed?
poorly absorbed from gut
What is the distribution of aminioglycosides?
don't penetrate cell walls very well and don't penetrate meninges (use intrathecal admin)
How are aminioglycosides eliminated?
excreted unchanged, primarily glomerular filtration
What are clinical uses of aminioglycosides?
serious g(-) infections, mixed infections, TB, MAC, biological warfare infections
What is the resistance of aminoglycosides?
enzymatic inactivation of drug (acetylase, adenylase, and phosphorylase)

decreased drug accumulation

decreased affinity for drug target (dec binding to 30S)

partial cross-resistance
What are adverse effects of aminoglycosides?
nephrotoxicity (AGs accumulate in proximal tubule causing tubular necrosis and impaired drug excretion--the most common cause of drug-induced kidney failure), ototoxicity, allergic rxns (rare)
What are aminoglycosides used in combo with?
synergistic effecst when combined w/ B-lactam antibiotics
What is the spectrum of gentamicin?
enterobacteriaceae, used in combo w/ b-lactams to treat enterococcus, staphylococcus, and pseudomonas
What are resistant to gentamicin?
streptococci and anaerobes
What is the major adverse effect of gentamicin?
ototoxicity (and some nephro)
What is the spectrum of tobramycin?
similar to gentamicin but slightly better activity against P. aeruginosa, resistance against inactivating enzymes
What are adverse effects of tobramycin?
ototoxicity (some nephro)
What is the spectrum of amikacin?
greater activity against P. aeruginosa, enterobacter, and MDR TB than gentamicin
What is the resistance of amikacin?
greater to drug modifying enzymes than other AGs
What is an adverse effect of amikacin?
ototoxicity
Is amikacin used freely?
no, reserved for infections that are resistant to other AGs
What is the least toxic AG but least active against P. aeruginosa and other g(-) bacilli
streptomycin
Why is streptomycin a single use agent?
it develops resistance rapidly due to decreased ribosomal affinity
What is streptomycin the DOC for?
Francisella tularensis
What are other susceptible orgs to streptomycin?
plague, MDR TB, brucellosis, endocarditis

(biological warfare)
What is the spectrum of neomycin?
active against G(-) and G(+)
What is an adverse effect of neomycin?
most nephrotoxic of all the AGs, limited to topical use and usually combined w/ bacitracin and polymixin, may eliicit hypersensitivity rxns w/ long-term topical use
What are 3 tetracyclines?
tetracycline (PO)
doxycycline (PO, parenteral)
minocycline (PO, parenteral
What is the chemistry of tetracyclines?
anthracycline derivatives produced by Streptomyces species, semi-synthetic
What is the MOA of tetracyclines?
inhibits binding of tRNA to 30S ribosome binding site (competitive)
What is the activity of tetracycline?
bacteriostatic, broad-spectrum
What is the distribution/absorption of tetracyclines?
well distributed, no CNS penetrations (except minocycline), absorption dec by polyvalent cations (dairy, iron, and antacids)
How are tetarcyclines eliminated?
renal and hepatic
What is tetracycline the DOC for?
rickettsia (RMSF), atypicals (M. pneumonia, C. trachomatis, ehrlichia), biological warfare (brucellosis, Y. pestis, F. tuarensis, B. anthracis), H. pylori, spirochetes (lyme dz), and proprionibacterium
What can tetracyclines help in mild cases?
MRSA
What are adverse effects of tetracyclines?
concentrates in growing teeth and bones, expired prep can breakdown into more toxic compounds, photosensitivity, alters GI flora (dec contraceptive levels)
What is the resistance of tetracyclines?
inc drug efflux, dec drug uptake (transmission of plasmids containing altered porin genes), altered target binding, enzymatic inactivation
What is the oral bioavailability of tetracycline, doxycycline, and minocycline?
T: 70%
D/M: 90%
How do tetracyclines bind?
divalent and trivalent cation (oral bioavailability dec w/ food intake, should not be taken w/ antacids, iron supplements, or Ca)
What is the chemistry of tigecycline?
similar to tetracycline
What is the MOA of tigecycline?
binds to the same region of 30S as tets but 5x more effectively
What is the spectrum of tigecycline?
same as tets, not active against pseudomonas
What is the resistance of tigecycline?
more resistant to inactivationg strategies than tets
What do you use for tx of syphilis?
doxycycline
What to you use to treat UTI?
fosfomycin
What are 4 groups of bacterial protein synthesis 50S inhibitors?
macrolides, clindamycin, chloramphenicol, and quinpristin-dalfopristin
What are 3 macrolides and how are they admin?
ACE: azithromycin (PO, parenteral, topical), clarithromycin (PO), erythromycin (PO, parenteral, topical)
What is the chemistry of macrolides?
14 atom lactone ring with 2 attached sugars
What is the activity of macrolides?
many orgs that cause URI and pneumonia, g(+) orgs, atypicals, and good alternative for PCN allergic pts
What is the MOA of macrolides?
inhibits translocation step of protein synthesis
What is the distribution of macrolides?
well absorbed and no CNS penetration
What is the metabolism/excretion of macrolides?
variable hepatic metabolism and biliary excretion (good for renal insufficient pts)
What are adverse effects of macrolides?
GI irritant (stomatitis, heartburn, nausea, anorexia, diarrhea), large IV doses of erythromycin cause ototoxicity and thrombophlebitis
What are clinical uses for macrolides?
infections caused by chlamydia and mycoplasma, otitis media, legionella, TB, MAC
What is the resistance of macrolides?
dec binding to 50S subunit, enzymatic inactivation, inc bacterial efflux
What is erythromycin the DOC for?
chlamydia pneumoniae and C. trachomatis, mycoplasma pneumoniae, legionella pneumonphila, corynebacteria diptheria, bordetella pertussis, campylobacter
What are klebsiella and streptococcus also susceptible to?
erythromycin
What does erythromycin do?
GI upset and venous irritation and inhibits CYP3A4 but has low bioavailability when PO
What is the absorption of clarithromycin?
good from gut, high tissue concentrations
Whatis the spectrum of clarithromycin?
similar to erythromycin
What is clarithromycin the DOC for?
H. pylori (used in combo w/ a PPI)
What are other susceptible organisms for clarithromycin?
mycobacterium avium intracellulare (MAC)
Does clarithromycin inhibit CYP3A4?
yes
What is the absorption/distribution of azithromycin?
good absorption from gut and higher tissue concentrations than erythromycin and clarithromycin
What is the effect of azithromycin on CYP3A4?
little
What is the activity of azithromycin?
similar to erythromycin, single dose tx for uncomplicated chlamydial urethritis, H. influenza, MAC
What is the chemistry of telithromycin?
structure similar to macrolides, more stable to stomach acids
What is the MOA of telithromycin?
binds to the 50S ribosomal subunit and inhibits translocation, binds to ribosome w/ greater affinity than macrolides (more potent)
How is telithromycin admin?
PO
What is the spectrum of telithromycin?
S. pneumoniae (MDR), Legionella, Chlamydia, H. influenza, Moraxella catarrhalis
What is the clinical use of telithromycin?
communtiy-acquired pneumonia (CAP) and used as an empiric tx
What are adverse effects of telithromycin?
nausea and diarrhea, inhibits CYP3A4, can prolong QT interval
What is the resistance of telithromycin?
less susceptible to drug efflu pumps than macrolides
What is the chemistry of clindamycin?
aminosugar compound, structurally unrelated to other antibiotics, isolated from streptomyces in soil sample
What is teh MOA of clindamycin?
binds to 50S ribosome and prevents translocation
What is the activity of clindamycin?
bacteriostatic, G(+), anaerobes
Are 50S inhibitors -cidal or -static?
bacteriostatic except for Q-D (-cidal & -static)
How is clindamycin admin?
oral, parenteral, topical
What is the distribution of clindamycin?
well distributed, no CNS penetration
How is clindamycin eliminated?
renal and biliary
What is clindamycin the DOC for?
clostridium perfringens (gangrene)--an anaerobe
What are other susceptible orgs to clindamycin?
bacteriodes fragilis, penicillin-resistant strep, CA-MRSA
What is the resistance of clindamycin?
cross resistance with macrolides
What are adverse effects of clindamycin?
increase incidence of GI superinfections caused by C. difficile, severe diarrhea
What is the chemistry of chloramphenicol?
nitrobeneze derivative, not related to any other antibiotic
What is the MOA of chloramphenicol?
inhibits peptide bond formation
What is the activity/clinical uses of chloramphenicol?
bacteriostatic, broad spectrum, meningitis, drug resistant orgs, but rarely used b/c of potential toxicities
What is the absorption/distribution of chloramphenicol?
highly lipophilic, well absorbed from gut, high CNS concentration (w/out meninges inflammation)
What is the metabolism/elimination of chloramphenicol?
inactivated by glucouronyl transferase, infants dec metabolism b/c of low gluc trans. levels, excreted in urine (tubular, some glomerular)
What is the spectrum of chloramphenicol?
RAMPH: rickettsiae, anaerobes & atypicals, meningococci, pneumococci, H. influenzae (sometimes streptococci)
What is the resistance of chloramphenicol?
enzymatic inactivation (chloramphenicol acetyltransferase (CAT))
What are adverse effects of chloramphenicol?
gray baby syndrome, bone marrow suppression, aplastic anemia (rare but fatal)
What is the chemistry of quinupristin-dalfopristin?
streptogramins
What is the activity of Q-D?
wide range of g(+) and VRE
What is the MOA of Q-D?
acts synergistically to inhibit bacterial protein synthesis, binds to separate sites on 50S ribosome
What does quinupristin do in Q-D?
prevents the addition of new AA to the nascent chain
What does Dalfopristin do in Q-D?
directly blocks peptide bond formation by inhibiting peptidyl transferase
How is Q-D admin?
parenteral converted to active metabolites
What is the distribution/excretion of Q-D?
good distribution, no CNS penetration, biliary excretion
What is the spectrum of Q-D?
S. aureus (MSSA and MRSA), S. pneumoniae, Enterococcus faecium, Pneumococci
What is the resistance of Q-D?
no cross resistance with other antibiotic classes
What are adverse effects of Q-D?
venous inflammation, inhibits CYP3A4, diarrhea/nausea
What is the chemistry of linezolid?
oxazolidinedioine
What is the MOA of linezolid?
binds to 23S ribosome, prevents formation of functional 70S initiation complex (makes cross-resistance unlikely)
What is the activity of linezolid?
aerobic gram (+) bacteria
How is linezolid admin?
oral for mild infections, parenteral for serious infections
What is the distribution/elimination of linezolid?
oral bioav. 100%, well distributed, excreted in urine (approx. 30% unchanged)
What are treated with linezolid?
MSSA, MRSA, VRE
What are adverse effects of linezolid?
N/V and MAO inhibitor
What is the chemistry of mupirocin?
structurally unrelated to other antimicrobials
What is the MOA of mupirocin?
competes for enzymes b/c structure is related to isoleucine, prevents addition of isoleucine to nascent peptides during protein synthesis (makes cross-resistance unlikely)
What is the activity of mupirocin?
mostly g(+), used for nasal colonization of MRSA in health care workers (can also be used for impetigo)
Hos is mupirocin admin?
topical or nasal
What is the spectrum of mupirocin?
staph (MSSA,MRSA) and strep
What is the synthesis of folates?
pteridine + PABA --> folate --> dihydrofolate --> tetrahydrofolate --> purines --> DNA
What blocks sequential steps in folate synthesis in bacteria?
sulfonamides and folate reductase inhibitors
How do humans get folic acid?
from diet
What are 5 sulfonamides?
sulfamethoxazole, sulfisoxazole, sulfadiazine, sulfadoxine, and sulfaslazine
What is the chemistry of sulfonamides?
substituted benzene sulfonic acid
What is the actiivty of sulfonamides?
broad spectrum, many g(+) and g(-), bacteriostatic
What is the MOA of sulfonamides?
structural analogues of PABA and competitive inhibitors of dihydropteroate synthase (competitive inhibition b/t sulfonamides and PABA)
How are sulfonamides admin?
oral, parenteral, and topical
What is the absorption/distribution of sulfonamides?
absorption varies, widely distributed, no significant CNS penetration
What is the metabolism/excretion of sulfonamides?
converted to inactive, toxic compounds by N-acetylation, excreted by glomerular filtration
What do acetylated metabolites do?
less soluble and precipitate in renal tubules (crystalluria)
What are sulfonamides the DOC for?
nocardia and pneumocystis carinii (PCP)
What are other susceptible orgs for sulfonamides?
H. influenza, actinomyctes, streptococci, chlamydiae
Are sulfonamides generally used alone?
no, used w/ dihydrofolate reductase inhibitors
What are clinical uses of sulfonamides?
UTI, nocardosis, PCP (+ DFRI), otitis media (+ erythromycin), IBD (sulfasalazine alone)
What is the resistance of sulfonamides?
dec affinity of drug target, dec drug permeability, overproduction of PABA, bacteria develop alternative metabolic pathway
What are adverse effects of sulfonamides?
allergic rxns, photosensitivity, crystalluria, hemolytic anemia, kernicterus
What is kernicterus?
rar, sulfonamides admin in 3rd trimester of pregnancy can cause inc bilirubin levels that compete w/ sulfonamides for albumin and deposits in brain
What are the rapidly absorbed, short acting sulfonamides?
sulfisoxazole and sulfamethoxazole (can cause crystalluria)
What is a poorly absorbed sulfonamides?
sulfasalazine (broken down into ASA and dec inflammation in GI)
What is a nonabsorbable, topical sulfonamide?
silver sulfadiazine (burn and superficial skin infections)
What is a folate reductase inhibitor?
trimethoprim
What is the chemistry of folate reductase inhibitors?
synthetic aminopyrimide, weak base
What is the MOA of trimethoprim?
inhibits enzymatic activity dihydrofolate reductase
What is the drug combination of trimethoprim?
maximal synergistic effects seen when a sulfonamide is combined w/ trimethoprim 20:1, S:T
What is the absorption/distribution of trimethoprim?
well absorbed from gut, widely distributed, including CNS, concentrated in acidic fluids such as prostate and vaginal fluids
What is the metabolism/excretion of trimethoprim?
hepatic metabolism and renal excretion
What is the spectrum of trimethoprim?
similar to sulfonamides
What is trimethoprim the DOC for?
PCP and norcardia asteroides
What are other susceptible orgs to trimethoprim?
H. influenza, actinomyctes, streptococci, chlamydiae, staph (MSSA,MRSA)
What are clinical uses of trimethoprim?
used alone to treat UTI and prostate infections, used in compo to treat: URI, LRI, GI infections
What is the resistance of trimethoprim?
inc DFRI production, dec affinity for drug target, dec drug entry
What are adverse effects of trimethoprim?
N/V, rash and other hypersensitivity rxns, HIV pts can get thrombocytopenia and leukopenia
What are 2 original fluoroquinolones?
ciprofloxacin and norfloxacin
What are 4 advanced generation FQ?
levofloxacin, moxifloxacin, gatifloxacin, and gemifloxacin
What is the chemistry of FQ?
fluorine moiety inc its antibacterial potency and binding affinity for DNA gyrase
What is the MOA of FQ?
inhibits bacterial DNA topo II (DNA gyrase) and topo IV
What does DNA gyrase do?
introduces neg supercoils into closed circular DNA to counteract the generation of positive supercoils created from DNA replication, relieves stress and prevents DNA from breaking
What is the primary target of FQ in G(-)?
topo II, FQ causes bacteria DNA breaks, cell swells, bursts, and dies
What is the target of FQ in g(+)?
topo IV, daughter chromosome cannot separate from mother chromosome
How are G1 FQ admin?
oral, topical
What is the activity of G1 FQ?
bactericidal, broad spectrum, g(+) and g(-)
What is the absorption/distribution of G1 FQ?
well absorbed from gut, widely distributed to tissues, accumulates in lung, kidney, liver, prostate, and ovaries, chelates divalent and trivalent cations (don't take w/ dairy products)
What is the metabolism/elimination of G1 FQ?
varying hepatic metabolism, excreted unchanged in urine, some metabolites have low level antimicrobial activity
What is the spectrum of G1 FQ?
P. aeruginosa, staphy, enterobacteriacea, enterococci, meningicocci, chlamydiae, TB, MAC, and rickettsiae
What are resistant organisms to G1 FQ?
anaerobes, mycoplasma, spirochetes, and resistance developing towards strep
What are clinical uses of G1 FQ?
UTI and prostatis, bacterial diarrhea, traveler's diarrhea, combo for intra-abdominal infections, inhalation of anthrax, resp tract infections, sinusitis/bronchitis, CAP, MAC, ocular infections
What is the resistance of G1 FQ?
alterations in target enzyme, dec access of drug to target from inc activity of efflux pumps and dec drug uptake
What are adverse effects of G1 FQ?
inhibits CYP1A2 (seizures w/ high caffeine), phototoxicity, prolong QT interval, cartilage deterioration, polyvalent cations dec bioavailability
What is the coverage and kinetics of G2 FQ compared to G1?
better
What are adverse effects of G2 FQ?
more rashes, less toxic, no inhibition of CYPs
What is MOA of G2 FQ?
mostly inhibit topo IV while G1 inhibit topo II
What is the chemistry of nitrofurantoin?
synthetic nitrofuran derivative
What is the activity of nitrofurantoin?
-static at low conc, -cidal at high conc
How is nitrofurantoin admin?
oral
What is the absorption/excretion of nitrofurantoin?
well absorbed in gut, inc by food intake, dec GI irritation w/ food, rapid urinary excretion
What is MOA of nitrofurantoin?
inhibits bacterial acetyl CoA (inhibits carbohydrate metabolism and production of ATP)
What is the spectrum of nitrofurantoin?
E. coli, enterococcus, klebsiella, staph
What are resistant to nitrofurantoin?
proteus, serratia, P. aeruginosa
What is a clinical use of nitrofurantoin?
UTI
What are adverse effects of nitrofurantoin?
some GI irritation, N/V/D
What is the chemistry of Daptomycin?
cyclic lipopeptide
What is the activity of daptomycin?
bactericidal
What is the MOA of daptomycin?
disrupts bacterial plasma membrane (cytoplasmic membrane) function
What is the spectrum of daptomycin?
drug resistant g(+) bacteria, MRSA, VRE
What are clinical uses of daptomycin?
skin infections, diabetic foot ulcers, burn wounds
What is the chemistry of polymyxin B?
polypeptide
What is the MOA of polymyxin B?
interacts with the phospholipid component of bacterial cell membranes to disrupt its integrity
How is polymyxin B admin?
topical, drug combo in ointments w/ bacitracin, neomycin, and trimethoprim
What is the spectrum of polymyxin B?
G(-) except proteus or serratia
What are resistant to polymyxin B?
proteus and serratia
What is a clinical use of polymyxin B?
skin infections caused by susceptible orgs
What are adverse effects of polymyxin B?
nephrotoxicity when given parenterally
How is rifaximin admin?
oral
What is the MOA of rifaximin?
inhibits bacterial RNA synthesis, binds to DNA-dependent RNA polymerase, inhibits binding of the enzyme to DNA, does not bind to RNA polymerase in eukaryotic cells
What is the spectrum of rifaximin?
E. coli, salmonella, campylobacter jejuni, and yersinia enterocolitica
What is a clinical use of rifaximin?
traveler's diarrhea
What are drugs that inhibit cell wall synthesis?
b-lactam, vancomycin, bacitracin, and fosfomycin
What are B-lactams and what do they do?
penicillins
cephalosporins
monobactams
carbapenems

inhibit the transpeptidase rxn that cross-links the peptidoglycan component of the cell wall
What is admin with B-lactam to prevent degradation of antibiotic by the bacteria?
b-lactamase inhibitor
What are narrow-spectrum PCN active against?
gram-positive cocci and spirochetes
What are penicillinase-resistant PCN used to treat?
staphylococcal infections
What are extended-spectrum PCN used for?
various gram-negative bacilli
Acid-stable PCN can be given ____ whearas acid-labile drugs must be given _____.
orally, parenterally
How are most PCN eliminated?
renal tubular secretion (inhibited by probenecid)
How are cephalosporins eliminated?
renal tubular secretion and some in bile
Does aztreonam cross-react with other B-lactam drugs?
no
What groups inhibit 30S ribosomal function?
aminoglycosides, tetracyclines, and spectinomycin
What groups inhibit 50S ribosomal function?
macrolides, clindamycin, chloramphenicol, and dlafopristin
Aminoglycosides are ____ charged cations in body fluids, ____ absorbed from the gut and no CNS penetration, excreted ____ in urine, and are active against gram-_____ ______.
positively, poorly, unchanged, negative bacilli
What is primarily used to treat rickettsiae, chlamydiae, and mycoplasmas?
tetracycline
What are macrolides primarily used to treat?
respiratory tract infections, otitis media and pneumonia
Telithromycin is a _____ antibiotic used to treat resp tract infections.
ketolide
What is active against gram-positive cocci and anaerobes resistant to PCN?
clindamycin
What is sometimes used to treat meningitis and rarely causes aplastic anemia?
chloramphenicol
What are Q-D and linezolid active against?
MRSA and VRE
What is used for impetigo and nasal colonization of MRSA?
mupirocin
What inhibit sequential steps in bacterial folic acid synthesis?
sulfonamides and trimethoprim
What inhibits dihydropteroate synthase and the synthesis of dihydrofolate?
sulfonamides
What inhibits folate reductase and the formation of tetrahydrofolate?
trimethoprim
What is primarily used to treat UTI, URI, and infections caused by P. carinii or N. asteroides?
sulfamethoxazole and trimethoprim (TMP-SMX)
What inhibits DNA gyrase and is bactericidal?
fluoroquinolones
What is used to treat CAP?
advanced FQ
Why are FQ not used in children?
b/c of risk of arthropathy and osteochondrosis
______ is used in UTI and ____ is used for superficial ocular and skin infections.
nitrofurantoin and polymyxin B
What is a unique lipopeptide antibiotic used to treat infections caused by methicillin and vancomycin-resistant stapph and VFE?
daptomycin
What are NSAIDs used as?
analgesic, anti-pyretic, anti-inflammatory, anti-platelet, and primary dysmenorrhea
Why are NSAIDs good?
b/c they have no tolerance, physical, or psychological dependence
Do NSAIDs keep doing more and more analgesic work as you increase the dose?
to a point but has a ceiling effect
How do NSAIDs work?
inhibition of cyclooxygenase enzyme preventing the formation and release of prostaglandins
What is the precursor to specific PGs?
PGH2 --> body does not store PGs (only produced when needed)
Which Cox yields effects from NSAIDs?
Cox-2
When does zero-order kintetics kick in w/ NSAIDs?
when taking ASA in large doses
Do NSAIDs have a high or low protein binding displacement of other drugs?
high
What do NSAIDs do to be better eliminated in the urine?
causes forced alkaline diuresis
When is drug toxicity likely with NSAIDs?
if the displaced drug's binding to plasma protein is also high and/or the Vd of the displaced drug is low
Analgesic activity is generally a ________ mechanism and anti-pyretic activity is a ________ mech.
peripheral, central
How does the anti-pyretic effect work?
no effect on normal body temp, lowers fever, site of action is in the hypothalamus
How does the anti-inflammatory aspect of NSAIDs work?
inhibits PGs and as a byproduct free oxygen radicals
What do PGs do?
potent vasodilators, enhance inflammatory effects of histamine and kinins, produce fever when injected intrahypothalamically, and cause hyperalgesia
What are oxygen free radicals?
mediators of inflammation produced as a byproduct of PG synthesis
What causes erythema and increased local blood flow?
PGE2/PGI2 (counteract the vasoconstrictor effects of substances such as NE and angiotensin)
What is the only NSAID that irreversibly blocks Cox-1 and Cox-2 for 24 hours?
aspirin
What are symptoms of primary dysmenorrhea?
painful abdominal cramps, nausea, breast tenderness, headache, and flushing
What is PGF2Alpha?
a potent vasoconstrictor, produces pain due to ischemia and release of histamine and bradykinin
Where is a marked elevation of PG found in primary dysmenorrhea?
endometrium, menstrual fluid, and peripheral circulation
What is reduced to allow blood to go to pulmonary artery in ductus arteriosus?
PGE2
If PGE2 production reduction does not cause ductal closure, what is used?
indocit IV (indomethacin has 90% ductal closure rate, sig fewer infants has an increase in serum creatinine conc)
What does PGI2 and PGE2 inhibition cause?
increased acid secretion and decreased secretion of cytoprotective mucus
Why does GI bleeding occur w/ NSAIDs?
antiplatelet effect
When should prophylaxis with misoprostol be considered?
in pts at high risk for hemorrhage and perforation from ulcers by ASA and non-selective NSAIDs
What are risk factors for NSAID-related complications?
age over 60, use of high dose, concurrent use of glucocorticoids, concurrent use of anticoagulants
In what pts should NSAIDs be avoided?
thrombocytopenic pts or clotting impairment
What happens w/ NSAIDs in hypovolemics?
greater retention of Cl and NA, greater activity of ADH (water retention), retention of salt and H2O --> bad for CHF and HTN
What are some side effects of NSAIDs?
allergies, prolongation of gestation or delay in spontaneous labor, hepatic, hematologic
What are side effects of ASA?
respiration inc at low dose and dec at high dose, urate excretion dec at low dose and inc at high dose, Reye's syndrome
What are some symptoms of salicylism in high doses?
headache, dizziness, tinnitus, hearing trouble, dimness in vision, mental confusion, drowsiness, sweating, hyperventilation
What is the urgent care tx of ASA toxicity?
stop the drug, assay for salicylate/acid-base/electrolytes, emesis induction/lavage/activated charcoal, cold water/alcohol sponge, IV fluid, forced alkaline diuresis
What are the half lives of naproxen and ibuprofen?
14 and 2 hours
What is the most potent inhibitor of COX isoenzymes?
indomethacin (used for mod to severe acute inflammatory conditions, in RA, and acute gout, patent ductus arteriosus
What are some side effects of indomethacin?
frequently CNS bc serotonin structure, severe frontal headache, dizziness, vertigo, light-headedness, menal confusion, severe depression, psychosis, hallucination, nausea, abdominal pain, risk of hematological toxicity
When is indomethacin contraindicated?
in pregnancy and nursing mothers, persons operating machinery, pts w/ psychiatric disorders, epilepsy, parkinsonism, renal disease or gastric ulcer
What is the first injectable NSAID?
ketorolac tromethamine (also used orally and topical opthalmic, potent analgesic for moderate to severe post-op pain, parenteral therapy limited to not more than 5 days)
What are the 2 Cox-2 inhibitors off the market?
rofecoxib and valdecoxib
What is the Cox-2 inhibitor still on the market?
celecoxib
What are selective cox-2 inhibitors approved for?
RA and OA, inhibits actiivty of CYP2D6 and may increase levels of drugs metabolized by CYP2D6
Do selective or non-selective NSAIDs have more GI symptoms?
non-selective
Do Cox-2 inhibitors affect platelet function?
no, TXA2 is dependent upon Cox-1
What are side effects of Cox-2 inhibitors?
diarrhea, nausea, dyspepsia, abdominal pain, lower extremity edema (NO COX-2 in stomach), renal toxicity, may cause allergies in pts allergic to sulfur
_____ is the good prostaglandin (potent vasodilator and platelet deaggregator) and ____ is the bad (potent vasoconstrictor and platelet aggregator).
PGI2, TXA2
What cancer do Cox-2 inhibitors lower the chemo doses needed?
colon cancer
What is the toxicity of acetaminophen?
hepatotoxic in large doses due to its toxic metabolite, long-term use may cause renal toxicity
What are symptoms of acetaminophen toxicity?
skin rash, neutropenia, nausea, vomiting, abdominal pain (classic signs of liver toxicity appear in 2-4 days)
What are guidelines for therapy in RA?
early diagnosis and tx, DMARDS in combo, drugs targeting cytokines, t outcomes assessment should include analysis of co-existing illnesses
What is methotrexate?
immunosuppressive drug, first choice in RA, rapid onset of action (weeks), less toxic than other DMARDs
What is hydroxychoroquine used for and what are adverse effects?
RA --> irreversible retinal damage, skin, CNS and bone marrow toxicities
What is an oral gold compound?
auranofin (better than parenteral)
What are 2 injectable gold compounds?
gold sodium thiomalate (teratogenic) and aurothioglucose
What are adverse effects of gold compounds?
GI, mucocutaneous, bone marrow, and renal toxicity
What is azathioprine?
immunosuppressive purine analog, used in refractory RA
What are adverse effects of azathioprine?
N/V, abdominal pain, hepatitis, reversible bone marrow depression
What is cyclosporine?
used when RA is severe, progressive and or not responding to other second-line drugs, long-term effects not est, potential renal toxicity
What is leflunomide?
decreases pyrimidine synthesis, active metabolite, high protein binding, refampin raises conc of active metabolite, inc renal excretion of uric acid
What are adverse effects of leflunomide?
liver toxicity (more serious when combined w/ methotrexate), teratogenic
What are contraindications for leflunomide?
liver impairment, heavy alcohol use, hepatitis
What are 3 TNF-Alpha antagonists?
infliximab, etanercept, and adalimimab
What are adverse effects of TNF-alpha antagonists?
opportunistic infections, liver disease, severe allergy
What is infliximab?
anti-TNF-alpha antibody
What is etanercept?
binds to both TNF-A and TNF-B
What is adalimimab?
recombinant human IgG1 monoclonal antibody that binds to human TNF-A with high affinity
What is gout?
increase stores of uric acid --> precipitates into tissues and joints --> inflammation
What is the tx of acute gout attacks?
NSAIDs such as indomethacin, naproxen, ibuprofen, or Cox-2 inhibitors then colchicine then corticosteroids (intraarticularly or parenterally)
What does colchicine do?
eliminates pain in an acute attack within 48 hours in most patients, severe GI toxicity, N/V, diarrhea, abdominal cramping
When do you stop tx of colchicine?
pain and inflammation improve sig, GI toxicity becomes intolerable, total dose reaches 6-10mg
What is prophylactic therapy for gout?
during initial months of therapy w/ allopurinol or uricosurics, chronic gout pts w/ frequent acute attack (2-3 per year), before and after surgery in pts w/ gout
When is long term gout tx needed?
when the cause of hyperuricemia cannot be corrected or serum urate conc cannot get below 7mg/dL, 2-3 attacks in a year, tophi are present, pt is convinced of need for tx
What do you use for long term therapy of gout?
first try uricosurics(probenecid) or sulfinpyrazone which will inc urinary uric acid, then allopurinol to inhibit uric acid production pathway
Before starting long term therapy what must happen?
pt is put on colchicine to prevent acute attack for a couple of months
What must happen in order to use uricosurics or sulfinpyrazone?
must have adequate renal function and uric acid cannot be at its maximal excretion
What minimizes the risk of acute attacks of gout?
concurrently admin one of prophylactic drugs, delaying urat-lowering therapy until several weeks after last attack, starting therapy w/ a low dose of the selected drug and gradually inc to max dose
What is urate stone formation in the kidneys minimized by?
excessive fluid intake
What do uricosurics do?
inc urinary excretion of urate by inhibiting urate renal tubular reabsorption
When are uricosurics contraindicated?
if urine output is < 1mL per min or if creatinine clearance < 50 mL/min
What does probenecid do?
increases renal excretion of urate by as much as 50% and inc renal clearance of other organic acid drugs, avoided in PUD
When is probenecid effective?
when renal function is normal and renal urate excretion is submaximal
What is sulfinpyrazone?
more potent than probenecid, inhibits platelet aggregation
When is allopurinol used?
in gout if renal function is not good and uric acid has met max excretion
When is allopurinol effective?
in primary hyperuricemia of gout and hyperuricemia secondary to hematological disorders or antineoplastic therapy
What do allopurinol and the active metabolite allozanthine do?
dec plasma uric acid, dec urinary uric acid, inc plasma and urinary uric acid precursors
Does allopurinol cause hypersensitivity rxn?
in 3-10% of pts leading to rash
What produces toxicity when used w/ allopurinol?
azathioprine and 6-mercaptopurine
What happens when allopurinol is combined w/ ampicillin?
rash
What happens with anticoagulants and allopurinol?
dec hepatic metabolism of anticoagulants w/ a corresponding inc in blood levels and possibility of loss of anticoagulant control
Allopurinol _______ risk of bone-marrow suppression when used with cytotoxic drugs especially with cyclophosphamide.
increases
What are 7 non-selective COX inhibitors?
acetaminophen, ASA, ibuprofen, indomethacin, ketoprofen, ketorolac, and naproxen
What is a minor metabolite of acetaminophen?
a potentially hepatotoxic quinone
What is a sulfhydryl compound that conjugates and inactivates the quinone metabolite of acetaminophen and is used as an antidote for acetaminophen hepatotoxicity?
acetylcysteine
Low doses of ASA produce ____ and _____ effects, but higher doses are needed to counteract _________.
analgesic and anti-pyretic and inflammation
What can toxic doses of ASA cause?
hyperventilation and resp alkalosis followed by met acidosis
What are DMARDs?
disease-modifying antirheumatic drugs --> slow progression of joint erosions in pts w/ RA (slow onset of action and may cause toxicity)
How do DMARDs work?
inhibit the proliferation and activity of lymphocytes and polymorphonuclear leukocytes
What is TNF?
tumor necrosis factor
What are some other back up DMARDs?
gold salts, glucocorticoids, leflunomide, hydroxychloroquine, sulfasalazine, and penicillamine
What are opioids?
natural and synthetic substances with morphine-like activity
What are opiates?
opioids subclass consisting of alkaloids extracted from opium such as morphine, codeine, as well as semi-synthetic derivatives of poppy plants
What do opioids alleviate?
somatic pain, visceral pain, superficial pain, and chronic pain
What are the 3 classes of opioid receptors and what do they cause?
mu: euphoria, kappa: mediates analgesia and dysphoria, delta: simlar to mu
What are CNS effects of opioid agonists?
analgesia, dysphoria or euphoria, inhibition of cough reflex, miosis, physical dependence, respiratory depression, and sedation
What are cardiovascular effects of opioid agonists?
dec myocardial oxygen demand, vasodilation, and hypotension
What are GI and biliary effects of opioid agonists?
constipation, inc biliary sphincter tone and pressure, and N/V
What are genitourinary effects of opioid agonists?
inc bladder sphincter tone, prolongation of labor, and urinary retention
What are neuroendocrine system effects of opioid agonists?
inhibition of release of luteinizing hormone and stimulation of release of antidiuretic hormone and prolactin
What are immune system effects of opioid agonists?
suppression of function of natural killer cells
What are dermal effects of opioid agonists?
flushing, pruritus, and urticaria or other rash
What are 3 endogenous opioid peptides?
enkephalins (widely distributed in our system), endorphins (like hormones but more localized), and dynorphins (similar to enkephalins)
What are 3 classes of opioids?
pure agonists (@ kappa center), mixed agonists-antagonists and partial agonists, and pure antagonists (@ mu center)
What are therapeutic effects of opioid agonists?
analgesia, sedation, anti-tussive, and anti-diarrheal
What is sedation?
drowsiness, apathy, inability to concentrate, short-term memory loss
What is the anti-diarrheal effect?
dec stomach and intestinal motility, inc tone, dec peristaltic contractions in the gut, inc intrabiliary pressure (atropine blocks the inc tone but not the dec in motility)
What are 10 undesirable effects of opioid agonists?
euphoria, respiratory depression, N/V, miosis, convulsions, neuroendocrine effects, urinary tract effects, uterine effects, cardiovascular effects, and skin effects
What is always the major cause of death from morphine OD and how does it occur?
respiratory depression, responses to CO2 and resp rhythmicity are impaired, morphine releases histamine
When is morphine contraindicated?
asthmatics and other hypoxic states (bronchoconstriction) and post op pts (pulmonary atelectasis)
Why does N/V occur with opioids?
stimulates chemoreceptor trigger zone in the area postrema of the medulla, may be some vestibular involvement
What is a classic sign of opiate OD?
miosis of the pupil (pinpoint pupils are pathognomonic)
Why does miosis occur with opioids?
excitatory action on the autonomic cholinergic segment of the Edinger-Westphal nucleus of oculomotor nerve
When are opioids contraindicated b/c of miosis?
head injuries and craniotomy pt
What antagonizes convulsions with opioids?
naloxone
What do opioids do in males in regards to neuroendocrine effects?
dec release of testosterone and dec libido
What do opioids do in females in regards to neuroendocrine effects?
dec LH and FSH release leading to amenorrhea and anovulation
Neuroendocrine effects of opioids also ______ prolactin and _____ growth hormone in plasma.
increase, increase
Where does tolerance develop to opioid effects?
on the hypothalamic releasing factors
What is the urinary tract effect of opioids and does tolerance develop?
dec urinary voiding reflex and yes
How do opioids prolong labor?
dec uterine motility during labor
What occurs in the cardiovascular system with opioids?
orthostatic hypotension and fainting, vasodilation b/c of histamine release and dec peripheral resistance and peripheral vasodilation
What happens to cerebral blood flow with opioids?
inc pCO2 causes inc cerebral blood flow due to cerebral vasodilation and cerebrospinal fluid pressure
What happens to the skin with opioids?
dilation of skin blood vessels, frequent flushing of the face, neck and upper thorax due to release of histamine and may also cause sweating, pruritis, and urticaria at the site of injection (not blocked by naloxone)
What are the 3 absolute and relative contraindications of opioids?
asthmatics and pts w/ hypoxic conditions, head injury and craniotomy pts, and in pts w/ hx of convulsive disorders or MI and recent gastric surgery (b/c of physical stress due to N/V)
What effects have a high degree of tolerance to opiates?
analgesia, euphoria, dysphoria, mental clouding, sedation, respiratory depression, antidiuresis, N/V, and cough suppression
What effects have a moderate degree of tolerance to opiates?
bradycardia
What effects have minimal or no degree of tolerance to opiates?
miosis, constipation, convulsions, and antagonist actions
What is the tx of nausea from opioids?
metocloparmide or phenergen
what is the tx of constipation from opioids?
1st: inc hydration and bulk agents, 2nd: lactulose or senokot or bisacodyl, 3rd: castor oil or products that contain Mg
What is the tx of sedation from opioids?
dextroamphetamine or methylphenidate
What is the tx of myoclonus from opioids?
clonaxepam or nifedipine
What is the tx of resp depression from opioids?
as long as pt is oxygenating, a temporary reduction in opioid dosage should suffice, if not use a diluted slowly admin dose of naloxone
What are drug interactions of opioids?
CNS depressant actions enhanced by barbiturates, benzodiazepines, major tranquilizers, and antihistamines, barbituates enhance opioids metabolism, amphetamine potentiates morphine analgesia (sympathomimetic)
What is Brompton's mixture?
amphetamine + opioids (used in Great Britain for terminally ill CA pt)
How is heroin abused?
snorting (most common), IV (mainlining), Sub Q (skin popping)
What happens in acute intoxication/OD of opioids?
drowsiness to coma, resp depression, and pinpoint pupils
What is the immediate therapy for opioid OD?
adequate airway, stabilization of pulmonary and cardiac status, opioid antagonist (naloxone) in pts w/ inadequate respiration
What causes the major effect of heroin?
6-monoacetyl morphine in the brain (heroin is more lipid soluble than morphine)
What is the flow of breakdown of heroin?
heroin --> 6-monoacetylmorphine --> morphine --> morpine-3-glucuronide and morphine-6-glucuronide
What can pile up if renal function is inadequate and is more polar and twice as active as morphine as an analgesic?
morphine-6-glucuronide
Does oxymorphone release histamine?
no
What does hydromorphone cause?
less N/V and constipation
What is the L-isomer?
levorphanol (5x more potent than morphine)
What is the D-isomer?
dextromethorphan (effective antitussive, lacks analgesic and other opioid effects, not to use w/ MAOI)
What is codeine sulfate?
O-methyl morphine, prototype antitussive agent, weaker analgesic than morphine, PO admin
What is a genetic polymorphism that causes no analgesic effect of codeine?
CYP2D6 change in 10% of caucasians
What is oxycodone used for?
moderate pain or cough, 10x as potent as codeine and admin PO
Where do opioid analgesics work?
primarily on the spinal cord and brain to inhibit the neurotransmission of pain
What are the primary afferent fibers transmitting nociceptive info?
Adelta (sharp pain) and C (dull pain)
What blocks the activation of spinothalamic neurons in the spinal cord?
descending inhibitory pathways from the midbrain and sensory AB fibers in peripheral tissues
Where are enkephalins released?
from neurons throughout the pain axis including those in the PAG, medulla, and spinal cord (block transmission of pain impulse)
What receptor family are opioid receptors a member of?
G-protein coupled
What is the DOC for pts with labor pain?
meperidine
What is tolerance?
dec in initial pharmacologic effect observed following chronic or long-term admin
What effects do not develop tolerance with opioids?
miosis and constipation
What is opioid tolerance usually associated with?
physical dependence
What is physcial dependence?
physiologic state in which a person's continued use of a drug is required for his or her well-being
Is morphine absorbed from the gut?
yes, but goes through considerable first-pass metabolism
What is the most potent opioid agonist group?
fentanyl and its derivatives
What is often used to treat opioid dependence or chronic pain?
methadone
What is the tx for opioid-dependent pts called?
methadone maintenance program
How are pain impulses transmitted?
by primary afferent neurons to the spinal cord, where ascending connections from the spinothalamic tract neurons project to limbic structures and the cortex
Descending inhibitory fibers from the ______ gray matter activate midbrain and spinal cord neurons that release ______, ________, and _______.
periaqueductal, enkephalins, serotonin, and NE
(opioids activate these pathways and inhibit ascending pain impulses)
What are mu receptors primarily responsible for?
analgesic effects, as well as resp depression and opioid dependence
What are the strong opioids and where do they act?
morphine, fentanyl, meperidine, and methadone (mu receptors)
What produce max analgesia at doses that cannot be tolerated, so they are usually combined w/ nonopioid analgesic?
moderate opioid agonists
What are the moderate agonists and what do they treat?
codeine, hydrocodone, and propoxyphene treat moderate or mild pain
What is a dual-action analgesic that activates opioid receptros and blocks neuronal reuptake of serotonin and NE?
tramadol
What are the mixed opioid agonist-antagonists?
buprenorphine, butorphanol, nalbuphine, and pentazocine
What receptors do mixed opioids work on?
partial agonist or antagonist activity at kappa receptros and agonist or antagonist acitivity at mu receptors
What class of opioids produces less respiratory depression and is associated w/ a lower risk of drug dependence?
mixed opioid agonist-antagonist
what are naloxone and naltrexone?
opioid antagonists
What do opioid antagonists do?
counteract adverse effects of opioids in OD or to prevent and treat opioid dependence
What drug mimics morphine but is more effective orally?
methadone HCl
What is methadone HCl used for?
detox of heroin addicts and as an analgesic for chronic pain (no "high" effect)
What does levomethadyl cause?
prolonged QT interval
What is d-propoxyphene?
weaker analgesic than codeine, not as abused b/c high doses cause psychosis and hallucinations, tissue damage after iv or subQ
What is Darvon Compound-65?
a combination of aspirin and d-propoxyphene
What may repeated use of d-propoxyphene cause?
naloxone-insensitive cardiac toxicity due to accumulation of norpropoxyphene metabolite
What is L-propoxyphene?
L-isomer that has antitussive but no analgesic/opioid activity
What is meperidine?
virtually identical to morphine except: restlessness, anti-muscarinic, shorter t/2, faster onset
What effects does meperidine have in terms of labor and babies?
no interference w/ uterine contractions and lesser degree of respiratory depression in newborns
Do people get addicted to meperidine?
yes, slow development and shorter and less sever abstinance
Why don't you give meperidine with MAOI?
excitation, delirium, hyperpyrexia, and convulsions
What are some side effects of meperidine?
mydriasis and tachycardia (caution in CHF), less spasmogenic in GI, biliary, and smooth muscle, can cause seizures and tremors
Does fentanyl release histamine?
no
What is droperidol used for?
neruoleptanalgesia
What is fentanyl and when is it used?
used in some awake diagnostic procedures (bronchoscopy) and is an extremely potent opioid
What is duragesic NOT used for?
acute or post-op pain, mild or intermittent chronic pain, starting dose higher than 25 microgram per hour, children under 12 or less than 18 <110 pounds
What is tramadol?
mu agonist that also blocks NE and 5-HT uptake (DO NOT use w/ MAOI), metabolite is potent analgesic, partially antag by naloxone, less resp depression than morphine, does NOT release histamine
What does diphenoxylate do?
low doses (lack usual opiate effects except strong inhibition of GI motility), high doses produce more typical opioid effects, not in kids <2 and in diarrhea b/c of salmonella
What is loperamide similar to?
diphenoxylate
What do mixed opioids do?
produce analgesia due to kappa agonist action, weak competitive antag at mu receptors, ceiling effect for resp depression, lesser propensity to produce physical dependence, ability to reserve agonist effects, produce abstinence syndrome in pts physically dependent on an opioid drug
Mixed opioids have prominent _______ effects.
psychotomimetic
What is pentazocine?
the only mixed opioid available PO and parenterally, may precipitate w/drawal but does not antag morphine's effects, resembles morphine, inc work load of heart
What can IV or subQ admin of pentazocine cause?
tissue damage
What occurs at higher doses of pentazocine?
hallucinations that can be antag by naloxone
What are 2 other mixed opioids?
butorphanol and nalbuphine
What is buprenorphine?
partial mu agonist that is first opioid for detox in doc's office
What is naloxone?
pure opioid antag that has no clinically important agonist actions, very potent and blocks ALL opioid agonist actions, can precipitate abstinance in pts dependent on morphine, DOC for opioid OD, tx of shock
What is naltrexone?
similar to naloxone but better PO bioavailability and longer DOA, no agonist action except at high doses
What is nalmefene?
pure opioid antag that has longer DOA, precipitated w/drawal is prolonged and not used in emergencies
What are adjuvant analgesics?
drugs w/ other specific indications that have been found to be effective in the management of selected types of pain
What are some adjuvant drugs in the tx of chronic pain?
steroids, antidepressants, anxiolytics, phenothiazines, and anticonvulsants
What do steroids do?
potentiate analgesia and elevate mood
What do antidepressants do?
potentiate opioid analgesia, elevate mood, induce sleep
What do anxiolytics do?
potentiate opioid analgesia, reduce anxiety, antiemetic, sedative
What do phenothiazines do?
produce moderate analgesia, reduce anxiety, antiemetic
What do anticonvulsants do?
dec abnormal CNS neuronal activity
What is the 3 step approach to chronic pain control?
1. nonopioid +/- adjuvants
2. weak opioid + nonopioid +/- adjuvants (if pain inc or persists)
3. stron opioid +/- nonopioid +/- adjuvants (if pain inc or persists)
Drug addiction is drug ______ not drug _______.
seeking NOT tolerance
Do opioids have a ceiling effect like NSAIDs?
no, keep inc til pain goes away
What is phase I of migraines?
5-HT (serotonin) released from neurons and platelets, 5-HT mediated cerebral vasoconstriction and ischemia
What is phase II in migraines?
important role of trigeminal nerurovascular system --> neurons release CGRP, longer than phase I, cerebral vasodilation and pain, inflammation of Pial an Dural vessles
What does calcitonin gene-related peptide (CGRP) cause?
intense vasodilation, vessel leakage, mast-cell degranulation, inflammation (stim of pain fibers causing pain)
What drugs are used for phase I migraines?
NSAIDs, 5-HT2 antag and anticonvulsants
What are the drugs used in phase II migraines?
5-HT1 agonists, ergot alkaloids, NSAIDs, opioids, anticonvulsants, B-blockers
T/F Morphine is not effective as an analgesic when admin PO.
False
T/F Oral morphine causes respiratory depression function.
True but not too much to be unsafe
T/F Cancer pts get addicted to morphine.
false
T/F Morphine tolerance is a sig clinical problem in CA pt.
False
What dose morphine not produce in CA pts?
unacceptable sedation and mental clouding
Is morphine better when saved as a last resort?
no, b/c there is no ceiling effect
What are 3 basic principles to treat TB?
multiple drugs, in tx failure--change ALL drugs, prolonged thearpy needed b/c it is a slow-growing bacteria
What is a TB vaccine used in other of the world?
Bacille Calmette-Guerin (BCG)
What are 6 first line TB drugs?
isoniazid (INH)
rifampin
ethambutol
pyrazinamide
streptomycin
amikacin
What are 7 second line drugs for TB?
rifapentine
rifabutin
fluroquinolones
cycloserine
capreopmycin
ethionamide
p-aminosalicylic acid
What is the tx for TB exposure?
prophylactic w/ isoniazid
What is the tx of active TB?
3 drug combo
What is the tx for TB if pt is HIV+ or known to be exposed to resistant strains?
4-5 drug combo
What is the only TB drug used ALONE for prophylaxis?
isoniazid
What are some facts about isoniazid?
can cause liver damage, slow and fast acetylators (slow has more side effects), peripheral neuritis (need Vit B6), don't drink alcohol, don't eat tuna, some cheeses, foods w/ tyramine due to MAOI effects of INH (could cause HTN crisis)
Why can't you use rifampin alone?
it will have resistance in about 3 days
What is rifampin?
broad specturm usually used w/ macrolide or quinolone
How dose rifampin work?
prevents DNA transcription in bacteria, metabolized in liver and induces liver enzymes (can change body fluids orange)
What does pyrazinamide do?
can cause hepatic injury and inc liver enzymes
What is major side effect of ethambutol?
optic neuritis (do NOT use in small kids)
How do you admin streptomycin and amikacin and what are 2 major side effects?
IM ONLY

ototoxicity and nephrotoxicity
What 4 drugs do you treat TB with initially?
rifampin, INH, pyrazinamide, choose 1 other
What are options for TB tx?
4 drugs for 2 months, 2 drugs for 4 months

4 drugs for 6 months

2 drugs for 9 months
What do you use if exposed to TB?
isoniazid for 3-6 months of 12 months
Why don't you use rifampin in HIV pts?
it dec serum levels of HIV meds due to inc liver enzymes (use rifabutin for slightly lower effects)
What do you use to treat active TB?
clarithromycin or azithromycin and maybe (quinolone, clofazimine, amikacin, or rifabutin)
What TB drug has red dye and causes blotchy skin?
clofazimine
What has a long incubation period and comes from armadillos???
leprosy
How do you treat leprosy?
sulfones: dapsone is retained in skin and inhibits folate biosynthesis
What is multidrug therapy for leprosy?
dapsone, rifampin, clofazimine, and thalidomide
What are 2 polyenes?
amphotericin B and nystatin
What are 5 non-topical azoles?
ketoconazole
itraconazole
fluconazole
voriconazole
posaconazole
What are 4 topical azoles?
miconazole
econazole
clotrimazole
terconazole
What are 2 allylamines?
terbinafine and naftifine* (only used topically)
What are 3 echinocandins?
caspofungin
micafungin
anidulafungin
What is amphotericin B?
wide spectrum drug that binds to ergosterol and makes pores, admin IV (liposomal delivery system or mixed w/ deoxycholate), 90% of pts will have permanent renal dmg, chills/fever/vomiting/pain* (always happens w/ first dose)
What is nystatin?
polyene that is not absorbed orally --> good for oral candidiasis and topical candida
What is natamycin?
polyene that is opthalamic suspension for tx of aspergillus, candida, fusarium, and penicillum
What do ALL azoles block?
synthesis of ergosterol (14-alpha demethylase)
Why is ergosterol important?
for fungal cell membrane
What are 2 azoles for systemic use?
ketoconazole and itraconazole
How are systemic azoles admin?
PO--need stomach acid for absorption and do NOT get in CNS, ketoconazole blocks steroid biosynthesis but itraconazole does not
What are uses of fluconazole?
histoplasmosis, blastomycosis, candida, cryptococcosis, other mycoses
How do you admin fluconazole?
oral or IV b/c stomach acid does not matter and it does get in CNS
What can be used in one pill for vaginal yeast infections causing some nausea?
fluconazole
What are new azoles effective against?
aspergillosis and resistnace candidiasis
What are 2 new azoles and what is a side effect?
voriconazole and posaconazole may cause some visual disturbances
What is caspofungin?
an echinocandin used for aspergillosis and candidiasis
How does caspofungin work?
glucan synthesis inhibitor preventing fungi from forming protective cell wall
What is a 2nd line systemic antifungal?
flucytosine admin oral or IV (usually used in combo w/ ampho B for candida or cryptococcus)
What is converted to 5-FU?
flucytosine and may cause bone marrow toxicity
What are oral agents for dermatophytes?
azoles (keto and itra), terbinafine, griseofulvin
What is terbinafine?
squaline epoxidase inhibitor that concentrates in skin, hair, and nails that causes some liver toxicity
What is griseofulvin?
accumulates in skin, hair, and nails and interferes w/ mitosis, keratin localization
What are drug interactions with griseofulvin?
induces microsomal enzymes and has important interaction w/ any drug metabolized in the liver
What is used to treat herpes and varicella zoster?
acyclovir, famiciclovir, and valacyclovir
What is used in herpes conjunctivitis?
trifluridine
What 2 drugs are reserved for resistant herpes?
foscarnet and ganciclovir
What are 3 drugs used to treat CMV?
ganciclovir
foscarnet
cidofovir
What are uses of acyclovir?
HSV-1 and HSV-2, varicella zoster
What is the MOA of acyclovir?
gets incorporated into DNA
How is acyclovir admin?
oral, IV, topical (t/2 2 hrs)
What are side effects and drug interactions of acyclovir?
minimal
Howreverse is famciclovir different?
converts to penciclovir which is active, longer t/2, higher blood levels
What does valacyclovir do?
converts to acyclovir and has longer t/2, higher blood levels, more side effects in immunosuppressed pts
What is a problem with CMV drugs?
bone marrow suppression
What are 4 major classes of HIV drugs?
reverse transcriptase inhibitors (nucleosides and non-nuc), protease inhib, fusion inhib, integrase inhib
How do nucs work?
get incorporated into DNA and inhibit reverse transcriptase
How do non-nucs work?
do NOT get in DNA, bind directly to reverse transcriptase
What are 4 nucs?
zidovudine, didanosine, stavudine, lamivudine
What does zidovudin cause and when is it used?
AZT used in preg and delivery and causes anemias
What is didanosine and what does it cause?
buffered tablets cause peripheral neuropathy and pancreatitis
What does stavudine cause?
peripheral neuropathy
What does lamivudine cause?
fewest side effects, least acitivity, mildest (also used in Hep B)
What are 3 non-nucs?
nevirapine, delavirdine, efavirenz
What does nevirapine cause?
rash, hepatic toxicity

used in preg
What does delavirdine cause?
rash, hepatic, pancreatitis
What does efavirenz cause?
rash, CNS side effects (most popular b/c of slower resistance)
What do non-nucs interfere with?
ALL interfere w/ drug metabolizing liver enzymes
What are 7 protease inhibitors?
saquinavir
ritonavir
indinavir
nelfinavir
amprenavir
atazanavir
darunavir
Which protease inhibitor has the most GI side effects?
ritonavir
What protease inhibitor was developed specifically for resistant HIV?
darunavir
What side effects and interactions do protease inhibitors have?
mostly GI and glucose intolerance

inhibit liver metabolizing enzymes
What do fusion inhibitors do?
inhibit binding and penetration of the HIV into the cell
What are 2 fusion inhibitors?
enfuvirtide and maraviroc
What is enfuvirtide?
36 aa peptide admin subQ BID, minimal side effects and drug interactions
What is maraviroc?
admin PO BID, side effects: cough, fever, rash, liver toxicity, sore muscles, dizziness

blocks CCR5 receptor
How do integrase inhibitors work?
block integration of the viral DNA into genetic code of the infected cell
What are 2 integrase inhibitors?
raltegravir and elvitegravir
What is raltegravir?
first in new class for HIV, oral agent, no food restrictions, relatively few sdie effects, minimal drug interactions
What is elvitegravir?
in phase III, boosted w/ ritonavir, fecal elimination
What is HAART?
highly active anti-retroviral therapy (triple and quadruble thearpy)
What is PEP?
post exposure prophylaxis (4 weeks of therapy either double or triple)
What are 2 older agents for influenza?
amantadine and rimantadine
What do drugs for influenza do?
block uncoating and penetration, blocks M2 ion channel on virus
How is amantadine admin and what are its effecst?
PO, CNS effects

excreted unchanged in urine
How is rimantadine admin and eliminated?
PO (minimal CNS effects), liver metabolism
What are 2 newer agents for influenza?
zanamivir (inhaled) and oseltamivir (PO)

they are neuraminidase inhibitors
What are interferons used for?
hep B and C, papilloma virus, genital herpes, HIV, melanomas, Kaposi's sarcoma, multiple sclerosis
What are interferon toxicities?
bone marrow suppression and flu-like symptoms
What is a long-acting interferon used in hep B and C?
pegylated interferon alfa-2B
What is an oral agent used to inhibit replication of Hep B?
lamivudine
What inhibits replication of hep A and C, and is also used for RSV?
ribavirin
What is the main cause of malaria and 3 minor?
PLASMODIUM FALCIPARUM

plasmodium vivax, plasmodium ovale, and plasmodium malariae
What is the course of malaria?
1. parasite goes to liver and stays for 2-3 weeks
2. parasite invades RBCs (this is when you see clinical effects)
What is an anti-malarial to use in exo-erythrocytic stage (liver)?
primaquine can cause methemoglobinemia and hemolysis of RBC
What are 3 drugs used in erythrocytic stage (blood) of malaria?
chloroquine (DOC for active malaria), mefloquine (once a week), doxycycline (daily)
What do you take while abroad for prevention of malaria?
chloroquine, meflouine, doxycycline, malarone*, fansidar* (interfere w/ folic acid synthesis)
What is malarone?
atovaquone + proquanil
what is fansidar?
pyrimethamine + sulfadoxine
What do you take to prevent malaria after returning?
primaquine (to make sure it's not in liver)
What are 4 drugs for amebiasis?
METRONIDAZOLE, TINIDAZOLE

paromomycin, chlroquine
What are 5 drugs for giardiasis?
METRONIDAZOLE, TINIDAZOLE, NITAZOXANIDE

furazolidone, paromomycin
What are 3 drugs for trichomoniasis?
METRONIDAZOLE, TINIDAZOLE

paromomycin
What must you do for a pt w/ trichomoniasis?
treat sexual partner as well
What is metronidazole?
good for anaerobic bacteria and protozoas
What is the MOA, kinetics, an interactions of metronidazole?
impairment of DNA function, well absorbed orally, metabolized extensively in liver, some drug interactions
What are side effects of metronidazole?
red-brown pigments in urine

DON'T take w/ EtOH!!!
What is Tinidazole?
similar to metronidazole, longer t/2, better tolerated, less drug for shorter period of time
What can be treated in shorter period of time w/ tinidazole?
giardiasis and trichomoniasis (one dose), amebiasis (3-5 days) anaerobes
What are main uses of nitazoxandine?
giardiasis and cryptosporidosis
What is the MOA of nitazoxanide (strawberry flavor)?
inhibits electron transfer reactions
What are kinetics of nitazoxanide?
liguid form, eliminated in urine and feces and has active metabolite
What is the DOC and alternate for pneumocystis?
DOC: trimethorpim-sulfamethoxazole (septra)

pentamidine (parenteral, aerosol)
What drugs treat lice?
permitrhin, lindane, ivermectin
What is used to treat scabies?
permithrin, ivermectin, malathion
98% of all worm infections can be treated w/ what 3 drugs?
mebendazole, pyrantel pamoate, and ivermectin
What is the only anti-helmintic that KILLS the worm?
mebendazole
What is used for shistosomes and tapeworms?
praziquantel
What are main uses of mebendazole?
pinworm, roundworm, hookworm, whipworm, and filariae
What is the MOA of mebendazole?
dec glucose transport and ATP
What are the kinetics of mebendazole?
oral agent, minimal systemeic absorption (give once)
When do you not take mebendazole?
when pregnant or with EtOH
What are the main uses of praziquantel?
flaworm, tapeworm, schistosomes, pargoniamus, clonorchis, cysticercosis
What is the MOA of praziquantel?
inc membrane permeability to Ca and paralyzes worm
How is praziquantel admin and what are side effects?
oral, systemic absorption, dizziness, headaches
What is the MOA of nitazoxanide (strawberry flavor)?
inhibits electron transfer reactions
What are kinetics of nitazoxanide?
liguid form, eliminated in urine and feces and has active metabolite
What is the DOC and alternate for pneumocystis?
DOC: trimethorpim-sulfamethoxazole (septra)

pentamidine (parenteral, aerosol)
What drugs treat lice?
permitrhin, lindane, ivermectin
What is used to treat scabies?
permithrin, ivermectin, malathion
98% of all worm infections can be treated w/ what 3 drugs?
mebendazole, pyrantel pamoate, and ivermectin
What is the only anti-helmintic that KILLS the worm?
mebendazole
What is used for shistosomes and tapeworms?
praziquantel
What are main uses of mebendazole?
pinworm, roundworm, hookworm, whipworm, and filariae
What is the MOA of mebendazole?
dec glucose transport and ATP
What are the kinetics of mebendazole?
oral agent, minimal systemeic absorption (give once)
When do you not take mebendazole?
when pregnant or with EtOH
What are the main uses of praziquantel?
flaworm, tapeworm, schistosomes, pargoniamus, clonorchis, cysticercosis
What is the MOA of praziquantel?
inc membrane permeability to Ca and paralyzes worm
How is praziquantel admin and what are side effects?
oral, systemic absorption, dizziness, headaches
What are main uses of ivermectin?
broad spectrum, filaria, threadworm, scabies, hookworm, cutaneous larva migrans
How does ivermectin work?
PO absorbed systemically and paralyzes worm
Do you give ivermectin in pregnancy?
no b/c teratogenic in lab animals
What is a chemical analogue of methadone used in combo w/ acetaminophen to treat mild to moderate somatic and visceral pain?
propoxyphene
_______ has significant antitussive activity and is used in tx of cough and diphenoxylate and loperamide which activate opioid receptors in GI smooth muscle are used in tx of _______.
dextropmethorphan and diarrhea
What do opioids agonist-antag have that is responsible for their partail activity?
large chmeical substituent on the nitrogen atom
What mixed opioid is rapidly absorbed from the nasal mucosa?
butorphanol
______ and ______ are kappa receptor agonists w/ partail activity at mu while ______ is a kappa receptor agonist w/ additional activity at sigma.
butorphanol and nalbuphine and pentazocine
What is admin IV to rapidly terminate respiratory depression in opioid OD?
naloxone
Naltrexone is also effective in the tx of ______ ______.
alcohol dependence
What is a method of IV admin that permits the pt to self-admin preset amts of an analgesic via a syringe pump that is interfaced w/ a timing device?
patient-controlled analgesia (PCA)
What are the most widely used coanalgesics?
antiepileptic and antidepressants
What are antiepileptic drugs that are particularly effective in tx of pain syndromes w/ intermitten lancinating quality?
carbamazepine, gabapentin, phenytoin, and valproate
What are the most widely used antidepressants for the tx of chronic pain?
tricyclic antidepressants
How are pain impulses transmitted?
by primary afferent neurons to the spinal cord where ascending connections from the spinothalamic tract neurons project to limbic structures and the cortex
What activates the midbrain and spinal cord neurons that release enkephalins, serotonin, and NE?
descending inhibitory fibers from the periaqueductal gray matter

(opioids activate these pathways and inhibit ascending pain impulses)
What do opioid agonists cause?
analgesia, sedation, euphoria, miosis, resp depression, peripheral vasodilation, constipation, and drug dependence
All opioid receptors mediate _______, and mu primarily does _____, _____, and _____.
analgesia, analgesia, resp depression, and opioid dependence
Why are moderate opioid agonists usually combined with a nonopioid analgesic?
b/c they produce max effects at doses that cannot be tolerated
What kinds of headaches are primary?
cluster, migraine, and tension
What are secondary headaches?
those that arise from organic disorders
What do prophylactic drugs do for headaches?
act by preventing the vasoconstrictive phase of the disorder
How do headache abortive meds work?
reverse the vasodilative phase or relieve pain and inflammation
What is the most widely used anticonvulsant for migraine prophylaxis?
valproate
What are adverse effects of valproate?
sedation, tremors, and weight gain
What are 3 types of antidepressants that can be used to prevent migraines and give an example of each?
1. selective serotonin reuptake inhibitors: fluoxetine

2. tricyclics: amitriptyline

3. MAOI: phenelzine
What can MAOIs cause when taken w/ tyramine-containing foods or w/ sympathomimetic amine drugs?
hypertensive crisis
How does naproxen prevent and treat headaches?
blocking trhomboxane synthesis and platelet aggregation and reduce release of serotonin
What is a drug that blocks 5-HT2 receptors and prevents the vasoconstrictive phase of migraines?
methysergide
What are ergot agents that are effective in tx of migraines and cluster headaches?
ergot alkaloids: ergotamine and dihydroergotamine
What are adverse effects of ergot alkaloids?
N/V, diarrhea, muscle cramps, cold skin, panesthesia, and vertigo
What should not be used concurrently w/ MAOIs or used within 24hrs of admin an ergot alkaloid or methysergide?
triptan drugs
What are cluster headaches?
sever, unitlateral, retro-orbital headaches that tend to group over time, burning pain that arises behind one eye w/out warning
What are tension headaches?
characterized by bilateral, nonpulsatile, bandlike pressure tha is mild or moderate in intensity
What do migraines result from?
neurovascular dysfunction at several levels in the CNS

cerebral vasoconstriction and ischemia are followed by vasodilation, inflammation, and a unilateral/pulsatile headache
What are drugs used for migraine prophylaxis?
anticonvulsants, antidepressants, NSAIDs, B-blockers, CCB, and serotonin 5-HT2 receptor antag
How long must prophylactic drugs be taken for benefits?
3-4 weeks
What are drugs that abort migraines and what do they stimulate?
ergot alkaloids and triptans

serotonin 5-HT(1D/1B)
How do migraine-aborting drugs work?
cause cerebral vasoconstriction, inhibit release of peptides and other mediators of inflammation and vasodilation from trigeminal neurons, inhibit activation of trigeminal nucleus in the brainstem
What are adverse effects of triptans?
tightness and drowsiness
In what pts are ergots and triptans contraindicated?
CAD
What are 3 other agents for aborting migraines?
NSAIDs, opioid analgesics, sympathomimetic (isometheptene)
What drugs can prevent cluster headaches?
lithium, methysergide, or verapamil
What drugs can terminate cluster headaches?
ergot alkaloids, sumatriptan, inhaled O2, intranasal lidocaine, glucocorticoids
What do tension headaches respond to?
NSAIDs and muscle relaxers
How does isoniazid work?
inhibits the synthesis of mycolic acid
What is ethambutol?
bacteriostatic TB drug that can cause optic neuritis, hyperuricemia, gout, hepatitis, thrombocytopenia and impaired red-green color discrimination
How does rifampin work?
binds to the B-subunit of DNA-dependent RNA polymease
What are adverse effects of rifampin?
impaired liver function, elevated serum bilirubin and transaminase levels, hepatitis, hypersensitivity rxn
What is R207910?
code name for diarylquinoline drug in clinical trials to treat TB
What are 2 chronic mycobacterial infections that often require tx w/ multiple drugs for months or years?
TB and leprosy
What are the drugs used to initially treat TB?
combo of isoniazid, rifampin, ethambutol, and pyrazinamide
What are pts treated w/ if suspected to have a resistant organism?
streptomycin, amikacin, or fluoroquinolone
How are pts w/ leprosy treated?
combo of dapsone and rifampin or combo of dapsone, rifampin, and clofazimine
What is given w/ isoniazid to prevent some of the side effects?
pyridoxine
What is a semisynthetic antibiotic w/ broad-spectrum activity used in tx of TB and leprosy and prevention of meningococcal and H. influenzae B infections?
rifampin
What is a synthetic drug that shortens the total duration of therapy for pts w/ TB?
pyrazinamide
What is usally given in combo w/ azithromycin or clarithromycin and ethambutol?
rifabutin
What is a synthetic dye that has antimycobacterial and anti-inflammatory activity?
clofazimine
What antibiotics increase the permeability of the fungal cell membrane?
polyene atnibiotics and ciclopirox
What drugs inhibit synthesis of plasma membrane ergosterol?
azole derivatives and allylamine drugs
What drug inhibits cell wall glucan synthesis?
caspofungin
Flucytosine is converted to _______ by fungal cells then incorpated into fungal RNA where it inhibits protein synthesis.
5-fluorouracil
What is flucytosine used in combo w/ for cryptococcal meningitis and candidiasis?
amphotericin B
Ampho B is used to treat severe systemic and subQ mycoses but often causes....
chills, fever, nephrotoxicity, and other effects
What formulations of ampho B have less toxicity?
lipid
What is used to treat blastomycosis, coccidioidomycosis, histoplasmosis, and sporotrichosis?
itraconazole
What is an azole derivative used to treat candidiasis and cryptococcosis?
fluconazole
What is used to treat invasive candidiasis and aspergillosis?
voriconazole and caspofungin
How does caspofungin work?
it inhibits the synthesis of a fungal cell wall component, B-(1,3)-D-glucan
What can treat superficial candida infections?
nystatin, azole derivatives, or ciclopirox
How can you treat dermatophyte infections?
topical or oral admin of an azole derivative or terbinafine, oral admin of griseofulvin or topical admin of ciclopirox, anftifine, or tolnaftate
What is given orally to treat onychomycosis?
itraconazole or terbinafine
What interferes with microtubule function and blocks mitosis, used orally in treating dermatophyte infections?
griseofulvin
What is prodrug that is converted to acyclovir in vivo?
valacyclovir
What 3 drugs are selectively phosphorylated to their monophosphate metabolites by viral kinases and then host cell kinases convert them to triphosphates?
acyclovir, canciclovir, and penciclovir
What do most nucs cause when they are incorporated into viral DNA?
chain termination
What is used to treat CMV and resistant HSV and VZV?
foscarnet
What is the most common combo of HIV tx?
2 nucs plus either a PI or non-nuc
Some PI and non-nucs interact w/ a number of drugs via inhiition or induction of _______.
cytochrome P450 isozymes
What drugs are used in prophylaxis and tx of influenza A?
amantadine and rimantadine

act by preventing the uncoating of influenza A virus
What are 2 neruaminidase inhibitors that inhibit the release and spreading of influenza A and B virions?
oseltamivir and zanamivir
What is used to treat RSV in neonates and hep C in combo w/ interferon alfa?
ribavirin
What is used to treat HBV, HBC, and anogenital warts?
interferon alfa
What are the 2 DOCs for tx of amebiasis, giardiasis, and trichomoniasis?
metronidazole and tinidazole
What is the only antimalarial drug that blocks exoerythrocytic schizogony?
primaquine
What are 2 drugs used to prevent malaria in regions that have chloroquine-resistant plasmodia?
mefloquine or doxycycline
What is used in vivax and ovale malaria?
chloroquine in combo w/ primaquine
__________ is usually given in combo w/ doxycycline or pyrimethamine-sulfadoxine to treat malaria caused by chloroquine-resistant plasmodia.
quinine sulfate
How do you treat toxoplasmosis?
pyrimethamine plus sulfadiazine
______ or _____ with melarsoprol is used to treat African trypanosomiasis whereas _______ is used to treat American trypanosomiasis (Chagas' disease).
pentamidine or suramin and nifurtimox
What is newer drug for treating visceral leishmaniasis (Kala azar)?
miltefosine
What does praziquantel do?
exposes parasite antigens to host cell immune mechanisms
What are used to treat intestinal nematode infections?
albendazole, mebendazole, and pyrantel
What are used to treat filarial nematode infections including river blindness?
diethylcarbamazine and ivermectin

(ivermectin also used for strongyloidiasis and cutaneous larva migrans)
What is the DOC for all forms of schistosomiasis and for most tissue fluke infections and tapeworm infections?
praziquantel
What is used to treat sheep liver fluke infections?
triclabendazole
What is the DOC for lice and scabies?
permethrin