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192 Cards in this Set
- Front
- Back
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penicillin resistance in MRSA or PRSP is due to:
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loss of target
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R group substituents on penicillin affect:
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penetration of porins, B-lactamase susceptibility, binding to target
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Monobactams have activity against _________ and are not susceptible to their ___________
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gram-negative aerobes, B-lactamases
drug name : aztreonam |
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R group substiuents on cephalosporins affect:
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penetration of porins, B-lactamase susceptibility, binding to target
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Carabenems are _________ spectrum and are not very susceptible to __________
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broad spectrum, B-lactamases
names: imipenem, cilastatin, meropenem |
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List the drug(s) that affect formation of peptidoglycan monomers
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fosfomycin, bacitracin, cycloserine
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List the drug(s) that affect linear polymer formation during cell wall biosynthesis
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Vancomycin
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List the drug class that affects cross-linking during cell wall biosynthesis
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B-lactams
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What does Penicillin G structurally resemble?
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D-ala D-ala, the substrate for the transpeptidase
Pen G = suicide substrate |
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What molecular biology technique was used early on to identify PBPs?
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14C-labeling, separation by electrophoresis, and detection by autoradiography
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PBPs differ structurally among bacterial species and have different affinities for B-lactam drugs.
True or False |
True, drug-target binding differences are the basis for differences in susceptibility between organisms
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What are two examples of bug strains that have PBP mutations resulting in greatly reduced drug-target interactions
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Methicillin-resistant Staph. aureus (MRSA)
Penicillin-resistant Strep. pneuomoniae (PRSP) Note: PRSP can also have an intermediate resistance phenotype |
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Why do bacteria explode after exposure to B-lactams?
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cytoplasm is hypertonic, reduced cell wall integrity allows water to rush in and blast the cell apart (lysis).
Note: essentially the same thing happens when you use regular soap |
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What bond is cleaved by B-lactamases?
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the C-N bond of the B-lactam ring
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There is one type of B-lactamase that is responsible for resistance in bacteria
True or False |
False, there are many different versions that vary in specificty
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What is penicillin acylase and what function does it serve?
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An enzyme that removes the acyl substituent (R group) from the B-lactam ring.
It is used for generating 6-aminopenicillanic acid, a lead compound for the generation of new semi-synthetic penicillins with novel properties |
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Penicillin acylase is a B-lactamase commonly used by bacteria as a means of resistance.
True or False |
False, it is used in drug discovery for generating a lead compound
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Once a B-lactam reaches a bug, what are three things it must do to carry out its antimicrobial duty? How do changes in these processes cause resistance?
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1. Penetrate outer membrane (gram neg) - lack of penetration = resist
2. Escape inactivation - B-lactamase = resist 3. Bind target enzymes - altered target PBPs = resist |
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What differences in activity do semi-synthetic penicillins offer over penicillin and how does these affect their antimicrobial spectrum?
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1. improved porin penetration
(enhance gram-negative activity) 2. decreased B-lactamase susceptibility (broadens spectrum) 3. altered PBP binding pattern (changes spectrum) |
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Penicillins vary in acid stability and oral availability
True or False |
True
penicillins are well-absorbed after IM or IV admin repository forms (procaine penicillin G and benzathine penicillin G) are absorbed slow, producing prolonged low concentrations |
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Penicillins easily enter the CNS
True or False |
False, only when the meninges are inflamed
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How are penicillins eliminated?
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they are polar, renal elimination
reduce dose in pt. w/ severe renal disease |
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What drug inhibits tubular secretion of penicillin, prolonging it's bioavailability
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probenecid
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How does a penicillin antigen form?
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isomerization of the B-lactam ring allows for covalent bond formation with a cell surface protein (benzylpenicillenic acid binds at a lysine residue, generating the antigen)
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What are the adverse effects effects of penicillins?
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1. allergic (hypersensitivty) reactions, assume cross-allergenicity among penicillins
2. N/D from Gi irritation or flora alterations 3. In renal failure, Na or K toxicity can produce seizures (from slide) |
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You have a positive gram stain result, but no culture results. Should you pursue empiric treatment? If so, what factors should you consider? It not, why is it important to wait for culture results?
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Yes, you should consider 1) presumptive microbiologic diagnosis
2) the patient's history (eg. drug allergies) typically you would use a broad-spectrum drug, switching to a narrow-spectrum once you have definitive culture results |
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Penicillin G is ___ spectrum and active against:
Is it B-lactamase susceptible? |
narrow (it is B-lactamase susceptible);
group A strep, T. pallidum, some enterococci also: suscpetible pneumococci, meningococci, and anaerobes |
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Nafcillin and Oxacillin are ____ spectrum and active against:
Is it B-lactamase susceptible? |
very narrow (it is B-lactamase resistant);
staphylococci (not MRSA) |
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Aminopenicillins (named?) are ____ spectrum and are active against:
Is it B-lactamase susceptible? |
ampicillin and amoxicillin
extended spectrum (it is B-lactamase susceptible); like Pen G but also active against E. coli, H. flu, Listeria, and P. mirabilis |
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Carboxypenicillins (named?) are ____ spectrum and are active against:
Is it B-lactamase susceptible? |
Ticarcillin
Extended spectrum (B-lactamase susceptible) like Pen G but also catches some pseudomonas and proteus species |
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Ureidopenicillins (named?) are _____ spectrum and have activity against:
Is it B-lactamase susceptible? |
Piperacillin
extended-spectrum (it is B-lactamase susceptible) similar to ticarcillin but extends to Klebsiella pneumoniae and Bacteroides fragilis |
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Extended-spectrum penicillins are often used in combination with a B-lactamase inhibitor
True or False |
True, since they are all B-lactamase susceptible the combination further extends their anti-bacterial spectrum
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What are the names of 3 B-lactamase inhibitors?
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clavulanic acid, sulbactam, tazobactam
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How do B-lactamase inhibitors work?
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they contain a B-lactam ring and bind B-lactamase enzymes with extremely high affinities
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A B-lactam drug plus a B-lactamase inhibitor enhance spectrum but do not produce a synergistic effect
True or False |
False, they can be synergistic because the combined effect is notably greater than the sum of their individual effects
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The MIC of ampicillin in the presence of clavulanate against P. mirabilis is on the order of 1000 times larger than the MIC of ampicillin alone against the same organism.
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False, it is 1000 times SMALLER
See lecture from 4-3-09 slide 7 |
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When a B-lactamase inhibitor is used in combo with an extended-spectrum penicillin, which component determines the antibacterial specificity of the combo?
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The penicillin, it is the part binding PBPs and thus must determine specificity, the inhibitor extends range but does not enhance specificity (the affinity of the drug for its target)
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What determines whether the inhibitor (in a penicillin + B-lactamase inhibitor combo) will expand the spectrum of the penicillin?
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It's ability to inhibit any B-lactamases present in the organisms
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Will a B-lactamase inhibitor + penicillin combo be active against organisms that are resistant because of an altered target?
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No, b/c the inhibitor does not influence the penicillin's specificity for its targets
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Cephalosporins target PBPs and are bactericidal
True or False |
True
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Cephalosporins have substituents on 7-aminocephalosproanic acid that influence what?
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1. porin penetration
2. B-lactamase susceptibility 3. target binding (to PBPs) *these factors determine the antibacterial spectrum |
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What are three ways bugs become resistant to cephalosporins?
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1. B-lactamase
2. target alteration 3. impaired access |
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What are the adverse effects of cephalosporins?
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Hypersensitivity (limited cross-allergenicity with penicillins but do NOT use in pts. with history of anaphylaxis)
GI (N/V, colitis) |
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What are the pharmacokinetics of cephalosporins?
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1. mostly parenteral
2. most do not enter CNS 3. most elim by renal excretion |
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What bugs do 1st generation cephalosporins kill?
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gram-positive cocci (including B-lactamase producers) plus E. coli, K. pneumoniae, P. mirabilis
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What bugs do 2nd generation cephalosporins kill?
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increased activity against gram-negative organisms such as H. flu and B. fragilis
different drugs in this group have different spectra |
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What bugs do 3rd and 4th generation cephalosprins kill?
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more active against enteric gram-negative bacilli, including nosocomial bugs that have MDR
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Which generation of cephalosporins are used in surgical prophylaxis?
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Depends on surgery.
1st - skin 2nd - respiratory 3rd/4th - high risk patient, peritoneal cavity |
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What is the appropriate drug class for empirical therapy of meningitis or sepsis?
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3rd and 4th generation cephalosporins
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What drug is used to treat gonorrhea infections?
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ceftriaxone, 3rd gen cephalosporin
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What is the classic monobactam?
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Aztreonam
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What is the target for monobactams?
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PBP 3 of gram-negative bacteria
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Are monobactams cidal or static? What bugs do they target?
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bactericidal towards gram-neg aerobes like E. coli, K. pneumo, H. flu, Proteus, Salmonella
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Monobactams exhibit synergy with aminoglycosides
True or False |
True
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What is the basis of resistance to monobactams?
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Gram-positive and anaerobes have intrinsic resistance (no target)
They are not susceptible to most B-lactamases in gram-negatives, so impaired access and target alterations are common resistance mechanisms |
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What are the adverse effects of monobactams?
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GI: N/V/D
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Can you give a patient with a history of penicillin and cephalosporin hypersensitivity a monobactam?
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Yes, not cross-allergenic
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What type of infection warrants use of a monobactam?
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Serious infection with drug-resistant gram-negative aerobes
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What are 3 carbapenems?
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imipenem/cilastatin
meropenem ertapenem |
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Are carbapenems static or cidal? What is their target?
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Bactericidal, PBPs
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What bugs do carbapenems kill?
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many gram-positive and gram-negative as well as some PRSP but not MRSA
not susceptible to many B-lactamases |
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What bugs are quickly developing resistance to carbapenems? What can be done about this?
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Pseudomonas, deliberately limit the use of the drug
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What are the adverse effects of carbapenems?
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hypersensitivty
GI CNS (seizures, usually in renal failure pts.) |
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Should you give a carbapenem to a patient with a history of anaphylaxis to penicillin?
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No, partial cross-sensitivity with the penicillins
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How are carbapenems administered?
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IV
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How are carbapenems eliminated?
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renal
reduce dose in pts with renal disease |
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Why are imipenem and cilastatin given together?
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renal dehydropeptidase I cleaves the B-lactam on imipenem, cilastatin inhibits the dehydropeptidase
improved pharmacokinetics |
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When would you use a carbapenem?
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mixed infections
empirically in immunocompromised hosts serious infection w/ MDR organisms |
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What kind of macromolecule are vancomycin and teicoplanin?
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They are glycopeptides
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How do vancomycin and teicoplanin affect cell wall biosynthesis? What is the molecular basis for this?
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They inhibit stage 2 of cell wall biosynthesis, the formation of linear polymer
They bind D-ala-Dala using 5 hydrogen bonds, inhibiting polymerization of the growing peptidoglycan chain |
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Why are most gram-negative bacteria intrinsically resistant to vancomycin?
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Since it is a massive glycopeptide, it has great difficulty traversing the outer membrane porins
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What is the most important resistance mechanism bugs utilize against vancomycin?
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Target alteration
D-ala D-ala -> D-ala D-lactate results in one hydrogen bond loss and a 1000-fold decrease in drug binding |
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What are the adverse effects of vancomycin?
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"red man syndrome" (histamine)
ototoxicity (hearing loss) possible nephrotoxicity |
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Does vancomycin have good oral bioavailability?
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No, use IV administration
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How is vancomycin eliminated?
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renal
adjust for pts. w/ renal disease |
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When would you consider using vancomycin?
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Serious infections w/ B-lactam-resistant organisms
MRSA and PRSP** |
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What is the drug of choice for the treatment of patients with MRSA or PRSP infections?
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Vancomycin (a glycopeptide)
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A patient presents with renal failure and an MRSA infection. What drug should you use and how should you adjust the dose?
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Use vancomycin, decrease the dose
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A patient presents with an E. coli infection and has a history of hypersensitivity to penicillins and cephalosporins. If you suggest vancomycin, why will the attending physician feel like slapping you? What drugs could you suggest to save the patient's life and avoid embarrassment?
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You will get slapped because gram negatives are (mostly) intrinsically resistant to vancomycin.
For this patient, you should suggest TMP-SMZ (#1 next to pen/ceph) or a quinolone, or an aminoglycoside |
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What does bacitracin target? What bugs are susceptible? What is the adverse effect? How is it administered?
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1. blocks lipid carrier dephosphorylation, preventing peptidoglycan transfer across the plasma membrane
2. gram positive organisms only 3. nephrotoxic 4. topical only |
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What does cycloserine target? What disease is it used in as a second-tier drug? What are the primary adverse effets?
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1. analog of D-ala, it inhibits alanine racemase and D-ala-D-ala ligase
2. TB 3. CNS toxicity |
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What does fosfomycin target?
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It inhibits enolpyruvate transferase, an early step in cell wall synthesis
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What bugs are fosfomycin active against?
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gram-positive and gram-negative
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When would you want to use fosfomycin?
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uncomplicated UTIs
safe in pregnant women when cost is not a major factor |
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What type of macromolecule is daptomycin?
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cyclic lipopeptide
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What is the target of daptomycin? How does it work?
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cell membrane.
Ca++-dependent insertion of lipid tail causes depolarization, disrupting macromolecule synthesis |
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Is daptomycin cidal or static? Towards what organisms?
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bactericidal, concentration-dependent with post-antibiotic effect
gram-positive organisms active vs MRSA, VRSA, VRE |
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When would you want to use daptomycin?
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endocarditis and complex skin infections due to MRSA, VRSA, VRE
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What are the adverse effects of daptomycin?
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GI
myopathy |
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How should you administer daptomycin?
What is the elimination mechanism? |
IV administration
Renal excretion |
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The bacterial ribosome is composed of a 30S and a 50S subunit, the entire ribosome is thus 80S (30+50)
True or False |
False, the entire subunit is 70S.
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What are the key protein synthesis processes targeted by drugs?
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1. initiation
2. elongation |
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What is the target of chloramphenicol?
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50S subunit
Inhibits peptide bond formation (blocks elongation) |
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Is chloramphenicol bactericidal or bacteriostatic?
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usually static, but kills H. flu and N. meningitidis
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Chloramphenicol is _______ spectrum, it has activity against:
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broad;
gram positive/negative, aerobes/anaerobes, rickettsiae |
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When would you use chloramphenicol?
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Rarely, because it is extremely toxic...
severe salmonella, bacteroides, or VR enteroccocus infection severe infections in pts. w/ penicillin allergy |
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What is the basis of resistance to chloramphenicol?
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enzymatic acetylation
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What are the adverse effects of chloramphenicol?
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GI N/V
C. albicans superinfection bone marrow depression - anemia, aplasia gray baby syndrome flaccidity hypotension hypothermia gray color |
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What is the oral bioavailability of chloramphenicol like? Is it widely distributed in the tissue?
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good, yes
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How is chloramphenicol processed?
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inactivated by hepatic glucuronyl transferase
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What are 5 tetracyclines?
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Doxycycline
Oxytetracylcine Minocycline Tetracycline Demeclocycline many more... |
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What do the tetracyclines target? How do they work?
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30S ribosomal subunit
inhibits aa-tRNA entry (blocks elongation) |
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tetracyclines are ______ spectrum and active against:
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broad;
gram pos/neg, anaerobes, mycoplasma, rickettsia |
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Tetracyclines are bactericidal
True or False |
False, they are static
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When would you consider using tetracyclines?
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mycoplasma, H. pylori, rickettsiae, chlamydiae
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What is the main resistance mechanism bugs utilize against tetracyclines?
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efflux pumps
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What are the adverse effects of tetracyclines?
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GI (N/V)
superinfection teeth/bones - discolor., dysplasia contradindicated <10yo hepatic+renal toxicity photosensitization |
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What are the pharmacokinetics?
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variable oralbioavail.
chelated by cations (Ca, Mg, Fe, Al) crosses placenta (do not use in pregnant women) |
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What is tigecycline? What bugs does it hit?
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a glycylcycline (bulky side chain protecting tetracycline against resistance)
active in vitro against VR enterococci, MRSA, PRSP, some MDR gram-negatives |
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What are the three important macrolides discussed in lecture?
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erythromycin, clarithromycin, azithromycin
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What do macrolides target? How do they work?
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50S
inhibits translocation (blocks elongation) |
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Macrolides are bacteriostatic or bactericidal?
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static
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What bugs do macrolides target?
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strep, staph, corynebacteria, mycoplasma, legionella, neisseria, some rickettsia, others
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When would you use a macrolide?
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CAP
corynebacterial/chlamydial infections sub for penicillin in allergic pts. |
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What are two ways bugs become resistant to macrolides?
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efflux (cross-resistance)
rRNA methylation (cross-resistance) |
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What are the adverse effects of macrolides? Which drug reduces these effects?
|
GI (N/V/D)
hepatocellular toxicity inhibits CYP3A4 azithromycin reduces these and does not inhibit CYP3A4 |
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What are the pharmacokinetics of macrolides?
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oral bioavail., wide distribution (not CNS), eliminated in bile
azithromycin - long half-life (3days) simple dosing |
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What are ketolides? What is the prototypical ketolide?
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erythromycin derivates that overcome MLS resistance;
Telithromycin |
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What do ketolides target? How do they work?
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50S
Inhibit translocation, 10X stronger binding than erythromycin (broad) |
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Ketolides are static or cidal? What about their spectrum?
|
static, similar to eryhtromycin
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What are the adverse effects of ketolides?
|
prolong QT (arrhythmias)
liver toxicity teratogen? inhibits CYP3A4 |
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What are the pharmacokinetics of ketolides?
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oral bioavail., hepatic metabolism
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When would you consider using a ketolide?
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CAP, bronchitis, sinusitis
many advise not to use because of toxicity |
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What is the target of clindamycin? How does it work?
|
50S
Inhibits translocation (blocks elongation) |
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Is clindamycin static or cidal?
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static vs. streptococci, staphylococci, and bacteroides spp.
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Why doesn't clindamycin work against gram-negative aerobes?
|
they are intrinsically resistant because of impermeability to the drug
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When would you consider using clindamycin?
|
bacteroides or mixed aerobic infections outside CNS
prophylaxis for endocarditis in penicillin hypersensitive pts. |
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What are the resistance mechanisms agaisnt clindamycin?
|
rRNA methylation
cross-resistance between macrolides and streptogramin (MLS resistance) |
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What are the adverse effects of clindamycin?
|
GI (N/V/D)
enterocolitis due to C. difficile |
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What are the pharmacokinetics of clindamycin?
|
oral bioavail., wide distribution (not CNS)
hepatic metabolism biliary and renal elim |
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What is the formulation used for streptogramins? (ratio)
|
30:70 quinupristin: dalfopristin
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What is the target of streptogramins? How do they work?
|
50S
inhibits translocation (blocks elongation) |
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What is the activity of streptogramins? spectrum?
|
cidal against strep, staph, enteroccocus faecium
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What bug is intrinsically resistant to streptogramins?
|
enterococcus fecalis (efflux pump)
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When would you use a streptogramin?
|
infection with VR enterococcus faecium (VRE)
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What are the adverse effects of streptogramins?
|
thromophlebitis at IV infusion site
CYP3A4 inhibition |
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What is the resistance mechanism bugs utilize against streptogramins?
|
rRNA methylation
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What are the pharmacokinetics of streptogramins?
|
IV administration
hepatic metabolism |
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What is the prototypical oxazolidinone?
|
Linezolid
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What do oxazolidinones target? How do they work?
|
50S rRNA
blocks formation of initiation complex |
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What is the activity of oxazolidinones (linezolid)?
|
static towards gram positive cocci
|
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When might you use linezolid?
|
VR enterococcus faecium and E. fecalis
MRSA PRSP |
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What is the resistance mechanism of bugs to linezolid?
|
rRNA mutation
no cross-resistance |
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What are the adverse effects of linezolid?
|
GI (N/V)
Thrombocytopenia, neutropenia (rare) |
|
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What are the pharmacokinetics of linezolid?
|
IV or oral admin
Renal elim |
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What are three aminoglycosides?
|
gentamicin, tobramycin, and amikacin
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What do aminoglycosides target? How do they work?
|
30S
multiple actions on protein synthesis inhibits initiation, produces misreading, inhibits elongation |
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What is the activity of aminoglycosides? spectrum?
|
cidal towards aerobic gram-negative enteric bacteria
concentration-dependent w/ post antibiotic effect |
|
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What organisms are intrinsically resistant to aminoglycosides? Why?
|
Anaerobes because drug-uptake is O2-dependent
Gram-positive organisms because they are impermeable |
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When would you use an aminoglycoside?
|
Serious gram-negative infections (sepsis, pneumonia)
Enterococcal endocarditis (use w/ B-lactam for synergy) TB |
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What mechanisms are responsible for resistance to aminoglycosides?
|
enzymatic inactivation by transferases
altered target (rare) altered porin (rare) |
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What are the adverse effects of aminoglycosides?
|
ototoxicity
nephrotoxicity |
|
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What are the pharmacokinetics of aminoglycosides?
|
parenteral admin
no CNS entry renal elim |
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Aminoglycosides are used against gram-negative enteric bacteria. What other drugs are used against these bugs?
|
3rd gen ceph
extended spectrum penicillins monobactam carbapenams |
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Why do aminoglycosides show synergy with penicillins?
|
cell wall disruption facilitates aminoglycoside entry
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Describe two examples of antibacterial synergy
|
1. ampicillin + clavulanate (B-lactam and B-lactamase inhibitor)
2. penicillin + aminoglycoside (leaky cell aids in aminoglycoside uptake) |
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Explain the importance of the finding that some antibiotics inhibit CYP3A4
|
Have to adjust dose of other drugs if they are metabolized by CYP3A4
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When should you use a borad-spectrum antibacterial?
|
When you treat empirically
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When should you use a narrow-spectrum drug?
|
When you know the one single bug responsible for infection
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Sulfonamide and trimethoprim are both antimetabolites.
True or False |
True
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Sulfonamide structurally resembles ______________ while trimethoprim resembles __________________
|
PABA
pteridine both are components of folic acid |
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What is the basis for selective toxicity of sulfa drugs?
|
Mammalian cells cannot synthesize folic acid
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What is the target of sulfonamides?
|
dihydropteroate synthase
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Are sulfonamides static or cidal?
|
static
|
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What bugs are covered by sulfonamides?
|
many gram pos and gram neg bacteria
|
|
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When would you use a sulfonamide?
|
uncomplicated UTIs
IBD burns |
|
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What are 3 ways for a bug to resist sulfonamides?
|
1. altered target
2. decreased permeability 3. increased PABA synthesis |
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What are the adverse effects of sulfonamides?
|
1. hypersensitivity
2. cross-allergenic with related drugs 3. GI (N/V/D) 4. CNS (kernicterus) 5. Hematologic (RBC hemolysis in G6PD deficiency) |
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What are the pharmacokinetics of sulfonamides? Why are they contraindicated in 3rd trimester of a pregnancy and in neonates?
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Oral, topical
wide distribution, enters CNS displaces unconj. bilirubin from plasma proteins --> dont use in 3rd tri or neonates hepatic metabolism/renal excretion |
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How does trimethoprim work? Why is it selectively toxic?
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inhibits dihydrofolate reductase
inhibits bacterial DHFR much more than mammalian DHFR |
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Is trimethoprim static or cidal? against what organisms?
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static against gram positive and negative organisms
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How do bugs become resistant to trimethoprim?
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1. altered target
2. overproduction of normal target |
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What are the adverse effects of trimethoprim?
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bone marrow depression
megaloblastic anemia, leukopenia, granulocytopenia |
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What are the pharmacokinetics of trimethoprim?
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oral, wide dist., renal elim
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When would you consider using trimethoprim?
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uncomplicated UTIs due to gram-negatives
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TMP-SMX is bacteriostatic against gram pos and gram neg organisms
True or False |
False, they synergize and together are bactericidal
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TMP and SMX have (similar or different) half lives?
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similar, 9-12 hours
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What is the optimal ratio of TMP:SMX for killing in vitro? How is this ratio different in vivo?
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1:20 in vitro
1:5 in vivo because VOD for TMP is 5X that of SMX |
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When would you use TMP-SMX?
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UTIs, shigella infections, traveler's diarrhea, otitis media, bronchitis, pneumocystis pneumoniae
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Why does the TMP-SMX combination produce a synergistic effect?
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They inhibit sequential steps in FA synthesis.
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What kinds of infections respond well to synergistic drug combinations?
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1. bacterial endocarditis (due to enterococci especially)
2. gram negative infections in neutropenic pts. 3. systemic pseudomonas infections |
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How do fluoroquinolones work? Are they cidal or static? Do they have a postantibiotic effect?
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inhibit DNA gyrase and topo IV
cidal yes, post antibiotic effect is present |
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How do different generations of fluoroquinolones differ? Explain the differences
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different antibiotic spectra
1st - both neg and pos 2nd - gram neg > gram pos 3rd - gram pos > gram neg 4th - like 3rd + anaerobes |
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When would you use a fluoroquinolone?
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many infections gram pos and gram neg
meningococcal prophylaxis M. tuberculosis infections |
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What is the basis for resistance to fluoroquinolones?
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1. altered target
2. efflux 3. cross-resistance among generations |
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What are the adverse effects of fluoroquinolones? Ok for pregnant women?
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GI (N/V/D)
damages developing cartilage do not use in pregnant or nursing women or <18yo children |
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What are the pharmacokinetics of fluoroquinolones?
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1. oral
2. wide distr. 3. renal elim. |
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Why should you always treat active TB with more than one drug?
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basis for resistance to the drugs is chromosomal, so single drug exerts selection pressure for pre-existing mutants
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What are the four drugs used for TB?
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isoniazid, pyrazinamide, ethambutol, rifampin
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Explain the target of isoniazid, it's action, resistance mechanisms, adverse effects, and pharmacokinetics
for TB |
target: mycolic acid synthesis
action: cidal for mycobacteria resistance: mutation in target or KatG (required enzyme) adverse: hepatitis, peripheral neuropathy pharmacokinetics: oral, enters CNS, caseous lesions, phagocytes, inactivated by hepatic N-acetyltransferase (poymorphisms) |
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Explain the target of pyrazinamide, it's action, resistance mechanisms, adverse effects, and pharmacokinetics
for TB |
target: mycolic acid synth
action: cidal towards active mycobacteria resistance: mutations in pcnA adverse: hepatoxicity, arthralgia PK: oral, hepatic metab, renal elim |
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Explain the target of rifamycins, it's action, resistance mechanisms, adverse effects, and pharmacokinetics
for TB |
target: bacterial RNAP (beta subunit)
action: cidal towards active myco and some gram pos and gram negs resistance: RNA pol mutations adverse: flu-like syndrome, induces CYP enzymes PK: oral, enters CNS, hepatic metabolism |
