Antimicrobials Flashcards

0
Q

Penicillin V

A

Prototype B lactam antibiotic–Oral form

MOA: binds PBPs and blocks transpeptidase crosslinking

Uses: mostly gram positive (s. Pneumo, s. Pyogenes, actinomyces); Also used for N? Meningitidis and T. pallidum. Bactericidal for gram positive cocci, gram positive rods, gram negative cocci, and spirochetes. Penicillinase sensitive.

TOXICITY: hypersensitivity reactions, hemolytic anemia.

RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B lactam ring

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1
Q

Penicillin G

A

Prototype B lactam antibiotic–IV and IM form

MOA: binds PBPs and blocks transpeptidase crosslinking

Uses: mostly gram positive (s. Pneumo, s. Pyogenes, actinomyces); Also used for N? Meningitidis and T. pallidum. Bactericidal for gram positive cocci, gram positive rods, gram negative cocci, and spirochetes. Penicillinase sensitive.

TOXICITY: hypersensitivity reactions, hemolytic anemia.

RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B lactam ring

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2
Q

Ampicillin

A

Penicillinase-sensitive penicillin

MOA: same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against B-lactamase.

USES: extended-spectrum penicillin–Haemophilus influenzae, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci (ampicillin/amoxicillin HELPSS kill enterococci)

TOXICITY: hypersensitivity reactions; rash; pseudo membranous colitis

RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B-lactam ring

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3
Q

Oxacillin

A

Penicillinase-resistant penicillin

MOA: same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B lactamase to B lactam ring.

USE: S. aureus (except MRSA; resistant because of altered PBP target site)

TOXICITY: hypersensitivity reactions, interstitial nephritis

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4
Q

Pipercillin

A

Antipsuedomonal

MOA: same as penicillin. Extended spectrum.

USES: Pseudomonas spp. And gram negative rods; susceptible to penicillinase; use with B lactamase inhibitors.

TOXICITY: hypersensitivity reactions

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5
Q

Cephalosporins

A

Inhibits peptidoglycan cross-linking; less susceptible to penicillinase than penicillin

1st generation: cefazolin, cephalexin

2nd generation: cefaclor, cefprozi, cefoxitin

3rd generation: cefpodoxime, cefotaxime, ceftriaxone

4th generation: cefepime

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6
Q

1st generation cephalosporins

A

Cefazolin, cephalexin

PEcK: Proteus mirabilis, E. coli, Klebsiella pneumoniae

Don’t penetrate CNS

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7
Q

2nd generation cephalosporins

A

Cefaclor, cefprozi, cefoxitin; extended gram negative spectrum

HEN PEcKS: Haemophilus influenzae, Enterobacter, Neisseria, Proteus, E. Coli, Klebsiella, Serratia

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8
Q

3rd generation cephalosporins

A

Cefpodoxime, cefotaxime, ceftriaxone

Serious gram negative infections resistant to other beta lactams

Penetrates the CNS-meningitis, gonorrhea, pseudomonas

Less effective against gram positive than 1st

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9
Q

4e generation cephalosporins

A

Cefepime

Increased activity against pseudomonas and gram positive

Enhanced resistance to beta lactamase

Crosses the BBB

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10
Q

Imipenem

A

Cabapenem

MOA: broad-spectrum, B-lactamase-resistant capbapenem. Inhibit cell wall synthesis. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decreased inactivation of drug in renal tubules.

USES: gram positive cocci, gram negative rods, and anaerobes. Wide spectrum, but significant side effects limit use to life threatening infections or after other drugs have failed.

TOXICITY: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.

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11
Q

Vancomycin

A

MOA: inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bacteriocidal.

USES: gram positive only–serious, multidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)

TOXICITY: well tolerated in general–but NOT trouble free. Nephrotoxicity, ototoxicity, thrombophlebitis, diffuse flushing–red many syndrome (can largely prevent by pretreatment with antihistamines and slow infusion rate)

RESISTANCE: occurs in bacterial via amino acid modification of D-ala D-ala to D-ala D-lac

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12
Q

Tobramycin

A

Aminoglycoside–30S inhibitor

MOA: bactericidal; inhibits formation of inititation complex and causes misreading of mRNA. Also blocks translocation. Requires O2 for uptake; therefore ineffective against anaerobes.

USES: severe, gram negative rod infections. Synergistic with B lactam antibiotics.

TOXICITY: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogenic.

RESISTANCE: bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.

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13
Q

Doxycycline

A

MOA: bacteriostatic; binds 30s and prevents attachment of aminoacyl-tRNA; limited CNS penetration. Doxycycline is fecally eliminated and can be used in patients with renal failure. Do not take with milk (calcium), antacids (calcium or magnesium), or iron-containing preparations because divalent cations inhibit absorption in gut.

USES: Borrelia burgdorferi, M pneumoniae. Drug’s ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne.

TOXICITY: GI distress, discoloration of Teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy.

RESISTANCE: decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps.

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14
Q

Erythromycin

A

Macrolide

MOA: binds 50S subunit and inhibits translocation. Bacteriostatic.

Uses: atypical pneumonias-mycoplasma, chlamydia, legionella, STDs (chlamydia), gram positive cocci (strep if allergic to penicillin)

TOXICITY: GI motility issues, arrhythmia caused by prolonged QT, Canute cholestatic hepatitis, rash, eosinophilia. Increases serum concentration of theophyllines, oral anticoagulants.

RESISTANCE: methylation of 23s rRNA-binding site prevents binding of drug.

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15
Q

Clindamycin

A

MOA: blocks peptide transfer (translocation) at 50s ribosomal subunit. Bacteriostatic.

USES: anaerobic infections (e.g. Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Group A strep infection. **treats anaerobes above the diaphragm vs metronidazole

TOXICITY: pseudomembranous colitis (C. Difficile overgrowth), fever, diarrhea

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16
Q

Linezolid

A

Oxazolidinone

MOA: inhibits protein synthesis by binding to 50S subunit and preventing formation of the initiation complex.

USES: gram positive species including MRSA and VRE

TOXICITY: bone marrow suppression (especially thrombocytopenia), peripheral neuropathy, serotonin syndrome

RESISTANCE: point mutation of ribosomal RNA

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17
Q

Sulfamethoxazole

A

Sulfonamide

MOA: inhibits folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic.

Uses: gram positive, gram negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.

TOXICITY: hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (Tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. Warfarin)

RESISTANCE: altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis

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18
Q

Trimethoprim

A

MOA: Inhibitor of dihydrofolate reductase. Bacteriostatic.

USES: used in combination with sulfonamides, causing sequential block of folate synthesis. Combination used for UTIs, shigella, salmonella, pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.

TOXICITY: megaloblastic anemia, thrombocytopenia, leukopenia

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19
Q

Ciprofloxacin

A

fluoroquinolone

MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids.

Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms

TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone.

RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.

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20
Q

Metronidazole

A

MOA: Forms free radical toxic metabolites in bacterial cell that Damage DNA. Bactericidal, antiprotozoal.

USES: treats GET GAP–Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. Difficile). Used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. Pylori.

TOXICITY: disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol (thought to be due to its inhibition of alcohol oxidizing enzymes–>accumulation of acetaldehyde); headache, metallic taste

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21
Q

Amoxicillin

A

Penicillinase-sensitive penicillin

MOA: same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against B-lactamase.

USES: extended-spectrum penicillin–Haemophilus influenzae, E. Coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci (ampicillin/amoxicillin HELPSS kill enterococci)

TOXICITY: hypersensitivity reactions; rash; pseudo membranous colitis

RESISTANCE: penicillinase in bacteria (a type of B lactamase) cleaves B-lactam ring

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21
Q

Nafcillin

A

Penicillinase-resistant penicillin

MOA: same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B lactamase to B lactam ring.

USE: S. aureus (except MRSA; resistant because of altered PBP target site)

TOXICITY: hypersensitivity reactions, interstitial nephritis

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22
Q

Dicloxacillin

A

Penicillinase-resistant penicillin

MOA: same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of B lactamase to B lactam ring.

USE: S. aureus (except MRSA; resistant because of altered PBP target site)

TOXICITY: hypersensitivity reactions, interstitial nephritis

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23
Ticarcillin
Antipsuedomonal MOA: same as penicillin. Extended spectrum. USES: Pseudomonas spp. And gram negative rods; susceptible to penicillinase; use with B lactamase inhibitors. TOXICITY: hypersensitivity reactions
24
Clavulanic acid
B-lactamase inhibitor. Often added to penicillin antibiotics to proct the antibiotic from destruction by B-lactamase (penicillinase)
25
Sulbactam
B-lactamase inhibitor. Often added to penicillin antibiotics to proct the antibiotic from destruction by B-lactamase (penicillinase)
26
Tazobactam
B-lactamase inhibitor. Often added to penicillin antibiotics to proct the antibiotic from destruction by B-lactamase (penicillinase)
27
Cefazolin
1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
28
Cephalexin
1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
29
Cefoxitin
2nd generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: HEN PEcKS (gram positive cocci)--Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
30
Cefaclor
2nd generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: HEN PEcKS (gram positive cocci)--Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
31
Cefuroxime
2nd generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: HEN PEcKS (gram positive cocci)--Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
32
Ceftriaxone
3rd generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bactericidal. USES: TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
33
Cefotaxime
3rd generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bactericidal. USES: serious gram negative infections resistant to other B-lactams TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
34
Ceftazidime
3rd generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bactericidal. USES: serious gram negative infections resistant to other B-lactams--Pseudomonas TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
35
Cefepime
4th generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bactericidal. USES: TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
36
Ceftaroline
5th generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bactericidal. USES: broad gram positive and gram negative organism coverage, including MRSA; does not cover pseudomonas. TOXICITY: 1st generation cephalosporin MOA: B-lactam drug that inhibits cell wall synthesis but are less susceptible to penicillinases. Bacteriocidal. USES: PEcK (gram positive cocci)--Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections TOXICITY: hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction (inhibits acetaldehyde dehydrogenase and causes hangover symptoms, severe flushing hypotension, tachycardia with alcohol). Exhibits cross reactivity with penicillins. Increases nephrotoxicity of aminoglycosides.
37
Aztreonam
MOA: a monobactam; resistant to B-lactamase. Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3. Synergistic with aminoglycosides. No cross-allergenicity with penicillins. USES: gram negative rods only--no activity against gram positive or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides. TOXICITY: usually nontoxic. Occasional GI upset.
38
Meropenem
Cabapenem MOA: B-lactamase-resistant capbapenem. Inhibit cell wall synthesis. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules. USES: gram positive cocci, gram negative rods, and anaerobes. Wide spectrum, but significant side effects limit use to life threatening infections or after other drugs have failed. TOXICITY: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels. **meropenem has a decreased risk of seizures and is stable to dehydropeptidase I
39
Ertapenem
Newer Cabapenem MOA: broad-spectrum, B-lactamase-resistant capbapenem. Inhibit cell wall synthesis. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decreased inactivation of drug in renal tubules. USES: gram positive cocci, gram negative rods, and anaerobes. Wide spectrum, but significant side effects limit use to life threatening infections or after other drugs have failed. Limited pseudomonas coverage. TOXICITY: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
40
Doripenem
Newer Cabapenem MOA: broad-spectrum, B-lactamase-resistant capbapenem. Inhibit cell wall synthesis. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decreased inactivation of drug in renal tubules. USES: gram positive cocci, gram negative rods, and anaerobes. Wide spectrum, but significant side effects limit use to life threatening infections or after other drugs have failed. Limited pseudomonas coverage. TOXICITY: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
41
Gentamicin
Aminoglycoside--30S inhibitor MOA: bactericidal; inhibits formation of inititation complex and causes misreading of mRNA. Also blocks translocation. Requires O2 for uptake; therefore ineffective against anaerobes. USES: severe, gram negative rod infections. Synergistic with B lactam antibiotics. TOXICITY: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogenic. RESISTANCE: bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
42
Neomycin
Aminoglycoside--30S inhibitor MOA: bactericidal; inhibits formation of inititation complex and causes misreading of mRNA. Also blocks translocation. Requires O2 for uptake; therefore ineffective against anaerobes. USES: severe, gram negative rod infections. Synergistic with B lactam antibiotics. Neomycin for bowel surgery. TOXICITY: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogenic. RESISTANCE: bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
43
Amikacin
Aminoglycoside--30S inhibitor MOA: bactericidal; inhibits formation of inititation complex and causes misreading of mRNA. Also blocks translocation. Requires O2 for uptake; therefore ineffective against anaerobes. USES: severe, gram negative rod infections. Synergistic with B lactam antibiotics. TOXICITY: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogenic. RESISTANCE: bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
44
Streptomycin
Aminoglycoside--30S inhibitor MOA: bactericidal; inhibits formation of inititation complex and causes misreading of mRNA. Also blocks translocation. Requires O2 for uptake; therefore ineffective against anaerobes. USES: severe, gram negative rod infections. Synergistic with B lactam antibiotics. TOXICITY: nephrotoxicity, neuromuscular blockade, ototoxicity (especially when used with loop diuretics), teratogenic. RESISTANCE: bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation, or adenylation.
45
Tetracycline
MOA: bacteriostatic; binds 30s and prevents attachment of aminoacyl-tRNA; limited CNS penetration. Do not take with milk (calcium), antacids (calcium or magnesium), or iron-containing preparations because divalent cations inhibit absorption in gut. USES: Borrelia burgdorferi, M pneumoniae. Drug's ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne. TOXICITY: GI distress, discoloration of Teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy. RESISTANCE: decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps.
46
Minocycline
MOA: bacteriostatic; binds 30s and prevents attachment of aminoacyl-tRNA; limited CNS penetration. Do not take with milk (calcium), antacids (calcium or magnesium), or iron-containing preparations because divalent cations inhibit absorption in gut. USES: Borrelia burgdorferi, M pneumoniae. Drug's ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne. TOXICITY: GI distress, discoloration of Teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy. RESISTANCE: decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps.
47
Azithromycin
Macrolide MOA: binds 50S subunit and inhibits translocation. Bacteriostatic. Uses: atypical pneumonias-mycoplasma, chlamydia, legionella, STDs (chlamydia), gram positive cocci (strep if allergic to penicillin) TOXICITY: GI motility issues, arrhythmia caused by prolonged QT, Canute cholestatic hepatitis, rash, eosinophilia. Increases serum concentration of theophyllines, oral anticoagulants. RESISTANCE: methylation of 23s rRNA-binding site prevents binding of drug.
48
Clarithromycin
Macrolide MOA: binds 50S subunit and inhibits translocation. Bacteriostatic. Uses: atypical pneumonias-mycoplasma, chlamydia, legionella, STDs (chlamydia), gram positive cocci (strep if allergic to penicillin) TOXICITY: GI motility issues, arrhythmia caused by prolonged QT, Canute cholestatic hepatitis, rash, eosinophilia. Increases serum concentration of theophyllines, oral anticoagulants. RESISTANCE: methylation of 23s rRNA-binding site prevents binding of drug.
49
Chloramphenicol
MOA: blocks peptidyltransferase at 50s ribosomal subunit. Bacteriostatic. USES: meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain Spotted Fever (Rickettsia rickettsii) TOXICITY: anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase) RESISTANCE: plasmid-encoded acetyltransferase inactivates the drug.
50
Sulfisoxazole
Sulfonamide MOA: inhibits folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic. Uses: gram positive, gram negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI. TOXICITY: hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (Tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. Warfarin) RESISTANCE: altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis
51
Sulfadiazine
Sulfonamide MOA: inhibits folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic. Uses: gram positive, gram negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI. TOXICITY: hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (Tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. Warfarin) RESISTANCE: altered enzyme (bacterial dihydropteroate synthase), decreased uptake, or increased PABA synthesis
52
Norfloxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
53
Levofloxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
54
Ofloxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
55
Sparfloxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
56
Moxifloxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
57
Gemifloxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
58
Enoxacin
fluoroquinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
59
Nalidixic acid
Quinolone MOA: inhibits DNA gyrate (topoisomerase II) and topoisomerase IV. bactericidal. Must not be taken with antacids. Uses: gram negative rods of urinary and GI tracts, Neisseria, some gram positive organisms TOXICITY: GI upset, super infections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnancy, nursing mothers, and children under 18 due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people over 60y and in patients taking prednisone. RESISTANCE: chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
60
Isoniazid
Antimycobacterial prophylaxis against M. Tuberculosis MOA: decreases synthesis of mycolic acids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolites USES: Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB. TOXICITY: neurotoxicity (usually presents as peripheral neuropathy),hepatotoxicity. Pyridoxine (vitamin B6) can prevent neurotoxicity (INH competes with B6 in synthesis of neurotransmitters and increases its urinary excretion leading to B6 deficiency) **INH is metabolized by acetylation in the liver. Different half-lives in fast vs. slow acetylators--bimodal curve of drug concentration show pharmacological polymorphism in drug metabolism.
61
Rifampin
MOA: inhibits DNA-dependent RNA polymerase USES: part of multi-agent drug therapy for Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus Influenzae type B. TOXICITY: minor hepatotoxicity and drug interactions (increases P-450); orange body fluids. Rifabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation. MECHANISM OF RESISTANCE: mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to resistance.
62
Rifabutin
MOA: inhibits DNA-dependent RNA polymerase USES: part of multi-agent drug therapy for Mycobacterium tuberculosis; delays resistance to dapsone when used for leprosy. Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with Haemophilus Influenzae type B. TOXICITY: minor hepatotoxicity and drug interactions (increases P-450); orange body fluids. Rifabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation.
63
Pyrazinamide
MOA: uncertain. Thought to acidify intracellular environment via conversion to pyrazinoic acid. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found. USES: P one RIPE therapy for Mycobacterium tuberculosis TOXICITY: hyperuricemia, hepatotoxicity
64
Ethambutol
MOA: decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase USES: Mycobacterium tuberculosis TOXICITY: optic neuropathy (red-green color blindness)
65
Prophylaxis-endocarditis with surgical or dental procedures
Penicillins
66
Prophylaxis-Gonorrhea
Ceftriaxone
67
Prophylaxis-history of recurrent UTI
TMP-SMX
68
Prophylaxis-meningococcal infections
Ciprofloxacin (DOC), rifampin for children
69
Prophylaxis-pregnancy women carrying group B strep
Ampicillin
70
Prophylaxis-prevention of gonococcal or chlamydial conjunctivitis in newborn
Erythromycin ointment
71
Prophylaxis-prevention of post surgical infection due to S. Aureus
Cefazolin
72
Prophylaxis-strep pharyngitis in child with prior rheumatic fever
Oral penicillin
73
Prophylaxis-syphillis
Benzathine penicillin G
74
Prophylaxis in HIV-Pneumocystis pneumonia
CD4<200 TMP-SMX
75
Prophylaxis in HIV-pneumocystis pneumonia and toxoplasmosis
CD4<100 TMP-SMX
76
Prophylaxis HIV-Mycobacterium avium complex
CD4<50 Azithromycin
77
Amphotericin B
Anti-fungal MOA: binds ergosterol and forms membrane pores that allow leakage of electrolytes USES: serious systemic mycoses, not for non-invasive infections. Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis. Supplement K+ and Mg++ because of altered renal tubule permeability. TOXICITY: fever/chills, hypotension, nephrotoxicity (causes both decreased GFR and divert toxic effects on tubular epithelium), arrhythmias, anemia, IV phlebitis. Hydration decreases nephrotoxicity. Liposomal Amphotericin decreases toxicity.
78
Nystatin
MOA: same as Amphotericin B (binds ergosterol and forms pores in membranes). Topical form because too toxic for systemic use. USES: only mucocutaneous infections, not systemic. "Swish and swallow" for oral candidiasis; topical for diaper rash or vaginal candidiasis.
79
Fluconazole
MOA: inhibits fungal (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to USES: local and less serious systemic mycoses; chronic suppression of cryptococcal meningitis in AIDS patients and Candida infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections. TOXICITY: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), increases levels of P450 metabolized drugs (cyclosporine, warfarin)
80
Ketoconazole
MOA: inhibits fungal (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to USES: local and less serious systemic mycoses; chronic suppression of cryptococcal meningitis in AIDS patients and Candida infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections. TOXICITY: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), increases levels of P450 metabolized drugs (cyclosporine, warfarin)
81
Clotrimazole
MOA: inhibits fungal (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to USES: local and less serious systemic mycoses; chronic suppression of cryptococcal meningitis in AIDS patients and Candida infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections. TOXICITY: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), increases levels of P450 metabolized drugs (cyclosporine, warfarin)
82
Miconazole
MOA: inhibits fungal (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to USES: local and less serious systemic mycoses; chronic suppression of cryptococcal meningitis in AIDS patients and Candida infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections. TOXICITY: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), increases levels of P450 metabolized drugs (cyclosporine, warfarin)
83
Itraconazole
MOA: inhibits fungal (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to USES: local and less serious systemic mycoses; chronic suppression of cryptococcal meningitis in AIDS patients and Candida infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections. TOXICITY: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), increases levels of P450 metabolized drugs (cyclosporine, warfarin)
84
Voriconazole
MOA: inhibits fungal (ergosterol) synthesis, by inhibiting the P-450 enzyme that converts lanosterol to USES: local and less serious systemic mycoses; chronic suppression of cryptococcal meningitis in AIDS patients and Candida infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections. TOXICITY: testosterone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), increases levels of P450 metabolized drugs (cyclosporine, warfarin)
85
Flucytosine
MOA: inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase--blocks thymidylate synthetase USES: systemic fungal infections (especially meningitis caused by cryptococcus) in combination with Amphotericin B TOXICITY: bone marrow suppression
86
Caspofungin
MOA: inhibits cell wall synthesis by inhibiting synthesis of B-glucan USES: invasive aspergillosis, candida. TOXICITY: GI upset, flushing (by histamine release)
87
Micafungin
MOA: inhibits cell wall synthesis by inhibiting synthesis of B-glucan USES: invasive aspergillosis, candida. TOXICITY: GI upset, flushing (by histamine release)
88
Anidulafungin
MOA: inhibits cell wall synthesis by inhibiting synthesis of B-glucan USES: invasive aspergillosis, candida. TOXICITY: GI upset, flushing (by histamine release)
89
Terbinafine
MOA: inhibits the fungal enzyme squalene epoxidase (ergosterol biosynthesis inhibitor) USES: used to treat dermatophytoses--especially onychomycosis (fungal infection in finger or toe nails) TOXICITY: GI upset, headaches, hepatotoxicity, taste disturbance
90
Griseofulvin
MOA: interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g. Nails) USES: oral treatment of superficial infections--inhibits growth of dermatophytes (tinea, ringworm) TOXICITY: teratogenic, carcinogenic, confusion, headaches, increases P450 and warfarin metabolism.
91
Chloroquine
MOA: blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia. USES: plasmodial erythrocyte infection (not liver). treatment of plasmodial species other than P. Falciparum (frequency of resistance to falciparum is too great). Resistance due to membrane pump that decreases intracellular concentration of drug. Treat P. Falciparum with artemether/lumafantrine or atovoquone/proguanil. For life-threatening malaria, use quinidine in US or artesunate. TOXICITY: retinopathy, pruritis
92
Artemether/lumefantrine
MOA: not known; drug combo artemisinin derivative and lumafantrine USES: acute, uncomplicated p. Falciparum; treat chloroquine-resistant strains; NOT prophylaxis or severe
93
Mebendazole
Anti-helminthic MOA: binds worm tubulin and interferes with organellar transport--immobilizes helminth. USES: enterobiasis (pinworm), trichuriasis (whip worm), ascariasis
94
Praziquantel
Antihelminthic therapy MOA: increases cellular calcium-->permeability leads to death of organism USES: all species of schistosoma, infection due to liver flukes
95
Zanamivir
MOA: inhibits viral neuraminidase--prevents new viral particles from being released USES: treatment and prevention of both influenza A and B
96
Oseltamivir
MOA: inhibits viral neuraminidase--prevents new viral particles from being released USES: treatment and prevention of both influenza A and B
97
Acyclovir
MOA: monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells, so few adverse effects. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination. USES: HSV and VZV. Weak activity against EBV. No activity against CMV. Used for HSV-induced mucocutaneous and genital lesions as well as encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV. Valacyclovir, a prodrug of acyclovir, has better oral bioavailability. TOXICITY: obstructive crystalline nephropathy and acute renal failure if not adequately hydrated. When the concentration in collecting duct exceeds it's solubility. RESISTANCE: mutated viral thymidine kinase,
98
Famciclovir
MOA: monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells, so few adverse effects. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination. USES: HSV and VZV. Weak activity against EBV. No activity against CMV. Used for HSV-induced mucocutaneous and genital lesions as well as encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV. Valacyclovir, a prodrug of acyclovir, has better oral bioavailability. TOXICITY: obstructive crystalline nephropathy and acute renal failure if not adequately hydrated. When the concentration in collecting duct exceeds it's solubility. RESISTANCE: mutated viral thymidine kinase,
99
Valacyclovir
MOA: monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells, so few adverse effects. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination. USES: HSV and VZV. Weak activity against EBV. No activity against CMV. Used for HSV-induced mucocutaneous and genital lesions as well as encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV. Valacyclovir, a prodrug of acyclovir, has better oral bioavailability. TOXICITY: obstructive crystalline nephropathy and acute renal failure if not adequately hydrated. When the concentration in collecting duct exceeds it's solubility. RESISTANCE: mutated viral thymidine kinase,
100
Ganciclovir
MOA: synthetic analog of 2-deoxyguanine. Converted to ganciclovir mono phosphate by CMV during infection; subsequently, cellular kinases catalyze the formation of gancyclovir diphosphate and triphosphate--activated drug inhibits DNA polymerase and suppresses chain elongation. USES: CMV, especially in immunocompromised patients. Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability. TOXICITY: leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir. RESISTANCE: mutated CMV DNA polymerase or lack of viral kinase.
101
Foscarnet
MOA: viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase. USES: CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-resistant HSVZ TOXICITY: nephrotoxicity, electrolyte abnormalities can lead to seizures. Foscarnet is a pyrophosphate analog that can chelate calcium and cause magnesium wasting leading to decreased PTH which exacerbates hypocalcemia. (Remember dramatic decreases in magnesium inhibit PTH) RESISTANCE: mutated DNA polymerase
102
Cidofovir
MOA: preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase. USES: CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long half life. TOXICITY: nephrotoxicity (co administer with probenecid and IV saline to decrease toxicity)
103
Ribavirin
MOA: inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase USES: RSV! Chronic hepatitis C TOXICITY: hemolytic anemia. Severe teratogen
104
Atazanavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria
105
Darunavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria
106
Fosamprenavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria
107
Indinavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria
108
Lopinavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria
109
Ritonavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. Ritonavir can boost other drug concentrations by inhibiting p-450 TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria. Inhibitor of CYP-450 so increases drug concentrations of those metabolized by CYP -450.
110
Saquinavir
Protease inhibitor MOA: assembly of virions depends on HIV-1 protease, which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses. TOXICITY: hyperglycemia, GI intolerance, lipodystrophy, nephropathy, hematuria
111
Abacavir
NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleoside--needs to be phosphorylated to be active. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
112
Didanosine
NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleoside--needs to be phosphorylated to be active. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
113
Emtricitabine
NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleoside--needs to be phosphorylated to be active. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
114
Lamivudine
NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleoside--needs to be phosphorylated to be active. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
115
Stavudine
NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleoside--needs to be phosphorylated to be active. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
116
Tenofovir
NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleotide--does NOT need to be phosphorylated to be active. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
117
Zidovudine
Formerly AZT NRTI MOA: competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3' OH group). Nucleoside--needs to be phosphorylated to be active. Used for general prophylaxis and during pregnancy to decrease risk of transmission to fetus. TOXICITY: bone marrow suppression (can be reversed with granulocyte-stimulating factor and erythropoietin), peripheral neuropathy, lactic acidosis, rash, anemia, pancreatitis
118
Efavirenz
NNRTI MOA: bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides. TOXICITY: rash and hepatotoxicity are common. Vivid dreams and CNS symptoms common with efavirenz. Contraindicated in pregnancy.
119
Nevirapine
NNRTI MOA: bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides. TOXICITY: rash and hepatotoxicity are common.
120
Delavirdine
NNRTI MOA: bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides. TOXICITY: rash and hepatotoxicity are common. Contraindicated in pregnancy.
121
Raltegravir
Integrase inhibitor MOA: inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase TOXICITY: hypercholesterolemia
122
Enfuvirtide
Fusion inhibitor MOA: binds gp41 and inhibits viral entry TOXICITY: skin reaction at injection site
123
Maraviroc
Fusion inhibitor MOA: binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120 TOXICITY: skin reaction at injection site
124
Daptomycin
MOA: lipopeptide that disrupts cell membrane of gram positive cocci. USES: S. Aureus skin infections, bacteremia, endocarditis, VRE TOXICITY: myopathy, rhabdomyolysis
125
Metronidazole
MOA: forms toxic free radical metabolites on the bacterial cell that damage DNA. Bactericidal, antiprotozoal. USES: treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. Difficile). Used with a proton pump and clarithromycin for triple therapy against h. Pylori. TOXICITY: disulfiram-like reactions (severe flushing, tachycardia, hypotension) with alcohol, headache, metallic taste
126
Interferons
MOA: glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties USES: IFN-a: chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma. IFN-B: MS. IFN-gamma: chronic granulomatous disease. TOXICITY: neutropenia, myopathy
127
Ribavirin
MOA: inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase. IMP cannot be converted to GMP. USES: chronic HCV, also used in RSV (palivizumab preferred in children) TOXICITY: hemolytic anemia, severe teratogen
128
Simeprevir
MOA: HCV protease inhibitor; prevents viral replication USES: chronic HCV in combination with ribavirin and peginterferon Alfa. TOXICITY: photosensitivity reactions, rash
129
Sofosbuvir
MOA: inhibits HCV RNA-dependent RNA polymerase acting as a chain terminator USES: chronic HCV in combination with ribavirin, +/- peginterferon Alfa. TOXICITY: fatigue, headache, nausea
130
Red man syndrome
Diffuse flushing following vancomycin treatment. Cn largely prevent by pretreatment with antihistamines and slow infusion rate
131
Prophylaxis for M. Tuberculosis
Isoniazid
132
Prophylaxis for M. Avium-intracellulare
Azithromycin, rifabutin
133
Palivizumab
Monoclonal antibody against F protein of paramyxoviruses. Prevents pneumonia caused by RSV infection in premature infants.
134
Fidaxomicin
Treatment for recurrent cases of C. Difficile. Inhibits sigma subunit of RNA polymerase. Oral drug with limited systemic absorption.