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Pharmacology > FA Antimicrobials > Flashcards

FA Antimicrobials Flashcards

1
Q

Penicillin G, V Mechanism

A

Bind penicillin-binding protein (transpeptidases). Block transpeptidase cross-linking of peptidoglycan. Activate autolytic enzymes.

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2
Q

Prototype β-lactam

A

Penicillin G (IV and IM form), penicillin V (oral)

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3
Q

Penicillin G, V Use

A

Mostly used for gram-positive organisms (S. pneumoniae, 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.

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4
Q

Penicillin G, V Toxicity

A

Hypersensitivity reactions, hemolytic anemia.

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5
Q

Penicillin G, V Resistance

A

Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

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6
Q

Aminopenicillins

A

Ampicillin, amoxicillin (penicillinase-sensitive penicillins)

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7
Q

Ampicillin, Amoxicillin Mechanism

A

Same as penicillin. Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against β-lactamase.
AmOxicillin has greater Oral bioavailability than ampicillin.

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8
Q

Ampicillin, Amoxicillin Use

A

Extended-spectrum penicillin—Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.

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9
Q

Ampicillin, Amoxicillin Toxicity

A

Hypersensitivity reactions; rash; pseudomembranous colitis.

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10
Q

Ampicillin, Amoxicillin Resistance

A

Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.

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11
Q

Penicillinase-resistant Penicillin

A

Oxacillin, nafcillin, dicloxacillin

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12
Q

Oxacillin, Nafcillin, Dicloxacillin Mechanism

A

Same as penicillin. Narrow spectrum; penicillinase resistant because bulky R group blocks access of β-lactamase to β-lactam ring.

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13
Q

Oxacillin, Nafcillin, Dicloxacillin Use

A

S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).

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14
Q

Oxacillin, Nafcillin, Dicloxacillin Toxicity

A

Hypersensitivity reactions, interstitial nephritis.

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15
Q

Antipseudomonal Penicillin

A

Ticarcillin, Piperacillin

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16
Q

Ticarcillin, Piperacillin Mechanism

A

Same as penicillin. Extended spectrum.

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17
Q

Ticarcillin, Piperacillin Use

A

Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with β-lactamase inhibitors

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18
Q

Ticarcillin, Piperacillin Toxicity

A

Hypersensitivity reactions.

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19
Q

β-lactamase Inhibitors

A

Include Clavulanic acid, sulbactam, tazobactam. Often added to penicillin antibiotics to protect the antibiotic from destruction by β-lactamase (penicillinase).

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20
Q

Cephalosporin Mechanism

A

β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.

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21
Q

1st Generation Cephalosporins

A

Cefazolin, Cephalexin

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22
Q

2nd Generation Cephalosporins

A

Cefoxitin, Cefaclor, Cefuroxime

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23
Q

3rd Generation Cephalosporins

A

Ceftriaxone, Cefotaxime, Ceftazimide

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24
Q

4th Generation Cephalosporins

A

Cefepime

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25
Q

5th Generation Cephalosporins

A

Ceftaroline

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26
Q

Cephalosporin Resistance

A

Do not cover LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Entercocci. Exception: ceftaroline covers MRSA.

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27
Q

1st Generation Cephalosporin Use

A

gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections.
1st gen: PEcK.

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28
Q

2nd Generation Cephalosporin Use

A

gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
2nd gen: HEN PEcKS.

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29
Q

3rd Generation Cephalosporin Use

A

Serious gram-negative infections resistant to other β-lactams.
Ceftriaxone—meningitis and gonorrhea.
Ceftazidime—Pseudomonas.

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30
Q

4th Generation Cephalosporin Use

A

↑ activity against Pseudomonas and gram-positive organisms.

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31
Q

5th Generation Cephalosporin Use

A

Broad gram-positive and gram-negative organism coverage, including MRSA; does not cover Pseudomonas.

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32
Q

Cephalosporin Toxicity

A

Hypersensitivity reactions, vitamin K deficiency. Low cross-reactivity with penicillins. ↑ nephrotoxicity of aminoglycosides.

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33
Q

Aztreonam Mechanism

A

A monobactam; resistant to β-lactamases. Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3. Synergistic with aminoglycosides. No cross-allergenicity with penicillins.

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34
Q

Aztreonam Use

A

Gram-negative rods only—no activity against gram-positives or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.

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35
Q

Axtreonam Toxicity

A

Usually nontoxic; occasional GI upset.

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36
Q

Carbapenems

A

Imipenem, Meropenem, Ertapenem, Doripenem

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37
Q

Imipenem, Meropenem, Ertapenem, Doripenem Mechanism

A

Imipenem is a broad-spectrum, β-lactamase– resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to ↓ inactivation of drug in renal tubules.
Newer carbapenems include ertapenem (limited Pseudomonas coverage) and doripenem.

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38
Q

Imipenem, Meropenem, Ertapenem, Doripenem Use

A

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. Meropenem has a ↓ risk of seizures and is stable to dehydropeptidase I.

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39
Q

Imipenem, Meropenem, Ertapenem, Doripenem Toxicity

A

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

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40
Q

Vancomycin Mechanism

A

Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal.

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41
Q

Vancomycin Use

A

Gram-positive only—serious, multidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)

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42
Q

Vancomycin Toxicity

A

Well tolerated in general—but NOT trouble free. Nephrotoxicity, Ototoxicity, Thrombophlebitis,
diffuse flushing—red man syndrome (can largely prevent by pretreatment with antihistamines
and slow infusion rate).

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43
Q

Vancomycin Resistance

A

Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.

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44
Q

Aminoglycosides

A

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

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45
Q

Aminoglycoside Mechanism

A

Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation. Require O2 for uptake; therefore ineffective against anaerobes.

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46
Q

Aminoglycoside Use

A

Severe gram-negative rod infections. Synergistic with β-lactam antibiotics.
Neomycin for bowel surgery.

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47
Q

Aminoglycoside Toxicity

A

Nephrotoxicity (especially when used with cephalosporins), Neuromuscular blockade, Ototoxicity (especially when used with loop diuretics). Teratogen.

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48
Q

Aminoglycoside Resistance

A

Bacterial transferase enzymes inactivate the drug by acetylation.

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49
Q

Tetracyclines

A

Tetracycline, doxycycline, minocycline

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50
Q

Tetracycline Mechanism

A

Bacteriostatic; bind to 30S and prevent 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 (Ca2+), antacids (Ca2+ and Mg2+), or iron-containing preparations because divalent cations inhibit its absorption in the gut.

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51
Q

Tetracycline Use

A

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

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52
Q

Tetracycline Toxicity

A

GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy.

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53
Q

Tetracycline Resistance

A

↓ uptake or ↑ efflux out of bacterial cells by plasmid-encoded transport pumps.

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54
Q

Macrolides

A

Azithromycin, clarithromycin, erythromycin

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55
Q

Macrolide Mechanism

A

Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.

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56
Q

Macrolide Use

A

Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram positive cocci (streptococcal infections in patients allergic to penicillin).

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57
Q

Macrolide Toxicity

A

MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophilia.
Increases serum concentration of theophyllines, oral anticoagulants.

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58
Q

Macrolide Resistance

A

Methylation of 23S rRNA-binding site prevents binding of drug.

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59
Q

Chloramphenicol Mechanism

A

Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.

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60
Q

Chloramphenicol Use

A

Meningitis (Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae) and Rocky Mountain spotted fever (Rickettsia rickettsii).
Limited use owing to toxicities but often still used in developing countries because of low cost.

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61
Q

Chloramphenicol Toxicity

A

Anemia (dose dependent), aplastic anemia (dose dependent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase).

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62
Q

Chloramphenicol Resistance

A

Plasmid-encoded acetyltransferase inactivates the drug.

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63
Q

Clindamycin Mechanism

A

Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.

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64
Q

Clindamycin Use

A 
Anaerobic infections (e.g. Bacteroides spp., Clostridium perfringens) in aspiration pneumonia, lung abscesses, and oral infections. Also effective against invasive Group A streptococcal (GAS) infection.
Anaerobes above the diaphragm vs. metronidazole (anaerobic infections below diaphragm).
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65
Q

Clindamycin Toxicity

A

Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea.

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66
Q

Sulfonamides

A

Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine

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67
Q

Sulfonamide Mechanism

A

Inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic.

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68
Q

Sulfonamide Use

A

Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.

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69
Q

Sulfonamide Toxicity

A

Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. warfarin).

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70
Q

Sulfonamide Resistance

A

Altered enzyme (bacterial dihydropteroate synthase), ↓ uptake, or ↑ PABA synthesis.

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71
Q

Trimethoprim Mechanism

A

Inhibits bacterial dihydrofolate reductase. Bacteriostatic.

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72
Q

Trimethoprim Use

A

Used in combination with sulfonamides (TMP-SMX), causing sequential block of folate synthesis. Combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis.

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73
Q

Trimethoprim Toxicity

A

Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folic acid).
TMP: Treats Marrow Poorly

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74
Q

Fluoroquinolones

A

Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, enoxacin (fluoroquinolones), nalidixic acid (a quinolone).

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75
Q

Fluoroquinolone Mechanism

A

Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV. Bactericidal. Must not be taken with antacids.

76
Q

Fluoroquinolone Use

A

Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms.

77
Q

Fluoroquinolone Toxicity

A

GI upset, superinfections, skin rashes, headache, dizziness. Less commonly, can cause tendonitis, tendon rupture, leg cramps, and myalgias. Contraindicated in pregnant women, nursing mothers, and children under 18 years old due to possible damage to cartilage. Some may cause prolonged QT interval. May cause tendon rupture in people > 60 years old and in patients taking prednisone.

78
Q

Fluoroquinolone Resistance

A

Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.

79
Q

Metronidazole Mechanism

A

Forms free radical toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.

80
Q

Metronidazole Use

A

Treats Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C. difficile). Used with a proton pump inhibitor and clarithromycin for “triple therapy” against H. pylori.
Treats anaerobic infections below the diaphragm vs. clindamycin (anaerobic infections above the diaphragm).

81
Q

Metronidazole Toxicity

A

Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; headache, metallic taste.

82
Q

M. tuberculosis Prophylaxis

A

Isoniazid

83
Q

M. tuberculosis Treatment

A

Rifampin, Isoniazid, Pyrazinamide, Ethambutol

84
Q

M. avium-intracellulare Prophylaxis

A

Azithromycin, rifabutin

85
Q

M. avium-intracellulare Treatment

A

More drug resistant than M. tuberculosis. Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin.

86
Q

M. leprae Treatment

A

Long-term treatment with dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form.

87
Q

Isoniazid (INH) Mechanism

A

↓ synthesis of mycolic acids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite.

88
Q

Isoniazid (INH) Use

A

Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.
Different half-lives in fast vs. slow acetylators.

89
Q

Isoniazid Toxicity

A

Neurotoxicity, hepatotoxicity. Pyridoxine (vitamin B6) can prevent neurotoxicity, lupus.

90
Q

Rifamycins

A

Rifampin, rifabutin

91
Q

Rifampin, Rifabutin Mechanism

A

Inhibits DNA-dependent RNA polymerase

92
Q

Rifampin, Rifabutin Use

A

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.

93
Q

Rifampin, Rifabutin Toxicity

A

Minor hepatotoxicity and drug interactions (↑ P-450); orange body fluids (nonhazardous side effect). Rifabutin favored over rifampin in patients with HIV infection due to less cytochrome P-450 stimulation.

94
Q

Pyrazinamide Mechanism

A

Mechanism uncertain. Thought to acidify intracellular environment via conversion to pyrazinoic acid. Effective in acidic pH of phagolysosomes, where TB engulfed by macrophages is found.

95
Q

Pyrazinamide Use

A

Mycobacterium tuberculosis

96
Q

Pyrazinamide Toxicity

A

Hyperuricemia, hepatotoxicity.

97
Q

Ethambutol Mechanism

A

↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.

98
Q

Ethambutol Use

A

Mycobacterium tuberculosis.

99
Q

Ethambutol Toxicity

A

Optic neuropathy (red-green color blindness).

100
Q

Prophylaxis: Endocarditis with surgical or dental procedures

A

Penicillins

101
Q

Prophylaxis: Gonorrhea

A

Ceftriaxone

102
Q

Prophylaxis: History of recurrent UTIs

A

TMP-SMX

103
Q

Prophylaxis: Meningococcal infection

A

Ciprofloxacin (drug of choice), rifampin for

children

104
Q

Prophylaxis: Pregnant woman carrying group B strep

A

Ampicillin

105
Q

Prophylaxis: Prevention of gonococcal or chlamydial conjunctivitis in newborn

A

Erythromycin ointment

106
Q

Prophylaxis: Prevention of postsurgical infection due to S. aureus

A

Cefazolin

107
Q

Prophylaxis: Prophylaxis of strep pharyngitis in child with prior rheumatic fever

A

Oral penicillin

108
Q

Prophylaxis: Syphilis

A

Benzathine penicillin G

109
Q

Prophylaxis: HIV CD4 < 200 cells/mm³

A

TMP-SMX to prevent Pneumocystis pneumonia

110
Q

Prophylaxis: HIV CD4 < 100 cells/mm³

A

TMP-SMX to prevent Pneumocystis pneumonia and Toxoplasmosis

111
Q

Prophylaxis: HIV CD4 < 50 cells/mm³

A

Mycobacterium avium complex

112
Q

Amphotericin B Mechanism

A

Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes.

113
Q

Amphotericin B Use

A

Serious, systemic mycoses. Cryptococcus (amphotericin B with/without flucytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis. Supplement K+ and Mg2+ because of altered renal tubule permeability.

114
Q

Amphotericin B Toxicity

A

Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”). Hydration ↓ nephrotoxicity. Liposomal amphotericin ↓ toxicity.

115
Q

Nystatin Mechanism

A

Same as amphotericin B. Topical form because too toxic for systemic use.

116
Q

Nystatin Use

A

“Swish and swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.

117
Q

Azoles

A

Fluconazole, ketoconazole, clotrimazole, miconazole, intraconazole, voriconazole.

118
Q

Azole Mechanism

A

Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol.

119
Q

Azole Use

A

Local and less serious systemic mycoses. Fluconazole for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types. Itraconazole for Blastomyces, Coccidioides, Histoplasma. Clotrimazole and miconazole for topical fungal infections.

120
Q

Azole Toxicity

A

Testosterone synthesis inhibition (gynecomastia, esp. with ketoconazole), liver dysfunction (inhibits cytochrome P-450).

121
Q

Flucytosine Mechanism

A

Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase.

122
Q

Flucytosine Use

A

Systemic fungal infections (esp. meningitis caused by Cryptococcus) in combination with amphotericin B.

123
Q

Flucytosine Toxicity

A

Bone marrow suppression.

124
Q

Echinocandins

A

Caspofungin, micafungin, anidulafungin.

125
Q

Caspofungin, Micafungin, Anidulafungin Mechanism

A

Inhibits cell wall synthesis by inhibiting synthesis of β-glucan.

126
Q

Caspofungin, Micafungin, Anidulafungin Use

A

Invasive aspergillosis, Candida.

127
Q

Caspofungin, Micafungin, Anidulafungin Toxicity

A

GI upset, flushing (by histamine release).

128
Q

Terbinafine Mechanism

A

Inhibits the fungal enzyme squalene epoxidase.

129
Q

Terbinafine Use

A

Dermatophytoses (especially onychomycosis—fungal infection of finger or toe nails).

130
Q

Terbinafine Toxicity

A

GI upset, headaches, hepatotoxicity, taste disturbance.

131
Q

Griseofulvin Mechanism

A

Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g., nails).

132
Q

Griseofulvin Use

A

Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).

133
Q

Griseofulvin Toxicity

A

Teratogenic, carcinogenic, confusion, headaches, ↑ P-450 and warfarin metabolism.

134
Q

Antiprotozoan Therapy

A

Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei), nifurtimox (T. cruzi), sodium stibogluconate (leishmaniasis).

135
Q

Chloroquine Mechanism

A

Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia.

136
Q

Chloroquine Use

A

Treatment of plasmodial species other than P. falciparum (frequency of resistance in P. falciparum is too high). Resistance due to membrane pump that ↓ intracellular concentration of drug. Treat P. falciparum with artemether/lumefantrine or atovaquone/proguanil. For life-threatening malaria, use quinidine in U.S. (quinine elsewhere) or artesunate.

137
Q

Chloroquine Toxicity

A

Retinopathy; pruritus (especially in dark-skinned individuals).

138
Q

Antihelminthic Therapy

A

Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel; immobilize helminths. Use praziquantel against flukes (trematodes) such as Schistosoma.

139
Q

Zanamivir, Oseltamivir Mechanism

A

Inhibit influenza neuraminidase → ↓ the release of progeny virus.

140
Q

Zanamivir, Oseltamivir Use

A

Treatment and prevention of both influenza A and B.

141
Q

Ribavirin Mechanism

A

Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.

142
Q

Ribavirin Use

A

RSV, chronic hepatitis C.

143
Q

Ribavirin Toxicity

A

Hemolytic anemia. Severe teratogen.

144
Q

Acyclovir, Famciclovir, Valacyclovir Mechanism

A

Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells → few adverse effects. Guanosine analog. Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination.

145
Q

Acyclovir, Famciclovir, Valacyclovir Use

A

HSV and VZV. Weak activity against EBV. No activity against CMV. Used for HSV-induced
mucocutaneous and genital lesions as well as for encephalitis. Prophylaxis in immunocompromised patients. No effect on latent forms of HSV and VZV. Valacyclovir, a prodrug of acyclovir, has better oral bioavailability.
For herpes zoster, use a related agent, famciclovir.

146
Q

Acyclovir, Famciclovir, Valacyclovir Toxicity

A

Obstructive crystalline nephropathy and acute renal failure if not adequately hydrated.

147
Q

Acyclovir, Famciclovir, Valacyclovir Resistance

A

Mutated viral thymidine kinase.

148
Q

Ganciclovir Mechanism

A

5′-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase.

149
Q

Ganciclovir Use

A

CMV, especially in immunocompromised patients. Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability.

150
Q

Ganciclovir Toxicity

A

Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.

151
Q

Ganciclovir Resistance

A

Mutated CMV DNA polymerase or lack of viral kinase.

152
Q

Foscarnet

A

Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase.

153
Q

Foscarnet

A

CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-resistant HSV.

154
Q

Foscarnet

A

Nephrotoxicity.

155
Q

Foscarnet

A

Mutated DNA polymerase.

156
Q

Cidofovir Mechanism

A

Preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase.

157
Q

Cidofovir Use

A

CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long half-life.

158
Q

Cidofovir Toxicity

A

Nephrotoxicity (coadminister with probenecid and IV saline to ↓ toxicity).

159
Q

HIV Therapy

A

Highly active antiretroviral therapy (HAART): initiated when patients present with AIDS-defining illness, low CD4 cell counts (< 500 cells/mm3), or high viral load. Regimen consists of 3 drugs to
prevent resistance:
[2 nucleoside reverse transcriptase inhibitors (NRTIs)] + [1 non-nucleoside reverse transcriptase inhibitor (NNRTI) OR 1 protease inhibitor OR 1
integrase inhibitor]

160
Q

Protease Inhibitors

A

Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir

161
Q

Protease Inhibitor Mechanism

A

Assembly of virions depends on HIV-1 protease (pol gene), 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 cytochrome P-450.
All protease inhibitors end in -navir.

162
Q

Protease Inhibitor Toxicity

A

Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy.
Nephropathy, hematuria (indinavir).

163
Q

Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

A

Abacavir (ABC), Didanosine (ddI), Emtricitabine (FTC), Lamivudine (3TC), Stavudine (d4T), Tenofovir (TDF), Zidovudine (ZDV, formerly AZT)

164
Q

NRTI Mechanism

A

Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3′ OH group). Tenofovir is a nucleoTide; the others are nucleosides and need to be phosphorylated to be active.
ZDV is used for general prophylaxis and during pregnancy to ↓ risk of fetal transmission.

165
Q

NRTI Toxicity

A

Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor [G-CSF] and erythropoietin), peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), anemia (ZDV), pancreatitis (didanosine).

166
Q

Non-nucleotide Reverse Transcriptase Inhibitors (NNRTIs)

A

Efavirenz, Nevirapine, Delavirdine

167
Q

NNRTI Mechanism

A

Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides.

168
Q

NNRTI Toxicity

A

Rash and hepatotoxicity are common to all NNRTIs. Vivid dreams and CNS symptoms are common with efavirenz. Delavirdine and efavirenz are contraindicated in pregnancy.

169
Q

Integrase inhibitors

A

Raltegravir

170
Q

Raltegravir Mechanism

A

Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.

171
Q

Raltegravir Toxicity

A

Hypercholesterolemia.

172
Q

Fusion Inhibitors

A

Enfuvirtide, Maraviroc

173
Q

Enfuvirtide Mechanism

A

Binds gp41, inhibiting viral entry.

174
Q

Enfuviride Toxicity

A

Skin reaction at injection sites

175
Q

Maraviroc Mechanism

A

Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.

176
Q

Interferon Mechanism

A

Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties.

177
Q

Interferon Use

A

IFN-α: chronic hepatitis B and C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma, malignant melanoma.
IFN-β: multiple sclerosis.
IFN-γ: chronic granulomatous disease.

178
Q

Interferon Toxicity

A

Neutropenia, myopathy.

179
Q

Pregnancy Adverse Effect: Kernicterus

A

Sulfonamides

180
Q

Pregnancy Adverse Effect: Ototoxicity

A

Aminoglycosides

181
Q

Pregnancy Adverse Effect: Cartilage Damage

A

Fluoroquinolones

182
Q

Pregnancy Adverse Effect: Embryotoxic

A

Clarithromycin

183
Q

Pregnancy Adverse Effect: Discolored Teeth, Inhibition of Bone Growth

A

Tetracyclines

184
Q

Pregnancy Adverse Effect: Teratogenic

A

Ribavirin (antiviral), griseofulvin (antifungal)

185
Q

Pregnancy Adverse Effect: “Gray Baby”

A

Chloramphenicol

Pharmacology (14 decks)

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