FA Antimicrobials Flashcards
(185 cards)
1
Q
Penicillin G, V Mechanism
A
Bind penicillin-binding protein (transpeptidases). Block transpeptidase cross-linking of peptidoglycan. Activate autolytic enzymes.
2
Q
Prototype β-lactam
A
Penicillin G (IV and IM form), penicillin V (oral)
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.
4
Q
Penicillin G, V Toxicity
A
Hypersensitivity reactions, hemolytic anemia.
5
Q
Penicillin G, V Resistance
A
Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.
6
Q
Aminopenicillins
A
Ampicillin, amoxicillin (penicillinase-sensitive penicillins)
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.
8
Q
Ampicillin, Amoxicillin Use
A
Extended-spectrum penicillin—Haemophilus influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.
9
Q
Ampicillin, Amoxicillin Toxicity
A
Hypersensitivity reactions; rash; pseudomembranous colitis.
10
Q
Ampicillin, Amoxicillin Resistance
A
Penicillinase in bacteria (a type of β-lactamase) cleaves β-lactam ring.
11
Q
Penicillinase-resistant Penicillin
A
Oxacillin, nafcillin, dicloxacillin
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.
13
Q
Oxacillin, Nafcillin, Dicloxacillin Use
A
S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site).
14
Q
Oxacillin, Nafcillin, Dicloxacillin Toxicity
A
Hypersensitivity reactions, interstitial nephritis.
15
Q
Antipseudomonal Penicillin
A
Ticarcillin, Piperacillin
16
Q
Ticarcillin, Piperacillin Mechanism
A
Same as penicillin. Extended spectrum.
17
Q
Ticarcillin, Piperacillin Use
A
Pseudomonas spp. and gram-negative rods; susceptible to penicillinase; use with β-lactamase inhibitors
18
Q
Ticarcillin, Piperacillin Toxicity
A
Hypersensitivity reactions.
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).
20
Q
Cephalosporin Mechanism
A
β-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
21
Q
1st Generation Cephalosporins
A
Cefazolin, Cephalexin
22
Q
2nd Generation Cephalosporins
A
Cefoxitin, Cefaclor, Cefuroxime
23
Q
3rd Generation Cephalosporins
A
Ceftriaxone, Cefotaxime, Ceftazimide
24
Q
4th Generation Cephalosporins
A
Cefepime
25
5th Generation Cephalosporins
Ceftaroline
26
Cephalosporin Resistance
Do not cover LAME: Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Entercocci. Exception: ceftaroline covers MRSA.
27
1st Generation Cephalosporin Use
gram-positive cocci, Proteus mirabilis, E. coli, Klebsiella pneumoniae. Cefazolin used prior to surgery to prevent S. aureus wound infections.
1st gen: PEcK.
28
2nd Generation Cephalosporin Use
gram-positive cocci, Haemophilus influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. coli, Klebsiella pneumoniae, Serratia marcescens.
2nd gen: HEN PEcKS.
29
3rd Generation Cephalosporin Use
Serious gram-negative infections resistant to other β-lactams.
Ceftriaxone—meningitis and gonorrhea.
Ceftazidime—Pseudomonas.
30
4th Generation Cephalosporin Use
↑ activity against Pseudomonas and gram-positive organisms.
31
5th Generation Cephalosporin Use
Broad gram-positive and gram-negative organism coverage, including MRSA; does not cover Pseudomonas.
32
Cephalosporin Toxicity
Hypersensitivity reactions, vitamin K deficiency. Low cross-reactivity with penicillins. ↑ nephrotoxicity of aminoglycosides.
33
Aztreonam Mechanism
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.
34
Aztreonam Use
Gram-negative rods only—no activity against gram-positives or anaerobes. For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides.
35
Axtreonam Toxicity
Usually nontoxic; occasional GI upset.
36
Carbapenems
Imipenem, Meropenem, Ertapenem, Doripenem
37
Imipenem, Meropenem, Ertapenem, Doripenem Mechanism
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.
38
Imipenem, Meropenem, Ertapenem, Doripenem Use
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.
39
Imipenem, Meropenem, Ertapenem, Doripenem Toxicity
GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels.
40
Vancomycin Mechanism
Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal.
41
Vancomycin Use
Gram-positive only—serious, multidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)
42
Vancomycin Toxicity
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).
43
Vancomycin Resistance
Occurs in bacteria via amino acid modification of D-ala D-ala to D-ala D-lac.
44
Aminoglycosides
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
45
Aminoglycoside Mechanism
Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA. Also block translocation. Require O2 for uptake; therefore ineffective against anaerobes.
46
Aminoglycoside Use
Severe gram-negative rod infections. Synergistic with β-lactam antibiotics.
Neomycin for bowel surgery.
47
Aminoglycoside Toxicity
Nephrotoxicity (especially when used with cephalosporins), Neuromuscular blockade, Ototoxicity (especially when used with loop diuretics). Teratogen.
48
Aminoglycoside Resistance
Bacterial transferase enzymes inactivate the drug by acetylation.
49
Tetracyclines
Tetracycline, doxycycline, minocycline
50
Tetracycline Mechanism
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.
51
Tetracycline Use
Borrelia burgdorferi, M. pneumoniae. Drug's ability to accumulate intracellularly makes it very effective against Rickettsia and Chlamydia. Also used to treat acne.
52
Tetracycline Toxicity
GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy.
53
Tetracycline Resistance
↓ uptake or ↑ efflux out of bacterial cells by plasmid-encoded transport pumps.
54
Macrolides
Azithromycin, clarithromycin, erythromycin
55
Macrolide Mechanism
Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic.
56
Macrolide Use
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella), STDs (for Chlamydia), and gram positive cocci (streptococcal infections in patients allergic to penicillin).
57
Macrolide Toxicity
MACRO: Gastrointestinal Motility issues, Arrhythmia caused by prolonged QT, acute Cholestatic hepatitis, Rash, eOsinophilia.
Increases serum concentration of theophyllines, oral anticoagulants.
58
Macrolide Resistance
Methylation of 23S rRNA-binding site prevents binding of drug.
59
Chloramphenicol Mechanism
Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic.
60
Chloramphenicol Use
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.
61
Chloramphenicol Toxicity
Anemia (dose dependent), aplastic anemia (dose dependent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase).
62
Chloramphenicol Resistance
Plasmid-encoded acetyltransferase inactivates the drug.
63
Clindamycin Mechanism
Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic.
64
Clindamycin Use
```
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).
```
65
Clindamycin Toxicity
Pseudomembranous colitis (C. difficile overgrowth), fever, diarrhea.
66
Sulfonamides
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
67
Sulfonamide Mechanism
Inhibit folate synthesis. Para-aminobenzoic acid (PABA) antimetabolites inhibit dihydropteroate synthase. Bacteriostatic.
68
Sulfonamide Use
Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas or SMX for simple UTI.
69
Sulfonamide Toxicity
Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (e.g. warfarin).
70
Sulfonamide Resistance
Altered enzyme (bacterial dihydropteroate synthase), ↓ uptake, or ↑ PABA synthesis.
71
Trimethoprim Mechanism
Inhibits bacterial dihydrofolate reductase. Bacteriostatic.
72
Trimethoprim Use
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.
73
Trimethoprim Toxicity
Megaloblastic anemia, leukopenia, granulocytopenia. (May alleviate with supplemental folic acid).
TMP: Treats Marrow Poorly
74
Fluoroquinolones
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, sparfloxacin, moxifloxacin, gemifloxacin, enoxacin (fluoroquinolones), nalidixic acid (a quinolone).
75
Fluoroquinolone Mechanism
Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV. Bactericidal. Must not be taken with antacids.
76
Fluoroquinolone Use
Gram-negative rods of urinary and GI tracts (including Pseudomonas), Neisseria, some gram-positive organisms.
77
Fluoroquinolone Toxicity
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
Fluoroquinolone Resistance
Chromosome-encoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps.
79
Metronidazole Mechanism
Forms free radical toxic metabolites in the bacterial cell that damage DNA. Bactericidal, antiprotozoal.
80
Metronidazole Use
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
Metronidazole Toxicity
Disulfiram-like reaction (severe flushing, tachycardia, hypotension) with alcohol; headache, metallic taste.
82
M. tuberculosis Prophylaxis
Isoniazid
83
M. tuberculosis Treatment
Rifampin, Isoniazid, Pyrazinamide, Ethambutol
84
M. avium-intracellulare Prophylaxis
Azithromycin, rifabutin
85
M. avium-intracellulare Treatment
More drug resistant than M. tuberculosis. Azithromycin or clarithromycin + ethambutol. Can add rifabutin or ciprofloxacin.
86
M. leprae Treatment
Long-term treatment with dapsone and rifampin for tuberculoid form. Add clofazimine for lepromatous form.
87
Isoniazid (INH) Mechanism
↓ synthesis of mycolic acids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite.
88
Isoniazid (INH) Use
Mycobacterium tuberculosis. The only agent used as solo prophylaxis against TB.
Different half-lives in fast vs. slow acetylators.
89
Isoniazid Toxicity
Neurotoxicity, hepatotoxicity. Pyridoxine (vitamin B6) can prevent neurotoxicity, lupus.
90
Rifamycins
Rifampin, rifabutin
91
Rifampin, Rifabutin Mechanism
Inhibits DNA-dependent RNA polymerase
92
Rifampin, Rifabutin Use
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
Rifampin, Rifabutin Toxicity
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
Pyrazinamide Mechanism
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
Pyrazinamide Use
Mycobacterium tuberculosis
96
Pyrazinamide Toxicity
Hyperuricemia, hepatotoxicity.
97
Ethambutol Mechanism
↓ carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase.
98
Ethambutol Use
Mycobacterium tuberculosis.
99
Ethambutol Toxicity
Optic neuropathy (red-green color blindness).
100
Prophylaxis: Endocarditis with surgical or dental procedures
Penicillins
101
Prophylaxis: Gonorrhea
Ceftriaxone
102
Prophylaxis: History of recurrent UTIs
TMP-SMX
103
Prophylaxis: Meningococcal infection
Ciprofloxacin (drug of choice), rifampin for
| children
104
Prophylaxis: Pregnant woman carrying group B strep
Ampicillin
105
Prophylaxis: Prevention of gonococcal or chlamydial conjunctivitis in newborn
Erythromycin ointment
106
Prophylaxis: Prevention of postsurgical infection due to S. aureus
Cefazolin
107
Prophylaxis: Prophylaxis of strep pharyngitis in child with prior rheumatic fever
Oral penicillin
108
Prophylaxis: Syphilis
Benzathine penicillin G
109
Prophylaxis: HIV CD4 < 200 cells/mm³
TMP-SMX to prevent Pneumocystis pneumonia
110
Prophylaxis: HIV CD4 < 100 cells/mm³
TMP-SMX to prevent Pneumocystis pneumonia and Toxoplasmosis
111
Prophylaxis: HIV CD4 < 50 cells/mm³
Mycobacterium avium complex
112
Amphotericin B Mechanism
Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes.
113
Amphotericin B Use
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
Amphotericin B Toxicity
Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”). Hydration ↓ nephrotoxicity. Liposomal amphotericin ↓ toxicity.
115
Nystatin Mechanism
Same as amphotericin B. Topical form because too toxic for systemic use.
116
Nystatin Use
"Swish and swallow" for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.
117
Azoles
Fluconazole, ketoconazole, clotrimazole, miconazole, intraconazole, voriconazole.
118
Azole Mechanism
Inhibit fungal sterol (ergosterol) synthesis, by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol.
119
Azole Use
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
Azole Toxicity
Testosterone synthesis inhibition (gynecomastia, esp. with ketoconazole), liver dysfunction (inhibits cytochrome P-450).
121
Flucytosine Mechanism
Inhibits DNA and RNA biosynthesis by conversion to 5-fluorouracil by cytosine deaminase.
122
Flucytosine Use
Systemic fungal infections (esp. meningitis caused by Cryptococcus) in combination with amphotericin B.
123
Flucytosine Toxicity
Bone marrow suppression.
124
Echinocandins
Caspofungin, micafungin, anidulafungin.
125
Caspofungin, Micafungin, Anidulafungin Mechanism
Inhibits cell wall synthesis by inhibiting synthesis of β-glucan.
126
Caspofungin, Micafungin, Anidulafungin Use
Invasive aspergillosis, Candida.
127
Caspofungin, Micafungin, Anidulafungin Toxicity
GI upset, flushing (by histamine release).
128
Terbinafine Mechanism
Inhibits the fungal enzyme squalene epoxidase.
129
Terbinafine Use
Dermatophytoses (especially onychomycosis—fungal infection of finger or toe nails).
130
Terbinafine Toxicity
GI upset, headaches, hepatotoxicity, taste disturbance.
131
Griseofulvin Mechanism
Interferes with microtubule function; disrupts mitosis. Deposits in keratin-containing tissues (e.g., nails).
132
Griseofulvin Use
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).
133
Griseofulvin Toxicity
Teratogenic, carcinogenic, confusion, headaches, ↑ P-450 and warfarin metabolism.
134
Antiprotozoan Therapy
Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei), nifurtimox (T. cruzi), sodium stibogluconate (leishmaniasis).
135
Chloroquine Mechanism
Blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia.
136
Chloroquine Use
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
Chloroquine Toxicity
Retinopathy; pruritus (especially in dark-skinned individuals).
138
Antihelminthic Therapy
Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel; immobilize helminths. Use praziquantel against flukes (trematodes) such as Schistosoma.
139
Zanamivir, Oseltamivir Mechanism
Inhibit influenza neuraminidase → ↓ the release of progeny virus.
140
Zanamivir, Oseltamivir Use
Treatment and prevention of both influenza A and B.
141
Ribavirin Mechanism
Inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase.
142
Ribavirin Use
RSV, chronic hepatitis C.
143
Ribavirin Toxicity
Hemolytic anemia. Severe teratogen.
144
Acyclovir, Famciclovir, Valacyclovir Mechanism
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
Acyclovir, Famciclovir, Valacyclovir Use
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
Acyclovir, Famciclovir, Valacyclovir Toxicity
Obstructive crystalline nephropathy and acute renal failure if not adequately hydrated.
147
Acyclovir, Famciclovir, Valacyclovir Resistance
Mutated viral thymidine kinase.
148
Ganciclovir Mechanism
5′-monophosphate formed by a CMV viral kinase. Guanosine analog. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase.
149
Ganciclovir Use
CMV, especially in immunocompromised patients. Valganciclovir, a prodrug of ganciclovir, has better oral bioavailability.
150
Ganciclovir Toxicity
Leukopenia, neutropenia, thrombocytopenia, renal toxicity. More toxic to host enzymes than acyclovir.
151
Ganciclovir Resistance
Mutated CMV DNA polymerase or lack of viral kinase.
152
Foscarnet
Viral DNA polymerase inhibitor that binds to the pyrophosphate-binding site of the enzyme. Does not require activation by viral kinase.
153
Foscarnet
CMV retinitis in immunocompromised patients when ganciclovir fails; acyclovir-resistant HSV.
154
Foscarnet
Nephrotoxicity.
155
Foscarnet
Mutated DNA polymerase.
156
Cidofovir Mechanism
Preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase.
157
Cidofovir Use
CMV retinitis in immunocompromised patients; acyclovir-resistant HSV. Long half-life.
158
Cidofovir Toxicity
Nephrotoxicity (coadminister with probenecid and IV saline to ↓ toxicity).
159
HIV Therapy
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
Protease Inhibitors
Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir
161
Protease Inhibitor Mechanism
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
Protease Inhibitor Toxicity
Hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy.
Nephropathy, hematuria (indinavir).
163
Nucleotide Reverse Transcriptase Inhibitors (NRTIs)
Abacavir (ABC), Didanosine (ddI), Emtricitabine (FTC), Lamivudine (3TC), Stavudine (d4T), Tenofovir (TDF), Zidovudine (ZDV, formerly AZT)
164
NRTI Mechanism
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
NRTI Toxicity
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
Non-nucleotide Reverse Transcriptase Inhibitors (NNRTIs)
Efavirenz, Nevirapine, Delavirdine
167
NNRTI Mechanism
Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides.
168
NNRTI Toxicity
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
Integrase inhibitors
Raltegravir
170
Raltegravir Mechanism
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase.
171
Raltegravir Toxicity
Hypercholesterolemia.
172
Fusion Inhibitors
Enfuvirtide, Maraviroc
173
Enfuvirtide Mechanism
Binds gp41, inhibiting viral entry.
174
Enfuviride Toxicity
Skin reaction at injection sites
175
Maraviroc Mechanism
Binds CCR-5 on surface of T cells/monocytes, inhibiting interaction with gp120.
176
Interferon Mechanism
Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties.
177
Interferon Use
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
Interferon Toxicity
Neutropenia, myopathy.
179
Pregnancy Adverse Effect: Kernicterus
Sulfonamides
180
Pregnancy Adverse Effect: Ototoxicity
Aminoglycosides
181
Pregnancy Adverse Effect: Cartilage Damage
Fluoroquinolones
182
Pregnancy Adverse Effect: Embryotoxic
Clarithromycin
183
Pregnancy Adverse Effect: Discolored Teeth, Inhibition of Bone Growth
Tetracyclines
184
Pregnancy Adverse Effect: Teratogenic
Ribavirin (antiviral), griseofulvin (antifungal)
185
Pregnancy Adverse Effect: “Gray Baby”
Chloramphenicol
