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Antimicrobials Flashcards

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1
Q

Penicillin G, V

MOA

A

> Binds penicillin-binding proteins (transpeptidases) and block them from cross-linking w/ peptidoglycan wall – loss of rigidity, susceptible to rupture.
Activates autolytic enzymes.

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2
Q

Penicillin G, V

Clinical use

A

> Bactericidal, Penicillinase-sensitive.
G(+) organisms (S. pneumoniae, GAS, Actinomyces).
G(-) cocci (N. meningitidis).
Spirochetes (T. pallidum).

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3
Q

Amoxicillin, Ampicillin

MOA

A

> Extended-spectrum, Bactericidal, Penicillinase-sensitive.
Binds to transpeptidases and blocks transpeptidase cross-linking w/ cell wall – susceptible to rupture.
Activates autolytic enzymes.

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4
Q 
Amoxicillin, Ampicillin
Clinical use (HHEELPSS)
A

> H. influenzae, H. pylori, E. coli, Enterococci, L. monocytogenes, Proteus, Salmonella, Shigella.
Combine w/ Clavulanic acid – protect against B-lactamase (co-amoxiclav).

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5
Q

Amoxicillin, Ampicillin

Toxicity

A

Pseudomembranous colitis (ex. C. difficile)

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6
Q

Dicloxacillin, Nafcillin, Oxacillin

MOA

A

> Narrow spectrum, Bactericidal, Penicillinase-resistant.
Binds to pencillin-binding protein and prevents them from cross-linking w/ cell wall – prone to rupture.
Activates autolytic enzymes.

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7
Q

Dicloxacillin, Nafcillin, Oxacillin

[Clinical use, Toxicity]

A

> S. aureus (except MRSA due to altered penicillin-binding protein site).
Toxicity: interstitial nephritis.

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8
Q

Piperacillin, Ticarcillin

MOA

A

> Antipseudomonals, Extended spectrum. Penicillinase-sensitive.
Binds to transpeptidases and prevents them from cross-linking w/ cell wall – prone to rupture.
Activates autolytic enzymes.

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9
Q

Piperacillin, Ticarcillin

Clinical use

A 
Pseudomonas
G(-) rods
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10
Q

Beta-lactamase inhibitors (CAST)

A

Clavulanic acid
Sulbactam
Tazobactam
*Add to penicillin antibiotics

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11
Q

Cephalosporins

MOA

A

> B-lactam drugs – Inhibit cell wall synthesis

*Less susceptible to Penicillinase, unless structural change in binding site.

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12
Q

Cephalosporins

Toxicity

A 
Autoimmune hemolytic anemia.
Vit K deficiency.
Disulfiram-like reactions.
Cross-reaction w/ penicillins.
Inc. nephrotoxicity w/ aminoglycosides.
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13
Q

Cephalosporins don’t cover w/c organisms? (LAME)

A

Listeria
Atypicals (Chlamydia, Mycoplasma)
MRSA (except ceftaroline)
Enterococci

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14
Q

Cephalosporins, gen I

[Drug names, Clinical use]

A

Cefazolin, Cephalexin
>G(+) cocci
>Proteus, E. coli, Klebsiella (PEcK)
*Cefazolin before surgery for S.aureus infections

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15
Q

Cephalosporins, gen II

[Drug names, Clinical use]

A

Cefoxitin, Cefaclor, Cefuroxime.
>G(+) cocci.
>H. influenzae, Enterobacter, Neisseria, Serratia (HENS).
>Proteus, E.coli, Klebsiella (PEcK).
>Cefoxitin is the only one that covers G(+), G(-), and anaerobes.

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16
Q

Cephalosporins, gen III

[Drug names, Clinical use]

A 
Ceftriaxone, Cefotaxime, Ceftazidime.
G(-) resistant to other Beta-lactams.
Can penetrate CSF.
>Ceftriaxone: meningitis, gonorrhea, disseminated Lyme dse.
>Ceftazidime: Pseudomonas
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17
Q

Cephalosporins, gen IV

[Drug names, Clinical use]

A

Cefepime
G(-) organisms.
*Inc. activity vs Pseudomonas, G(+) organisms.

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18
Q

Cephalosporins, gen V

[Drug names, Clinical use]

A

Ceftaroline
Broad G(+/-) coverage
Includes MRSA
*Doesn’t include Pseudomonas

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19
Q

Carbapenems

Drug names

A

Imipenem, Meropenem, Ertapenem, Doripenem

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20
Q

Carbapenems

MOA

A

Inhibit cell wall synth by binding to penicillin-binding proteins (same MOA as penicillin).
>Imipenem: broad spectrum, Penicillinase-resistant; Administer w/ Cilastatin (inhibits renal dehydropeptidase I) – dec. inactivation in renal tubules.

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21
Q

Carbapenems

Clinical use

A

G(+) cocci, G(-) rods, anaerobes.

>Only use in life-threatening infections or if other drugs failed – major side effects

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22
Q

Carbapenems

Toxicity

A

CNS toxicity (seizures)
GI distress, skin rash
*Meropenem has less risk of seizure and more stable to dehydropeptidase I

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23
Q

Vancomycin

MOA

A

> Binds to D-ala D-ala of cell wall precursors – inhibits cell wall peptidoglycan formation.
Resistant bacteria have D-ala D-lac modification.

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24
Q

Vancomycin

Clinical use

A

G(+) only.

Includes MRSA, S. epidermidis, Enterococcus, C. difficile

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25
Vancomycin | Toxicity
Generally well-tolerated. Nephrotoxic, ototoxic. *Thrombophlebitis -- Red man syndrome: diffuse flushing due to nonspecific mast cell degranulation (pretreat w/ slow-infusing antihistamines).
26
``` Aminoglycosides Drug names (GNATS) ```
Gentamicin, Neomycin Amikacin, Tobramycin Streptomycin
27
Aminoglycosides | MOA
Bactericidal. >Binds to 30s subunit -- inhibits initiation complex -- inhibits transcription of bacterial mRNA, causes misreading of mRNA. >Needs O2 for uptake (useless w/ anaerobes).
28
Aminoglycosides | Clinical use
``` Severe G(-) rod infections. Synergistic w/ Beta-lactams ```
29
Aminoglycosides | Toxicity
Nephrotoxicity, Ototoxicity. Neuromuscular blockade. Teratogen.
30
Tetracyclines | Drug names
Tetracycline Doxycycline Minocycline
31
Tetracylines | [MOA, don't give with what]
>Binds 30s subunit -- prevents attachment of new AA-tRNA -- inhibits protein elongation. *CI w/ milk (Ca2+), Antacids (Ca2+, Mg2+), or iron-containing preparations (Fe2+) -- divalent ions inhibit absorption.
32
Tetracyclines | [Clinical use, CI]
Borrelia, M. pneumoniae. Rickettsia, Chlamydia (accumulates intracellularly). Contraindicated in pregnancy.
33
Clindamycin | MOA
Bacteriostatic. | Blocks peptide transfer (translocation) at 50s subunit -- blocks transfer of peptidyl-tRNA to P site.
34
Clindamycin | Clinical use
Anaerobic (Bacteroides, C. perfringens). Aspiration pneumonia, lung abscesses, oral infections. Invasive GAS infection. *Treats anaerobic infxns ABOVE diaphragm (vs. metronidazole)
35
Clindamycin | Toxicity
Pseudomembranous colitis (C. difficile overgrowth)
36
Linezolid | [MOA, clinical use, toxicity]
Binds to 50s -- no initiation complex -- inhibits protein synthesis. For G(+), MRSA, VRE. Toxicity: bone marrow suppression, peripheral neuropathy, serotonin syndrome.
37
Macrolides | Drug names
Azithromycin Clarithromycin Erythromycin
38
Macrolides | MOA
Bacteriostatic. | Binds 23s rRNA (50s) -- blocks translocation -- inhibits protein synthesis.
39
Macrolides | Clinical use
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella). STI (chlamydia). G(+) cocci (streps allergic to Penicillin). B. pertussis.
40
Macrolides | Toxicity (MACRO)
``` Motility (GI) issues Arrhythmia Cholestatic hepatitis Rash Eosinophilia ```
41
Trimethoprim | [MOA, clincal use]
>Inhibits bacterial dihydrofolate reductase; combined w/ sulfonamides. >For UTI, Shigella, Salmonella. >For P. jirovecii pneumonia prophylaxis and tx; Toxoplasmosis prophylaxis.
42
Sulfonamides | MOA
Bacteriostatic. Inhibit folate synthesis. Compete w/ PABA to bind and inhibit dihydropteroate synthase.
43
Sulfonamides | Clinical use
G(+/-) Nocardia, Chlamydia UTI (SMX)
44
Sulfonamides | Toxicity
Hemolysis if G6PD deficient. Nephrotoxic. Photosensitivity. Displaces other drugs from albumin (warfarin).
45
Fluoroquinolones | Drug names
Ciprofloxacin, Norfloxacin Levofloxacin, Ofloxacin Moxifloxacin, Gemifloxacin Enoxacin
46
Fluoroquinolones | MOA
Bactericidal. Inhibits prokaryotic topoisomerase II (DNA gyrase), topoisomerase IV. *Don't take w/ antacids
47
Fluoroquinolones | Clinical use
G(-) rods of UT/GIT (Pseudomonas) | Neisseria
48
Fluoroquinolones | Contraindications
>Pregnant women, Nursing mothers, Kids below 18 -- possible cartilage damage. >Elderly over 60 y.o, prednisone-takers -- tendonitis, tendon-rupture.
49
Metronidazole | MOA
Bactericidal, Antiprotozoal. | >Forms toxic free radical metabs -- DNA damage.
50
Metronidazole | Clinical use
>Antiprotozoal: Giardia, Entamoeba, Trichomonas, Gardnerella. >Anaerobes: Bacteroides, C. difficile. >Triple therapy vs H.pylori (if w/ Pen allergy). *Anaerobic infxns below diaphragm (vs. clindamycin).
51
Rifampin, Rifabutin | [MOA, clinical use]
>Inhibits DNA-dependent RNA polymerase. >For M. tuberculosis, meningococcal prophylaxis, prophylaxis for contacts of pts w/ Hib. >Monotherapy leads to rapid resistance.
52
Rifampin, Rifabutin | Toxicity
Orange body fluids. | Rifabutin favored in pts w/ HIV infection (less CYP450 stimulation).
53
Isoniazid | [MOA, clinical use, toxicity]
>Inhibits mycolic acid synthesis. >For M. tuberculosis; can be used as solo prophylaxis against TB. >Neurotoxicity (give vit B6), hepatotoxicity.
54
Pyrazinamide | [MOA, clinical use, toxicity]
MOA uncertain. For M. tuberculosis Toxicity: Hyperuricemia, hepatotoxicity
55
Ethambutol | [MOA, clinical use, toxicity]
>Blocks arabinosyl transferase -- inhibits carb polymerization of mycobacterial wall. >For M. tuberculosis. >Optic neuropathy (red-green color blindness).
56
Drugs against MRSA organisms
Vancomycin, Daptomycin Linezolid, Tigecylcine Ceftaroline
57
Drugs against VRE organisms
Linezolid | Streptogramins (quinupristin, dalfopristin)
58
Tx for Multidrug-resistant P. aeruginosa
Polymyxins B and E (colistin)
59
Amphotericin B | MOA
Binds ergosterol in fungal membranes -- forms membrane pores -- electrolytes leak out
60
Amphotericin B | Clinical use
>Systemic mycoses. >Cryptococcus, Histoplasma, Blastomyces, Coccidioides, Candida, Mucor. >Supplement K and Mg (altered renal tubule permeability)
61
Amphotericin B | Toxicity
Fever/chills ("shake and bake"). Nephrotoxicity, arrhythmias, anemia. IV phlebitis
62
Nystatin | [MOA, clinical use]
>Binds to ergosterols in fungal membranes and creates pores -- electrolyte leakage. *Topical use only (too toxic for systemic). >For oral candidiasis ("swish and swallow"), diaper rash, vaginal candidiasis.
63
Flucytosine | [MOA, clinical use, toxicity]
>Inhibits DNA and RNA synthesis (Uracil on fungal mRNA converted to 5-FU by cytosine deaminase). >For systemic mycoses (combined w/ AmphoB) -- Cryptococcal meningitis. Toxicity: Bone marrow suppression
64
Azoles | Drug names
Clotrimazole, Fluconazole Itraconazole, Ketoconazole Miconazole, Voriconazole
65
Azoles | MOA
Inhibit 14-alpha-demethylase (CYP450) -- inhibits conversion of lanosterol to ergosterol (inhibit ergosterol synthesis). *Ergosterol needed for fungal cell membrane
66
Azoles | Clinical use
Local mycoses, less serious systemic mycoses. >Fluconazole: cryptococcal meningitis in AIDS, candidal infections. >Itraconazole: Blastomycoses, Coccidioides, Histoplasma. >Clotrimazole, Miconazole: topical.
67
Azoles | Toxicity
``` Testosterone synthesis inhibition (ketaconazole, gynecomastia). Liver dysfunction (inhibit CYP450). ```
68
Terbinafine | [MOA, clinical use, toxicity]
>Inhibits squalene epoxidase -- no lanosterol (ergosterol) synthesis. >For dermatophytes (onchymycosis). >Toxicity: taste disturbance, hepatotoxicity, GI upset.
69
Echinocandins | [Names, MOA, use, toxicity]
Anidulafungin, Capsofungin, Micafungin. >Inhibits B-glucan synth -- inhibits fungal wall synth. >For invasive aspergillosis, Candida. >Toxicity: flushing (histamine release).
70
Griseofulvin | [MOA, use, toxicity]
>Interferes w/ microtubule function; disrupts mitosis. >Oral tx of superficial infxns (dermatophytes). >Toxicity: carcinogenic, teratogenic, induces CYP450 and warfarin metab.
71
Chloroquine | [MOA, use, toxicity]
>Blocks plasmodium Heme polymerase -- blocks detoxification of heme into hemozoin -- heme accumulates -- toxic to plasmodia. >For Plasmodium (except P. falciparum w/c is often resistant). >Toxicity: retinopathy, pruritus
72
Antiprotozoan therapy | Toxoplasmosis, T. brucei, T. cruzi, Leishmaniasis
>Toxoplasmosis: Pyrimethamine + Sulfadiazine. >T. brucei: Suramin (acute, blood-borne) and Melarsoprol (chronic, CNS penetration). >T. cruzi: Benznidazole, Nifurtimox. >Leishmaniasis: AmphoB, Sodium stibogluconate.
73
Antihelminthic therapy
``` Mebendazole Pyrantel pamoate Ivermectin Diethylcarbamazine Praziquantel ```
74
Oseltamivir, Zanamivir | [MOA, use]
>Inhibit influenza neuraminidase -- dec. release of viral progeny. >Tx and prevention of Influenza A and B
75
Acyclovir, Famciclovir, Valacyclovir | [MOA, use, toxicity]
>Requires phosphorylation by viral thymidine kinase. >Inhibits viral DNAp by chain termination -- inhibits viral replication. >For HSV, VZV; weak against EBV, nonactive against CMV. >Tox: obstructive crystalline nephropathy, ARF -- hydrate well.
76
Ganciclovir | [MOA, use, toxicity]
>Inhibits viral DNAp by chain termination. >For CMV. >Toxicity: leukopenia, neutropenia, thrombocytopenia, renal toxicity
77
Foscarnet | MOA
>Viral DNAp/RNAp inhibitor, HIV reverse transcriptase inhibitor. >Binds to pyrophosphate-binding site. *Doesn't need phosphorylation by viral kinases.
78
Foscarnet | [Clinical use, toxicity]
>CMV retinitis in IC patients when ganciclovir fails. >Acyclovir-resistant HSV. >Toxicity: nephrotoxic, electrolyte abnormalities can lead to seizures (Ca, PO, K).
79
HAART therapy for HIV consists of what 3 types of drugs?
2 NRTI | 1 NNRTI / Protease inhibitor / Integrase inhibitor
80
``` Protease inhibitors (-navir) Drug names (at least 3) ```
Atazanavir, Darunavir Fosamprenavir, Indinavir Lopinavir, Ritonavir Saquinavir
81
Protease inhibitors | MOA
>HIV-1 protease (pol gene) cleaves polypeptide provirus into functional parts. >Protease inhibitors prevent this maturation of new viruses.
82
Protease inhibitors | Toxicity, CI
Hyperglycemia, lipodystrophy. Nephropathy, hematuria (indinavir). *Contraindicated w/ Rifampin -- can decrease protease inhibitor concentrations.
83
``` NRTIs Drug names (at least 3) ```
Abacavir (ABC), Didanosine (ddl) Emtricitabine (FTC), Lamivudine (3TC) Stavudine (d4T), Tenofovir (TDF) Zidovudine (ZDV, formerly AZT)
84
NRTIs | MOA
>Inhibits HIV-DNA synthesis from RNA template by terminating DNA chain elongation. >Competitive RT inhibitors. *Nucleosides need to be phosphorylated (Tenofovir is the only nucleotide). *ZDV can be used in pregnancy to dec. fetal transmission.
85
NRTIs | Toxicity
Bone marrow suppression Lactic acidosis (nucleosides) Anemia (ZDV) Pancreatitis (didanosine)
86
``` NNRTIs Drug names (3) ```
Delavirdine Efavirenz Nevirapine
87
NNRTIs | MOA
>Allosteric RT inhibitors, terminates DNA chain elongation of HIV-DNA. *Don't require phosphorylation to be active or compete w/ nucleotides
88
NNRTIs | Toxicity (esp Efavirenz), CI
Rash, hepatotoxicity. >Efavirenz: vivid dreams, CNS sx >CI in pregnancy: Efavirenz, Delavirdine
89
``` Fusion inhibitors (Efuvirtide, Maraviroc) [MOA] ```
>Efuvirtide: binds gp41 -- inhibits viral entry. >Maraviroc: binds CCR5 co-receptor on T cells and monocytes -- inhibits interaction w/ gp120 (inhibits viral attachment).
90
Interferons (alpha, beta, gamma) | Clinical use
>IFN-alpha: chronic hep B and C, Kaposi sarcoma, hairy cell leukemia, condyloma accuminata, RCC, malignant melanoma. >IFN-beta: multiple sclerosis. >IFN-gamma: CGD.
91
Ribavirin | [MOA, use, toxicity]
>Inhibits IMP dehydrogenase -- inhibits guanine synthesis. >For chronic HCV, also RSV. >Toxicity: hemolytic anemia, severe teratogen.
92
``` Integrase inhibitors (-gravir) Drug names ```
Dolutegravir | Raltegravir
93
Integrase inhibitors | MOA
Inhibits HIV-DNA integration into host genome
94
Chloramphenicol | MOA
Bacteriostatic. | >Blocks peptidyltransferase at 50s subunit -- blocks growing peptide from attaching to AA in A site.
95
Chloramphenicol | Use, toxicity
>Meningitis (H. influenza, N. meningitides, S. pneumonia). >Rocky Mountain Spotted Fever (R. rickettsi). >Limited use due to Toxicity: anemia, aplastic anemia; gray baby syndrome (prematures lack liver UDP-glucuronyl transferase).

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