Antibiotics First Aid Flashcards
1
Q
What drugs have the mechanism of action to block cell wall synthesis by inhibition of peptidoglycan cross linking?
A
Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, imipenam
2
Q
What drugs have the mechanism of action to block peptidoglycan synthesis?
A
Bacitracin
Vancomycin
3
Q
What drugs have the mechanism of action to block nucleotide synthesis?
A
Sulfonamides
Trimethoprim
4
Q
What drugs have the mechanism of action to block DNA topoisomerases?
A
Fluoroquinolones
5
Q
What drugs have the mechanism of action to block mRNA synthesis?
A
Rifampin
6
Q
What drugs have the mechanism of action to damage DNA?
A
Metronidazole
7
Q
What drugs have the mechanism of action to block protein synthesis at 50S ribosomal subunit?
A
Choramphenicol, macrolides, clindamycin, streptogramins (quinupristin, dalfopristin), linezolid
8
Q
What drugs have the mechanism of action to block protein sysnthesis at 30S ribosomal subunit?
A
Aminoglysosides
Tetracyclines
9
Q
Mechanism of Penicillin?
A
- Bind penicillin-binding proteins
- Block transpeptidase cross-linking of peptidoglycan
- Activate autolytic enzymes
10
Q
Clinical use of Penicillin
A
Mostly for gram-pos organisms (S. pneumoniae, S. pyogenes, Actinomyces) and syphilis.
Bactericidal for gram-pos cocci, gram-pos rods, gram (-) cocci, and spirochetes.
Not penicillinase resistant
11
Q
Penicillin toxicity?
A
Hypersensitivy reactions
Hemolytic anemia
12
Q
What causes penicillin resistance?
A
B-lactamases cleaving B-lactan ring
13
Q
Drugs that are penicillinase-resistant penicillins?
A
Methicillin
Nafcillin
Dicloxacillin
14
Q
Mechanism for penicillin-resistant penicillins
A
Same as penicillin. Narrow spectrum; penicillinase resistant because of bulkier R group.
“Use naf (nafcillin) for staph”
15
Q
Clinical use for penicillinase-resistant penicillins
A
S. aureus (except MRSA; resistant because of altered PBP protein target site)
“Use naf (nafcillin) for staph”
16
Q
Toxicity of penicillinase-resistant penicillins
A
Hypersensitivity reactions
Methicillin –> interstitial nephritis
17
Q
Ampicillin and amoxicillin are what type of penicillin?
A
Aminopenicillins
18
Q
Mechanism for aminopenicillin
A
Same as penicillin
Wider spectrum; penicillinase sensitive
Also combine with clavulanic acid to protect against B-lactamase.
Amoxicillin has greater oral bioavailability than ampicillin
19
Q
Clinical use of aminopenicillins
A
Extended-spectrum penicillin - H. influenzae, E.coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci.
“Ampicillin/amoxicillin HELPSS kill enterococci”
20
Q
Toxicity of aminopenicillins
A
Hypersensitivy reactions
Ampicillin rash
Pseudomembranous colitis
21
Q
What causes resistance to aminopenicillins (amoxicillin/ampicillin)?
A
B-lactamases
22
Q
What drugs are antipseudomonals?
A
Ticarcillin
Carbenicillin
Piperacillin
23
Q
Mechanism of action of ticaricillin, carbenicillin, peperacillin?
A
Same as penicillin
Extended spectrum
24
Q
Clinical use of antipseudomonals
A
Pseudomonas species and gram (-) rods; susceptible to penicillinase; use with clavulanic acid
TCP: Takes Care of Pseudomonas
25
Toxicity of antipseudomonals
Hypersensitivy reactions
26
What are the B-lactamse inhibitors?
**C**lavulonic **A**cid, **S**ulbactam, **T**azobactam.
Often added to penicillin abx to protect the abx from destruction by B-lactamase (penicillinase)
**CAST**
27
Mechanism of Cephalosporins
B-lactam drugs that inhibit cell wall synthesis
BUT less susceptible to penicillinase.
Bactericidal
28
What are the organisms not covered by cephalosporins?
**L**isteria, **A**typicals (Chlamydia and Mycoplasma), **M**RSA, and **E**nterococci
**LAME**
29
Clinical use for 1st generation cephalosporins and drugs of 1st gen?
Cefazolin and cephalexin
Gram (+) cocci, **P**roteus mirabilis, **E**. **c**oli, **K**lebsiella pneumonia
**PEcK**
30
Clinical use for 2nd gen cephalosporins and the drugs for it
Cefoxitin, Cefaclor, cefuroxime
Gram (+) cocci, **H**. influenzae, **E**nterobacter aerogenes, **N**eisseria spp, **P**roteus mirabilis, **E**. **c**oli, **K**lebsiella pneumoniae, **S**erratia marcescans.
**HEN PEcKS**
31
Clinical use for 3rd gen cephalosporins and the drugs for it
Ceftriaxone, cefotaxime, ceftazidime
Serious gram (-) infections resistant to other B-lactams
**Ceftriaxone**: meningitis and gonorrhea
**Ceftazidime**: *Pseudomonas*
32
Clinical use for 4th gen cephalosporins and drugs for it
Cefepime
Increased activity against *Pseudomonas* and gram (+) organisms
33
Cephalosporin toxicity
Hypersensitivy reactions, vit K deficiency.
Cross-hypersensitivy with penicillin occurs in 5-10% of patients.
Increased nephrotoxicity of aminoglycosides; disulfiram-like reaction with ethanol (in cephalosporins with a methltheitetrazole group, eg cefamandole)
34
Mechanism of action for **Aztreonam**
A monobactam resistant to B-lactamases.
Inhibits cell wall synthesis (binds to PBP3).
Synergistic with aminoglycosides.
No cross-allergenicity with penicillins
35
Clinical use for **Aztreonam**
**Gram-negative rods only**
No activity against gram (+) or anaerobes.
For penicillin-allergic patients and those with renal insufficiency who cannot tolerate aminoglycosides
36
Toxicity of **Aztreonam**
Usually nontoxic; occasional GI upset.
No cross-sensitivity with penicillins or cephalosporins
37
Mechanism of action for **Imipenem/cilastatin and meropenem**
**Imipenem** is a broad-spectrum, B-lactamase resistant carbapenem. Always administered with **cilastatin** (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
With imipenem, "the kill is **LASTIN**' with ci**LASTATIN**"
38
Clinical use for imipenem/cilastatin and meropenem
Gram (+) cocci, gram (-) rods, and anaerobes.
Wide spectrum, but significant side effects limit use to life-threatening infections, or after other drugs have failed.
Meropenem, however, has a reduced risk of sezures and is table to dehydropeptidase I.
39
Toxicity of imipenem/cilastatin and meropenem
GI distress
Skin rash
CNS toxicity (seizures) at high plasma level
40
Mechanism of **Vancomycin**
Inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of cell wall precursors.
Bactericidal
41
Clinical use for Vancomycin
**Gram-positive only** - serious, multidrug-resistant organisms, including S. aureus, enterococci, and C.difficile (oral dose for pseudomembranous colitis)
42
Toxicity for **Vancomycin**
**N**ephrotoxicity, **O**totoxicity, **T**hrombophlebitis, diffuse flushing - "red man syndrome" (can largely prevent by pretreatment with antihistamines and slow infusion rate). Well tolerated in general - does **NOT** have many problems
43
What causes resistance to **Vancomycin?**
Occurs with amino acid change of D-ala D-ala to D-ala D-lac.
"Pay back **2 D-ala**s (dollars) for **van**dalizing"
44
What antibiotic drugs are 30S inhibitors?
Aminoglycosides
Tetracyclines
45
What antibiotics are 50S inhibitors?
Chloramphenicol
Clindamycin [bacteriostatic]
Erythromycin (macrolides) [bacteriostatic]
Liniezolid (variable)
46
What drugs are aminoglycosides?
**G**entamycin, **N**eomycin, **A**mikacin, **T**obramycin, **S**treptomycin
"**Mean" GNATS** can**NOT** kill anaerobes
47
Mechanism of aminoglycosides
Bactericidal; inhibit formation of initiation complex and cause misreading of mRNA.
Require O2 for uptake; therefore ineffective against anerobes.
48
Clinical use of aminoglycosides
Severe **gram (-) rod** infections.
Synergistic with B-lactam abx
Neomycin for bowel surgery.
49
Toxicity of aminoglycosides
Nephrotoxicity (especially when used with cephalosporins)
Ototoxicity (especially when used with loop diuretics)
Teratogen
50
How is resistance to aminoglycosides developed?
Transferase enzymes that inactivate the drug by:
Acetylation
Phosphorylation
Adenylation
51
What drugs are tetracylines?
Tetracyline, doxycycline, demeclocycline, minocycline
"**D**emeclocycline - ADH antagonist; acts as a **D**iuretic in SIADH"
52
Mechanism of Tetracyclines
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.
Must NOT take with milk, antacids, or iron-containing preparatins because divalent cations inhibit absorption in the gut.
53
Clinical use of Tetracyclines
*Borrelia burgdorferi, M. pneumoniae.*
Drug's ability to accumulate intracellularly makes it very effective against *Rickettsia* and *Chlamydia*
54
Toxicity of Tetracycline
GI distress
Discoloration of teeth and inhibition of bone growth in children
Photosensitivity
Contraindicated in pregnancy
55
How is resistance to tetracyclines developed?
Decrease uptake into cells or increase efflux out of cell by plasmid0encoded transport pumps
56
What drugs are macrolides?
**A**zithromycin
**C**larithromycin
**E**rythromycin
"**ACE**"
57
Mechanism of macrolides
Inhibit protein synthesis by blocking translocation ("macro**Slides**")
Bind to 23S rRNA of the 50S ribosomal subunit
Bacteriostatic
58
Clinical use of Macrolides
**Atypical pneumonias (*Mycoplasma, Chlamydia, Legionella)***, URIs, STDs, gram (+) cocci (streptococcal infections in patients allergic to penicillin, and *Neisseria*
59
Toxicity of Macrolides
Prolonged QT interval (especially erythromycin), GI discomfort (most common cause of noncompliance), acute cholestatic hepatitis, eosinophila, skin rashes.
Increases serum concentration of theophyllines, oral anticoagulants
60
How is resistance to macrolides developed?
Methylation of 23S rRNA binding site
61
Mechanism of Chloramphenicol
Blocks peptide bond formation at 50S
Bacteriostatic
62
Clinical use of Chloramphenicol
**Meningitis** (*H. influenzae, Neisseria meningitidis, S. pneumoniae)*
63
Toxicity of Chloramphenicol
Anemia, anaplastic anemia (both dose dependent)
Gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase)
64
How is resistance to Chloramphenicol developed?
Plasmid-encoded acetyltransferase that inactivates drug
65
Mechanism of Clindamycin
Blocks peptide formation at 50S
Bacteriostatic
66
66
Clinical use of Clindamycin
**Anaerobic infections** (e.g *Bacteroides fragilis, Clostridium perfringens*) in aspiration pneumonia or lung abscesses
Treats anaerobes **above** the diaphragm vs metronidazole (anaerobic infections **below** diaphragm)
67
Toxicity of Clindamycin
Pseudomonas colitis (C. difficile overgrowth)
Fever
Diarrhea
68
What drugs are Sulfonamides?
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
69
Mechanism of sulfonamides
PABA antibmetabolites inhibit dihydropteroate synthase.
Bacteriostatic
70
Clinical use of Sulfonamides
Gram (+), gram (+), *Nocardia, Chlamydia.*
Triple sulfas or SMX for simple UTI
71
Toxicity of sulfonamides
Hypersensitivity reactions, hemolysis if G6PD deficient, nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (eg warfarin)
72
How is resistance to sulfonamides developed?
Altered enzyme (bacterial dihydropteroate synthase), decrease uptake, or increased PABA synthesis
73
Mechanism of Trimethoprim
Inhibits bacterial dihydrofolate reductase
Bacteriostatic
**T**rimethoprim = **TMP**: "**T**reats **M**arrow **P**oorly"
74
Clinical use of Trimethoprim
Used in combo with sulfonamides (TMP-SMX) causing sequential block of folate synthesis.
Combination used for UTIs, *Shigella, Salmonella, Pneumosystis jiroveci* pneumonia
75
Toxicity of Trimethoprim
Megaloblastic anemia, leukopenia, granulocytopenia
May alleviate with supplemental folinic acid (leucovorin rescue)
76
What drugs are fluoroquinolones?
Ciprofloxacin, norfloxacin, levofloxacin, moxifloxacin, enoxacin, nalidixic acid (a quinolone)
**"-floxacin"**
77
Mechanism of fluroquinolones
Gram (-) rods of urinary and GI tracts (including *Pseudomonas*), *Neisseria,* some gram (+)
78
Toxicity of Fluoroquinolones
GI upset, superinfections, skin rashes, headache, dizziness.
Contraindicated in pregnant women and in children because animal studies show dmg to cartilage.
Tendonitis and tendon rupture in adults; leg cramps and myalgias in kids
"Fluoroquino**LONES** hurt attachments to your **BONES**"
79
Resistance mechanism to fluoroquinolones
Chromosome-encoded mutation in DNA gyrase
80
Mechanism of Metrodinazole
Forms free radical toxic metabolites in the bacterial cell that damage DNA.
Bactericidal, antiprotazoal
81
Clinical use of Metrodinazole
Treats ***G**iardia, **E**ntamoeba, **T**richomonas, **G**ardnerella vaginalis,* **A**naerobes (*Bacteroides, C. difficile*).
Used with bismuth and amoxicillin (or tetracycline) for "triple therapy" against *H. **P**ylori*
"**GET GAP** on the **METRO**!"
Anaerobic infection below the diaphragm
82
Toxicity of Metronidazole
Disulfiram-like reaction with alcohol; headache, metallic taste
83
Prophylaxis for M. tuberculosis
Isoniazid
84
Treatment for M. tuberculosis
**R**ifampin, **I**soniazid, **P**yrazinamide, **E**thambutol
**RIPE**
85
Prophylaxis for M. avium-intracellulare
Azithromycin
86
Treatment for M. avium intracellulare
Azithromycin, rifampin, ethambutol, streptomycin
87
Treatment for M. leprae
Dapsone, rifampin, clofazimine
88
Mechanism of INH
Decrease synthesis of mycolic acids.
Bacterial catalase peroxidase (KatG) needed to convert INH to active metabolite
89
Clinical use of INH
M. tuberculosis. Only agent used as solo prophylaxis against TB
90
Toxicity of INH
Neurotoxicity, hepatoxicity, lupus.
Pyridozine (vitamine B6) can prevent neurotoxicity, lupus
"**INH I**njures **N**eurons and **H**epatocytes"
91
Mechanism of rifampin
Inhibits DNA-dependent RNA polymerase
**R**ifampin **4 R's**:
**R**NA polymerase inhibitor
**R**evs up microsomal P450
**R**ed/orange bloody fluids
**R**apid resistance if used alone
92
Clinical use of rifampin
M. tuberculosis
Delays resistance to dapsone when used for leprosy.
Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with H. influenzae type B
93
Toxiciy of rifampin
Minor hepatotoxicity and drug interactions (increase P450)
Orange body fluids (nonhazardous)
94
Mechanism and clinical use of Pyrazinamide
Inhibits mycolic acid production by pyrazinamidase
Effective in acidic pH of phyagolysosomes, where TB engulfed by macrophages is found
M. tuberculosis
95
Toxicity of Pyrazinamide
Hyperuricemia
Hepatoxicity
96
Mechanism and clinical use of Ethambutol
Decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
M. tuberculosis
97
Toxicity of Ethambutol
Optic neuropathy (red-green color blindness)
98
Meningococcal infection prophylaxis
**Ciprofloxacin (DOC)**
Rifampin
Minocycline
99
Prophylaxis for gonorrhea
Ceftriaxone
100
Prophylaxis for syphillis
Benzathine penicillin G
101
Propylaxis for recurrent UTIs
TMP-SMX
102
Prophylaxis for Endocarditis with surgery/dental procedures
Penicillins
103
Treatment for MRSA
vancomycin
104
Treatment for VRE
Linezolid and streptogramins (quinupristin/dalfopristin)
105
Empiric therapy for CAP in outpatient setting
Macrolides
106
Empiric therapy for CAP in inpatient setting
Fluoroquinolones
107
Empiric therapy for CAP in ICU setting
B-lactam + fluoroquinolone/azithromycin
108
Mechanism of Amphotericin B
Binds ergosterol (unique to fungi)
Forms membrane pores that allow leakage of electrolytes
Disrupts membrane function
109
Clinical use for Amphotericin B
**Serious, systemic mycoses**
Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses).
*1st line treatment for cryptococcal meningitis*
Intrathecally for fungal meningitis
Supplement K and Mg because of altered renal tubule permeability
110
Toxicity of Amphotericin B
Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmieas, anemia, IV phlebitis ("amphoterrible").
Hydration reduces nephrotoxicity
Liposomal amphotericin reduces toxicity
111
Mechanism of Nystatin
Same as amphotericin B. Topical form because too toxic for systemic use
112
Clinical use for Nystatin
"Swish and swallow" for oral candidiasis (thrush)
Topical for diaper rash and vaginal candidiasis
113
Name a couple -azoles
Fluconazole
ketoconazole
miconazole
itraconazole
114
Mechanism of "-azoles"
**Inhibit fungal sterol (ergosterol) synthesis**, by inhibiting the P450 enzyme that converts lanosterol to ergosterol
115
Clinical use of "-azoles"
Systemic mycoses
_Fluconazole_ for **cryptococcal meningitis in AIDS** and **candidal infections** of all types
_Ketoconazole_ for Blastomyces, Coccidioides, Histoplasma, Candida albicans; hypercortisolism
_Clotrimazole and miconazole_ for topical fungal infections
116
Toxicity of "-azoles"
Hormone synthesis inhibition (gynecomastia), liver dysfucntion (inhibits P450), fever, chills
117
Mechanism of Flucytosine
**Inhibits DNA synthesis** by conversion to 5-FU by cytosine deaminase
118
Clinical use of Flucytosine
Used in systemic fungal infections (e.g **Cryptococcus**) in combination with amphotericin B
119
Toxicity of Flucystosine
Nausea, vomiting, diarrhea, bone marrow suppression
120
Mechanism of Caspofungin
Inhibits cell wall synthesis by inhibiting synthesis of B-glucan
121
Clinical use of Caspofungin
**Invasive aspergillosis**, *Candida*
122
Toxicity of Caspofungin
GI upset
Flushing
123
Mechanism of Terbinafine
Inhibits fungal enzyme squalene epoxidase; inhibits ergosterol synthesis
124
Clinical use of Terbinafine
Dermatophytoses (especially **onychomycosis** - fungal infection of finger or toe nails)
125
Toxicity of Terbinafine
Abnormal LFTs
Visual disturbances
126
Mechanism of Griseofulvin
Interferes with microtubule function; disrupts mitosis
Deposits in keratin containing tissues (eg nails)
127
Clinical use of Griseofulvin
Oral treatment of superficial infections
Inhibits growth of **dermatophytes** (tinea, ringworm)
128
Toxicity of Griseofulvin
Teratogenic, carcinogenic, confusion, headaches, increase P450 and warfarin metabolism
129
What is the antiprotozoan therapy?
_Pyrimethane_: toxoplasmosis or *Plasmodium falciparum*
_Suramin and melarsoprol_: *Trypanosoma brucei*
_Nifurtimox_: *T. cruzi*
_Sodium stibogluconate_: leshmaniasis
130
Mechanism of Chloroquine
Blocks plasmodium heme polymerase
131
Clinical use for Chloroquine
*Plasmodium* species
Also _mefloquine_ (for treatment/ppx)
_Quinine_ for resistant species in combination with pyrimethamine/sulfonamide
132
Toxicity of Chloroquine
Retinopathy
G6PD hemolysis
133
What is the antihelminthic therapy?
Mebendazole
Pyrantel pamoate
Ivermectin
Diethylcarbamazine
Praziquantel
(Immobilize helminths)
