Antimicrobial Drugs Flashcards
(170 cards)
1
Q
Block cell wall synthesis by inhibition of peptidoglycan cross-linking
A
Penicillin, Methicillin, Ampicillin, Piperacillin, Cephalosporins, Aztreonam, Imipenem
2
Q
Block peptidoglycan synthesis
A
Bacitracin, Vancomycin
3
Q
Block nucleotide synthesis by inhibiting folic acid synthesis (involved in methylation)
A
Sulfonamides, trimethopram
4
Q
Block DNA topoisomerases
A
Fluoroquinolones
5
Q
Block mRNA synthesis
A
Rifampin
6
Q
Damage DNA
A
Metronidazole
7
Q
Block protein synthesis at 50S ribosomal subunit
A
Chloramphenicol, Macrolides, Clindamycin, Streptogramins (Quinupristin, Dalfopristin, Linsezolid)
8
Q
Block protein synthesis at 30S ribosomal subunit
A
Aminoglycosides, Tetracyclines
9
Q
Penicillin
A
Penicillin G (IV and IM form), penicillin V (oral), Prototype B-lactam antibiotics
10
Q
Penicillin Mechanism
A
Bind penicillin-binding proteins (transpeptidases)
Block transpeptidase cross-linking in peptidoglycan
Activate autolytic enzymes
11
Q
Penicillin Clinical Use
A
Mostly used for gram-positive organisms (S. pneumoniae, S. pyogenes, Actinomyces)
Bacterocidal for gram-positive rods, gram-negative cocci, and spirochetes
12
Q
Penicillin: Penicillinase resistant?
A
No. Duh!
13
Q
Penicillin Toxicity
A
Hypersensitivity reactions, Hemolytic anemia
14
Q
How does penicillin resistance occur?
A
B-lactamases cleave B-lactam ring
15
Q
Penicillinase resistant penicillins
A
Oxacillin, Nafcillin, Dicloxacillin
16
Q
Penicillinase resistant penicillins Mechanism
A
Narrow spectrum Bind penicillin-binding proteins (transpeptidases)
17
Q
How are the “-cillins” penicillinase resistant?
A
Bulky R group blocks access of B-lactamase to B-lactam ring
18
Q
Penicillinase resistant penicillins Clinical Use
A
S. aureus (except MRSA; resistant because of altered penicillin-binding protein target site)
19
Q
Penicillinase resistant penicillins Toxicity
A
Hypersensitivity reactions, interstitial nephritis
20
Q
Aminopenicillins
A
Ampicillin, Amoxicillin
21
Q
Aminopenicillins: Mechanism
A
Same as penicillin but wider spectrum
22
Q
Aminopenicillins: Penicillinase resistant or penicillinase sensitive
A
Penicillinase sensitive Also combine with clavulanic acid to protect against B-lactamase
23
Q
Which has greater oral bioavailability? Amoxicillin or Ampicillin
A
Amoxicillin
24
Q
Aminopenicillins (Ampicillin, Amoxicillin) : Clinical Use
A
Extended spectrum penicillin - (HELPSS) Haemophilus influenzae, E.coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci
25
Aminopenicillin (Ampicillin, Amoxicillin) Toxicity
Hypersensitivity reactions; ampicillin rash; pseudomembranous colitis
26
Aminopenicillin (Ampicillin, Amoxicillin) Resistance
B-lactamases cleave B-lactam ring
27
Antipseudomonals
Ticarcillin, Piperacillin
28
Antipseudomonals (Ticarcillin, Piperacillin) Mechanism
*Same as penicillin* Extended spectrum
29
Ticarcillin, Piperacillin Clinical Use
Pseudomonas spp. and gram-negative rods
30
Ticarcillin, Piperacillin: Penicillinase resistant or Penicillinase sensitive?
*Penicillinase sensitive* Use with clavulanic acid to protect against B-lactamase
31
B-lactamase inhibitors
*CAST* - *C*lavulanic *A*cid *S*ulbactam, *T*azobactum
32
Cephalosporins: Mechanism
B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal
33
Which organisms are not covered by cephalosporins?
Organisms typically not covered by cephalosporins are *LAME*:
Listeria, Atypicals (Chlamydia, Mycoplasma), MRSA, and Enterococci
34
Which cephalosporin is the exception to the *LAME* organism rule?
Ceftaroline covers MRSA
35
1st generation cephalosporins
Cefazolin, Cephalexin
36
1st generation cephalosporins coverage
1st generation - *PEcK*
Proteus
E.Coil
Klebsiella
37
2nd generation cephalosporins
Cefoxitin, Cefaclor, Cefuroxime
38
2nd generation cephalosporin coverage
```
2nd generation cephalosporins - *HEN PEckS*
H.influenza
Enterobacter
Neisseria
Proteus
E.Coli
Klebsiella
```
39
3rd generation cephalosporins
Ceftriaxone, Cefotaxime, Ceftazidime
40
3rd generation cephalosporins coverage
Serious gram-negative infections resistant to other B-lactams
41
4th generation cephalosporins
Cefepime
42
4th generation cephalosporin coverage
Cefepime - increased activity against Pseudomonas and gram-positive organisms
43
Cephalosporin Toxicity
Hypersensitiity reactions, vitamin K deficiency.
44
Aztreonam: Mechanism
A monobactam resistant to B-lactamases. Prevents peptidoglycan cross-linking by binding to PBP3
Synergistic with aminoglycosides. No cross-allergy with penicillins
45
Aztreonam: Clinical 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*
46
Imipenem/Cilastatin, Meropenem: Mechanism
Imipenem is a broad-spectrum, B-lactamase-resistant carbapenem. Always administered with *cilastatin* (inhibitor of renal dehydropeptidase I) to decreased inactivation of drug in renal tubules.
47
Imipenem/Cilastatin, Meropenem: Clinical Use
Gram-positive cocci, gram-negative rods, and anaerobes.
48
Discuss Meropenem and seizure risk
Unlike imipenem/cilastatin, meropenem has reduced risk of seizures, and is stable to dehydropeptidase I
49
Imipenem/Cilastatin, Meropenem: Toxicity
GI distress, skin rash, and CNS toxicity (seizures at high plasma levels)
50
Vancomycin: Mechanism
Inhibits cell wall peptidoglycan formation by binding *D-ala D-ala* portion of cell wall precursors. Bactericidal
51
Vancomycin: Clinical Use
Gram-positive only - serious, amultidrug-resistant organisms, including MRSA, enterococci, and Clostridium difficile (oral dose for pseudomembranous colitis)
52
Vancomycin: Toxicity
```
Well tolerated in general - does *NOT* have many problems
N-ephrotoxicity
O-totoxicity
Tthrombophlebitis
Diffuse flushing
```
53
How can one prevent *red man syndrome*?
Red man syndrome - associated w/ vancomycin toxicity.
| - mediated by histamine
54
Vancomycin Resistance
Occurs with amino acid change of *D-ala D-ala* to D-ala D-lac.
55
Protein synthesis inhibitors target which bacterial ribosome?
70S (made up of 50S and 30S subunits), which leave 80S ribosome (human ribosome) unaffected
56
Aminoglycosides
*G*entamicin, *Neomycin*, *Amikacin, *T*obramycin, *S*treptomycin
57
Macrolide: Clinical Use
Atypical pneumonias (Mycoplasma, Chlamydia, Legionella)
STDs (for Chlamydia)
Gram-positive cocci (Streptococcal infections in patients allergic to penicillin
58
Macrolides: Toxicity
*MACRO*: *M*otility issues, *A*rrhythmia caused by prolonged QT, acute *C*holestatic hepatitis, *R*ash, e*O*sinophilia. Increases serum concentration of theophyllines, oral anticoagulants
59
Macrolide Resistance
Methylation of 23S rRNA binding site
84
30 S inhibitors
"AT" 30
Aminoglycosides
Tetracyclines
85
50S inhibitors
CCEL at 50
Chloramphenicol, Clindamycin
Erythromycin (macrolides)
Linezolid
86
Aminoglycoside: Mechanism
Bacteriocidal
- bind to 30S ribosomal subunit unit to inhibit formation of initiation complex and cause misreading of mRNA
- blocks translocation
- Requires oxygen for uptake thus inaffective against anaerobes
87
Aminoglycoside: Clinical USe
Severe gram-negative rod infections
Syngergistic with B-lactam antibiotics
Neomycin for bowel surgery
88
Amingoglycoside Toxiciity
Nephrotoxicity (esp. when used with cephalosporins)
Neuromusclar blockade
Ototoxicity (esp. when used with loop diuretics - furosemide)
Teratogen
89
Aminoglycoside resistance
Transferase enzymes that inactivate trug by acetylation, phosphorylation or adenylation
90
Tetracycline
Tetracycline, Doxycycline, Demeclocycline
91
Demeclocycline
- ADH antagonist
| - acts as diuretic in SIADH. Rarely used as an antiobiotic
92
Tetracycline mechanism
Bacterostatic:
bind to 30S and prevent attachment of aminoacyl-tRNA
limited CNS prenetration
93
Contraindications for tetracyclines
Don't use with milk, antacids, or Fe-containing substances because divalent cations inhibit absorption in gut
94
Doxycycline special considerations
fecally eliminated
| can be used in patients with renal failure
95
Tetracyclines: Clinical Use
Borellia borgdoferi
M. pneuominae
- ability to accumulate intracellularly makes it effective against Ricksettia and Chlamydia
96
Tetracycline: Toxicity
GI distress
Discoloration of teeth and inhibition of bone growth in children
Photosensitivity
Contraindicated in pregnancy
97
Tetracycline: Resistance
Decreased uptake into cells
| Increased efflux out of cell by plasmid-encoded transport pumps
98
Macrolides
azithromycin, clarithromycin, erythromycin
99
Macrolide: Mechanism
Inhibit protein synthesis by blocking translocation;
| bind to 23S rRNA of 50 S ribosomal subunit
100
Chloramphenicol
- blocks peptidyltransferase at 50S ribosomal subunit
- used for Meninigitis (H. influenzae, N. meningitis, S. pneumoniae)
- not used widely because of toxicity
101
Chloramphenicol: Toxicity
anemia (dose dependent)
aplastic (dose INDEPENDENT)
Gray baby syndrome - in premature babies because they lack liver UDP-gluconyl transferase
102
Chloramphenicol: Resistance
Plasma-encoded acetyltransferase that inactivates drug
103
Clindamycin
- blocks peptide transfer (transpeptidation) at 50S ribosomal subunit. Bacteriostatic
- used to treat ANAEROBIC infections in aspiration pneumonia or lung abscesses
- also treats oral infections with mouth anaerobes
104
Metronidazole vs. Clindamycin
Clindamycin - treats anaerobes ABOVE diaphragm
Metronidazole - treats anaerobes BELOW diaphragn
105
Clindamycin: Toxicity
Pseudomonas colitis ( C. difficile overgrowth), fever, diarrhea
106
Sulfonadmides:
SMX, Sulfisoxiazole, Sulfadiazine
107
Sulfonamide
PABA antimetabolit inhibit dihydropteroate synthase. Bacteriostatic
- treats gram-positive, gram-negative, Nocardia, Chlamydia,
- Triple sulfas or SMX for simple UTI
108
Sulfonamide: Toxicity
```
Hypersensitivity reactions
Hemolysis if G6PD deficiency
Nephrotoxicity (tubulointerstitial nephritis)
Photosensitivity
Kernicterus in infants
Displace other drugs from albumin
```
109
Trimethoprim
- inhibits bacterial dihydrofolate reductase. Bacteriostatic
- used in combination with sulfonamides (TMP-SMX), causing sequential block of folate synthesis
- used for UTIs, Shigella, Salmonella, PCP (treatment & prophylaxis)
110
Trimethoprim: Toxicity
Megaloblastic anemia, Leukopenia, Granulocytopenia
* * Treat Marrow Poorly
- May be alleviated with folinic acid (leuvovorin rescue)
111
Fluoroquinolones
"-floxacin" , "enoxacin", nalidixic acid
| Ciprofloxain, Norflozacin
112
Fluoroquinolones
Inhibit DNA gyrase (topoisomerase II) and topoisomerase IV)
- Don't take with antacids
- use to treat gram-negative rods of urinary and GI tracts (e.g Psuedomonas, Neisseria, gram-positive organisms)
113
Floroquinolones: Toxicity
GI upset
Superinfections
Skin rashes
Dizziness
- Can cause tendon rupture (esp. in Achilles tendon) in patients > 60
- Contraindicated in pregnant women and children because may damage cartilate
114
Floroquinolone: Resistance
Chromosome-encoded mutation in DNA gyrase
Plasma mediated resistance
Efflux pumps
115
Metronidazole
- forms free radical toxic metabolites in bacterial cell that damages DNA. Bactericdial, Antiprotozoal
- treats "GET GAP" - Giardia, Entoameoba, Trichomonas Gardnerella vaginalis, Anaerobes
- Used with proton pump inhibitor and clarithromycin for "triple therapy" for H. pylori
116
Metronidazole: Toxicity
Disulfram-like reactiin with alcohol
Headache
Metallic Taste
117
Treatment from M. tuberculosis
Prophylaxis: Isoniazid
Treatment: RIPE (Rifampin, Isoniazid, Pyrazinamide, Ethamutol)
118
Treatment for M. avium-intracellulaire
Prophylaxis: Azithromycin
Treatment: Azithromycin, Rifampin, Ethambutol, Streptomycin
119
Treatment for M. leprae
NO PROPHYLAXIS
Tuberculoid: Dapsone and Rifampin for 6 months
Lepromatous: Dapsone, Rifampin, Clofazimine for 2-5 years
120
Isoniazid:
- inhibits mycolic acid synthesis. Bacterial catalase-peroxidase (KatG) needed to convert INH to active form
- used for M. tuberculoisis. Only solo prophylaxis for TB
121
Isoniazid Metabolism
- Different INH half lives in fast vs. slow acetylators
| - seen in bi-modal plasma concentration graphs
122
Isoniazid: Toxicity
Neurotoxicity
Hepatotoxicity
Pyroxidine (VB6) can prevent neurotoxicity, lupus
B6 needed to make NTs (e.g. GABA)
123
Rifampin
- inhibits DNA dependent RNA polymerase
- treats M. tuberculosis
- delays resistance to dapsone when leprosy
- Used for meningococcal prophylaxis and chemoprophylaxis in contacts of children with H. influenzae type b
124
Rifampin: Toxicity
minor hepatotoxicity and drug interactions (increase in P-450)
Orange body fluids
125
Pyrazinamide
- uncertain mechanism but may acidify intracellular enviroment by converting to pyrazinoic acid
- effective in acidic pH of phagolysosomes where TB is engulfed by macrophages are found
- used to treat TB
126
Pyraniamide: Toxicity
Hyperuricemia, Hepatotoxicity
127
Ethambutol
- decreased carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
- treats TB
128
Ethambutol: Toxicity
optic neuritis
- central scotomas
- decreased visual acuity
- red-green color blindness
129
Prophylaxis for meningococcal infection
Ciprofloxacin (1st line)
| Rifampin for children
130
Prophylaxis for Gonorrhea
Ceftriazone
131
Syphilis prophylaxis
Penicillin G
132
Hx of recurrent UTIs
Penicillins
133
Encocarditis with surgical or dental procedures - Prophylaxis
Penicillins
134
Pregnant women carrying Group B Strep prophylaxis
Intrapartum ampicillin
135
Prophylaxis of strep pharyngitis in child with prior rheumatic fever
Oral penicillin
136
Prevention of post surgical infection due to S. aureus
Cefazolin
137
Prevention of gonoccocal or chlamydial conjunctivitis in newborn
Erythomycin ointment
138
HIV prophylaxis : CD4 < 200 cells/mm3
TMP-SMX to prevent PCP pneumonia
139
HIV prophylaxis: CD4 < 100 cells/mm3
TMP-SMX to prevent PCP pneumonia and Toxoplasmosis
140
HIV prophylaxis: CD4 < 50 cells/mm3
Azithromycin to prevent M. avium complex
141
Treatment of Vancomycin Resistance Enterococci
Linezolid
| Streptogramins (Quinupristin/Dalfopristin)
142
Amphotericib B
- binds to ergosterols in fungi - forms membrane pores that allow leakage of electrolytes
- treats systemic mycoses (Cryptococcus, Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
- Intrathecally for fungal meningitis
- Supplement K and Mg for altered renal tubule permeability
143
Amphotericin B: Toxicity
```
Fever/chills ("shake and bake")
Hypotension
Nephrotoxicity
IV phlebitis
Hydration reduces nephrotoxicity
Liposomal amphotericin reduces toxicity
```
144
Nystatin
- bind to ergosterols
- can only be used topically
- used to treat oral candiadis (thrush)
- topic for diaper rash or vaginal candiadiasis
145
Azoles
- inhibit fungal sterol (ergosterol) synthesis by inhibiting P-450 enzyme that converts lanosterol to ergosterol
- treats local and less serious mycoses
146
Fluconazole
used for chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types
147
Itraconazole
treats Blastomycoses, Coccidoides, Histoplasma
148
Clotrimazole and Miconazole
treats topical fungal infections
149
Azoles: Toxicity
testerone synthesis inhibition - leads to gynecomastia esp. with ketoconazole
- Liver dysfunction (inhibits P-450)
150
Flucytosine:
- inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytoseine deaminase
- used in systemic fungal infections (esp. in meningitis caused by Cryptococcus) in combination with amphotericin B
TOXICITY:: causes bone marrow suppression
151
Caspofungin, Micafungin
inhibits cell wall synthesis by inhibiting synthesis of B-glucan
- treats invasive aspergillosis, Candida
** associated with GI upset, flushing (histamine release)
152
Terbinafine
- inhibits fungal enzyme 2,3 squalene epoxide (thus inhibiting sterol synthesis)
- used to treat dermatophytes (esp. fungal infections of skin and nails)
** associated with abnormal LFTs, visual disturbances
153
Griseofulvin
- interferes with microtubule function; disrupts mitosis.
- deposits in keratin containing tissues (e.g. nails)
- used for oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
154
Griseofulvin: Toxicity
```
teratogenic
carcinogenic
confusion
headaches
-increase P450 and warfarin metabolism
```
155
Antiprotozan therapy
Pyrimethamine (toxoplasmosis)
Suramin and Melarsoprol (T. cruzei)
Nifuritmox (T. cruzei)
Sodium Stibogluconate (Leischmaniasis)
156
Chloroquine
- blocks detoxification of heme into hemoizin. Heme accumulates and is toxic to plasmodia
- treats plasmodial species EXCEPT P. falciprum (resistance too high)
* * resistance due to membrane pump that decreases intracellular concentration of drug
* ** associated with retinopathy
157
Treatment of P. falciprum
- treatment with artemether/lumifantrine
| - atovaquone/proguanil
158
Antihelminthic therapy
Metrobendole
Pyrantel pamoate
Ivermectin
Diethycarbamazine
159
Zanamivir
inhibit influenza neuraminase, decreasing release of progeny virus
- treats and prevents both influenza A and B
160
Ribavirin
inhibits synthesis of guanine nucleotide by competively inhibiting IMP dehydrogenase
- used to treat RSV, chronic Hep C
* ** associated with hemolytic anemia
* * Severe teratogen
161
Acyclovir
- monophosphoryalated by HSV/VZV thymidine kinase
- Guanosine analog
- Triphosphate formed by cellular enzymes. Preferentially inhibits viral DNA polymerase by chain termination
162
Acyclovir: Use
- treats HSV and VZV
- Weak against EBV
- NO ACTIVITY against CMV
- Used for mucotaneous and genital lesions and for encephalitis
- Prophylaxis in immunocompromised patients
- Valacyclovir, a prodrug has better oral bioavailability
* * Few serous side effects
163
Acyclovir Resistance
Mutated viral thymidine kinase
164
Ganciclovir
5'-monophophate formed by a CMV viral kinase
Guanosine analong
Triphosphate formed by cellular kinases
Preferentially inhibits viral DNA polymerase
- treats CMV esp in immunocompromised patients
- Valganiclovir - has better oral bioavailability
165
Ganciclovir: Toxicity
mutated CMV DNA polymease or lack of viral kinase
166
Foscarnet
- viral DNA polymerase inhibitor that binds to pyrophosphate binding site of enzyme
- does not require activation by viral enzyme
- treats CMV retinits in immunocompromised patients when ganciclovir fails
- treats acyclovir resistant HSV
** associated with nephrotoxicity
167
Forscarnet Resistance
mutated DNA polymerase
168
Cidofovir
preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase
- CMV retinintis in immunocompromised patients
- acyclovir resistant HSV
- Long half-ide
*** associated with nephrotoxicity (coadminister with probenecid and IV saline to reduce toxicity
169
HIV therapy
HAART - highly active antiretroviral therapy
- 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
170
HIV therapy HAART cocktail
```
TWO NRTIs (nucleoside reverse transcriptase) +
1 non-nucleoside reverse transcriptase inhibitor OR 1 protease inhibitor OR integrase inhibitor
```
171
Protease inhibitors ("-inavirs")
Assembly of virions depends on HIV-1 protease which cleaves polypeptide products of HIV mRNA into their functional parts
- Protease inhibitors prevent maturation of new viruses
172
Ritonavir and drug concentrations
Ritonavir can book other drug concentrations by inhibiting cytochrome P-450
173
Protease inhibitor (-inavir) Toxicity
```
Hyperglycemia
GI intolerance (nausea, diarrhea)
Lipodystrophy
Nephropathy
Heamturia (assciated with indinavir)
```
174
NRTIs ("-vudine"), Emtrictabine, Abacavir, Didanosine
- competitively inhibit nucleotide binding to reverse transcriptase and terminate DNA chain (lack a 3' OH group)
175
Special note about NRTI activation
Tenofovir is a nucleoTide analog and doesn't have to be activated
Other NRTIs are nucleoSide analog and have to be phosphorylated to bec active
176
Drug used for HIV prophylaxis and during pregnancy to reduce risk of fetal transmission
Zidovudine
| - formerly known as AZT
177
NRTI Toxicity
```
Bone marrow suppression
- can be reversed with G-CSF and erythropoietin
Peripheral neuropathy
Lactic acidosis (nucleosides)
Anemia (ZDV/ AZT)
```
178
Non- Nucleoside Reverse Transcriptase INhibitors
Nevirapine, Efavirenz, Delavirdine
179
NNRTIs
bind to reverse transcriptase at site different from NRTIs
| - do not require phosphorylation to be active or compete with nucleotides
180
NNRTI Toxicity
Bone marrow suppression (can be reversed with G-CSF and erythropoietin)
Peripheral neuropathy
Rash
181
Raltegravir
inhibits HIV genome integration into host cell chromosome by reversible inhibiting HIV integrase
** associated with hypercholestermias as toxicity
182
Interferons
- glycoproteins synthesized by virus-infected cells; block replication of both RNA and DNA viruses
183
IFN-alpha as treatment
- treats chronic hepatitis B and C, Kaposi's sarcoma
184
IFN-alpha
treats Multiple sclerosis
185
IFN-gamma
treats NADPH oxidase deficiency
186
IFN- Toxicity
Neutropenia, Myopathy
187
Sulfonamide effect on pregnacy
Kernicterus (accumulation of bile in the brain - associated with sever jaundice in newborns)
188
Aminoglycosides' effect on pregnacy
Ototoxicity
189
Floroquinolones' effect on fetus
Cartilage damage
190
Clarithromycin's effect on fetus
Embryotoxic
191
Tetracyclines' effect on fetus
Discolored teeth
| Inhibition of bone growth
192
Ribavirin (antiviral) effect on fetus
Teratogenic
193
Griseofulvin (anti-fungal) effect on fetus
Teratogenic
194
Chloramphenicol effect on fetus
"Gray baby"
