Antimicrobials Flashcards
(137 cards)
1
Q
Penicillin G,V: Clinical use
A
Mostly used for gram + organisms (S.pneumo, S.pyogenes, Actinomyces
Also used for gram - cocci (N.meningitidis) and spirochetes (T.pallidum)
Bacteriocidal for Gram + cocci, Gram + rods, Gram - cocci and spirochetes
Penicillinase sensitive
2
Q
Penicillin G,V: Adverse effects
A
Hypersensitivity reactions
direct Coomb’s positive hemolytic anemia
3
Q
Penicillin G,V: resistance
A
Penicillinase in bacteria (a type of beta-lactimase) cleaves the beta-lactam ring
4
Q
Penicillin G,V: Mechanism
A
D-Ala-D-Ala structural analog. Binds penicillin binding protein (PBP) a transpeptidase
Blocks transpeptidase cross-linking of peptidoglycan in cell wall
Activates autolytic enzymes
5
Q
Penicillinase-sensitive penicillins: Mechanism
A
Amoxicillin, ampicillin, aminopenicillins
Same as penicillin (PBP protein blocking transpeptidation)
Wider spectrum; penicillinase sensitive. Also combine with clavulanic acid to protect against destruction by beta-lactamases
AMinoPenicillins are AMPed-up penicillin. AmOxicillin has greater Oral bioavailability than ampicillin
6
Q
Penicillinase-sensitive penicillins: Clinical Use
A
Amoxicillin, ampicillin, aminopenicillins
Extended spectrum penicillin - H.influenzae, H.pylori, E.coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, enterococci
Coverage: ampicillin/amoxicillin HHELPSS kill enterococci
7
Q
Penicillinase-sensitive penicillins: Adverse Effects
A
Amoxicillin, ampicillin, aminopenicillins
Hypersensitivity reactions, rash, pseudomembrane colitis
8
Q
Penicillinase-sensitive penicillins: Resistance
A
Amoxicillin, ampicillin, aminopenicillins
Penicillinase in bacteria (type of beta lactamase) cleaves beta-lactam ring
9
Q
Penicillinase-resistant penicillins: Mechanism
A
Dicloxacillin, nafcillin, oxacillin
Same as penicillin (PBP binding so transpeptidation cannot occur)
Narrow spectrum; penicillinase resistant because of bulky R group which blocks access of beta-lactamase to beta-lactam ring
10
Q
Penicillinase-resistant penicillins: Clinical Use
A
Dicloxacillin, nafcillin, oxacillin
S.aureus (except MRSA; resistant because of altered PBP target site)
Use naf for staph
11
Q
Penicillinase-resistant penicillins: adverse effects
A
Dicloxacillin, nafcillin, oxacillin
Hypersensitivity reactions; interstitial nephritis
12
Q
Antipseudomonal penicillins
A
Piperacillin, ticarcillin
MOA: same as penicillin but extended spectrum
Clinical use: pseudomonas spp. And gram - rods; susceptible to penicillinase; used with beta lactamase inhibitors
SEs: hypersensitivity reactions
13
Q
Beta-lactamase inhibitors
A
Include Clavulanic Acid, Sulbactam and Tazobactam
Often added to penicillin antibiotics to protect from antibiotic destruction
14
Q
Cephalosporins: Mechanism
A
Beta lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases
Bactericidal
Organisms typically not covered by 1-4th generation are LAME
-Listeria, Atypicals (chlamydia, mycoplasma), MRSA, and Enterococci
Exception is ceftaroline (5th gen)
15
Q
Clinical use of 1st gen cephalosporins
A
Cefazolin, cephalexin
Gram + cocci
PEcK
Proteus mirabilis, E.coli, Klebsiella pneumoniae
Cefazolin used prior to surgery to prevent S.aureus wound infections
16
Q
Clinical use of 2nd gen cephalosporins
A
Cefaclor, cefoxitin, cefuroxime (Fake fox fur)
Gram + cocci
HENS PEcK
H.influenzae, Enterobacter aerogenes, Neisseria spp, Serratia marcescens, Proteus mirabilis, E.coli, Klebsiella pneumoniae
17
Q
Clinical use for 3rd gen cephalosporins
A
Ceftriaxone, cefotaxime, ceftazidime
Serious gram - infections resistant to other beta lactams
Ceftriaxone - meningitis, gonorrhea, disseminated Lyme disease
Ceftazidime - pseudomonas
18
Q
Clinical use of 4th gen cephalosporins
A
Cefepime
Gram - organisms with increased activity against pseudomonas and gram + organisms
19
Q
Clinical use for 5th gen cephalosporins
A
Ceftaroline
Broad gram + and gram - organism coverage, including MRSA
Does not cover pseudomonas
20
Q
Cephalosporins: adverse effects
A
Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, Exhibit cross reactivity with penicillins, increased nephrotoxicity of aminoglycosides
21
Q
Cephalosporins: resistance
A
Structural change in PBP (transpeptidases)
22
Q
Carbapenems: Mechanism
A
Imipenem, meropenem, ertapenem, doripenem
Imipenem- broad spectrum, beta-lactamase resistant carbapenem. Always administered with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules (the kill is lastin’ with cilastatin)
23
Q
Carbapenems: clinical use
A
Imipenem, meropenem, ertapenem, doripenem
Gram + cocci, gram - rods and anaerobes
Wide spectrum, but significant SEs limit use to life-threatening infections or after other drugs that have failed.
Meropenem has a decreased risk of seizures and is stable to dehydropeptidase
24
Q
Carbapenems: Adverse Effects
A
Imipenem, meropenem, ertapenem, doripenem
GI distress, skin rash, CNS toxicity (seizures) at high plasma levels
25
Monobactams: Aztreonam
MOA: less susceptible to beta-lactamases. Prevents peptidoglycan cross-linking by binding PBP 3. Synergistic with aminoglycosides. No cross-allergenicity with penicillins
Clinical Use: gram - rods only, no activity against gram + rods or anaerobes. For penicillin-allergic pts and those with renal insufficiency who cannot tolerate aminoglycosides
SEs: usually non-toxic, occasional GI upset
26
Vancomycin: Mechanism
Inhibits cell wall peptidoglycan from forming by binding D-ala-D-aka portion of cell wall precursors.
Bactericidal against most bacteria (bacteriostatic against C.difficile)
Not susceptible to beta-lactamases
27
Vancomycin: Clinical Use
Gram + bugs only
Serious, mutlidrug resistant organisms, including MRSA, S.epidermidis, sensitive Enterococci species, and Clostridium difficile (oral dose for pseudomembranous colitis)
28
Vancomycin: Adverse Effects
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)
29
Vancomycin: resistance
Occurs in bacteria via amino acid modification
D-ala-D-ala to D-ala-D-lac
*Pay back 2 D-alas (dollars) for vandalizing (vancomycin)*
30
Protein synthesis inhibitors
Specifically target smaller bacterial ribosomes (70S=30S+50S) leaving the human ribosome (80S) unaffected
30S inhibitors: Aminoglycosides and Tetracyclines
50S inhibitors: chloramphenicol, Clindamycin, Erythromycin (macrolides), Linezolid
*Buy AT 30, CCEL at 50*
31
Aminoglycosides: Mechanism
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
*Mean (aMINoglycosides) GNATs caNNOT kill anaerobes*
Bactericidal; irreversible inhibition of initiation complex through binding of the 30S subunit
Can cause misreading of mRNA. Also block translocation. Require O2 for uptake therefore are ineffective against anaerobes
32
Aminoglycosides: Clinical Use
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
Severe gram - rod infections. Synergistic with beta-lactam antibiotics
Neomycin for bowel surgery
33
Aminoglycosides: Adverse effects
Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin
| Nephrotoxicity, Neuromuscular blockade, Ototoxicity (esp. When used with loop diuretics), Teratogen
34
Aminoglycosides: Resistance
Bacterial transferase enzymes inactivate the drug by acetylation, phosphorylation or adenylation
35
Tetracyclines: Mechanism
Tetracycline, doxycycline, minocycline
Bacteriostatic
Bind to 30S and prevent attachment of aminoacyl tRNA; limited CNS penetration.
Doxycycline is recalls eliminated and can be used in pts with renal failure. Do not take tetracyclines with milk (Ca2+), antacids (Ca2+ or Mg2+), or iron-containing preparations because diva lent cations inhibit drugs absorption in the gut
36
Tetracyclines: Clinical use
Tetracycline, doxycycline, minocycline
Borrelia burgodorferi, M.pneumoniae
Drugs' ability to accumulate intracellularly makes them very effective against Rickettsia and Chlamydia
Also used to treat acne
37
Tetracylcines: Adverse Effects
Tetracycline, doxycycline, minocycline
GI distress, discoloration of tweet and inhibition of bone growth in children, photosensitivity
Contraindicated in pregnancy
38
Tetracyclines: Resitance
Decreased uptake or increased efflux out of bacterial cells by plasmid encoded transport pumps
39
Chloramphenicol: mechanism
Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic
40
Chloramphenicol: Clinical Use
Meningitis (H.influenzae, Neisseria meningitidis, S.pneumoniae) and RMSF (rickettsia rickettsii)
Limited use owing to toxicities but often used in developing countries due to lost cost
41
Chloramphenicol: Adverse Effects
Anemia and aplastic anemia (both dose dependent), gray baby syndrome (in premature infants because they lack liver UDP-glucoronyl transferase
42
Chloramphenicol: resistance
Plasmid encoded acayltransferases inactivate drugs
43
Clindamycin: Mechanism
Blocks peptide transfer (translocation) at 50S ribosomal subunit. Bacteriostatic
44
Clindamycin: Clinical use
Anaerobic infections (Bacteroides spp, Clostridium perfringens) in aspiration pneumonia, lung abscesses and oral infections
Also effective against invasive group A strep infection
Treats anaerobic infections ABOVE the diaphragm vs. metronidazole (anaerobic infections BELOW diaphragm)
45
Oxazollidinones (Linezolid)
MOA: inhibit protein synthesis by binding to the 50S subunit and preventing formation of the initiation complex
Clinical use: gram + species including MRSA and VRE
SEs: BM suppression (esp thrombocytopenia), peripheral neuropathy, 5HT syndrome
Resistance: point mutation of ribosomal RNA
46
Macrolides: Mechanism
Azithromycin, clarithromycin, erythromycin
Inhibit protein synthesis by blocking translocation (*macroSLIDES*)
Bind to the 23S rRNA of the 50S subunit
Bacteriostatic
47
Macrolides: Clinical use
Atypical pneumoniae (mycoplasma, chlamydia, legionella), STIs (chlamydia), gram + cocci (strep infections in pts allergic to penicillin) and B.pertussis
48
Macrolides: Adverse Effects
Azithromycin, clarithromycin, erythromycin
*MACRO*: gastrointestinal Motility issues, Arrhythmia caused by prolonged QT interval, acute Cholestatic hepatitis, Rash, eOsiniophilia.
Increases serum concentration of theophylline, oral anticoagulants. Clarithromycin and erythromycin inhibit CYP450
49
Macrolides: Resistance
Azithromycin, clarithromycin, erythromycin
| Methylation of 23S rRNA-binding site prevents binding of drug
50
Sulfonamides: mechanism
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
Inhibit dihyrdopteroate synthase, thus inhibiting folate synthesis
Bacteriostatic (bactericidal when combined with trimethoprim)
51
Sulfonamides: Clinical use
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
| Gram +, gram -, nocardia, chlamydia, SMX for simple UTI
52
Sulfonamides: Adverse effects
Hypersensitivity reaction, hemolysis of G6PD deficient, nephrotoxicity (tubulointersitial nephritis), photosensitivity, kernicterus in infants, displace other drugs from albumin (eg warfarin)
53
Sulfonamides: resistance
```
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
Altered enzyme (bacterial dihyrdopteroate synthase), decreased uptake or increased PAABA synthesis
```
54
Dapsone
MOA: similar to Sulfonamides, but structurally distinct
Clinical use: leprosy (lepromatous, tuberculoid), pneumocystis jirovecci prophylaxis
SEs: hemolysis if G6PD deficient
55
Trimethoprim
MOA: inhibits bacterial dihydrofolate reductase. Bacteriostatic
Clinical use: used in combo with sulfonamides (TMP-SMX) causing sequential block of folate synthesis; combination used for UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia treatment and prophylaxis, toxoplasmosis prophylaxis
SEs: megaloblastic anemia, leukopenia, granulocytopenia (may alleviate with supplemental folinic acid)
*TMP Treats Marrow Poorly*
56
Fluroquinolones: Mechanism
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
Inhibit prokaryotic enzymes topoisomerase II (DNA grade) and topoisomerase IV
Bactericidal
Must not be taken with antacids
57
Fluoroquinolones: Clinical use
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
Gram - rods of urinary and GI tracts (including pseudomonas), Neisseria, some gram + organisms
58
Fluoroquinolones: Adverse Effects
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
GI upset, superinfections, skin rashes, HA, dizziness
Less commonly: leg cramps and myalgias
Contraindicated in pregnant women, nursing mothers, children
59
Fluoroquinolones: Resistance
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
Chromosome encoded mutation in DNA grade, plasmid mediated resistance, efflux pumps
60
Daptomycin
Mechanism: lipopeptide that disrupts cell membrane of gram + cocci
Clinical use: S.aureus skin infections (esp MRSA), bacteremia, endocarditis, VRE
Not used for pneumonia (avidly binds and inactivates surfactant)
SEs: myopathy, rhabdomyolysis
61
Metronidazole: Mechanism
Forms toxic free radical metabolites in the bacterial cell that damage DNA
Bactericidal, antiprotozoal
62
Metronidazole: Clinical Use
Treats Giardiasis, Entamoeba, Trichomonas, Gardnerella vaginalis, Anaerobes (Bacteroides, C.difficile)
Used with PPI and Clarithromycin for "triple therapy" against H.pylori
*GET GAP on Metro with metronidazole*
Treat infections below the diaphragm
63
Antimicrobial drugs: for M.tuberculosis
Prophylaxis: Isoniazid
Treatment: Rifampin, Isoniazid, Pyrazinamide, Ethambutol (RIPE)
64
Antimicrobial drugs: for M.avium-intracellular even
Prophylaxis: Azithromycin, rifabutin
Treatment: more drug resistant that M.tb - Azithromycin or Clarithromycin + ethambutol (can add rifabutin or ciprofloxacin)
65
Antimicrobial drugs: for M.leprae
no prophylaxis
| Treatment: long term with dapsone and rifampin for tuberculoid form, add clofazimine for lepromatous form
66
Rifamycins (Rifampin, Rifabutin): mechanism
```
Inhibit DNA-dependent RNA polymerase
*4 Rs of Rifampin*
RNA polymerase inhibitors
Ramps up microsomal CYP450 (not rifabutin)
Red/Orange body fluid
Rapid resistance if used alone
```
67
Rifamycins (Rifampin, Rifabutin): clinical use
Mycobacterium tuberculosis; delay resistance to dapsone when used for leprosy
Used for meningococcal prophylaxis and chemoprophylaxis in contact of children with HiB
68
Rifamycins (Rifampin, Rifabutin): adverse effects
Minor hepatotoxicity and drug interactions (increases CYP450)
Orange body fluids (nonhazardous)
Rifabutin favored over rifampin in pts with HIV infection due to les CYP450 stimulation
69
Isoniazid: Mechanism
Decreased synthesis of mycolic acids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolite
70
Isoniazid: clinical use
Mycobacterium tuberculosis
The only agent used as solo prophylaxis against TB. Also used as monotherapy for latent TB
Different INH half lives in fast vs slow acetylators
71
Isoniazid: adverse effects
Hepatoxicity, P450 inhibition, drug induced SLE, Vitamin B6 deficiency (peripheral neuropathy, sideroblastic anemia). Administer with pyridoxine (B6)
INH: Injures Neurons and Hepatocytes
72
Isoniazid: resistance
Mutations leading to underexpression of KatG
73
Pyrazinamide
MOA: uncertain, Pyrazinamide is a prodrug that is converted to the active compound pyrazinoic acid. Works best at acidic pH (host phagolysosomes)
Clinical: mycobacterium tuberculosis
SEs: hyperuricemia, hepatotoxicity
74
Ethambutol
MOA: decreased carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
Clinical use: mycobacterium tuberculosis
SEs: optic neuropathy (red-green color blindness) (*EYEthambutol*)
75
Streptomycin
MOA: interferes with 30S component of ribosome
Clinical use: mycobacterium tuberculosis (second line)
SEs: tinnitus, vertigo, ataxia, nephrotoxicity
76
Antimicrobial prophylaxis: amoxicillin
High risk for endocarditis and undergoing surgical or dental procedures
77
Antimicrobial prophylaxis: Ceftriaxone
Exposure to gonorrhea
78
Antimicrobial prophylaxis: TMP-SMX
History of recurrent UTIs
79
Antimicrobial prophylaxis: Ceftriaxone, ciprofloxacin or rifampin
Exposure to meningococcal infection
80
Antimicrobial prophylaxis: intrapartum penicillin G or ampicillin
Pregnant woman carry group B strep
81
Antimicrobial prophylaxis: erythromycin ointment of eyes
Prevention of gonococcal conjunctivitis in newborn
82
Antimicrobial prophylaxis: Cefazolin
Prevention of post-surgical infection due to S.aureus
83
Antimicrobial prophylaxis: benthazine penicillin G or oral penicillin V
Strep pharyngitis in a child with prior rheumatic fever
84
Antimicrobial prophylaxis: benzathine penicillin G
Exposure to syphilis
85
Prophylaxis in HIV pts: CD4
TMP-SMX
| For pneumocystis pneumonia
86
Prophylaxis in HIV pts: CD4
TMP-SMX
| Pneumocystis pneumonia and toxoplasmosis
87
Prophylaxis in HIV pts: CD4
Azithromycin or Clarithromycin
| Mycobacterium avium complex
88
Treatment for MRSA
Vancomycin, daptomycin, Linezolid, tigecycline, ceftaroline
89
Treatment for VRE
Linezolid and streptogramins (quinipristin, dalfopristin)
90
Treatment of multidrug resistant P aeruginosa & acinetobacter
Polymixins B & E (colistin)
91
Amphotericin B: mechanism
```
Binds ergosterol (unique to fungi) and forms membrane pores that allow leakage of electrolytes
*amphoTERicin "TEARs" holes in the fungi membrane
```
92
Amphotericin B: Clinical use
Serious, systemic mycoses
Cryptococcus (+/- flu cytosine for cryptococcal meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor
Intrathecally for fungal meningitis
Supplement K+ & Mg2+ because of altered renal tubule permeability
93
Amphotericin B: Adverse effects
Fevers/chills (shake and bake), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (amphoterrible).
Hydration decreases nephrotoxicity
Liposomal amphotericin decreases toxicity
94
Nystatin
MOA: same as amphotericin B (pokes holes in membrane)
| Clinical use: swish and swallow for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis
95
Flucytosine
MOA: inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase
Clinical use: systemic fungal infections (esp meningitis caused by Cryptococcus) in combo with amphotericin B
SEs: BM suppression
96
Azoles
MOA: inhibit fungal sterol (ergosterol) synthesis by inhibiting CYP450 enzyme that converts lanosterol to ergosterol
Clinical use: local and less serious systemic mycoses
-fluconazole from chronic suppression of cryptococcal meningitis in AIDS pts and candidal infections of all types
-Itraconazole for Blastomyces, Coccidioides, Histoplasma
-Clotrimazole and miconazole for all types of fungal infections
SEs: testosterone synthesis inhibition (gynecomastia esp in ketoconazole) liver dysfunction (inhibits CYP450)
97
Terbinafine
MOA: inhibits fungal enzyme squalene epoxidase
Clinical use: dermatophytoses (esp onychomycosis -fungal infection of finger or toenail)
SEs: GI upset, HA, hepatotoxicity, taste disturbance
98
Enchinocandins
Anidulafungin, caspofungin, micafungin
MOA: inhibit cell wall synthesis by inhibiting synthesis of beta-glucan
Clinical use: invasive aspergillosis, Candida
SEs: GI upset, flushing (by histamine release)
99
Griseofulvin
MOA: interferes with microtubule function; disrupts mitosis. Deposits in keratin containing tissues (nails)
Clinical use: oral treatment of superficial infections, inhibits growth of dermatophytes (tinea, ringworm)
SEs: teratogenic, carcinogenic, confusion, HA, increased CYP450 and warfarin metabolism
100
Antiprotozoan therapy
Pyrimethamine - toxoplasmosis
Suramin and melarsoprol - trypanosoma brucei
Nifurtimox - T.cruzi
Sodium stibogluconate - leishmaniasis
101
Chloroquine
MOA: blocks detoxification of heme into hemozoin. Heme accumulates and is toxic to plasmodia
Clinical use: treatment of plasmodial species other than P.falciparum (frequency of resistance is too high); resistance due to membrane pump that decrease intracellular concentration of drug.
-treat P.falciparum with artemether/lumefantrine or atovaquone/proguanil
-for life threading malaria use quinidine in USA (quinine elsewhere) or artesunate
SEs: retinopathy, pruritis (esp in dark skinned individuals)
102
Antihelminthic therapy
Mebendazole (microtubule inhibitor), pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel
103
Oseltamivir, zanamivir
MOA: inhibit influenza neuraminidase to decrease release of progeny virus
Clinical use: treatment and prevention of both influenza A & B
104
Acyclovir, famciclovir, valcyclovir: Mechanism
Guanosine analogs
Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells (fewer SEs)
Triphosphate formed by cellular enzymes
Preferentially inhibit viral DNA polymerase by chain termination
105
Acyclovir, famciclovir, valacyclovir: clinical use
```
HSV & VZV
-mucocutaneous and genital lesions as well as for encephalitis
-no effect on latent forms
Weak activity agains EBV
No activity against CMV
Prophylaxis in immunocompromised pts
Valacyclovir: prodrug of acyclovir, better bioavailability
herpes zoster - famciclovir
```
106
Acyclovir, famciclovir, valacyclovir: adverse effects
Obstructive crystalline nephropathy and acute renal failure if not adequately hydrated
107
Acyclovir, famciclovir, valacyclovir: Resistance
Mutated viral thymidine kinase
108
Ganciclovir
MOA: 5'-monophosphate formed by a CMV viral kinase; guanosine analog, triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase
Clinical use: CMV, esp immunocompromised pts (Valganicilovir - prodrug - has better bioavailability)
SEs: BM suppression (leukopenia, neutropenia, thrombocytopenia), renal toxicity
-more toxic to host enzymes than acyclovir
Resistance: mutated viral kinase
109
Foscarnet
MOA: viral DNA/RNA polymerase inhibitor and HIV RT inhibitor; binds to pyrophosphate-binding site of enzyme; does not require kinase activation
Clinical use: CMV retinitis in immunocompromised pts when ganciclovir fails; acyclovir resistant HSV
SEs: nephrotoxicity, electrolyte abnormalities which can lead to seizures
Resistance: mutated DNA polymerase
110
Cidofovir
MOA: preferentially inhibits viral DNA polymerase. Does not require phosphorylation by viral kinase
Clinical use: CMV retinitis in immunocompromised pts; acyclovir resistant HSV. Long half-life
SEs: nephrotoxicity (coadminister with probenecid and IV saline to decrease toxicity)
111
HIV therapy
Highly active antiretroviral therapy (HAART): often initiated at the time of HIV diagnosis
Strongest indication for pts presenting with AIDS-defining illness, low CD4 count (
112
NTRIs
Abacavir (ABC), didanosine (ddl), Emtricitabine (FTC), Lamivudine (3TC), Stavudine (d4T), Tenofovir (TDF), Zidovudine (ZDV, formally AZT)
113
NTRIs: mechanism
Competitively inhibit nucleotide binding to RT and terminate the DNA chain (lack a 3'OH group)
Tenofovir is an nucleoTide; the others are nucleosides and need to be phosphorylated to be active
ZDZ can be used for general prophylaxis and during pregnancy to decrease risk of fetal transmission
*HaVE YOU DINED (vudine) with my nuclear (nucleosides) family?*
114
NTRIs: toxicity
```
BM suppression (can be reversed with G-CSF and EPO), peripheral neuropathy, lactic acidosis (nucleosides), anemia (ZDV), pancreatitis (didanosine)
Abacavir contraindicated if pt has HLA-B5701 mutation
```
115
NNTRIs
Delavirdine
Efavirenz
Nevirapine
116
NNTRIs: mechanism
Bind to RT at site different from NTRIs
| Do not require phosphorylation to be active or compete with nucelotides
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NNTRIs: toxicity
Rash and hepatotoxicity are common to all NNTRIs
efavirenz- vivid dreams and CNS symptoms
Delavirdine and efavirenz are contraindicated in pregnancy
118
Protease inhibitors
Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir
*Navir (never) tease a protease*
119
Protease inhibitors: mechanism
Assembly of visions depends on HIV-1 protease (pol gene) which cleaves the polypeptide products of HIV mRNA into their functional maturation of new viruses
Ritonavir can boost other drugs concentrations by inhibiting CYP450
120
Protease inhibitors: toxicity
hyperglycemia, GI intolerance (nausea/diarrhea), lipodystrophy (Cushing-like syndrome)
Nephropathy, hematuria (Indinavir)
Rifampin (a potent CYP/UGT inducer) contraindicated with protease inhibitors because it can decrease the protease concentration
121
Integrase inhibitors
Raltegravir
Elvitegravir
Dolutegravir
*tegra* in common
122
Integrase inhibitors: mechanism
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
123
Integrase inhibitors: toxicity
Increased creatine kinase
124
Fusion inhibitors: Enfuvirtide
MOA: binds gp41, inhibiting viral entry
SEs:: skin reaction at injection sites
125
Fusion inhibitors: maraviroc
Binds CCR-5 on surface of Tcells/monocytes, inhibiting interaction with gp120
126
Interferons: Mechanism
Glycoproteins normally synthesized by virus infected cells, exhibiting a wide range of antiviral and antitumoral properties
127
Interferons: clinical use
IFN-alpha: chronic hepatitis B&C, Kaposi sarcoma, hairy cell leukemia, condyloma acuminatum, renal cell carcinoma and malignant melanoma
IFN-beta: MS
IFN-gamma: chronic granulomatous disease
128
Interferons: Adverse Effects
Flu-like symptoms, depression, neutropenia, myopathy
129
HepC therapy: Ribavirin
MOA: inhibits synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate hydrogenated
Clinical use: chronic HCV, also used in RSV (palivizumab preferred in children)
130
HepC therapy: Sofosbuvir
MOA: inhibits HCV RNA-dependent RNA polymerase acting as a chain terminator
Clinical Use: chronic HCV in combo with Ribavirin +/- peginterferon alpha
-do not use as monotherapy
SEs: fatigue, HA, nausea
131
HepC therapy: SImeprevir
MOA: HCV protease inhibitor; prevents viral replication
Clinical use: chronic HCV in combo with ledipasvir (NS5A inhibitor)
-do not use as monotherapy
SEs: photosensitivity reactions, rash
132
Autoclave
Pressurized steam at >120 degrees C
| May be sporicidal
133
Alcohols
Denature proteins and disrupt cell membrane
| Not sporicidal
134
Chlorhexidine
Denatures proteins and disrupts cell membranes
| Not sporicidal
135
Hydrogen peroxide
Free radical oxidation
| Sporicidal
136
Iodine and iodophors
Halogenation of DNA, RNA & proteins
| May be sporicidal
137
Antimicrobials to avoid in pregnancy
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*SAFe Children Take Really Good Care*
Sulfonamides - kernicterus
Aminoglycosides - Ototoxicity
Fluoroquinolones - cartilage damage
Clarithromycin - embryotoxic
Tetracyclines - Discolored teeth, inhibition of bone growth
Ribavirin - teratogenic
Griseofulvin - teratogenic
Chloramphenicol - gray baby syndrome
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