Antimircobials Flashcards
(170 cards)
1
Q
Folic acid synthesis (DNA methylation) inhibitors
A
Sulfonamides
Trimethoprim
2
Q
DNA topoisomerase inhibitor
A
Fluoroquinolones
3
Q
Damages DNA
A
Metronidazole
4
Q
mRNA synthesis (RNA polymerase) inhibitor
A
Rifampin
5
Q
Protein synthesis (50S subunit) inhibitors
A
Chloramphenicol, Clindamycin, Linezolid
Macrolides
Streptogramins
6
Q
Protein synthesis (30S subunit) inhibitors
A
Aminoglycosides
Tetracyclines
7
Q
Peptidoglycan cross-linking (of the cell wall) inhibitors
A
Penicillinase-sensitive penicillins Penicillinase-resistant penicillins Antipseduomonals Cephalosporins (I-V) Carbapenems Monobactams (Aztreonam)
8
Q
Peptidoglycan synthesis (of the cell wall) inhibitors
A
Glycopeptides (bacitracin, vancomycin)
9
Q
Penicillinase-sensitive penicillins
A
Amoxicillin
Ampicillin
Penicillin G, V
10
Q
Pencillinase-resistant penicillins
A
Dicloxacillin
Nafcillin
Oxacillin
11
Q
Antipseudomonals
A
Piperacillin
Ticarcillin
12
Q
Cephalosporins (I-V)
A
1st-Cefazolin, Cephalexin (1 ZObra named LEXI) 2nd-Cefoxitin, Cefaclor, Cefuroxime (2 FOXes went into the FACtory and came out as FUR) 3rd-Ceftriaxone (3 taxidermists TRI to sell a DIMEsaur) 4th-Cefepime (I'm + 4 PIMEcones turned green/blue) 5th-Ceftaroline (5 TARred birds are MRSArible)
13
Q
Carbapenems
A
Doripenem
Imipenem
Meropenem
Ertapenem
14
Q
Aminoglycosides
A
Gentamicin Neomycin Amikacin Tobramycin Streptomycin Min (amino) GNATS caNNOT kill anerobes
15
Q
Tetracyclines
A
Doxycline
Minocyline
Tetracycline
16
Q
Macrolides
A
Azithromycin
Clarithromycin
Erthyromycin
17
Q
Streptogramins
A
Dalfopristin
Quinupristin
18
Q
Fluoroquinolones
A
Ciprofloxacin
Levofloxacin
19
Q
Sulfonamides
A
Sulfadiazine
Sulfamethoxazole
Sulfisoxazole
20
Q
Penicillin G, V
A
MOA: B-lactam antibiotics: bind penicillin-binding proteins (transpeptidases that build cell walls)
Use: Mostly used for Gram + (also N. meningitidis, T. pallidum)
Tox: Hypersensitivity reactions, hemolytic anemia
Penicillinase (a B-lactamase) sensitive
21
Q
Amoxicillin, ampicillin
A
MOA: Broad spectrum B-lactam antibiotics
Oral bioavailability: AmOxicillin>ampicillin
Use: H. influenzae, H. pylori, E. Coli Listeria, Proteus, Salmonella, Shigella, Enterococci (HHELPSS kill enterococci)
Tox: Hypersensitivity reactions, rash, pseudomembranous colitis
Penicillinase sensitive: Combine w/ clavulanic acid to inhibit penicillinase
22
Q
Dicloxacillin, oxacillin, nafcillin
A
“DON has a narrow mind and only Staphs certain people, even though he is not MRSAble”
MOA: Narrow spectrum B-lactam antibiotics
Use: S. aureus (except MRSA)
Tox: Hypersensitivity reactions, interstitial nephritis
Penicillinase resistant (bulky R-group blocks B-lactamase
23
Q
Piperacillin, ticarcillin
A
“PIPER and TICA are on an EXTENDED jail sentence for using NEGATIVE language and hurting people with RODS
MOA: Antipseudomonals: Extended spectrum B-lactam antibiotics
Use: Pseudomonas and gram - rods
Tox: Hypersensitivity reactions
Penicillinase sensitive: Combine w/ clavulanic acid to inhibit penicillinase
24
Q
B-lactamase inhibitors
A
Clavulanic acid, sulbactam, tazobactam (CAST)
Added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase)
25
Cephalosporin-1st generation
Cefazolin, cephaLEXIn (1 ZObra named LEXI)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Gram + cocci, Proteus, E. coli, Klebsiella, Pre-surgery prophylaxis to prevent S. aureus wound infections
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
26
Cephalosporin-2nd generation
Cefoxitin, cefaclor, cefuroxime (2 FOXes go to the FACtory and come out as FUR)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Gram + cocci, H. influenzae, Enterobacter aerogenes, Neisseria spp., Proteus mirabilis, E. Coli, Klebsiella, Serratia marcescens
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
27
Cephalosporin-3rd generation
Cefotaxime, Ceftriaxone, , cefazidime (3 TAXidermists TRI to sell a DIMEsaur)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Serious gram - infections resistant to other B-lactams
Ceftriazone-meningitis, gonorrhea, disseminated lyme dz
Ceftazidime-Pseudomonas
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
28
Cephalosporin-4th generation
CefePIME (I'm +/- (unsure) if 4 PIMEcones turned green/blue)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: gram - org., esp Pseudomonas, gram + org.
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
29
Cephalosporin-5th generation
CefTARoline (5 TARred birds are MRSArible)
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP), less susceptible to penicillinases. Bactericidal.
Use: Broad gram + and gram - org., including MRSA
Tox: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency, exhibit cross-reactivity with penicilllins,
increases nephrotoxicity of aminoglycosides
30
Mechanism of resistance to cephalosporins
Structural change in penicillin-binding proteins (transpeptidases)
31
CarbaPENEMs
Imipenem, meropenem, ertapenem, doripenem
MOA: B-lactams, peptidoglycan cross-linking inhibitors (bind PBP)
Use: Gram + cocci, gram - rods, anaerobes
Wide spectrum, but side effects that limit use to last resort
Tox: GI distress, skin rash, and CNS toxicity (seizures) at high plasma levels
32
Meropenem
Carbapenem: has a decrease risk of seizures and stable to dehydopeptidase I
33
Imipenem
Carbapenem: broad spectrum, B-lactamase resistant.
| Take with cilastatin (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules.
34
Monobactams
Aztreonam
MOA: B-lactam, peptidoglycan cross-linking inhibitors (bind PBP3).
Less susceptible to B-lactamases & synergistic with aminoglycosides.
No cross-allergenicity with penicillins
Use: Gram - rods ONLY. For penicillin-allergic patients and those with renal insufficiency who can't use aminoglycosides
Tox: Occasional GI upset
35
Vancomycin
MOA: Inhibits cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Bactericidal. B-lactamase resistant
Use: Gram + ONLY. Serious, multidrug resistant organisms, including MRSA, S. epidermis, sensitive Enterococcus spp, and C. Diff. (oral dose for pseudomembranous colitis)
Tox: Well tolerated except NOT. Nephrotoxicity, Ototoxicity, Thrombophlebitis. Red man syndrome (prevent with H1 antagonist and slow infusion)
Resistance: bacterial aa modification, D-ala D ala-> D-ala D-lac
36
Aminoglycosides: names
Gentamicin, neomycin, amikacin, tobramycin, streptomycin
37
Aminoglycosides: MOA
Bactericidal. Irreversible inhibition of initiation complex through binding of the 30s subunit. Misreading of mRNA. Ineffective against anaerobes (needs 02)
38
Aminoglycosides: Use
Severe gram - rod infections. Synergistic with B-lactam antibiotics. Neomycin for bowel surgery
39
Aminoglycosides: Toxicity and resistance
Tox: Nephrotoxicity, neuromuscular blockade, ototoxicity, (esp. with loop diuretic), teratogen.
Resistance: Bacterial transferase enzymes inactivate the drug by acteylation, phosphorylation, adenylation
40
Tertracycline: names
Tetracyline, doxycline, minocycline
41
Tertracycline: MOA
Bacteriostatic: binds to 30S and presents tRNA binding.
CNS penetration.
Can't take with milk (ca2+), anatacids (Ca2+/Mg2+) or iron containing preparations. All inhibit absorption.
42
Tertracycline: Clinical use
Borrelia burgdorferi. M. pneumoniae. Rickettsia. Chlamydia. Acne.
BM CAR makes your teeth YELLOW
43
Tertracycline: toxicity
GI distress, discoloration of teeth, inhibition of bone growth in children, photosensitivity, contraindicated in pregnancy..
Doxycycline is fecally eliminated so can give with renal failure.
44
Tertracycline: Mechanism of resistance
Decrease uptake or ^ efflux out of bacterial cells by plasmid-encoded transport pumps
45
Chloramphenicol: MOA
Blocks peptidyltransferase at 50S ribosomal subunit.
| Bacteriostatic
46
Chloramphenicol: Clinical use
Meningitis (H. influ, N. meningitidis, S. pneumo)
| Rocky mountain spotted fever (Rickettsia rickettsii)
47
Chloramphenicol: toxicity
Anemia (dose dependent), aplastic anemia (dose independent), gray baby syndrome (premature infants lack UDP-glucuronyl transferase)
48
Chloramphenicol: Mechanism of resistance
Plasmid-encoded acteryltransferase that inactivates the drug
49
Clindamycin: MOA
Blocks peptide transfer at 50S ribosomal subunit.
| Bacteriostatic
50
Clindamycin: Clinical use
"Clinda the good witch kills the anaemy (anaerobic) above the diaphragm"
Anaerobic infections (Bacteriodes, C. perfringens) due to aspiration pneumonia, lung abscess, and oral infection.
Also effective against group A strep
*Treats anaerobic infections above the diaphragm. Metronidazole treats anaerobic infections below the diaphragm
51
Clindamycin: toxicity
Pseduomembranous colitis (C. diff overgrowth), fever, diarrhea
52
Linezolid: MOA
Inhibits protein synthesis by binding to 50S subunit and preventing formation of the initiation complex
53
Linezolid: Clinical use
Gram+ species including MRSA and VRE
54
Linezolid: toxicity
Bone marrow suppression (thrombocytopenia)
Peripheral neuropathy
Serotonin syndrome
55
Linezolid: Mechanism of resistance
Point mutation of ribosomal RNA
56
Macrolides: names
Azithromycin, Clarithromycin, Erythromycin
57
Macrolides: MOA
Inhibit protein synthesis by blocking translocation (macroslides). Bind to 23S rRNA of the 50S ribosomal subunit
58
Macrolides: Clinical use
Atypical pneumonias (Mycoplasma, chlamydia, legionella)
59
Macrolides: toxicity
MACRO: Motility issues in GI, Arrhythmia (prolonged QT interval), acute Cholestatic hepatitis, Rash, eOsinophilia
Increases serum theophyllines, oral anticoagulants.
Clarithro and Erythro inhibit p450
60
Macrolides: mechanism of resistance
Methylation of 23S rRNA binding site prevents binding of drug
61
Trimethoprim: MOA
Inhibits bacterial dihydrofolate reductase.
| Bacteriostatic
62
Trimethoprim: Clinical use
Use with sulfonamides (TMP-SMX)-->sequential block of folate synthesis.
UTIs, shigella, Salmonella, P. Jirovecii
Prophylaxis for P. Jirovecii and toxoplasmosis
63
Trimethoprim: toxicity
Megaloblastic anemia, leukopenia, granulocytopenia
| TriMethoPrim: Treats Marrow Poorly
64
Sulfonamides: names
Sulfamethoxazole (SMX), sulfisoxazole, sulfadiazine
65
Sulfonamides: MOA
Inhibits folate synthesis by inhibiting dihydropteroate synthase (PABA-->dihydropteroic acid)
Bacteriostatic alone. Bacteriocidal with TMP.
Dapsone for leprosy works in a similar way
66
Sulfonamides: clinical use
Gram positives, gram negatives, Nocardia, Chlamydia
| Triple sulfas or SMX for simple UTI
67
Sulfonamides: toxicity
Hypersensitivity reactions, hemolysis if G6PD deficient.
Nephrotoxicity (tubulointerstitial nephritis), photosensitivity, kernicterus (bilirubin in the brain) in infants, displace other drugs from albumin (warfarin)
68
Sulfonamides: Mechanism of resistance
Altered enzyme (bacterial dihydropteroate synthase), decrease uptake, ^PABA synthesis
69
Fluoroquinolones: names
Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin, gemifloxacin, enoxacin
70
Fluoroquinolones: clinical use
Gram negative rods or urinary and GI tracts including pseudomonas, Neisseria, some gram +
71
Fluoroquinolones: toxicity
GI upset, superinfections, skin rashes, HA, dizziness.
Less common: leg cramps, myalgias
Contraindicated: pregnancy, nursing, children under 18.
May cause tendonitis or tendon rupture in people >60 and those taking prednisone
72
Fluoroquinolones: mechanism of resistance
CHromosome-endcoded mutation in DNA gyrase, plasmid-mediated resistance, efflux pumps
73
Daptomycin: clinical use
S. aureus skin infections, esp. MRSA, bacteremia, endocarditis, and VRE
74
Daptomycin: MOA
Lipopeptide that disrupts cell membrane of gram + cocci
75
Fluoroquinolones: MOA
Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and topo. IV.
Bactericidal. Don't take with antacids!
76
Daptomycin: Toxicity
myopathy, rhabdomyolysis
77
Metronidazole: MOA
Forms toxic free radical metabolites in the bacterial cell that damage DNA.
Bactericidal and antiprotozoal.
78
Metronidazole: Clinical use
GET on the metro: Giardia, Entamoeba, Trichomonas
| Mind the GAP: Gardnerella vaginalis, Anaerobes (bacteriodes/C. Diff. , h. Pylori
79
Metronidazole: toxicity
Disulfiram-like reaction with alcohol.
HA
Metallic taste
Treats anerobic infections below the diaphragm (vs. clindamycin)
80
M. Tuberculosis prophylaxis
Isoniazid
81
M. Tuberculosis treatment
RIPE:
| Rifampin, isoniazid, pyrazinamide, ethambutal
82
M. avium prophylaxis
Azithromycin, rifabutin
83
M. avium treatment
Most drug resistant that TB.
Azithromycin or clarithromycin + ethambutol
Can add rifabutin or ciprofloxacin
84
M. leprae treatment
Dapsone+ rifampin=tuberculoid form
| Dapsone+rifampin+clofazimine=lepromatous form
85
Mycobacterial drugs that target the cell wall
Isoniazid-Mycolic acid synthesis
| Ethambutol-Arabinogalactan synthessi
86
Mycobacterial drugs that target mRNA synthesis
Rifabutin
| Rifampin
87
Rifamycins (Rifabutin/Rifampin): MOA
Inhibit DNA-dependent RNA polymerase (mRNA synthesis)
88
Rifamycins (Rifabutin/Rifampin): clinical use
Mycobacterium tuberculosis
Delay resistance to dapsone when used for leprosy
Meningococcal prophylaxis and chemoprophylaxis in contacts with children with HIB
89
4 R's of rifampin
```
RNA polymerase inhibitor
Ramps up microsomal cytochrome p450
Red/orange body fluids
Rapid resistance if used alone
(rifabutin does not ramp up p450
```
90
Rifamycins (Rifabutin/Rifampin): toxicity
Minor hepatotoxicity and drug interactions (^cytochrome p450)
Orange body fluids
Rifabutin flavored over rifampin in HIV patients due to less p450 stimulation
91
Rifamycins (Rifabutin/Rifampin): Mechanism of resistance
Mutations reduce drug binding to RNA polymerase.
| Monotherapy rapidly leads to resistance
92
Isoniazid: mechanism of action
Decrease synthesis of mycolic acids.
| Bacterial catalase peroxidase (encoded by KatG) needed to convert INH to active metabolite
93
Isoniazid: clinical use
Mycobacterium tuberculosis
| Only prophylaxis against TB
94
Isoniazid: toxicity
Neurotoxicity, hepatotoxicity.
| Pyridoxine (B6) can prevent neurotoxicity
95
Isoniazid: mechanism of resistance
Mutations leading to underexpression of KatG (lack of activation)
96
Pyrazinamide: MOA
Uncertain
97
Pyrazinamide: Clinical use
Mycobacterium tuberculosis
98
Pyrazinamide: toxicity
Hyperuricemia, hepatotoxicity
99
Ethambutol: MOA
Decreases carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
100
Ethambutol: clinical use
Mycobacterium tuberculosis
101
Ethambutol: toxicity
```
Optic neuropathy (colorblindness)
"EYEthembutol"
```
102
Clinical scenario prophylaxis:
| High risk for endocarditis and undergoing surgical/dental procedures
Amoxicillin
103
Clinical scenario prophylaxis:
| Exposure to gonorrhea
Ceftriaxone
104
Clinical scenario prophylaxis:
| History of recurrent UTIs
TMP-SMX
105
Clinical scenario prophylaxis:
| Exposure to meningococcal infection
Ceftriaxone, ciprofloxacin, or rifampin
106
Clinical scenario prophylaxis:
| Pregnant women carrying group B strep
Penicillin G
107
Clinical scenario prophylaxis:
| Prevention of gonococcal conjunctivitis in newborn
Erythromycin ointment
108
Clinical scenario prophylaxis:
| Prevention of post-surgical infection due to S. aureus
Cefazolin
109
Clinical scenario prophylaxis:
| Prophylaxis of strep pharyngitis in child with prior rheumatic fever
Benzathine penicillin G or oral peniCillin V
110
Clinical scenario prophylaxis:
| Exposure to syphilis
Benzathine penicillin G
111
How do you treat MRSA?
Vancomycin, daptomycin, linezolid, tigecycline, ceftaroline
112
How do you treat VRE?
Linezolid and streptogramins (50S inhibitors)
113
Amphotericin B: MOA
```
Binds ergosterol (component of fungal cell membrane)
Forms membrane pores that allow leakage of electrolytes
```
114
Amphotericin B: clinical use
Serious, systemic mycoses:
Cryptococcus (with flucytosine for cryptococcal meningitis)
Blastomyces, Coccidioides, Histoplasma, Candida
INtrathecally for funal meningitis. Supplement K+ and Mg2+ because of altered renal tubule permeability.
115
Amphotericin B: toxicity
Fever/chills "shake and bake"
Hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis.
Hydration decreases nephrotoxicity
Liposomal amp decreases toxicity
116
Nystatin: MOA
Binds erogsterol and forms membrane pores that allow leakage of electrolytes
117
Nystatin: clinical use
Oral candidiasis (thrush), topical for diaper rash or vaginal candidiasis
118
Flucytosine: MOA
Inhibits fungal DNA and RNA biosynthesis by conversion of 5-fluorouracil by cytosine deaminase
119
Flucytosine: clinical use
Systemic fungal infections (esp. meningitis caused by cryptococcus) in combination with amp B
120
Flucytosine: toxicity
Bone marrow suppression
121
-m/nazole: MOA
Inhibit fungal ergosterl synthessi by inhibiting the p450 enzyme that converts lanosterol to ergosterol
122
-m/nazole: clinical 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, Coccidiodes, Histoplasma.
Clotrimazole and miconazole for topical fungal infections
123
-m/nazole: toxicity
Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction-inhibits p450
124
Terbinafine: MOA
Inhibits the fungal enzyme squalene epoxidase to prevent lanosterol synthesis (precursor of ergosterol)
125
Terbinafine: clinical use
Dermatophytoses (esp onychomycosis)
126
Terbinafine: toxicity
GI upset, hepatotoxicity, taste disturbance
127
Echinocandins: names
Anidulafungin, capofungin, micafungin
128
Echinocandins: MOA
Inhibit cell wall synthesis by inhibiting synthesis of B-glucan
*MAC won't let people discriminate and put up WALLS to ruin the FUNgin
129
Echinocandins: clinical use
Invasive aspergillosis, candida
130
Echinocandins: toxicity
GI upset, flushing (by histamine release)
131
Griseofulvin: MOA
Interferes with microtubule function; disrupts mitosis.
| Deposits in keratin-containing tissues (ie nails)
132
Griseofulvin: clinical use
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
133
Griseofulvin: toxicity
Teratogenic, carcinogenic, confusion, HA, ^ p450 and warfarin metabolism
134
Antiprotozoan therpy
Pyrimethamine (toxoplasmosis), suramin and melarsoprol (Trypanosoma brucei), nifurtimox (t. cruzi), sodium stibogluconate (leishmaniasis)
135
Anti-mite/louse therapy
Permethrin (blocks Na+ channels->neurotoxicity)
Malathion (acetylcholinesterase inhibitor)
Lindane (blocks GABA channels->neurotoxicity)
Used to treat scabies (Sarcoptes scabiei) and lice (pediculus and pthirus)
136
Chloroquine: MOA
Blocks detoxification of heme into hemozosin. Heme accumulates and is toxic to plasmodia
137
Chloroquine: clinical use
Treatment of plasmodial species other than P. falciparum (frequency of resistance in P. falciparum is too high)
138
Antihelminthic therapy
Mebendazole, pyrantel pamoate, ivermectin, diethylcarbamazine, praziquantel
139
Cholorquine: toxicity
Retinopathy, pruritus
| If you're in the chlorine pool too long your eyes get blurry and your body gets itchy
140
Oseltamivir, zanamivir: MOA
Inhibit influenza neuraminidase--> decreased release of progeny virus
Gpa Ose and gma Zana and can't get the flu out of them every winter
141
Oseltamivir, zanamivir: clinical use
Treatment and prevent of Influenza A and B
142
famiciclovir, acyclovir, valacyclovir: MOA
My FAV animal is an iGUANA
Guanosine analogs. Monophosphorylated by HSV/VZV thymidine kinase and not phosphorylated in uninfected cells-->few adverse effects.
Triphosphate formed by cellular enzymes.
Preferentially inhibit viral DNA polymerase by chain termination
143
Acyclovir, famiciclovir, valacyclovir: Clinical use
HSV (mucocutaneous and genital lesions as well as for encephalitis) and VZV. Prophylaxis in immunocompromised
Weak activity against EBV.
No activity against CMV.
Prophylaxis in immunocompromised patients.
No effects on latent forms of HSV and VZV.
Valacyclovir: prodrug of acyclovir, better oral bioavailability.
Herpes zoster: famciclovir
144
Ganciclovir: MOA
Guanosine analog. 5-monophosphate formed by a CMV viral kinase. Triphosphate formed by cellular kinases. Preferentially inhibits viral DNA polymerase by chain termination.
145
Ganiciclovir: clinical use
CMV, esp. in immunocompromised.
| Valganciclovir, a prodrug of ganciclovir with ^ bioavailability
146
Ganiciclovir: Toxicity
Leukopenia, neutropenia, thrombocytopenia, rental toxicity.
More toxic to host enzymes than acyclovir.
Resistance: mutated viral kinase
147
Foscarnet: MOA
Viral DNA/RNA polymerase inhibitor and HIV reverse transcriptase inhibitor. Binds pyrophosphate binding site of enzyme. No activation required.
"binds to PyroFOSphate binding site of polymerase analog"
148
Foscarnet: clinical use
CMV retinitis in immunocompromised when ganciclovir fails.
| Acyclovir resistant HSV.
149
Foscarnet: toxicity
Nephrotoxicity, electrolyte abnormalities can lead to seizures
Mech. of resistance: mutated DNA polymerase
150
Cidofovir: MOA
Inhibits viral DNA polymerase. Does not require activation by viral kinase.
151
Cidofovir: clinical use
CMV retinitis in immunocompromised patients.
| Acyclovir-resistant HSV.
152
Cidofovir: toxicity
Nephrotoxicity (give with probenecid and IV saline to decrease toxicity)
153
What drugs do you give for acyclovir-resistant HSV?
Foscarnet or cidofovir
154
HIV therapy
HAART: Highly active antiretroviral therapy initiated at the time of HIV diagnosis.
Strongest indication for patients present with AIDS defining illness, low CD4 cell counts or high viral load.
2 NRTIs +
1 NNRTI OR protease inhibitor OR integrase inhibitor
155
Protease inhibitor: MOA
-navir
| Prevents maturation of new viruses by cleaving HIV1 protease, preventing required mRNA cleaving.
156
Protease inhibitor: toxicity
```
Hyperglycemia, GI intolerance, lipodystrophy
Nephropathy, hematuria
Rifampin contraindicated (decreased protease inhibitor concentration)
```
157
NTRIs: MOA
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain.
Tenofavir is the nucleoTide and does not need to be virally activated like the others.
"Have you dined (vudine) with my nuclear(side) family?
158
NTRI: toxicity
Bone marrow suppression-reverse with G-CSF and EPO.
| Peripheral neuropathy, lactic acidosis, anemia (ZDV), and pancreatitis
159
NNRTIs: names
Delavirdine, Efavirenz, Nevirapine
| "Okay, DEN, we gotta get rid of this HIV with one of DEmN NNRTI's
160
NNRTIs: MOA
Bind reverse transcriptase at site different from NRTIs. No activation needed.
161
NNRTIs: toxicity
Rash and hepatotoxicity.
Efavirenz: vivid dreams, CNS symptoms
NOT with pregnancy: delavirdine and efavirenz
162
Integrase inhibitor: MOA and toxicity
Raltegravir
Inhibits HIV genome intergration into host cell Cr by reversibly inhibiting HIV integrase
^creatine kinase
163
Enfuvirtide: MOA and toxicity
Fusion inhibitor
| Binds p41: inhibits viral fusion (skin reaction at injection site)
164
Maraviroc: MOA and toxicity
Binds CCR-5 on surface T cells/monocytes and inhibits interaction with gp120
165
Interferons: MOA
Glycoproteins normally synthesized by virus-infected cells, exhibiting a wide range of antiviral and antitumoral properties
166
Interferons: clinical use
IFN-a: chronic hepatitis B/C, kaposi sarcoma, hairy cell uekemia, condyloma acuminatum, RCC, malignant melanoma
IFN-B: Multiple sclerosis
IFN-g: CGD
167
Interferons: toxicity
Neutropenia and myopathy
168
Hepatitis C therapy
Ribavirin
Simeprevir
Sofosbuvir
169
Antibiotics to avoid in pregnancy
```
SAFe Children Take Really Good Care
Sulfonamides- Kernicterus
Aminoglycosides- Otoxicity
Fluoroquinolones- Cartilage damane
Clarithromycin-Embryotoxic
Tetracyclines- Discolored teeth, inhibition of bone growth
Ribarvirin (antiviral)- teratogenic
Griseofulvin (antifungal)- teratogenic
Chloamphenicol- grey baby syndrome
```
170
What viral drugs do not need to be activated?
Foscarnet, cidofovir, Tenofovir (NRTI)
