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138 Cards in this Set

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Name four classes of Beta-Lactam antibiotics
1. Natural Penicillins
2. Aminopenicillins
3. antistaphylococcal penicillins
4. antipseudomonal penicillins
what is an aminopenicillin?
a penicillinase resistant penicillin
List two natural penicillins
1. Penicillin G
2. Penicillin V
list two aminopenicillins
1. ampicillin
2. amoxicillin
list an antistaphylococcal penicillin
Nafcillin
list an antipseudomonal penicillin
Piperacillin (Pipracil)
How many generations of cephalosporin antibiotics are there?
4
list a parenteral first generation cephalosporin
Cefazolin
(Ancef, Kefzol)
list an oral first generation cephalosporin
Cephalexin
(Keflex)
list three parenteral second generation cephalosporins
1. Cefoxitin (Mefoxin)
2. Cefuroxime (Zinacef)
3. Cefotetan (Cefotan)
oral second generation cephalosporin antibiotics (2)
1. Cefuroxime (Claforan)
2. Cefprozil (Cefzil)
parenteral third generation cephalosporin antibiotics (3)
1. Cefotaxime (Claforan)
2. Ceftriaxone (Rocephin)
3. Ceftazidime (Fortaz, Tazidime, Tazicef)
parenteral fourth generation cephalosporin antibiotic (1)
Cefepime (Maxipime)
oral third/fourth generation cephalosporin (1)
Cefdinir
(Omnicef)
carpepenem antibiotics (2)
1. Imipenem/Cilastin (Primaxin)
2. Ertapenem (Invanz)
monobactam antibiotic (1)
Aztreonam
(Azactam)
combinations with Beta-Lactimase inhibitors (3)
1. Clavulanic Acid/Amoxicillin (Augmentin)
2. Sulbactam/Ampicillin (Unasyn)
3. Tazobactam/Piperacillin (Zosyn)
what is the prototype of a glycopeptide antibiotic?
Vancomycin
aminoglycosides (2)
1. Gentamycin
2. Tobramycin
macrolides (3)
1. Erythromycin
2. Azithromycin
3. Clarithromycin
Ketolides (1)
Telithromycin (Ketek)
Tetracyclins (2)
1. Tetracycline
2. Doxycyclin
Lincosamides (2)
1. Clindamycin
2. Chloramphenicol
Streptogramins (2)
Quinupristin
Dalfopristin
(both Synercid)
Oxazolidinones (1)
Linezold (Zyvox)
Sulfonamides (1)
Trimethoprim/Sulfamethoxazole
Fluoroquinolones (4)
1. Ciprofloxacin (Cipro)
2. Levofloxacin (Levaquin)
3. Gatifloxacin (Tequin)
4. Moxifloxacin (Avelox)
antiviral for Respiratory Syncytial Virus (RSV)
Ribavarin (Virazole)
agents for herpes and varicella viruses (4)
1. Acyclovir (Zovirax)
2. Valcyclovir (Valtrex)
3. Famciclovir (Famvir)
4. Penciclovir (Denavir)
Agents for CMV (4)
1. Cidofovir (Vistide)
2. Foscarnet (Foscavir)
3. Ganciclovir (Cytovene)
4. Valganciclovir (Valcyte)
What are these agents used to treat?
1. INF-alpha (PEG_Intron, Pegasys)
2. Ribavarin (Copegus, Rebetol)
3. Lamivudine (#TC, Epivir HBV)
4. Adefovir (Hepsera)
Agents used to treat HepB and C
Classes of HIV treatment agents (3)
1. Antiretrovirals
2. Protease Inhibitors (PIs)
3. Fusion Inhibitors
Three types of antiretrovirals
1. Nucleoside reverse transcriptase inhibitors (NRTI)
2. Nucleotide analog reverse transcriptase inhibitors
3. Non-nucleoside reverse transcriptase inhibitors (NNRTI)
What class of drug?
Used to treat?
1. Abacavir (Ziagen)
2. Didanosine (ddI) (Videx)
3. Lamivudine (3TC, Epivir)
4. Stavudine (d4T, Zerit)
5. Zalcitabine (ddC, Hivid)
6. Emtricitabine (Emtriva)
Nucleoside reverse transcriptase inhibitors (NRTI)

Used to treat HIV/AIDS
Tenofovir (Viread)
Nucleotide analog reverse transcriptase inhibitor
1. Delaviridine (Rescriptor)
2. Efavirenz (Sustiva)
3. Nevirapine (Viramune)
Non-nucleoside reverse transcriptase inhibitors (NNRTI)
1. Indinavir (Crixivan)
2. Nelfinavir (Viracept)
3. Ritonavir (RTV) (Norvir)
4. Saquinavir (SQV) (Invirase, Fortovase)
5. Amprenavir (Agenerase)
6. Atazanavir (Reyataz)
Protease inhibitors (PIs)
Fusion Inhibitor (1)
Enfuvirtide (Fuzeon)
Azoles (Antifungals) (4)
1. Ketoconazole (Nizoral)
2. Itraconazole (Sporanox)
3. Fluconazole (Diflucan)
4. Miconazole (Monistat)
Antimycobacterial agents (5)
1. Isoniazid (INH)
2. Ethambutol (ETB)
3. Rifampin (RIF)
4. Rifabutin (Mycobutin)
5. Pyrazinamide (PZA)
Antiparasitics (4)
(1,2,3-antimalarials)
(4-antiprotozoal & antihelminthic)
1. Chloroquine
2. Primaquine
3. Doxycycline
4. Metronidazole
what is the primary prevention approach to viral disease?
vaccination
what are the two general mechanisms used to treat viral disease?
1. antivirals
2. stimulation of host defense mechanisms
what must first happen to an antiviral drug before it is active?
phosphorylation inside the cell
why do antivirals have no effect on latent viruses?
antivirals inhibit stages of viral replication (the virus must be active in order for antivirals to have an effect)

Latent viruses are not undergoing replication, therefore the antivirals have no effect.
what is the drug of choice for treatment of herpes simplex virus?
Acyclovir
(antiviral, DNA polymerase inhibitor)
What is the drug of choice for CMV?
Gancyclovir (Cytovene)
(antiviral, DNA polymerase inhibitor)
which antiviral is a synthetic guanine nucleoside analog?
Acyclovir
acyclovir is not useful against which virus? (a virus in the herpes class) Why?
CMV
CMV does not have thymidine kinase (TK)
describe the acyclovir MOA
IRREVERSIBLE TERMINATION OF VIRAL DNA SYNTHESIS

1. phosphorylated by thymidine kinase (TK) in infected cell. TK is a viral encoded enzyme
2. cellular encoded kinases form ACV-triposphate (ACV-TP)
3. ACV acts as a competitive inhibitor of viral DNA polymerase: thus it irreversably terminates viral DNA synthesis
acyclovir adverse effects?
1. reversible crystalline nephropathy
2. CNS effects
valacyclovir is another drug used to treat HSV. What is it's MOA?
valacyclovir is a prodrug of Acyclovir. It converts to ACV in the liver (this increases serum ACV levels)
Rest of MOA same as ACV
what is the advantage of using Valacyclovir vs. Acyvlovir to treat HSV?
less frequent dosing
what is the one other drug that is used to treat HSV and what is it's mechanism of action?
Famciclovir
Competitive inhibitor of viral DNA polymerase -> stops viral replication
when is the best time to initiate antiviral treatment?
ASAP after onset of signs and symptoms
ideally 24-48 hrs.
which drug is used to treat CMV (seeing as acyclovir won't)
Gangcyclovir (GCV)
(DNA polymerase inhibitor)
Gangciclovir MOA?
1st phosphorylation catalyzed by viral specific protien kinase, results in a competitive inhibitor of DNA polymerase
Gangciclovir adverse effects?
VERY TOXIC: 32% INTERRUPT OR DISCONTINUE THERAPY

1. Myelosuppression (reversible)
- neutropenia
- thrombocytopenia
2. CNS effects
what is the prodrug of gancyclovir called?
what activates the prodrug?
Valganciclovir
intestinal and hepatic esterases convert valganciclovir to ganciclovir
which antiviral is often used in the following situations:
ganciclovir intolerance
ACV resistant HSV
CMV retinitis
Foscarnet
MOA of foscarnet?
- pyrophosphate analog
- noncompetitive inhibitor of viral DNA Polymerase and reverse transcriptase
what is the major adverse effect seen with foscarnet?
renal failure, nephrotoxicity
what is so special about cidofovir?
it is viral independent
MOA of cidofovir?
1. converted by host cell kinases into active form
2. competitive inhibitor of viral DNA polymerase
3. one insertion slows replication; two halts it
Indication of codofovir?
CMV retinitis in HIV
Two standard therapies for influenza?
amantadine
rimantadine
difference between amantadine and rimantadine?
EQUAL EFFICACY

amantadine - adjust dose in renal failure
rimantadine - safer agent for the elderly (does not require dose adjustments in renal failure)
rimantidine also has 4-10x greater activity than amantadine
MOA of amantadine and rimantadine?
INHIBITION OF VIRUS UNCOATING

targets M2 protein of influenza A
MOA of resistance to amantidine?
single mutations in the M2 protien
what type of antivirals are Zanamivir and Oseltamivir?
Neuraminidase inhibitors
MOA of neuraminidase inhibitors
scialic acid analogues, inhibit viral neuraminidase -> virus can't exit cell as easily (they clump and don't disperse)
spectrum of neuraminidase inhibitors?
treatment of influenza A and B
how do neuraminidase inhibitors effect the influenza symptoms?
- reduce signs/symptoms by 1-1 1/2 days
- reduce severity of symptoms
which neuraminidase inhibitor is administered as a dry powder inhalation?
Zanamivir
(therefore use caution in asthma, COPD)
prodrug of zanamivir?
oseltamivir
which antiviral is a guanosine analog and is effective against RNA viruses?
Ribavarin
which viruses would you use Ribavarin for? (3)
- RSV
- HCV (w/interferon)
- hantavirus
how is ribavarin administered?
significance?
via aerosol
could be toxic to health care workers and pregnant women
adefovir MOA?
inhibits HBV DNA polymerase - results in DNA chain termination
1. indications for adefovir?
2. advantage?
1. chronic HBV
2. 1 time daily dosing
MOA of interferons?
inhibit viral RNA and DNA synthesis
which type of interferon is most commonly used to treat viruses?
IFN-alpha
what can be done to IFN-alpha to increase its half life?
"peglated IFN-a"

IFN covalently bound to polyethylene glycol (PEG)
increases half life by 5x - allows once weekly injections
IFN-a is the therapy of choice for which virus?
HCV
how do you measure the viral burden (load) in an HIV patient?
CD4
vRNA copies/mL
what are some problems with HIV therapy? (4)
1. combination regimens (medically complex)
2. lots of side effects/drug interactions
3. compliance is NECESSARY for success (this is a challenge)
4. Cost
what are the two types of antiretroviral drugs?
1. NRTI - Nucleoside Reverse Transcriptase Inhibitors
2. NNRTI - Non-Nucleoside Reverse Transcriptase Inhibitors
besides the antiretroviral drugs, what other therapies are available for HIV? (2)
1. PIs - Protease Inhibitors
2. Fusion Inhibitor
HAART stands for?
Highly Active Retroviral Therapy
(combination therapy for HIV)
what is the MOA of
1. NRTIs
2. NNRTIs
1. NRTIs are nucleotide analogs. They prematurely terminate HIV DNA elongation (must be phosphorylated by TP to be active)

2. NNRTIs bind to viral reverse transcriptases (no intracellular phosphorylation)
Major difference between NRTIs and NNRTIs?
NRTIs must be phosphorylated intracellularly
NNRTIs are not phosphorylated
name the first antiviral agent to show benefit in AIDS (it is still a first line anti-HIV medication)
Zidofudine (ZDV, AZT)
Name 3 uses of zidofuvine (AZT)
1. combination HIV therapy

2. reduce vertical HIV transmission to 2%.

3. postexposure prophylaxis for needlesticks and mucosal exposure
downside of NRTIs?
LOTS of adverse effects
- lactic acidosis
- pancreatitis
adverse effect of NNRTIs?
P450 inhibitors or inducers - cause drug interactions
MOA of protease inhibitors?
HIV protease is required for virus production
inhibition prevents replication
* does not need intracellular activation*
which two anti HIV agents are either inhibitors or inducers of the P450 system?
1. PIs (inhibitor)
2. NNRTIs (some inhibit, some induce)
regarding malaria prophylaxis - what has occured that renders the original antimalarial drugs ineffective?
chloroquine resistance
what prophylactic agent would you use for chloroquine sensitive malaria?
chloroquine phosphate
name 3 prophylactic antimalarials that can be used in chloroquine resistant areas
1. Mefloquine (Larium)
2. Atovaquone/Proguanil (Malarone)
3. Doxycycline
LARIUM (mefloquine)
1. dosing
2. adverse effects
1. once per week (start 2 wks before, end 4 wks after)
2. GI, sleep disturbances, dreams, rare siezures or psychosis
Malarone (atovaquone/proguanil)
1. dosing
2. adverse effects?
1. daily (start 1-2 days before, end 7 days after)
2. GI, headache
dosing of doxycycline as malarial prophylaxis?
daily (starting 1-2 days before, end 4 wks after)
use of suladiazene + pyrimethamine?
(Fansidar)
can be used as a self treatment dose in the event of onset of malaria
which antimalarial targets the latent liver forms of malaria? (not the erythrocytic forms like the others do)
Primaquine
what is the firstline protozoal/antihelminth?
metronidazole
what are some other uses for metronidazole?
1. anaerobic infections
2. C. difficile colitis, Trichomoniasis, BV, giardia, amebiasis
metronidazole side effects? (4)
metallic taste
GI upset
DISULFRAMLIKE EFFECT WITH ETOH
carcinogenic?
what is mebendazole used to treat?
treats worms (intestinal nematodes)
How does mebendazole work?
PARALYZES WORMS
binds to helminthic beta-tubulin and prevents microtubule assembly
difference between mebendazole and albendazole?
albendazole has greater efficacy as a 1x dose
also has a very broad spectrum
use of pyrantel pamoate
drug can be used as an alternative to mebendazole or albendazole to treat nematodes
why is TB so hard to treat?
resistance keeps evolving

*leading cause of death worldwide*
signs of active TB
+ sputum culture
+ acid fast stain
+ CXR
+ PPD
signs of latent TB
+ PPD
have had previous infectious process
what is the most widely used TB medication?
Isoniazid (INH)
(unless TB is INH resistant)
most serious adverse effect of INH?
liver toxicity
(can develop hepatitis)

MUST MONITOR LIVER FUNCTION
MOA of Rifampin (RIF)
what else does it cover?
inhibits DNA dependant RNA polymerase of mycobacterium

(also covers strep, MRSA, Bacteroides fragilis and more)
what is the problem with RIF?
resistance develops rapidly

(To minimize, prescribe with another drug)
metabolism of Rifampin?
p450 ACTIVATOR

MANY drug interactions
(ie. OCs)
adverse effects of Rifampin?
- body secretions are an orange color
- hepatotoxicity
hallmark side effect of ethambutol (ETB)?
retrobulbar neuritis
(dose related)
(monitor eye exams)
which TB drug should you not combine with Rifampin? Why?
Pyrazinamide (PZA)
severe hepatotoxicity
recommendations for latent TB treatment?
min. 9 months of INH
-OR-
Rifampin for 4 mo. (less effective than INH)
what is a major cause of TB treatment failure?
noncompliance
how is the problem of compliance with TB medications resolved?
DOTs (Directly Observed Treatment) - directly monitor medicine taking
which two drugs are associated with parenteral infusion reactions from too fast of administration?
vancomycin
amphotericin B
what is a major limiting factor (adverse effect) in amphotericin B use?
nephrotoxicity
(can be reduced if saline infusion is given before each dose)
MOA of Flucytosine?
inhibits function of RNA and DNA. (Converted to 5-fluoruoracil, a chemotherapeutic)
which antifungal group is used routinely, are safest, and has the widest spectrum?
Azoles
MOA of Azoles?
inhibit synthesis of ergesterol - results in altered membrane permeability. (inhibits cyp-450 dependant fungal enzyme)
what is unique about the metabolism of ketoconazole?
orally administered: requires acid to solubilize the tablet
which azole is a better choice than ketonazole?
Itraconazole
(broader spectrum, less side effects)
which azole has the highest CSF penetration?
significance?
Fluconazole
(great drug for cryptococcus meningitis)
arrange from lowest to highest spectrum of activity:
ketoconazole
voriconazole
fluconazole
itraconazole
ketoconazole
itraconazole
fluconazole
voriconazole
indications for voriconazole?
Many, but for the most part has been reserved for severe fungal infections
what is the drug of choice to treat dermatophytes?
terbinafine
terbinafine > azoles > griseofulvin
what is the best strategy for treatment of onychomycosis with terbinafine?
pulse dosing (daily 1 week out of 4)