Pharmacology Quiz 4 (Dr. Coon)
Name some DNA viruses
*Herpesvirus* (ds DNA) -Chickenpox, shingles -Herpes *Papillomavirus* (ds DNA) -Warts *Adenovirus* (ds DNA) -Conjunctivitis, sore throat *Hepadenovirus* (ds DNA RT) -Hepatitis B
Which antifungal is most commonly combined with Flucytosine and why?
Amphotericin B This is because flucytosine is only fungistatic, whereas Amphotericin B is fungicidal against most organisms.
What viruses is ganciclovir used to treat?
CMV and EBV
What are the oral forms of the HSV treating guanine nucleoside analogs?
Check! Valcyclovir, acyclovir, famciclovir, valganciclovir
T/F: Influenza is an RNA virus and therefore does not enter the host cell nucleus
False It is an RNA virus but it does enter host cell nucleus (exception to the rule)
In regards to viruses, what establishes latency?
Latency occurs when there is incorporation of viral genetic material into the host cell genome = extremely difficult (currently impossible) to eradicate from the human genome.
Why are M-2 inhibitors not used anymore?
Loads of resistance A single amino acid substitution on the M2 protein can result in complete resistance to the drug
What enzyme do RNA viruses use for replication?
RNA polymerase
How are the HSV treating guanine nucleoside analogs eliminated?
Renal
How does the influenza virus uncoat once it has entered the host cell?
Within the endosome, M2 matrix protein creates hydrogen ion channels that result in an acidic environment that allows uncoating of the virus
Name the location (cytoplasm or nucleus) of the following DNA life cycle stages: Replication of viral DNA
nucleus
What are the most likely of the fungal organisms to cause disease?
yeast
Go back to slide 19 in Antiviral and ~30 in L32 to buff up these cards
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Echinocandins are great because they do not have a lot of DDIs. Which echinocandin does have mild DDIs and why?
*Capsofungin* -It's metabolized to a small extent by the liver -Coadministration with cyclosporin (immunosuppressant/anti-rejection agent) *increases capsofungin* plasma levels → risk of hepatotoxicity Coadministration with tacrolimus *decreases tacrolimus* levels → risk for organ rejection (therapeutic drug monitoring is needed) Strong inducers increase its metabolism → *decreases capsofungin levels* (need to increase capsofungin levels in this case)
Anytime you see a drug ending in -azole on a patient's chart, what is the first thing that should pop into your head?
*DDIs!!!* *Think: ↑plasma levels of co-administered drugs* Azoles have MANY CYP450-mediated interactions because *they are both substrates and significant inhibitors of CYP450 enzymes* -they slow down the metabolism of different CYP450 systems -because azoles are substrates of CYP450s, their own metabolism can be sped up if they are given with a CYP450 inducer. --carbamazepine and phenytoin are two drugs that can induce the metabolism of azoles (↓ their plasma concentrations).
What are the major differences between fungi and bacteria?
*Fungi differ from bacteria in key cellular structures:* 1. *Fungi are eukaryotes* (vs prokaryotes for bacteria) -eukaryotes have a complex membrane-bound nucleus 2. *Fungi cell wall is chitin* (vs peptidoglycan for bacteria) 3. *Fungi contain ergosterol* in their cell membrane (bacteria do not produce ergosterol) -this is an important differentiation between fungi and mammalian cells, which contain cholesterol. -in fungal cells ergosterol works to maintain fungal cell fluidity and integrity of plasma membrane. 4. *Fungi are more likely to cause chronic infections* (vs acute infections for bacteria)
What are some herpes infections and diseases?
*HSV-1* (from abdominal area and up) -Mouth -face -skin -brain (HSV encephalitis [can affect immunocomp, elderly, and neonates who are born to an HSV+ mother]) *HSV-2* -Genitalia -rectum -hands -meninges *Cytomegalovirus (CMV)* ~40% of adults infected (globally); but most are asymptomatic carriers unless they are immunocompromised or elderly *Varicella-zoster virus (VSZ)* -Chicken pox -shingles
What are the major differences between imidazoles and triazoles?
*Imidazoles* are the *older* subclass -they have *quicker metabolism (require more frequent dosing)* -they have *more side effects* due to having *LESS specificity for the enzyme that synthesizes ergosterol* vs the human enzyme that synthesizes cholesterol (i.e. imidazoles have a higher affinity for the enzyme that synthesizes cholesterol in humans) -they are *only available in topical formulations* and are therefore *only used for superficial infections* (due to more side effects) *Triazoles* are the *newer* subclass -they have *a little bit broader of a spectrum of activity* -they have *fewer ADRs* -they are more commonly used for *systemic infections* because of they have fewer ADRs than imidazole
Are retroviruses RNA or DNA viruses?
*RNA* They are encapsulated as RNA viruses -once released into the host cell cytoplasm, the RNA has to be reverse transcribed into DNA before the subsequent life cycle of the virus can occur.
What is the MOA of azoles?
*Suppression of ergosterol synthesis* via the *inhibition of 14-α-sterol demethylase* This results in the *accumulation of 14-α-methylsterols* *→ disruption of close packing of phospholipid acyl chains* in the cell membrane *→ impairment of membrane-bound enzyme systems functions* (e.g. ATPase and the electron transport system) *→ growth inhibition* of the fungal cell
True or False: Imidazoles and Triazoles have the same MOA and a *similar* antifungal spectrum.
*True* The triazoles are the newer azoles and they have *a little bit* broader spectrum of activity than the imidazoles.
Name some reasons why ketoconazole is not a very popular azole.
-Higher resistance (particularly candida spp.) -Decreased tolerability due to endogenous corticosteroid suppression (lower testosterone levels, lower sex drive, and gynecomastia [breast enlargement] in men with long term use) -Only in topicals: shampoos and athlete's foot creams -Oral administration has low tolerability due to interference with cholesterol synthesis in humans
Why are viruses not really considered organisms?
-Just packaged genetic material -They lack components of metabolism, replication and reproduction without a host
What are some ADR to the HSV treating guanine nucleoside analogs?
-N/V -Nephrotoxicity -Myelosuppression (neutropenia, thrombocytopenia) -Neurotoxicity (altered mental status, seizures, headache)
Which classes of antifungals affect the cell membrane / cell wall?
-Terbinafine (Synthetic allylamine) -Polyenes (amphotericin B and nystatin) -Azoles -Echinocandins
What is the MOA of guanine nucleoside analogs used to treat Herpes infections?
-Triphosphorylated to active drug -Irreversibly binds to DNA polymerase (inhibiting any further activity of the enzyme) OR it can incorporate into viral DNA to cause chain termination (Either way, screws up DNA replication)
Flucytosine can be converted into two different active forms which have different fungistatic MOAs--5-FdUMP and 5-FUTP. Please describe their MOAs. 1. 5-FdUMP 2. 5-FUTP
1. *5-FdUMP is a false nucleotide that inhibits DNA synthesis* 2. *5-FUTP is incorporated into RNA and disrupts protein synthesis*
What are the major classwide ADRs associated with azoles?
1. *Hepatotoxicity* -↑ LFTs 2. *QTc prolongation* -prolongation in conduction time within the heart 3. *Hypokalemia* -low potassium (particularly in long-term azole antifungal therapy)
What are the two subclasses of azoles?
1. *Imidazoles* -older 2. *Triazoles* -newer
Describe the PK of flucytosine.
1. *Short half life (t½: 3-6 hours)* so must be *administered frequently* 2. *Oral admin only* -recall that this is always administered with another antifungal, which is most commonly amphotericin B. Also recall that amphotericin B is only administered IV. Thus the regimen for this treatment will likely include two different routes of administration, further complicating its use. 3. *High Renal elimination (80%)*
To become active, most HSV antivirals need to be triphosphorylated. Describe this process.
1. *Viral* thymidine kinase adds the first phosphate 2. Host cell phosphorylates the drug for the second and third time
What are the mechanisms of resistance to the guanine nucleoside analogs?
1. Absent or altered production of viral TK 2. Altered TK substrate specificity (e.g. phosphorylates thymidine but not acyclovir) 3. Altered viral DNA polymerase (less common)
What are the two polyenes?
1. Amphotericin B -Drug of choice for treatment of life-threatening systemic mycoses. -Only available for IV administration 2. Nystatin -Topical use -minimal GI absorption
What are the adverse drug reactions to flucytosine?
1. Bone marrow suppression -clinically similar to immunosuppression (neutropenia [↓WBC], thrombocytopenia [↓platelet production]) 2. Hepatotoxicity 3. N/V
Resistance is more common in the flucytosine. What are the mechanisms of resistance?
1. Decreases in the production of the cytosine-permease enzyme that allows the drug to enter the cell 2. Downregulation in the production of enzymes that activate the drug (e.g. thymidylate synthase)
What is the MOA of flucytosine?
1. Enters cell by fungi specific permease enzyme 2. Converted to its active forms -*5-FdUMP is a false nucleotide that inhibits DNA synthesis* -*5-FUTP is incorporated into RNA and disrupts protein synthesis*
How often is voriconazole dosed?
2 times per day t½: 6 hours
What is smut in regards to fungus?
A topical/superficial fungal infection on top of grain (e.g. wheat, oats, rye) -a problem for agriculture production. Note: Smuts do not infect humans
Polyenes have some major adverse drug reactions. What are they?
Acute kidney injury (very common) that may lead to anemia If administered too fast can cause fever, hypotension, rigors and thrombophelbitis
Why do we have valcyclovir if it does the same thing as acyclovir?
Acyclovir has a supah short half life (required frequent dosing) and has low bioavailability Valacyclovir has a lipophilic group (valine) that increases gastric absorption to improve dosing -as it passes through the intestinal lumen it is rapidly hydrolyzed at the ester bond into the active form (i.e. acyclovir) which has the hydroxyl group that is able to be phosphorylated.
Why is it possible to use (pretty much) the same dose for IV and oral fluconazole
Almost 100% bioavailable so there isn't much of a difference between the plasma concentrations via IV and oral when giving the same dose
What are M-2 inhibitors and what is their MOA?
Amantadine and Rimantadine Inhibits the ion channel of M2 matrix protein that allows the virus to uncoat within the host endosome
What is the DOC for life threatening systemic mycoses?
Amphotericin B
What antifungal class is considered the most common?
Azoles They are widely used because of their broad spectrum of activity and their good tolerability. Note: Similar to the vast majority of other antifungals, azoles are associated with a high potential to cause liver toxicity and damage.
Azoles have ______ (fungistatic or fungicidal?) activity against yeasts and ______ (fungistatic or fungicidal?) activity against molds.
Azoles have *fungistatic* activity against yeasts and *fungicidal* activity against molds. YeaSTs = FungiSTatic MolDs = FungiciDal
What is the MOA of polyenes like Amphotericin B and nystatin?
Bind to ergosterol which is already embedded in the membrane bilayer to alter cellular permeability →Creates pores and leakage which causes rapid cell death You can almost think of the polyenes as acting like surfactants
Why can't we use acyclovir, valacyclovir, famciclovir and penciclovir for CMV infections?
CMC is *intrinsically resistant* to acyclovir due to the *absence of viral TK*
What are the adverse effects of M-2 inhibitors?
CNS-like (insomnia and seizures), teratogenic
Voriconazole is primarily metabolized by which CYP?
CYP2C19 -also metabolized by CYP2C9 and CYP3A4 Note: The significance of CYP2C19 as the predominant metabolizer is due to polymorphisms that slow the metabolism of voriconazole. -CYP2C19 genetic polymorphisms: >4-fold ↑ in AUC
What are TK-ase independent HSV agents? What is their MOA?
Cidofivir and Foscarnet Noncompetitive inhibitors of DNA polymerase Already phosphorylated so not limited by presence of TK or UL97
When are cidofivir and foscarnet used?
Cidofivir only for CMV retinitis in HIV pts Foscarnet only as a second line treatment for resistant CMV, HSV and VZV Both are only IV
Coadministration of capsifungin with cyclosporin (an immunosuppressant/anti-rejection agent) _____________ (increases or decreases?) capsofungin plasma levels.
Coadministration of capsifungin with cyclosporin (an immunosuppressant/anti-rejection agent) *increases* capsofungin plasma levels.
Coadministration of capsifungin with tacrolimus (an immunosuppressant/anti-rejection agent) _____________ (increases or decreases?) tacrolimus plasma levels.
Coadministration of capsifungin with tacrolimus (an immunosuppressant/anti-rejection agent) *decreases* tacrolimus plasma levels.
In general, which type of virus will enter the nucleus of the host?
DNA viruses -DNA viruses incorporate their DNA into the host cell nucleus RNA viruses typically do not enter host nucleus however this isn't a rule (ex. influenza and HIV)
Which class of antifungals is the newest?
Echinocandins
What type of viruses are herpesviruses?
Enveloped DNA -they rely on Host-cell nucleus entry
What is the MOA of echinocandins?
Even though Echinocandins act on enzymes that are already embedded within the cell wall, their effect is to disrupt the synthesis of the fungal cell wall. Noncompetitive inhibition of β-glucan synthase →Reduced cell wall integrity and eventual cell death
T/F: There are many species of fungi that cause pathogenic infections in humans
False
T/F: Capsofungin is only given orally
False All echinocandins are only IV administered because they lack oral bioavailability
True or False: Azoles have broad-spectrum fungicidal activity against both yeasts and molds.
False Azoles have broad-spectrum *antifungal* activity against both yeasts and molds. -azoles have fungi*static* activity against yeasts and fungi*cidal* activity against molds.
T/F: Terbinafine is only available in topical formulations
False Both topical and oral
True or False: Echinocandins would be a good choice for the treatment of an aspergillus infection.
False Echinocandins are not preferred agents for molds
True or False: In general, azoles tend to increase the plasma levels of co-administered pro-drugs due to their actions on CYP450 enzymes.
False In general azoles are significant inhibitors of CYP450s so they would *increase the plasma levels of co-administered drugs that are already in their active form* and would decrease the plasma levels of pro-drugs that require the metabolism of a CYP450 enzyme to activate them.
True or False: Echinocandins would be a good antifungal agent for the treatment of meningitis.
False It is highly protein bound (>97%) which contributes to its poor penetration into the CSF.
T/F: Voriconazole exhibits linear PK
False Nonlinear: higher doses cause greater than linear increases in plasma concentrations Note: this nonlinear increase is unpredictable from patient to patient.
True or False: Amphotericin B has poor tolerability because it has low specificity for ergosterol vs cholesterol.
False Preferential, hydrophobic ergosterol binding >> cholesterol Low tolerability is due to their significant ADRs. [recall that amphotericin B is only given IV; and due to it's low water solubility it must be complexed with bile salt (deoxycholate) or lipid formulations] -Acute Kidney Injury (~50%) -Infusion-related reactions (fever, hypotension, rigors, thrombophlebitis) if given too rapidly -Anemia (following Acute Kidney Injury)
T/F: Only DNA viruses are double standed
False RNA virus can be double stranded. Additionally, you can have a single stranded DNA virus
What is the most commonly used azole on the market?
Fluconazole Widely used initial empiric antifungal agent
Which classes of antifungals affect DNA/protein synthesis?
Flucytosine (Synthetic fluorinated pyrimidine)
HSV antivirals are not curative and only inhibit actively replicating viruses. Therefore, what is their use?
For chronic suppression of viral replication in pts with impaired immune systems or recurrent infections
Polyenes are considered fungistatic or fungicidal for the most part?
Fungicidal Good against Candida and Aspergillus
Some of the side effects caused by polyenes may be attributed to a compound that must be given with the drug. Why is the compound present?
Given with salt deoxycholate because it has low water solubility. This salt disassociates when drug enters the plasma Lipid formulations may improve the side effect profile ???? ~45 in L31
Based on their PK characteristics, why are echinocandins a good choice for patients with renal impairment and/or polypharmacy?
Good for patients with renal impairment because they are primarily excreted in the feces or they undergo slow chemical degradation. -i.e. they are not renally excreted ↓DDIs -Most of them (with the exception of capsifungin) do not undergo hepatic metabolism
What viruses are acyclovir and penciclovir used to treat?
HSV-1, HSV-2 and VSV
What is the most common adverse drug reaction associated with most antifungals?
Hepatotoxicity
While resistance to polyenes is low, what is one mechanism by which it can occur?
If the fungi intrinsically has low levels of ergosterol in their membranes
What is the MOA of terbinafine?
Inhibits squalene-2,3-epoxidase to cause ergosterol synthesis inhibition
What is 14-α-sterol demethylase?
It is a microsomal/fungal cytochrome P450 system that is *responsible for the final step in ergosterol synthesis*.
In order for Flucytosine to become activated, what is the first thing that needs to happen?
It must enter the fungal cell. -it uses a cytosine-specific permease (which mammalian cells lack), to enter the cell. --the implication of this is that human cells are not effectively able to transport flucytosine intracellularly (the basis for it's specificity for fungus and it's non-toxicity towards host cells)
What is an issue of voriconazole's low water solubility?
Must be administered with a solubilizing agent (cyclodextrin) which is renally metabolized. Therefore, it cannot be used in pt's that are renally impaired. Recall that voriconazole has poor water solubility. Thus when it is given IV, it must be administered with a cyclodextrin, which is a solubilizing agent. Cyclodextrin can accumulate in people whose renal function is impaired (i.e. creatinine clearance << 50 ml/min). -However, you can use oral voriconazole for these patients instead of the IV.
What is a major limitation of neuraminidase inhibitors?
Must be given within 48 hours of symptom onset or exposure Not efficacious if given after this window Even if given within window of time, only moderate symptom alleviation and duration of infection
Which one is complementary to the mRNA of the virus: positive or negative sense RNA stand?
Negative sense (Think of positive sense as actually BEING the mRNA)
What are the ADRs of TK-ase independent HSV agents?
Nephrotoxicity Bone marrow suppression Teratogenic Carcinogenic
What are the names of the surface proteins found on influenza virus?
Neuraminidase and hemagluttinin
What are the antiviral therapies for Ebola?
Nucloside/tide analogs (Favipiravir and brincidovir) RNA silencing molecules Monoclonal Antibodies (target Ebola's glycoprotein core)
What are some neuraminidase inhibitors?
Oseltamivir (Tamiflu) Zanamivir (Relenza) Penamivir (Rapivab)
Name some RNA viruses
Picornavirus (+ssRNA) -Hep A, common cold, poliomyletitis Coronoavirus (+ssRNA) -common cold, SARS *Flavivirus* (+ssRNA) -Hep C, West Nile, Yellah fevah *Orthomyxovirus* (-ssRNA) -Influenza *Filovirus* (-ssRNA) -Eeeeebola! Rhabdovirus (-ssRNA) -Rabies Paramyxovirus (-ssRNA) -Measles, mumps *Lentivirus* (ssRNA RT) -HIV-1 and 2
What is positive sense RNA virus and negative sense RNA virus?
Positive sense RNA viruses can immediately start synthesis of proteins once entering the host cell. +ssRNA = mRNA Negative sense RNA viruses must be converted into a positive sense strand before it can be translated into proteins.
Name some positive traits of fluconazole
Pretty broad spectrum Very high oral bioavailability -Near complete GI absorption; equivalent plasma concentrations whether given PO or IV >90% excreted via renal elimination Once a day dosing (t½: 25-30 hours) Good CSF penetration (treats cryptococcal meningitis) -CSF concentrations range 50-90% of plasma values Lacks ketoconazole's endocrine adverse reactions Low Protein binding ~11-12% -"The ideal compound to treat CNS infections is of small molecular size, is moderately lipophilic, has a low level of plasma protein binding, has a volume of distribution of around 1 liter/kg, and is not a strong ligand of an efflux pump at the blood-brain or blood-CSF barrier."
What is the MOA of neuraminidase inhibitors?
Sialic acid analogs that act as competitive and reversible inhibitors of neuraminidase so that it cannot cleave the bond between sialic acid and hemagluttinin This cleavage is required to release the virus from the infected cell
Describe an Ebola infection
Starts as an acute febrile illness Progresses very rapidly to immunosuppression, sepsis, organ failure, disseminated intravascular coagulation and death
What infections is terbinafine especially good at treating?
Superficial dermatophytoses and onychomycoses
How is the lifecycle of RNA viruses different from that of DNA viruses?
The generally remain in cell cytoplasm and *do NOT enter the nucleus* for their replication or synthesis. Translation: using host ribosomes, virion serves as own mRNA template → viral polypeptides, proteins, enzymes (RNA polymerase) Replication: RNA polymerase synthesizes mRNA + genomic RNA Figure: -note that once the RNA virus is uncoated it is able to go directly to the ribosome and begin making polypeptides. This is because Hepatitis C is a +ssRNA virus and thus it does not need to synthesize a complementary strand before beginning translation. +ssRNA = mRNA
Name the four sites of action of antifungals
There are three major classes with differing mechanisms of action against cell wall or membrane function: 1. Cell wall synthesis 2. Membrane function inhibition 3. Ergosterol synthesis _________________________________________ 4. Nucleic acid synthesis -Only a handful of agents with nucleic acid synthesis inhibition and mitotic spindle formation inhibition
What are the similarities of the HSV Antiviral Agents?
These are guanine nucleoside analogues that have similar... -MOAs (impair DNA synthesis/replication) -nomenclature -pharmacokinetics -ADRs Acyclovir: 1st in class -Initial agents plagued by frequent dosing due to poor bioavailability prodrug/drug formulations increase bioavailability → decreased dosing frequency → increased compliance
Why can we use ganciclovir and valganciclovir to treat CMV infections?
These two drugs are monophosphorylated via protein kinase phosphotransferase, UL97 and NOT TK. CMV has UL97 but does not have TK
List some narrow therapeutic drugs affected by the co-administration of azoles.
Think: ↑plasma levels of co-administered drugs Including narrow therapeutic window (high potential for toxicity) agents like: -carbamazepine -cyclosporine -digoxin -methadone -phenytoin -tacrolimus -warfarin Note: Cyclosporine and tacrolimus are used to induce immunosuppression in organ transplant patients. Recall that most fungal infections are opportunistic infections that occur in immunocompromised patients.
True or False: HSV Antiviral Agents have low toxicity to uninfected mammalian cells.
True
True or False: Reactivation of latent viral infections is due to changes in T-cell immunity following "stress" and, in immunocompromised individuals, it is often times more serious than the initial infection.
True
True or False: Two advantages of echinocandins are that, for the most part, they have few drug-drug interactions, and only mild ADRs.
True
T/F: In normal healthy individuals there is a low risk of fungal infection.
True Fungal infections are often opportunistic
T/F: Flucytosine is only fungistatic and must always be administered with another antifungal
True It is primarily targeted against yeast The agent it is most commonly combined with it amphotericin B, which is rapidly fungicidal for most organisms.
T/F: The visual adverse effects of voriconazole are not permanent
True Once drug is dc'd, the visual disturbances stop
True or False: An increase in Liver Function Tests (LFTs) can be observed in a patient that is on an azole antifungal.
True Recall that one of the major ADRs associated with azoles is hepatotoxicity. -Liver enzyme tests, formerly called liver function tests (LFTs), are a group of blood tests that detect inflammation and damage to the liver. They can also check how well the liver is working. -When liver cells are damaged or destroyed, the enzymes in the cells leak out into the blood, where they can be measured by blood tests. -This is why an increase in LFTs most likely indicates that liver damage is present.
True or False: Polyenes have broad-spectrum fungicidal activity against both yeasts and molds.
True These also have low fungal resistance, so they are a good choice for a patient when you don't know what the fungal organism is.
True or False: Anytime an MOA is targeted toward the disruption/inhibition of DNA synthesis, the chance of resistance is high.
True This is because both bacteria and fungi have mechanisms in place (referred to as SOS mechanisms in bacteria) where sloppy proof-reading takes place which leads to an increase in mutations → resistance
T/F: Herpes infections are not curable
True: Becomes a latent virus once it incorporates into genetic material of the host cell genome -Periods of reactivation and inactivation Note: Primary infection and reactivation are serious in immunocompromised patients -Reactivation is due to changes in T-cell immunity following "stress" often times more serious than initial infection in immunocompromised
Which of the following agents are prodrugs? (select all that apply) Ganciclovir, famciclovir, valcyclovir, acyclovir, valganciclovir, penciclovir
Valcyclovir Famciclovir Valganciclovir *prodrug/drug formulations increase bioavailability → decreased dosing frequency → increased compliance* Note: The prodrugs are able to be administered orally, whereas the parent drugs are administered IV
What is one noteworthy adverse effect of voriconazole?
Visual disturbances: -sensitive to light (photophobia) --council against night driving because it can cause blurred night vision -altered colors (blueish-greenish tinge there are also some auditory hallucinations Note: These adverse effects are more likely to happen with the IV formulation than the oral formulation and these side effects are NOT permanent as there is no evidence of structural damage to the retina.
What is one major difference between fungal resistance and bacterial resistance?
With successive exposure of bacteria to antibiotics we can select for different resistance mutations, or sometimes bring out intrinsic resistance within the bacteria while on treatment. For fungal resistance, the majority of the time, instead of talking about resistance that is generated while on treatment, we're talking about organisms that have baseline resistance that we select for over time. -For example, yeast infections in humans is most commonly caused by candida albicans; fortunately it has the greatest susceptibility to azole antifungals. However, over the past 2 decades where we've seen increased use of azole antifungals, we've selected against candida albicans, and now we see other spp. that are much less susceptible to first line agents like fluconazole. So instead of just being a phenomenon of causing resistance within a single species that has been exposed to the drug, we're actually selecting for other species that have intrinsic or baseline lower susceptibility.
Echinocandins have better activity against which one: yeasts or molds?
Yeasts--->FungiCIDAL (For molds they are only FungiSTATIC) Note: This is the opposite of what it was for the azoles. These are not preferred agents for molds.
Which neuraminidase inhibitor is only found in an inhaled formulation?
Zanamivir (Relenza) Working on getting an IV version
Which hard to treat microorganism is voriconazole effective against?
aspergillus spp. -mold
Name the location (cytoplasm or nucleus) of the following DNA life cycle stages: Translation of viral mRNA into peptides
cytoplasm
Is ketoconazole an imidazole or a triazole?
imidazole
Why are DDIs an important consideration when using voriconazole?
it is extensively metabolized via the hepatic CYP 450 system
What is the term for human fungal infections?
mycoses There are two types of mycoses: 1. Superficial 2. Systemic
Name the location (cytoplasm or nucleus) of the following DNA life cycle stages: Synthesis of viral DNA
nucleus
Name the location (cytoplasm or nucleus) of the following DNA life cycle stages: Transcription of viral DNA into mRNA
nucleus
Is Fluconazole an imidazole or a triazole?
triazole