okay welcome to immune pharmacology 2 we're going to go over antifungals and antivirals and
be a little more specific about that but we'll first cover antifungal medications
next anti-mycobacterial agents which is a fancy way of saying Tb or tuberculosis. Three is the
non-HIV antivirals and then four is going to be the HIV antivirals so for fungi, not bacteria or
viruses so the two major categories are the systemic mycoses and the superficial mycoses
so the systemic mycoses are those that are in the bloodstream and then the superficial mycoses are
those that are either dermatologic or outside the body so nystatin for thrush fluconazole
for vaginal yeast infections butenafine maybe athlete's foot things like that
amphotericin B which is fungizone or nystatin which is Mycostatin these bind to sterols
they're polyene antifungals they bind to sterols and some cell membranes and increase permeability
so cations like potassium sand odium especially they can be fungostatic or fungicidal based on the
concentration so just like we had bacteriostatic and bactericidal the fungostatic is going to
stop the growth and then fungicidal will kill the fungi they're really toxic because they
also bind to human cell membranes and they bind to cholesterol and causes the same effects so
fungal cell membranes not cell membranes have ergosterol while we have cholesterol and because
those look alike that's where the danger comes in but again some of these systemic fungal infections
are life-threatening so it's really benefit versus risk and the benefit outweighs the risk of death
antifungals are azoles are like fluconazole or Diflucan this inhibits our ergosterol synthesis
preventing cell membrane formation and causes increased membrane permeation a fancy way of just
saying that it weakens the fungi and you can use them for both systemic and superficial fungal
infections the big difference between the two the polyenes that we just saw as they work on the
outside of the membrane to bind to sterols and increase permeation and they're really
toxic because they bind to the mammal sterol cholesterol azoles work on the inside of the cell
to prevent sterol formation increase permeation they're minimally toxic because only the fungal
only the fungi uptake them an over-the-counter option is something like butenafine which is
Lotrimin it's a topical antifungal so you could treat superficial mycoses mycosis which s
a fancy way of saying fungal infection it causes the fungus to create excessive squalene which is
normally converted to ergosterol and then large amounts of that squalene is toxic to the fungi
Antimicrobial agents. So, we're really talking about tuberculosis and the pathology so there
are bacteria and they're covered in this kind of waxy mycolic acid shell and
that's what gives them the name mycobacteria they need oxygen-rich environments so they want to be
in the lungs and they are respiratory infectors and both versions of TB must be treated so the one
that's controlled by the immune system the latent tuberculosis can't be spread there are no symptoms
but then there's that which is uncontrolled by the immune system active tuberculosis easily
spread and causes mortality there are a number of options that we have and multiple medications are
used at the same time usually three to four to prevent inadequate drug therapy so TB can become
resistant to a single med very easily but it leads to multi-drug resistance so TB grows very slowly
and most antibiotics target fast replicating cells so the four biggies are rifampin Rifadin isoniazid
INH pyrazinamide PZA ethambutol Myambutol use them for six to eighteen months continuously
depending on the combination so a little more detail on each of these rifampin prevents
RNA synthesis and causes this harmless orange red coloration to the bodily fluids isoniazid
inhibits mycolic acid synthesis preventing cell wall formation pyrazinamide disrupts cell wall
cell membrane function in transport and then ethambutol inhibits cell wall formation as well
antiviral agents, we'll start with some OTC and non-HIV agents so the targets of an antiviral
these are obligate parasites which means that they're challenging to treat
there they have an obligation to the host so they rely entirely upon the host cells
and synthetic commands for replication so there's a viral attachment and entry where
palivizumab works and this is for RSV or respiratory syncytial virus
there's the nucleic acid synthesis where acyclovir and valacyclovir work and then viral release
where oseltamivir and zanamivir work so those three are the big ones and
those are the ones that we're really targeting when we're talking about non-HIV infections
so with influenza obviously prevention through Fluzone Flumist which Ibelieve came back
it changes yearly to best predict the prevalent strains and it's given as an IM injection or an
intranasal mist whereas once someone has the influenza treatment is with the neuro
neuraminidase inhibitors like oseltamivir which is brand Tamiflu, zanamivir which is Relenza that's
an inhalation delivery so sometimes difficult for patients to use it but both are effective
they prevent viral release from the host cell and unfortunately, they're ineffective if you give
them more than 48 hours after showing symptoms so someone that waits to go and get treatment
unfortunately, it might be too late HSV and VZV so herpes simplex virus and varicella zoster virus
acyclovir and valacyclovir stops viral replication by inhibiting
nucleic acid production it's available as oral and IV formulations on the other side
valacyclovir has the same mechanism as acyclovir but it's only available as oral tablets so it
kind of depends on how you need to get it to the patient respiratory syncytial virus or RSV
it's a virus that causes respiratory infections usually seasonally and it's called brand
Synagis and it's a monoclonal antibody you can see that by the -mab at the end of the name but the
key is that it affects these premature infants and young children with chronic lung diseases
so this is what it's meant to do. It's a monthly injection given through the winter months
HIV antivirals we really want to look at how this all happens and that's how we can know where they
work so HIV replication cycle is to attach to fuse we have reverse transcription replication
integration transcription translation assembly then budding off and HIV protease processing
what we want to first look at is okay well what step are they stopping things at and if you look
at the cellular and this is why we we call them CCR5s but cellular chemokine receptor 5 antagonists
like Maraviroc which is cells entry some HIV strains require the CCR5 to gain entry to the cell
wherever it binds to the CCR5 preventing the virus from entering the cell on the other end
you've got the fusion inhibitor enfuvirtide and this prevents the virus from fusing
with the cell membrane so we're halting that step two we talk about and this is getting
a little deep into the acronyms but NNRTI and NRTIs the non-nucleoside reverse transcriptase inhibitor
with the nucleotide reverse transcriptase inhibitors nrti efavrons entrocytobean
and tenofovir which is Atripla so you have three drugs that's where the trip comes from
efavirenz is an NNRTI it binds to an enzyme responsible for reverse transcriptase it changes
the structure of the new DNA formed to be faulty so it doesn't work emtricitabine and
tenofovir both are NRTIs that nucleoside reverse transcriptase inhibitor and they're incorporated
into DNA at the reverse transcription step and causing faulty DNA to be produced
the next one step five is the integrase strand transfer inhibitor so raltegravir
integrase is an enzyme halted or used by the HIV virus to insert its viral DNA into host DNA
and take over host production machinery so the integrase strand transfer inhibitors halt this
process and then there are the hiv antivirals protease inhibitors so derunavir this is the
last step in the HIV replication processing by HIV protease without protease the virus is inert and
unable to infect other host cells protease inhibitors prevent the viral mu maturation
and they're very effective so again when looking at hiv we really look at where
it happens and then how we match those drugs to that area