Anti-Microbials

 Fungal Infections
o 2 major types of mycoses
 Superficial and systemic
 Antifungals
o Not a lot of drug choices very limited
o Use is limited by their toxicity
o By treating fungi
 Need to compare with virus and bacteria
 Need to know sites of attack
 Antifungals: Polyenes
o Act by binding to sterols

ergosterol phospholipid

o Amphotericin B (not in notes)

 Used parenterally/topically
 High doses for more resistant fungi, lower dosees for
UTI/esophageal infections
 Not penetrate BBB well (Still used)
 Extensive LV metabolism (?)
• Biomechanism pathway not sure of, so don’t know how it
is broken down
 Slow renal excretion, biphasic t1/2
• If were to graph it’s conc in the body it goes down and
comes back up a little bit.
 • The first 24 hrs would lose a substantial amount, but the
small conc. Bodies would still last a long time (up to 15
days). This is where toxicity issues come into play
o Amphotericin B: ‘Amphoterrible’ (not in notes)
 Most toxic antibiotic used today
 80% nephrotoxicity (causing azotemia, hypokalemia,
hypomagnesemia)
 Acute LV failure, cardiac arrhythmias, hematopoetic disorders
 Less severe sx: n+v, chills, fever, HA
 Nystatin
o Limited to more topical use
o Very minimal side effects compared to amphotericin
o Poor absorption in via mucous membrane
 Azoles
o Can be fungistatic or fugicidal
o Will inhibit synthesis of ergosterol (stop production of the sterol before it’s
incorporated into the membrane)
o Acetyl CoA  squaliene (conversion by p450 enzyme)  Langosterol
Ergosterol
o Decreased ergosterol leads to decreased fluidity
o Problems with replication, transformation of candidal cells to hyphae
o Effecting the ergosterol in different places in different ways
 Fluconazole
o Inhibits P450 so also has some interactions with other drugs
o Hypoglycemic agents are most commonly seen
o Good agent to treat KI infections
 Urinary tract Candida
o Tends to conc in certain areas including the CSF
o Where it has excellent penetration
o Don’t need to know what it’s active against
 Antifungals: Azoles (not all in notes)
o Fluconazole absorption is decreased 15-20% by cimetidine and may alter
warfarin-adjusted PT time (benzo’s, HMG-coA reductase (-))
o Usually well tolerated
o Systemic tx: skin rash, elevated LV enzymes/LV injury, hematopoietic
toxicity, GI distress (N+V, diarrhea)
 Antifungals: Allylamines
o Terbinafine
 Metabolism via P450 mechanisms
 Primary treatment for superficial dermatophitic infection
 Anti-Malarials
o Look at diagram on last slide of package
 Malaria
 o 4 malarial species
o P. falciparum
 Fever every few days
 Makes RBC sticky
 If treated no relapses
o P. malariae
 Not as aggressive
o P. ovale
 Rare
o P. vivax
 Less severe, rarely fatal
 Problem: can persist for years and years
o Best way to treat is to avoid it
o Prevents digestion of Hemoglobin
 Parasite then does not have AA to work with to build more of itself
 Increase in Heme in the cell which is toxic to that organism
o Choroquin
 Well ablsorbed orally but can still be given iv/im
 Concentrates in the parasitized RBC regardless of method
delivered
 Lasts in body for long time
 Anti-virals
o Herpes simplex
o Resistance
 Usually d/t the development of mutations
 Anti-viral Tx
o Most anti-viral drugs are anti-metabolites
o Don’t kill of virus directly but freeze it (Stop replication – up to our body
to get rid of it)
o Resistance can happened
o Successful anti-viral treatment depends on the host
o