static
interfere with growth or replication of organism but does not kill (inhibitory)
cidal
anti-infective-mediated death of the organism (lethal)
bacterial cell structure
may or may not have outer capsule (hard shell to protect bacteria). Plasma membrane
and cell wall. DNA is free floating in the cytoplasm of the cell. Ribosomes are sites of
protein synthesis for the bacteria. All these things will be targets for classes of drugs.
gram positive bacteria
include ones like streptococcus, staphylococcus, and listeria. Include inner plasma
membrane, middle periplasmic space, and outer peptidoglycan layer.
gram negative bacteria
include ones like E. coli, salmonella, and pseudomonas. Have inner plasma membrane,
middle periplasmic space, peptidoglylcan layer, and outer membrane of
lipopolysaccharide and protein. These are harder to treat with broad spectrum
antibiotics because of that final outer layer.
beta-lactams
cell wall inhibitors that include penicillins, cephalosporins, and ampicillins. These attach
to penicillin binding proteins (PBP) membrane. Results in inhibition of enzymes that
form crosslinks in cell wall. The consequence is to weaken the cell wall so it cannot
withstand osmotic pressure, resulting in cell lysis and death-bacteriocidal. Penicillins
can cause toxic reactions in massive doses causing CNS irritation (convulsions), renal
damage, and anemia. May cause allergic reactions*** like shock, rash, and oral lesions.
Cephalosporins can cause neurotoxicity, superinfection, and allergic reaction.
Upgrade to remove ads
Only $1/month
bacterial cell wall synthesis
final step in synthesis of this is the cross-linking of peptidoglycans via the enzymatic
reactions that bind a cell wall substrate (penicillin binding proteins or PBPs). PBPs are
involved in assembly, maintenance, and regulation of these. Inhibited by beta-lactams.
beta-lactam resistance
inactivation of beta lactam ring (via beta-lactamase which evolved from PBPs),
alterations of PBP's leading to genetic cell wall changes (MRSA gram positive, lower
affinity for these drugs), reduction of antibiotic access to PBP (bacteria hinder ingress of
large molecules into cell wall; gram negative); elaboration of eflux mechanisms (eject
antibiotics, gram negative).
protein synthesis inhibitors
inhibit protein synthesis. Include macrolides, tetracyclines, aminoglycosides, and
clindamycin. Bind to either 30S or 50S subunit to cause inhibition.
macrolides
protein synthesis inhibitors; 50S inhibitors. Interfere with protein synthesis by inhibiting
the enzyme peptidyl transferase. Bacteriostatic!* Drug interactions - increases serum
levels of drugs metabolized in the liver (so anything also metabolized in liver is
affected), decreases effectiveness of oral contraceptives.
clindamycin
protein synthesis inhibitors; 50S inhibitors. Interfere with protein synthesis by inhibiting
the enzyme peptidyl transferase. Bacteriostatic!* Allergy may develop.
tetracyclines
protein synthesis inhibitors; 30S inhibitors. Interfere with the synthesis of bacterial
proteins by binding to bacterial ribosomes. Bacteriostatic!* Incorporated into calcifying
structures. Hepatotoxic and nephrotoxic. Drug interactions include calcium
supplements, vitamins reduce absorption - this can lead to bacterial resistance if not
working effectively!
aminoglycosides
protein synthesis inhibitors; 30S inhibitors. Disrupt the initiation of protein synthesis.
Bacteriocidal!Toxicity of these limits its use due to ototoxicity and nephrotoxicity
(concentrate in renal cortex). Only really used for systemic infections that result from
organ transplants and immunosuppression.
folic acid inhibitors
include sulfonamides and trimethoprim. Inhibit folic acid synthesis in bacterial cell wall.
Sulfonamides and trimethoprim are structurally similar compounds that act as
competitive inhibitors to steps in the synthesis of folic acid.
folic acid
essential for growth of microorganisms. Bacteria are unable to use preformed version,
but humans can. Bacteria must synthesize this for use. Used for DNA in bacterial wall.
sulfonamides
folic acid inhibitor; block conversion of PABA to dihydrofolic acid. Bacteriostatic. Inhibit
folic acid NOT DNA synthesis. High concentrations can cause crystal formation (kidney
obstruction). Compete for sites that bind bilirubin. In newborns, unbound bilirubin can
lead to toxic encephalopathy.
trimethoprim
folic acid inhibitor; blocks conversion of dihydrofolic acid into tetrahydrofolic acid.
Selectively toxic to bacteria. Adverse effects are rare except in patients with AIDS.
Because it interferes with folic acid metabolism, use in pregnancy may affect the fetus.
cell replication inhibitors
include quinolones, fluoroquinolones, and nitrofurans. Quinolones - inhibit DNA
synthesis by inhibiting DNA gyrase activity-prevents DNA unwinding.
Fluoroquinolones - target topoisomerase IV; this can be bacteriostatic but can
become bacteriocidal. Quinolone adverse reactions - CNS effects,
hypersensitivity, vision disturbances, joint pain, not for pregnant women, metal
ions reduce absorption! (vitamin supplements, antacids, etc.).
Upgrade to remove ads
Only $1/month
topoisomerase IV
enzyme responsible for separating daughter cells after division. Targeted by
fluoroquinolones. Specific to microorganisms.
nitrofurans
type of cell replication inhibitor. Metabolites of this effect DNA/RNA synthesis and
protein synthesis of bacteria. Selectively toxic. For long term prophylaxis and treatment
of women with chronic UTIs. Resistance is almost never seen - so good for long term.
Adverse reactions include interference with red blood cell enzyme systems in babies
and contraindicated in pregnant women near term.
fungal call structure
more similar to mammalian cell than plan cell. Nuclear bound, phospholipid bilayer cell
membrane, nuclear bound nucleus, ER, mitochondria, vacuoles. Major difference is the
presence of rigid cell wall.
yeasts
type of fungi; unicellular organisms. Opportunistic pathogesn cause cryptococcosis,
candidiasis. Particularly seen in HIV and AIDs patients.
molds
type of fungi; grow in multicellular filaments called hyphae. Have multiple genetically
identical nuclei and is considered single organism (mycelium). Mold spores are
ubiquitous and can cause number of health related issues. Opportunistic pathogens
include aspergillus spp (black mold infection).
fungal infections
once considered trivial and non-life threatening. Include tinea pedis, tinea unguium, and
tinea corporis. Have grown more promiennt because of population mobility, growing
population of immunocompromised (via surgery, cancer, HIV/AIDS, age). But usually,
the human body is not ideal for these. If these are chronically present, then there may
be some underlying cause allowing these to proliferate.
polyenes (membrane disrupting agents)
include causing disruption of membrane function, ergosterol synthesis, nucleic acid
synthesis, and cell wall synthesis. Binds sterols (preferentially ergosterol) and disrupts
osmotic integrity of cell membrane - therefore fungicidal! Extremely toxic. Cause the
cells to leak intracellular cations and proteins. May cause nephrotoxicity which is the
major limitation to AMB! Toxicity is dose dependent and transient depending on drug
interactions. Increased accumulation of renally-cleared drugs.
azoles
ergosterol synthesis inhibitors. Include imidazoles (older and OTC) and triazoles
(newer). These are metabolized more slowly than imidazoles and have less effect on
human sterol synthesis than imidazoles. Inhibits lanosterol demethylase and impair the
synthesis of ergosterol - fungistatic! Well tolerated, may cause hepatotoxicity,
hypertension, visual impairment. Some fungi are resistant to this. Many drug
interactions - via changes in pH (H2 antagonists, proton pump inhibitors) and metal ion
complexation (antacids, vitamin supplements); also interactions with cytochrome p450 -
these drugs are reversible inhibitors of p450 enzymes so will cause issues.
allylamines
ergosterol synthesis inhibitors. Blocks synthesis via inhibition of squalene epoxidase, an
enzyme needed for the creation of sterols. So fungicidal!* Include oral and topical
formulations. Terbinafine for treatment of dematophytosis. Combined with fluconazole
can be successful in treatment of fuconazole-resistant Candida spp.
echinocandins
glucan synthase inhibitors. Block cell wall synthesis via beta-1,3 glucan synthesis
inhibition. Fungicidal! IV only. For candida, aspergillus spp. Salvage therapy for
invasive aspergillosis and orophargyngeal/esophageal candidiasis. No cross
resistance!
viruses
utilize host cell biosynthetic machinery for replication. DNA and RNA viruses can be
either double stranded or single stranded. Effective antivirals inhibit virus-specific
replicative events or virus-directed nucleic acid synthesis and/or protein synthesis. In
order to get into cell, it will uncoat and transfer its DNA to host nucleus which will cause
protein synthesis of stuff for the enzyme and a new assembly of virion for release.
Herpes is type of this.
acyclovir (and valacyclovir)
antiviral for type I and II herpes virus. Affinity for viral TK is 200 times greater than
cellular kinase. Anti hepatic affinity. Will only go into affected cells. Isn't an active drug.
Needs to undergo 3 steps before it can be active. First is mono-phosphorylation which
only happens by the viral herpes thymidine kinase. But if that isn't there, then this drug
is useless and won't be transformed to have an effect. 2nd and 3rd steps are completed
by own cell and it is converted into triphosphate which incorporates into virus DNA and
because there isn't a 3 hydroxyl group, it acts as a chain terminator in synthesis and
prevents virus from continuing to grow. Also can block viral DNA polymerase.
adverse effects of acyclovir
renal insufficiency and CNS side effects, including neurotoxicity. Drug interactions -
somnolence and lethargy with zidovudine (antiretroviral) and cyclosporine increases
nephrotoxicity.
ganciclovir (and valganciclovir)
inhibits all herpes viruses and is especially active against CMV (type of herpes). Inhibits
viral DNA synthesis by competitive inhibition of viral DNA polymerase. Phosphorylated
by viral TK (HSV). Phosphorylated by a viral phosphotransferase encoded in CMV
genome. Will not CURE herpes virus but will reduce the symptoms. ADverse effects
include myelosuppression, neutropenia, thrombocytopenia, and CNS side effects
(coma). Nephrotoxic agents increase this toxicity. Resistance can develop - mutations to
phosphotransferase and mutations to viral DNA polymerase.
Powered by TCPDF (www.tcpdf.org)
