Pharmaceutical microbiology Flashcards
What type of micro organisms are fungi?
They are eukaryotic
Common targets of antifungal agents are
Plasma membrane and cell wall
What is ergosterol
It is a lipid responsible for the fluidity and permeability of the membrane
It is also used for the function if fungal integral membrane proteins
Types of antifungals include
Azoles-fluconazole,cotrimazole,
Polyenes-Nystatin, Amphotericin B
Allylamines-Terbinafine ,naftifine
Nucleosides-5-flucytocine
Echinocandins-caspofungin, micafungin
Moa of Azoles
They inhibit ergosterol biosynthesis via the cytochrome p450 enzyme 14 alpha demethylase.
It catalyzes the conversion of lanosterol to ergosterol
Azoles alter the morphology and inhibit the growth of fungal membranes.
Moa of polyenes
They bind to ergosterol to form a complex that is capable of disrupting the membrane and leading to leakage monovalent ions
It is also involved in an oxidation reaction and interaction with lipoproteins which impairs membrane permeability through the release of free radicals
Moa of Allylamines
They inhibit the enzyme squalene epoxidase by inhibiting the early steps of ergosterol biosynthesis,which leads to accumulation of squalene
Allylamines are highly effective against what type of fungal infection
Dermatophytes because it accumulates in the skin and nail beds relative to the blood
What does fungal cell wall comprise of.
Glucans,glycoproteins, mannans,chitin
Function of the fungal cell wall is
for adhesion and fungal pathogenesis
it also serves as a protective barrier
which of the following is not an example of echinocandins?
A)neomycin
b)caspofungin
c)micafungins
d)anidulafungins
moa of echinocandins
they target the protein complex responsible for the synthesis of beta 1,3 glucans by blocking the enzyme glucan synthase
which antifungal agents target chitin synthase?
Nikkomycin and polyoxins
role of chitin synthase
the enzyme is responsible for the elongation of the chitin chain
moa of 5-flucytosine
it inhibits nucleic acid synthesis which stops the conversion to5-fluororacil by the enzyme cytosine deaminase and then the conversion to 5-fluroroudylic acid by UMP pyrophosphorylase.
moa of Griseofulvin
it interferes with intracellular synthesis and the production of microtubles thus inhibiting fungal mitosis.
5-FC in combination with AmB or azoles shows synergistic effect against the treatment of what condition?
crytococcal meningitis
sensitivity of organisms to antimicrobials can be measured using?
MIC-minimum concentration needed to inhibit their growth and
MBC-minimum concentration needed to kill the bacteria.
antimicribial resistance can be measured by
monitoring the MICs and MBCs.
Natural resistance means
it is the resistance that is chromosomally mediated and predictable.
mutational or secondary resistance means
secondary occurs after therapy with the antimicrobial
mutational resistance is pre existing.
Induction resistance is when
the organism(bacteria) is initially sensitive but because of the damaging effect of the drug, the bacteria no longer takes up the drug. hence the conc of the drug should be maintained at high levels such as when using aminoglycosides.
Transferrable resistance is when
extrachromosomal DNA containing code for the mechanism of resistance is transferred from one organism to another.
What are the ways by which resistance can be transferred from one organism to another?
1)conjugation
2)Bacteriophage mediated transduction
3)transposons
what is meant by conjugation
this is when resistance is transferred to several drugs at once. it is common against gram negative organisms
what is Bacteriophage mediated transduction?
it is when molecular biologists transfer genetic material in both plant and animal genetic research eg in gram possitive(staphylococci)
what is transporons?
these are minute pieces of DNA that can be part of plasmids which can be translocated into other plasmids or into the normal genome of the bacteria
what is drug inactivation in biochemical mechanism of resistance
1)Drug inactivation- this involves the enzymatic hydrolysis of the beta lactam ring of penicillins and cephalosporins and the addition of substituents to certain sites on the aminoglycoside antibiotics.
what is decreased accumulation/increased efflux
in this mechanism, organisms develop the ability to transport drugs out of their cytoplasm which leads to insufficient conc inside the cell to be effective eg of this is tetracyclines. eg of decreased penetration is seen in gonococci and penicillin G.
what is decreased affinity/binding
it is when there is changes to the enzymes or receptors which leads to decreased affinity for the drug.
what is metabolic by pass?
it is when organisms synthesize new dihydrofolate reductase hence there is overproduction of the affected enzyme
empiric therapy means
administering broad spectrum antibiotics to cover infection caused by several organisms
the term anti-infective refers to
antibacterial,antifungal,antiviral and anti parasitic.
antibiotics generally refers to?
antibacterial agents obtained from natural sources.
Beta lactam antibiotics includes
penicillins eg penicillin G and V
Cephalosporins eg cephalexin
macrolides
eg erythromycins
what bonds are found in aminoglycosides?
Glycosidic bonds eg gentamycin, neomycin
what bonds are found in polypeptides
peptide bonds eg vancomycin
inhibition of cell wall synthesis
this is a characteristic of beta lactams and vancomycin
moa of aminoglycosides
Irreversibly inhibits protein synthesis
moa of quinolones
they inhibit nucleic acid synthesis by inhibiting DNA topoisomerases
moa of sulfanamides
they inhibit nucleic acid synthesis by inhibiting de novo synthesis of purine bases
Broad spectrum antibiotics is when
the drugs have no predlection for gram positive or negative and may even act against other antimicrobials.
Narrow spectrum is when
the drugs act specific to the type of bacteria eg penicillin G is effective against gram positive while Gentamicin against gram negative
Drugs used to treat HIV are called
Antiretrovirals
Antiviral drugs are aimed to
target and identify viral proteins or their parts.
Drugs used to restrict the developement of viral proteins include
-Amantadine and rimantadine act on the penetration and uncoating of viral RNA
-reverse transcriptase inhibitors, integrase splice the syntheiszed DNA into the host cell genome
Goals of treatment using antiretroviral therapy
- prolong survival of patient
-improve CD4+ T cell count
-reduce viral load
-improve quality of life
-reduce risk of transmission to others
what is the rationale for using combination antiretroviral therapy?
it aims to target different steps of the HIV life cycle which provides a synergistic effect and leads to suppresion of viral replication.
What are antibacterial drugs?
they are small molecules which may be synthetic,semi-synthetic or natural occurring.
what are the consequences of resistant microorganisms
it leads to the use of last result ,older antibiotics that were abandoned due to toxicity for regular use.
The resistant microorganisms have become stronger than they once were
disruption of normal microbial flora
