Micro Final Antimicrobial Medications

What was the first sulfa drug developed?

Sulfanilamide.

What was originally used to treat streptococcal infections in animals?

Red dye Prontosil.

What are two examples of chemotherapeutic agents that were used in early development of antimicrobial drugs.

Red dye Prontosil and Salvarsan.

Research proved which antibiotic to be the first naturally produced anti-microbial?

Penicillin G.

Define selective toxicity.

Causes greater harm to microbes than to human host.

Why is selective toxicity difficult for antiviral medications?

Difficult with respect to antiviral medications because viruses rely on human cells for their replication.

*Antivirals are only effective against replicating viruses.

How is toxicity measured/expressed?

Therapeutic index.

How is therapeutic index calculated?

LD50/ED50

Define high therapeutic index.

Means the drug is safer.

You must monitor patients that take drugs that are ____ on the therapeutic index?

Low.

Define therapeutic window.

The range between the therapeutic dose and the toxic dose.

Explain how penicillin G works.

Interferes with cell wall synthesis.

Has a high therapeutic index.

High therapeutic window.

Bacteriostatic vs bacteriocidal.

Static - inhibits bacterial growth

Cidal - KILLS

Are antibiotics typically bacteriostatic or cidal?

Static - inhibit protein synthesis and cell growth.

What is the problem with broad-spectrum antibiotics?

Disrupts microbiome that helps keep out other pathogens.

When are broad spectrum antibiotics beneficial?

For treatment of acute life threatening diseases and diseases when there is no time to culture for identification.

How can bacteriostatic and bacteriocidal antimicrobials be antagonistic?

Bacteriostatic antimicrobials that prevent cell division interfere with bacteriocidal antimicrobials that kill only dividing cells.

Why must normal medication doses be adjusted in patients with kidney and/or liver disease?

Because they excrete or metabolize medications more slowly.

What can chloramphenicol cause?

aplastic anemia.

Define dysbiosis.

Imbalance in the microbiome.

"Broad-spectrum antimicrobials may allow growth of Clostridium difficile without competition, resulting in diarrhea or colitis". This is an example of what?

Dysbiosis.

What kinds of bacteria lack intrinsic (innate) resistance?

Bacteria that lack cell walls (ex: mycoplasma or outer membrane of gram negative bacteria).

Why does the outer membrane of gram negative bacteria block many antibiotics?

Because of LPS membrane. Blocks beta-lactam antibiotics.

How can bacteria develop acquired resistance?

spontaneous mutations, horizontal gene transfer.

What are examples of beta-lactam antibiotics that have high therapeutic index?

Penicillins, cephalosporins carbapenems

Glycopeptide antibiotics and monobactam.

What do beta-lactam antibiotics target?

Penicillin-binding proteins (PBPs), which are enzymes that build the bacterial cell wall. They are only effective against actively growing cells.

*beta-lactam antibiotics inhibit cell wall synthesis.

What are beta-lactamases?

Breaks beta-lactam rings. Destroying the activity of antibiotics.

Gram-negatives produce a more extensive array of β-lactamases than Gram-positives

Natural penicillins are developed from which bacterium?

Penicillium chrysogenum.

Penicillinase-resistant penicillins are devloped from which bacterium?

S. aureus strains.

"Narrow-spectrum penicillin that acts against Gram-positives and a few Gram-negatives; deactivated by penicillinases".

Natural penicillins.

Why is MRSA resistant to penicillin?

Because it can produce altered PBPs to which β-lactam antibiotics do not bind well.

Give 2 examples of broad spectrum penicillins.

Ampicillin, amoxicillin.

Extended spectrum penicillins have greater activity against which strands?

Enterobac-teriaceae, Pseudomonas species.

Meaning reduced activity against many gram positives.

Penicillin + Beta-Lactamase Inhibitor.

Augmentin.

Why is bacitracin limited to topical applications?

•toxicity limits to topical applications

•interferes with transport of peptidoglycan precursors across membrane

Prokaryotes and mitochondria have ___S ribosomes and eukaryotes have ___S.

70

80

How do fluoroquinolones work?

•Inhibit topoisomerases, enzymes that maintain supercoiling of DNA; bactericidal against wide variety of bacteria

•DNA gyrase in particular

•Resistance usually due to alteration in DNA gyrase target

•Used extensively in the past; severe side effects limit their use

How do rifamycins work?

•Block prokaryotic RNA polymerase; prevents initiation of transcription

•Rifampin is bactericidal against Gram-positives, some Gram-negatives, Mycobacterium

•Resistance develops quickly due to mutation in RNA polymerase gene

How does fidaxomicin work?

•Binds to RNA polymerase; interferes with transcription

•Relatively new; bactericidal

•Not absorbed in intestinal tract; effective in treating C. difficile infections

How does metronidazole (flagyl) work?

•Anaerobic metabolism required to convert to active form

•Active form binds DNA, interferes with synthesis, causes breaks

•Used to treat bacterial vaginosis and C. difficile infection

How do sulfonamides (sulfa drugs) and trimethoprim work?

Inhibiting folate synthesis. Both have synergistic effect on each other.

Sulfonamides (sulfa drugs) competitively inhibit what?

PABA enzyme.

Sulfonamides (sulfa drugs) and trimethoprim are able to inhibit which bacteria?

Mycobacterium.

Why is combination therapy effective for first line treatment with drugs?

Its the least toxic and it decreases chance of development of resistant mutants.

Combination therapy is especially used in treating which two viruses?

HIV and HEP C.

What antibacterial inhibits mycolic acid synthesis?

Isoniazid.

What antibacterial interferes with protein synthesis?

Pyrazinamides.

What test is routinely used to determine susceptibility of bacterial strain to antibiotics?

Kirby-Bauer disc diffusion.

Drugs diffuse outward on agar plate and establish concentrations.

What is the zone of inhibition on a kirby-bauer disc diffusion test?

The zone is compared with specially prepared charts to determine whether strain is susceptible, intermediate, or resistant.

What would cause decreased uptake of medication in gram negative bacteria?

Changes in porin proteins.

What are 4 mechanisms of acquired resistance to antimicrobials?

1) medication inactivating enzymes

2) alteration in binding molecule

3) decreased uptake of medication

4) increased elimination of medication (efflux pumps)

Why can't herpes and HIV virus not be cured?

Because they remain latent in cells.

What 3 HIV medications prevent viral entry?

1) post attachment inhibitors

2) CCR5 antagonists

3) Fusion inhibitors

How do post attachment inhibitors work for HIV?

mAb (antibody) binds to HIV receptor CD4 and prevents HIV particle from undergoing a change required for the virus to bind to a co-receptor.

How do CCR5 antagonists work?

Maraviroc (MCV) blocks the HIV co-receptor CCR5.

How do fusion inhibitors work for HIV?

Enfuvirtide (ENF) binds to an HIV protein that promotes fusion of the viral envelope with the cell membrane.

Define uncoating.

The process by which the nucleic acid of a viral particle is released from the protein coat.

What 2 medications prevent the uncoating of HEP A?

Amantadine and rimantadine (however not that widely used anymore because of resistance).

Acyclovir (treatment for herpesvirus - cold sores and chicken pox) does little harm to unaffected cells. Why?

Since converted by virally encoded enzymes in infected cells.

Which drug is highly effective against hepatitis C when used with another anti-HCV medication?

Sofosbuvir.

Nucleotide reverse transcriptase inhibitors (NRTIs) are used to treat what?

HBV, HIV.

•Ex: zidovudine (anti-HIV), tenofovir (anti-HBV)

Used to treat sight-threatening cytomegalovirus (CMV) infections in immunocompromised.

Ganciclovir.