Exam 4 - Antimicrobials/Antivirals Flashcards
What are the important differences between gram positve and gram negative structure?
- Gram (+) - Contains a very thick cell wall comprised of peptidoglycan. Stains purple.
- Gram (-) - Contains additional outer membrane as well as Lipopolysaccharide (LPS). LPS become endotoxins when released into bloodstream (bad). Stains pink.
What are the 5 general properties of antimicrobial agents?
- Selective toxicity
- Spectrum of activity
- Modes of action
- Side effects
- Resistance of microorganisms.
Differentiate spectrum of activity and selective toxicity?
Spectrum of activity – Narrow vs broad spectrum. Broad spectrum work on a number of bacteria, including gram (+) and gram (-). Narrow spectrum work on either a specific type of bacteria such as gram (+) or even a specific bacterium.
Selective toxicity – Antibiotics usually have a larger therapeutic index. Additionally, they are usually toxic to bacterial cells and not human cells. However, at higher doses they can become toxic to human cells.
Describe cell wall synthesis inhibition and the drugs that work by this mechanism?
- Used primarily for gram (+) bacteria
- Selectively damages bacterial and fungal cells by the B-lactam ring attaching to the enzymes that cross link peptidoglycans and prevent cell wall synthesis.
- Penicillins, cephalosporin, carbapenems, vancomycin
Describe disruption of the cell membrane and the drugs that work by this mechanism?
- Used primarily in gram (-)
- Creates pores in cell membranes leading to cell death.
- Polymyxin, daptomycin
Describe inhibition of protein synthesis and the drugs that work by this mechanism?
- Uses selective toxicity to target 70S ribosomes on bacteria, acts as a bacteriostatic, slowing down growth
Tetracycline, erythromycin, azithromycin, neomycin
Describe inhibition of nucleic acid synthesis and the drugs that work by this mechanism?
Inhibit RNA polymerase (Rifamycin)
Describe inhibition of folic acid synthesis and the drugs that work by this mechanism?
Competively block PABA and preventing folic acid synthesis which prevents DNA/RNA synthesis
Drugs: sulfonamides, trimethoprim
Describe bacterial resistance to beta lactam antibiotics?
Penicillin resistant bacteria like MRSA contain beta-lactamase that breaks down the beta lactam ring of the drug, allowing the cell wall to continue to be synthesized.
Describe the antibacterial activity of carbapenems and its clinical uses?
Beta lactam antibiotic but is more resistant to beta-lactamase
Wide spectrum of activity, penetrates the CNS, drug of choice for enterobacter
Describe the antibacterial activity of vancomycin and its uses?
Beta-lactam antibiotic
Resistant to beta lactamase
Drug of last resort due to high incidence of VRE
What are the major side effects with penicillins and cephalopsporins?
- Hypersensitivity (most common)
- anaphylactic shock (0.05%)
- skin rash (<1%)
- oral lesions
- hemolytic anemia
- interstitial nephritis
- GI upset
Describe the effects of premature termination of antibiotics?
The highly resistant organisms have not all been killed, allowing them to continue to grow creating a relapse in infection and possible spread to other hosts leading to more drug resistant infections.
Describe the MOA of polymyxins and daptomycin and their bacterial target?
MOA: disrupts the cell membrane by binding to phospholipids and creating an open pore in the cell wall.
Target: Gram (-) bacteria, used in triple antibiotic ointments (Neosporin) or as a last resort systemic drug to resistant gram (-) strains.
Describe why inhibitors of protein synthesis are broad spectrum, their MOA, and toxicities?
- They are readily absorbed and widely distributed and selectively target only bacterial cells (gram (-) and gram (+)).
- Work by inhibiting 70S ribosomes found only in bacteria preventing protein synthesis.
- Toxicities: GI upset, destroys normal microbiota leading to c. diff, discoloration of bone and teeth, allergy, ototoxicity, and nephrotoxicity.
What drugs are examples protein synthesis inhibitors?
Tetracycline, erythromycin, azithromycin, neomycin
How do sulfonamides and trimethoprim affect bacterial folic acid synthesis?
Competitively inhibit the enzyme that converts PABA to folic acid preventing DNA and RNA synthesis.
What are the components of a virus and their function?
- Nucleic acids - contains DNA or RNA that will reprogram the host cell
- Capsid – Shell surrounds the nucleic acid.
- Envelope – Usually a modified piece of the host cell membrane.
- Spikes – Found on both naked and enveloped viruses. Project from either the nucleocapsid or envelope and target specific cell protiens within in the host.
What is the MOA of acyclovir?
- Normally the virus will replicate by growing the DNA chain by attaching phosphate groups to the ribose sugar of the DNA substrate.
- Acyclovir looks exactly like the host DNA except that the ribose sugar is missing.
- The virus cannot tell the difference between Acyclovir and endogenous DNA. So, the virus will attempt to use acyclovir to grow the DNA chain but because there is nowhere to attach the next group, the DNA replication cycle is terminated.
Called a “chain terminator”
