38 Questions
What is the name of the fungal infection that occurs with prolonged use of antibiotics?
Candidiasis
What generation of cephalosporins has an expanded spectrum of activity against Gram-positive bacteria, including MRSA, and has a high affinity for binding?
5th generation
What is the primary route of excretion for cephalosporins?
Renal tubular secretion
What is the primary mechanism of action for aminoglycosides in inhibiting bacterial protein synthesis?
Inhibition of initiation by interfering with codon-anticodon interaction, causing mRNA misreading
What is the primary mechanism of action for tetracyclines in inhibiting bacterial protein synthesis?
Inhibition of tRNA binding to the A site
What is the primary mechanism of action for macrolides in inhibiting bacterial protein synthesis?
Inhibition of elongation and/or translocation
What is a common adverse effect of aminoglycosides?
Ototoxicity
What is a common adverse effect of tetracyclines?
GI disturbance and tooth discoloration
What is a common mechanism of resistance to macrolides?
Target modification and drug degradation by esterases
What is a common risk factor for fungal infections?
Prolonged use of broad-spectrum antibiotics
What is the target of Fostemsavir, a prodrug and the first in its class?
Gp120
What is the target of Enfuvirtide, a 36 AA peptide and the first in its class?
Gp41
What is the target of Ibalizumab, the first monoclonal antibody?
CD4
What is the target of Maraviroc, the only CCR receptor agonist?
CCR5
What are the roles of the p66 and p51 subunits in HIV reverse transcriptase?
p66: catalytic role (polymerase, ribonuclease); p51: structural
What are the three roles of HIV polymerase?
- RNA-dependent DNA polymerase: ssRNA > ssDNA; 2. Ribonuclease (RNase H): degrades RNA in RNA-DNA duplex; 3. DNA-dependent DNA polymerase: ssDNA > dsDNA
What is the mechanism of action of nucleoside reverse transcriptase inhibitors (NRTIs)?
Analogues of ACGT; phosphorylated to form triphosphate; incorporated into ssDNA to terminate elongation
What are the components of Truvada and DESCOVY?
Truvada: emtricitabine + tenofovir disoproxil fumarate; DESCovy: emtricitabine + tenofovir alafenamide
What are the targets of non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
Distinct binding site > hydrophobic pocket p66 subunit; conformational change > inhibit enzyme activity
What is the role of HIV protease?
Cleaves gag-pol fusion polyprotein into individual proteins
What is the primary challenge in developing antifungal drugs, and how does it relate to the similarities between human cells and fungal cells?
The primary challenge is the similarity between human cells and fungal cells, both being eukaryotes, which makes it difficult to develop a drug that targets fungal cells without harming human cells. The distinctive sterols in fungal cells, such as ergosterol, can be targeted to overcome this challenge.
What is the mechanism of action of echinocandins, and how does it target the fungal cell wall?
Echinocandins target the b-1,3-glucan in the fungal cell wall, binding to the b-1,3-glucan synthase and inhibiting its synthesis.
What is the role of ergosterol in fungal cells, and how does it relate to the antifungal activity of polyenes?
Ergosterol regulates cellular processes, including membrane stability and fluidity, and is the target of polyenes, which bind directly to it, causing leakage of intracellular contents by forming pores.
What is the difference between the spectrum of action of echinocandins and polyenes, and how does it relate to their use in treating fungal infections?
Echinocandins are fungicidal for Candida and fungistatic for Aspergillus, whereas polyenes have a broad spectrum of action, being effective against most fungi and yeasts. This difference in spectrum of action affects the choice of drug for treating specific fungal infections.
What is the primary advantage of liposomal formulations of amphotericin B, and how does it relate to the drug's toxicity?
The primary advantage of liposomal formulations of amphotericin B is reduced toxicity, particularly nephrotoxicity, compared to traditional formulations.
What is the mechanism of action of allylamines, and how does it relate to their use in treating fungal infections of the nail?
Allylamines, such as terbinafine, are synthetic fungicides that inhibit the synthesis of fungal cell membrane ergosterol, making them effective in treating fungal infections of the nail, such as onychomycosis.
What is the primary advantage of azole antifungal drugs, and how does it relate to their use in treating systemic fungal infections?
The primary advantage of azole antifungal drugs is their broad spectrum of action, making them effective in treating systemic fungal infections, and their ability to be administered orally.
What is the difference between HIV-1 and HIV-2, and how does it relate to their transmission and infectivity?
The difference between HIV-1 and HIV-2 lies in one accessory protein, which decreases the infectivity of HIV-2, making it less transmissible and more limited to West Africa.
What is the primary mode of transmission of HIV, and how does it relate to risky behaviors and exposure?
The primary mode of transmission of HIV is through unprotected sexual contact, and is exacerbated by risky behaviors such as injecting drug use and exposure to infected blood and bodily fluids.
What is the structure of the HIV virion, and how does it relate to the virus's replication cycle?
The HIV virion consists of a genome of ~9kb, including 9 genes and 15 proteins, which are essential for the virus's replication cycle, including binding, fusion, uncoating, and reverse transcription.
What is the mechanism of action of penicillins?
Inhibit cell wall synthesis
What is the mechanism of action of tetracyclines?
Inhibit protein synthesis at tRNA by inhibiting aa-tRNA binding to A site
Name two cell wall synthesis inhibitors.
Penicillin and cephalosporin
What is the core structure that cell wall synthesis inhibitors have in common?
B-Lactam
What causes penicillin resistance?
Alterations at PBPs, prevention of B-lactams from accessing PBPs, and expression of B-lactamase
What type of drugs inhibit protein synthesis?
Aminoglycosides, tetracyclines, amphenicols, and macrolides
What is the classification of penicillins and cephalosporins?
B-lactams
What is the mechanism of penicillin resistance involving B-lactamase?
Breakdown of B-lactams by B-lactamase
Study Notes
Antibacterial Agents
- Penicillins: inhibit cell wall synthesis, mechanism of action involves binding to penicillin-binding proteins (PBPs), causing cell lysis
- Tetracyclines: inhibit protein synthesis by preventing aminoacyl-tRNA binding to A-site of ribosome
Cell Wall Synthesis Inhibitors
- B-Lactams: Penicillins and Cephalosporins; share a common core structure (B-Lactam ring)
- Alterations at PBPs: decrease drug binding ability, leading to penicillin resistance
- Prevention of B-Lactams: from accessing and entering pore channels and reaching PBPs in Gram-negative bacteria
- Expression of B-Lactamase: in certain bacteria, leads to penicillin resistance
Protein Synthesis Inhibitors
- Aminoglycosides, Tetracyclines, Amphenicols, and Macrolides: inhibit protein synthesis
- B-Lactams: inhibit cell wall synthesis
Penicillins
- Amoxicillin: synthetic, broad-spectrum, no B-Lactamase resistance
- Clavulanic acid: synthetic, B-Lactamase inhibitor
- Pharmacokinetics: acid stability varies, lipid-insoluble, eliminated renally
- Resistance: alterations in PBPs, preventing B-Lactams from accessing and transversing pore channels, producing B-Lactamase
- Adverse reactions: opening B-Lactam ring, Type 1 & 2 sensitivity reactions, superinfection (e.g., Candidiasis)
Cephalosporins
- 5th generation: expanded Gram positive, including MRSA; common Gram negative
- Binding with high affinity: Ceftaroline
- Pharmacokinetics: acid-stable, administered parenterally; few orally, distributed in extracellular fluid, some cross blood-brain barrier
- Elimination: mostly renal tubular secretion
- Adverse reactions: similar to penicillins, cross-reactivity between penicillins and cephalosporins causes ADR
Bacterial Protein Synthesis Inhibitors
- Inhibit 1 of 4 key steps: in bacterial protein synthesis
- Most are bacteriostatic: (Aminoglycosides are bactericidal)
Aminoglycosides
- Inhibit initiation: of protein synthesis
- Mechanism of action: [30s] inhibit codon-anticodon interaction, causing mRNA misreading
Tetracyclines
- Inhibit tRNA binding: to A-site of ribosome
- Mechanism of action: [30s] inhibit aminoacyl-tRNA binding to A-site
Amphenicols
- Inhibit transpeptidation: of peptide bond formation
- Mechanism of action: [50s] inhibit peptide bond formation
Macrolides
- Inhibit elongation &/or translocation: of protein synthesis
- Mechanism of action: [50s] prevent transfer of tRNA with growing peptide from A-site to P-site
Antifungal Agents
- Challenges: similarities to human as eukaryotes, can be toxic to host, distinctive sterols (ergosterol in fungal cells vs. cholesterol in human cells)
Echinocandins
- Inhibit cell wall synthesis: target β-1,3-glucan in fungal cell wall
- Mechanism of action: binds to β-1,3-glucan synthase, inhibiting synthesis
Polyenes
- Natural, broad-spectrum antifungal macrolides: interact with ergosterol, key to antifungal activity
- Mechanism of action: causes leakage of intracellular contents by forming pores, stops interactions at surface of cell membranes
Azoles
- Broad-spectrum, synthetic fungistatic drugs: inhibit ergosterol biosynthesis
- Mechanism of action: inhibition of 14α-demethylase, a cytochrome P-450 enzyme involved in ergosterol biosynthesis
Quiz about the mechanism of action of penicillins and tetracyclines, including cell wall synthesis inhibitors and antibiotic resistance.
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