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236 Cards in this Set
- Front
- Back
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What is the most commonly used pharmacological agents?
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Antibacterial agents
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Misuse of antibacterial agents is related to what 4 things?
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1. Nature of dose-response relationship
2. Diagnostic failure 3. Drug residues in food-producing animals 4. Emergence of resistance |
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*What is the goal of antibacterial therapy?
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Produce an effective concentration of antibacterial agent at the site of infection, for a duration sufficient to achieve elimination of the infection, without harm to the patient, and to do so in the most economically feasible manner available
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What 2 antimicrobials have a mechanism of action that has selective action of cell walls?
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Beta-lactams
Bacitracin |
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What 5 antimicrobials have a mechanism of action that disrupt protein synthesis?
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1. Aminoglycosides
2. Tetracycline 3. Chloramphenicols 4. Macrolides 5. Lincosamides |
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What antimicrobial agent has a mechanism of action that destroys cell membranes?
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Polymyxins
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What antimicrobial agent has a mechanism of action that interferes with intermediary metabolism?
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Nitrofurans
-Inhibit oxidative carboxylation of pyruvate to acetyl CoA, affecting energy metabolism |
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What 4 antimicrobial agents have a mechanism of action that inhibits nucleic acid metabolism?
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1. Sulfonamides/trimethoprim
2. Rifampin 3. Fluoroquinolones 4. Metronidazole |
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What are the 3 properties that confer bacterial resistance?
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1. Drug inactivation by bacterial enzymes
e.g. beta-lactamase production that cleaves open part of the structures of penicillin so stops working 2. Changes in target site of action e.g. in nucleic acid or ribosome 3. Failure to achieve adequate antimicrobial concentration at the site of action |
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What are the 3 mechanisms by which resistance is acquired?
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1. Random mutation
2. Changes in gene expression 3. Transfer b/w bacteria |
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What are the 3 methods that bacteria use to transfer resistance mechanisms?
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1. Transformation
2. Transduction 3. Conjugation |
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What should you do when the mutant selection window is wide? Why?
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Use combinations of antimicrobial agents because it can be difficult to establish a concentration that exceeds the MPC to eliminate resistant bacteria without hurting the animal .
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What should you do when the mutant selection window is narrow?
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Use doses that result in tissue concentrations that exceed the mutant prevention concentration
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What is the mutant selection window?
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Difference b/w minimum inhibitory concentration and mutant prevention concentration
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What are the adverse effects of beta-lactams?
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Allergic reactions (penicillins, cephalosporins)
Nephrotoxicity (cephalosporins) |
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Are beta-lactams basic or acidic?
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Weak organic acids
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True or false. Beta-lactams have good oral absorption.
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True
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Beta-lactams have good oral absorption, but what's the exception?
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Natural penicillins
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What beta-lactams can penetrate the blood-brain barrier only with inflammation? Why?
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Penicillins and 1st generation cephalosporins because they are moderately charged
-3rd generation cephalosporins can cross BBB w/o inflammation |
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What beta-lactams are moderately lipid soluble?
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3rd generation cephalosporins
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How are beta-lactams removed from the system?
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Renal excretion unchanged
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How does bacterial resistance against aminoglycoside antibiotics develop?
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Inactivation by conjugative enzymes that are secreted into the periplasmic space.
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What are the 3 adverse effects of aminoglycoside antibiotics?
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1. Nephrotoxicity
2. Ototoxicity 3. Neuromuscular blockade |
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Are aminoglycoside antibiotics acidic or basic?
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Weak organic bases
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Are aminoglycosides lipid soluble?
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No, they are a highly charged specie
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True or false. Aminoglycosides are highly protein bound.
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False, they are low protein binding
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How are aminoglycoside antibiotics removed from the system?
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Renal excretion (glomerular filtration)
-Highly charged species |
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What are 3 specific aminoglycosides?
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1. Neomycin
2. Amikacin 3. Gentamycin |
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What is the spectrum of activity of gentamicin?
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Aerobic, gram-negative bacteria
-Pseudomonas, staphylococcus |
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What is the spectrum of activity of neomycin?
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Aerobic, gram-negative bacteria
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What is the spectrum of activity of amikacin?
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Aerobic, gram-negative bacteria
-Pseudomonas |
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How is bacterial resistance to tetracycline antibiotics developing?
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Impermeability related to passive diffusion across the outer cell wall or active transport across the inner cell membrane.
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What are the 3 adverse effects of tetracycline antibiotics?
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1. GIT effects
2. Tooth discoloration and enamel dysplasia 3. Hepatotoxicity/nephrotoxicity |
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Are tetracycline antibiotics acidic or basic?
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Are amphoteric so have both basic and acidic properties
-Amphoteric=tetracyclines & fluoroquinolones |
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Are tetracycline antibiotics lipid soluble?
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Moderately lipid soluble (oxytetracycline) to highly lipid soluble (doxycycline)
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How are tetracycline antibiotics removed from the system?
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Renal or hepatic excretion (Enterohepatic circulation)
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What are 2 specific agents that are tetracycline antibiotics?
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Oxytetracycline
Doxycycline |
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What is the spectrum of activity of tetracycline antibiotics?
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Broad spectrum including gram-positive & gram-negative bacteria (including anaerobes), rickettsia, and protozoa.
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What bacteria is generally resistant to tetracycline antibiotics?
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Pseudomonas
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How has bacterial resistance against chloramphenicol and florfenicol developed?
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Production of an acetyltransferase acetylates the antibiotic.
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**What are the adverse effects of chloramphenicol and florfenicol?
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1. Reversible and/or irreversible bone marrow depression
2. GIT disturbances 3. Inhibition of cytochrome p450 |
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Are chloramphenicol and florfenicol acidic or basic?
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Neither organic acid nor base
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What antibacterial agent is absorbed particularly well in monogastrics?
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Chloramphenicol/florfenicol
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Are chloramphenicol and florfenicol lipid soluble?
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Yes, highly lipid soluble
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How are chloramphenicol and florfenicol eliminated from the system?
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Metabolized by nitro-reduction/ glucuronide conjugation
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What is the spectrum of activity of chloramphenicol and florfenicol?
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Broad spectrum including gram-positive and gram-negative bacteria (including anaerobes), rickettsia and chlamydia
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What bacteria are generally resistant to chloramphenicol and florfenicol?
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Pseudomonas
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How do bacteria develop resistance to macrolide antibiotics?
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Structural changes in ribosomal target site
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Cross resistance is common between macrolides and what other drug?
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Lincosamides
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What are the 2 adverse effects of macrolide antibiotics?
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1. GI disturbances
2. Cardiac toxicity (tilmicosin) |
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Are macrolide antibiotics acidic or basic?
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Organic bases
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What is unique about the disposition of macrolide antibiotics pertaining to per os dosing?
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The erythromycin base is unstable in the stomach so enteric coating, salts and esters are employed for PO dosing
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How are macrolide antibiotics eliminated from the body?
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Active biliary excretion/metabolism
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What is it about the "nature" of the dose-response relationship of antimicrobial agents that leads to misuse?
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It is hard to correlate the patient's response to anti-microbials because is affecting the bacteria not the host
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What drug residues in food-producing animals are the most common?
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Over the counter anti-bacterial agents
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What is a broad spectrum drug? Narrow spectrum?
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Broad spectrum: acts against gram positive and gram-negative bacteria
Narrow spectrum: gram-negative or gram-positive bacteria |
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What is a bactericidal drug? Bacteriostatic?
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Bactericidal: kills bacteria
Bacteriostatic: drug inhibits bacterial growth |
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What do bacteriostatic drugs rely on to eliminate the bacteria?
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The immune system to finish the job
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True or false. Whether or not a drug is a bactericidal or bacteriostatic is dose dependent.
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True e.g. gentamicin generally achieves bactericidal concentrations compared to sulfonamides generally achieve bacteriostatic concentrations
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A steer is pulled from a feedlot pen because of poor appetite, depressed body posture, and evidence of labored respiration. On physical exam the body temperature is 104F and the respiratory rate is higher than normal. What is most likely wrong with the steer?
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Shipping fever (Mannheimia haemolytica, gram-negative bacteria)
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A steer is pulled from a feedlot pen because of poor appetite, depressed body posture, and evidence of labored respiration. On physical exam the body temperature is 104F and the respiratory rate is higher than normal. Assuming that antimicrobial therapy is indicated, what would you like to know about available antibacterial agents for rational drug selection? (4)
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1) Pharmacokinetics (drug residues)
2) Pharmacodynamics (spectrum etc.) 3) Adverse effects 4) Cost |
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How are antibacterial agents classified?
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By their mechanism of action
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What are the 5 classifications of antimicrobial agents?
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1. Selective action of cell walls
-Beta-lactams; bacitracin 2. Disruption of protein synthesis -Aminoglycosides, tetracyclines, chloramphenicol, macrolides, lincosamides 3. Destruction of cell membranes -Polymyxins 4. Interference w/ intermediary metabolism -Nitrofurans 5. Inhibition of nucleic acid metabolism -Sulfonamides/trimethoprim; rifampin; fluoroquinolones; metronidazole |
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What is the definition of bacterial resistance?
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When the concentration of antibacterial agent needed to cure the infection is so high that the dose needed cannot be tolerated by the host
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What is random mutation (in relation to resistance)?
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Errors that arise during replication that result in a phenotype that confers antimicrobial resistance
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True or false. Random mutation in bacteria is rare.
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False, bacteria replicate very frequently so the chance of random mutation is quite high
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How can changes in gene expression cause bacterial resistance?
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There are an array of genes in bacteria that have the capacity to produce or confer antimicrobial resistance but not always expressed, then become expressed under selective pressure
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True or false. Transformation of bacteria has to do with acquiring naked nucleic acid from the environment.
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True
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What is bacterial conjugation?
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the transfer of genetic material between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells.
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What are 2 ways that genetic material is exchanged via bacterial conjugation?
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Plasmids
Transposons |
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Explain how plasmids are conjugated between bacteria using intercellular bridges.
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Donor and recipient bacteria develop an intercellular bridge and nucleic acid that originates from a plasmid is transferred.
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What is transposition?
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Jumping genes, involves the ability of certain gene sequences or transposons to move from one nucleic acid strand to another
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Plasmids tend to be more unstable than chromosomal DNA, but what can happen to plasmid DNA to make it more stable?
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Can transfer conjugated gene to the chromosome
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How do integrases and antibiotic resistance cassettes promote transfer of resistance by conjugation and transposition?
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Gene cassettes are added onto an integron, allowing genes to accumulate on the integron and the bacteria can then transfer multiple genes of drug resistance at once. Results in conferring of multiple drug resistance.
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What enzyme is responsible for inserting gene cassettes in an integron?
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Integrase
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What is responsible for the transcription of gene cassettes inserted on an integron?
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A promoter
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In order for a drug to act on a ribosome, what does it have to get through first?
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Outer membrane & cytoplasmic membrane
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What is an example of multidrug resistance (not integrons) conferred by an individual mechanism?
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Efflux pumps: pump drug out of bacteria
Porins: reduces entry of water soluble drugs -Neither are specific to one group of drug=multidrug resistance |
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What happens if a bacterium increases expression of genes that code for efflux pumps?
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Increases drug resistance because it increases the ability to pump out the drug before it damages the bacteria
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Why is the plot of % of strains VS MIC a bimodal plot?
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There's generally 2 peaks, a bigger and a smaller peak. The bigger peak shows that under most circumstances the MIC is acheived, but there's a subpopulation of bacteria that require a higher dose of drug to kill or inhibit the population.
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Say an E. coli infection is treated with an average concentration of 2 ug/mL, what's going to happen to the bacteria population?
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The isolates will be killed that can't tolerate 2 ug/mL, but the resistant strains won't be affected except no longer compete w/ the other population so they replicate and become dominant in the environment.
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True or false. Non-pathogenic bacteria don't contribute to antibacterial resistance.
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False, non-pathogenic bacteria can share resistance with pathogenic strains
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True or false. Antimicrobial agents are the primary focus of many new molecular entities today.
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False, they are not. The focus today are things like erectile dysfunction, bladder hyperactivity and anxiety.
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True or false. According to the Infectious Disease Society of America, bacteria infections such as Enterococcus Faecium, Staphylococcus Auerus and Klebsiella pneumoniae only respond to a very limited number of antimicrobial agents.
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True
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What are 3 ways to prevent and control bacterial resistance?
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1) Lower antimicrobial consumption by restricting antimicrobial use to well defined indications for control of susceptible target microorganisms
2) Institute surveillance measure 3) Rotate use of different antimicrobial agents |
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When should antibacterial agents be used?
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When bacterial infection is confirmed or strongly suspected to exist
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What is the purpose of using in vitro testing and pharmokinetic data when treating an animal with antimicrobials?
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Used to assure attainment of an efficacious concentration of antibacterial drug at the site of infection
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Why is it better to use a narrow spectrum drug than a broad spectrum drug?
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It's more likely to achieve an appropriate concentration and kill the select bacteria, compared to broad spectrum drugs will kill some bacteria but expose other to low concentrations and select for resistance
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True or false. At the drug concentration that falls in the mutant select window resistant bacteria are killed.
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False, this is where it kills most of the susceptible bacteria and allows resistant bacteria to survive and increases resistant population.
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Why are antibiotics in feed and water a concern for bacterial reistance?
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Because some animals are eating lots of food and some are eating smaller amounts and these animals have the bacteria exposed to low doses of antibacterial agents--> selective pressures--> resistant strains emerge
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What is the mechanism of action of beta-lactam antibiotics (penicillins, cephalosporins)?
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Drug binds transpeptidase (the enzyme responsible for cross linking glycine chains to form peptidoglycan) preventing formation of peptidoglycan cross links--> compromises integrity of bacteria
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How does beta-lactamase result in bacterial resistance?
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Cleave apart the beta-lactam nucleus of the penicillin so it no longer mimics the alanine chain on bacteria that binds transpeptidase
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*What drug group is most likely to cause an allergic reaction?
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Beta-lactams
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True or false. Beta-lactamase production is specific to gram-negative bacteria.
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False, beta-lactamase production is very wide spread and includes gram-negative and gram-positive bacteria.
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True or false. Allergic reactions to beta-lactams is a dose-dependent effect.
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False, not a dose dependent effect
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Why can drug residues in food be dangerous to humans?
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Can cause hypersensitivity reactions if residue of beta-lactams in the food, maybe is the first exposure to drug that leads to hypersensitivity reaction upon exposure
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True or false. Nephrotoxicity due to cephalosporin use is a rare side affect in veterinary medicine.
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True, the cephalosporins used in vet med rarely cause nephrotoxicity
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Why do beta-lactams have good oral absorption?
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They are weak organic acids, which achieve the highest concentrations at basic places so beta-lactams are absorbed easily into the basic plasma to get out of stomach (acidic)
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Why aren't natural penicillins absorbed good orally?
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They are unstable in acidic environments and are degraded in the stomach
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What is the main difference b/w the different types of Penicillin G:
Na & K Penicillin G Procaine penicillin G Benzathine penicillin G? |
The rate of absorption & duration-
Na & K Penicillin G: rapidly absorbed, short duration Procaine penicillin G: absorption is rate limiting step, longer duration Benzathine penicillin G: absorption is rate limiting step, longer duration |
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Aminopenicillins are altered versions of penicillin G, what is different?
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Became a broad spectrum antibiotic compared to Penicillin G is only affective against gram-positive bacteria
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How do we establish long lasting forms of Penicillin G that doesn't have slow absorption?
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Mix the different types of penicillin G
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What Penicillins are susceptible to B-lactamase?
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Penicillin G
Aminopenicillins Antipseudomonal -All except the beta-lactamase resistant |
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What are the 3 penicillin Gs?
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1) Na & K Penicillin G
2) Procaine penicillin G 3) Benzathine Penicillin G |
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What are the 2 aminopenicillins?
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Ampicillin
Amoxycillin |
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What is the beta-lactamase resistant beta-lactam?
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Cloxacillin
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What beta-lactam is an antipseudomonal antimicrobial agent?
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Ticarcillin
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Do antipseudomonal drugs have a broad or narrow spectrum?
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Broad spectrum (aminopenicillins too)
-Anti-Pseudomonas: Ticarcillin, cephalosporins (3rd gen), aminoglycosides, polymyxin B, fluoroquinolones |
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What does clavulanate do?
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Binds and inactivates beta-lactamase so if combine w/ aminopenicillins can have a broad spectrum drug that's resistant to beta-lactamase
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What is the spectrum of activity of first and third generation cephalosporins?
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1st generation: Gram-positive and gram-negative (focus on gram-positive)
3rd generation: gram-positive and gram-negative (focus on gram-negative) |
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Are 1st and/or 3rd generation cephalosporins susceptible to beta-lactamase?
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Yes, both have variable resistance to beta-lactamase
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What is an example of a first generation cephalosporin?
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Cefadroxil
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What are 3 3rd generation cephalosporins?
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1) Ceftiofur (most common)
2) Cefpodoxime 3) Cefovecin |
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What is the mechanism of action of aminoglycoside antibiotics?
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1. Passive diffusion through aqueous channels
2. Active oxygen dependent pump 3. Get to bacterial ribosome and interfere w/ translation and cause misreading of mRNA so form non-functional proteins |
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Are aminoglycosides effective against aerobic or anaerobic bacteria? Why?
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Aerobic bacteria because need oxygen for the active transport to get into the bacterial cell
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Compare the therapeutic indexes of bacteria, viral particles, fungus and anticancer agents.
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1. Antibacterial agents=widest therapeutic index
2. Antifungals 3. Antivirals 4. Anticancer agents (greatest similarity to host cells) |
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Why do aminoglycosides cause nephrotoxicity?
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The proximal tubular cells have an active transport mechanism that does receptor mediated endocytosis that causes accumulation of aminoglycosides within the renal cells so aminoglycosides are toxic to kidney cells
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True or false. Nephrotoxicity from aminoglycosides is not normally reversible.
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False, normally reversible except in patients who are already predisposed to nephrotoxicity.
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What are some predisposing factors to nephrotoxicity?
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Animal has endotoxemia, prior renal insufficiency, old animal w/ reduced kidney function, dehydrated animal
-Combining other drugs w/ nephrotoxic effects |
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True or false. Parenteral aminoglycosides can be used in feed animals.
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False, they don't know the withdrawl times so don't give parenteral aminoglycosides to feed animals
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True or false. Topical aminoglycosides can be used in feed animals.
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True
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How does ototoxicity manifest?
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As vestibular and auditory signs- effects balance and hearing
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When are you more likely to see ototoxicity as a side effect of aminoglycosides? Why?
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When the animal is on Furosemide because diuretic agents promote the secretion of sodium and causes loss of K+ which may be related to adverse side effects
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True or false. It is okay to give cattle injectable aminoglycosides.
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False, that's when you will see neuromuscular blockade
-Not to mention feed animal use is not allowed |
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Are aminoglycosides acidic or basic?
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Weak organic base
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Are aminoglycosides charged?
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Highly charged
-glycoside=sugars, which are charged! |
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Are aminoglycosides absorbed well per os?
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No, they are bases so trapped in the acidic pH of the stomach
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How are aminoglycosides excreted?
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Renal excretion
-Highly charged-makes sense |
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How could you get aminoglycosides into the CNS?
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Have to inject into the CSF because it's a highly charged specie
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Why is amikacin used more often then gentamycin and neomycin?
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Works better on resistant bacteria like pseudomonas
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What is the mechanism of action of tetracycline?
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Inhibits the binding of tRNA to the A site
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Why do tetracycline antibiotics cause GI disturbances?
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Because they are broad spectrum antibiotics that affect anaerobic bacteria so they effect the normal flora of the GI tract.
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Why won't some vets use tetracycline in horses?
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Because can cause serious GI disturbances
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What animals will have their teeth most affected by tetracycline?
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Pregnant animals and neonates because it affects the teeth during development.
-Have to assess risk and benefit of individual patient |
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Will doxycycline or oxytetracycline have higher bioavailability?
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Doxycycline (highly lipid soluble)
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Will doxycycline or oxytetracycline have a higher distribution?
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Doxycycline (highly lipid soluble)
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How will oxytetracycline be eliminated? Doxycycline?
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Doxycycline: hepatic (highly lipid soluble)-metabolized
Oxytetracycline: renal (relatively charged-excreted unchanged) |
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Why can relatively high concentrations of tetracycline be maintained longer than expected?
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Enterohepatic circulation recycling
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True or false. Tetracyclines are commonly used against staph infections.
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False, rarely used against staph infections
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What is the spectrum of activity of oxytetracycline and doxycycline?
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Broad spectrum including gram-positive and gram-negative bacteria (including anaerobes), rickettsia, and protozoa.
-Pseudomonas are generally resistant |
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What antibacterial is commonly used to treat ehrlichiosis in dogs?
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Tetracycline
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What is the mechanism of action of chloramphenicol & florfenicol?
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Inhibits peptidyl transferase and inhibits bond formation b/w amino acids so prevents bacterial protein synthesis
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Why can't chloramphenicol be used in feed animals?
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Because the food residue can cause reversible or irreversible bone marrow suppression in people
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Why can chloramphenicol be used in people, but not in feed animals?
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Because the physician can weight the risks and benefits of the person taking chloramphenicol, wheras with food you don't know who ingests it
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Why does chloramphenicol and florfenicol cause GIT disturbances?
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Because broad spectrum drug and kills anaerobic bacteria so messes w/ normal flora
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Can florfenicol be used in feed animals?
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Yes, it's structurally different from chloramphenicol and doesn't cause bone marrow suppression so can use in people
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Do you want to give chloramphenicol to a dog that you're going to operate on?
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No, because it inhibits cytochrome p450 so animals can't metabolize the anesthetic
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What is the mechanism of action of macrolide antibiotics?
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Inhibits translocation of developing peptides from the A to P site
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What 3 drugs act at a similar ribosomal site and competitively inhibit one another?
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Chloramphenicol, macrolides, and lincosamides
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*What animals are most likely to have gastrointestinal disturbances as an adverse effect of macrolide antibiotics?
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Adult horses, for some reason foals are less likely to have problems
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Tilmicosin is approved for use in what animals?
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Feed animals- have a wide therapeutic index, but it's a narrow therapeutic index in other animals and will cause cardiac toxicity
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True or false. Macrolide antibiotics are highly lipid soluble and are used to treat CNS infections.
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False, they are highly lipid soluble but for some reason are not widely distributed in the CNS
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True or false. Erythromycin tablets can be broken in half to dose for smaller animals.
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False, the enteric coating won't work if you break the pill
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What are the 3 macrolide antibiotics?
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1. Erythromycin
2. Tilmicosin 3. Tulathromycin |
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What is the spectrum of activity of macrolide antibiotics?
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Gram-positive and selected gram-negative (Mannheimia spp.) bacteria and mycoplasma
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What is the mechanism of action of lincosamide antibiotics?
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Inhibits protein synthesis
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How do bacteria develop resistance against lincosamide antibiotics?
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Structural changes in ribosomal target site
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What are the adverse effects of lincosamides?
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GI disturbances
Neuromuscular blockade (rare) |
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Why do lincosamide antibiotics cause GI disturbances?
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Has to do with overgrowth of various clostridial species
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Are lincosamide antibiotics acidic or basic?
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Organic bases
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True or false. Lincosamide antibiotics are absorbed good when given per os.
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True
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How do bacteria develop resistance against lincosamide antibiotics?
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Structural changes in ribosomal target site
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What are the adverse effects of lincosamides?
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GI disturbances
Neuromuscular blockade (rare) |
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Why do lincosamide antibiotics cause GI disturbances?
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Has to do with overgrowth of various clostridial species
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Are lincosamide antibiotics acidic or basic?
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Organic bases
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True or false. Lincosamide antibiotics are absorbed good when given per os.
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True
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True or false. Lincosamide antiobitcs are highly lipid soluble, but are poorly distributed in the CNS.
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True
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How are lincosamides eliminated from the system?
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Metabolized
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What is an example of a lincosamide?
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Clindamycin
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What is the spectrum of activity of clindamycin?
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Gram-positive aerobic and particularly anaerobic bacteria. Most aerobic gram-negative bacteria are resistant
-Max effect=gram-positive anaerobes, minimum=gram-negative aerobes |
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What potentiates sulfonamide?
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Trimethoprim-acts on same pathway
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What is the mechanism of action of sulfonamides?
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Chemically silver to PABA so the enzyme grabs sulfonamide instead of PABA, which blocks the pathway that synthesizes biochemical components-especially purines
-Competitive inhibition |
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Why is it important to keep sulfonamide concentrations higher than most drugs?
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Because competes with PABA to bind to the enzyme necessary to complete the biosynthetic pathway, so it's concentration dependent!
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What is the benefit of having trimethoprim and sulfonamide acting on the same pathway?
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Because if the sulfonamide is outcompeted by the PABA for the enzyme then the trimethoprim can hopefully catch the pathway in the next step, can use lower concentration of sulfonamide and avoid toxicity
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What happens to the spectrum of activity when use a combination of drugs?
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Has a broader spectrum of activity than a single drug
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What are the 3 methods of bacterial resistance against sulfonamides?
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1) Impermeability
2) Absorption of exogenous folate 3) Production of large quantities of PABA |
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How does using a combination of trimethoprim and sulfonamide affect the development of bacterial resistance?
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Combination slows development of resistance
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What are 2 adverse effects of all sulfonamides?
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1) Precipitation of insoluble acetylates cause nephrotoxicity (precipitate forms crystals)
2) Keratoconjunctivitis sicca in dogs (bc of less tear production) |
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What are 5 ways to decrease the chances of nephrotoxicity with sulfonamides?
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1) Increase pH of urine so more of drug is charged and water soluble
2) Increase water in system using a diuretic (make sure have lots of water!) 3) Use sulfonamides with long half life 4) Use potentiated sulfonamide to decrease dose 5) Independent solubility- use combination of sulfonamides (precipitate out based on own concentration) |
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What sulfonamide has been shown to be carcinogenic in rats?
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Sulfamethazine
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What is an adverse effect of trimethoprim?
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Folate deficiency--> anemia, leukopenia, thrombocytopenia
-Decrease folate then effects ability to produce DNA and replace cells. -Usually used in low doses so don't get adverse effects |
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Are sulfonamides acidic or basic?
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Sulfonamides=organic acids
(organic acids=Penicillin, cephalosporins, sulfonamides, nitrofurans) |
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What are the 2 agents that potentiate sulfonamides?
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1) Trimetoprim
2) Pyrimethamine |
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Are trimethoprim and pyrimethamine organic acids or bases?
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Bases
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Do sulfonamides have good oral absorption?
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Yes, they are organic acids and follow the rules!
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True or false. Sulfonamides are moderately lipid soluble so sulfa/TMP drugs are well distributed into the CNS.
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True
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How are sulfonamides eliminated?
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Acetylation followed by urinary excretion
(moderately lipid soluble) |
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True or false. Potentiating sulfonamides are good candidates for CNS infections.
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True, moderately lipid soluble and good CNS distribution
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What are 4 examples of sulfonamides?
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1) Sulfadiazine
2) Sulfadimethoxine 3) Sulfamethazine 4) Silver sulfadiazine |
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What is the spectrum of activity of sulfonamides?
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Gram-positive & gram-negative bacteria and protozoa
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What is the spectrum of activity of trimethoprim?
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Increases spectrum of activity and enhances bactericidal activity of sulfadiazine
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What is the spectrum of activity of pyrimethamine?
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Protozoa (Sarcocystis)-treatment
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True or false. Rifampin is commonly used in veterinary medicine.
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False, not approved for use in vet med but use off-label
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What is the mechanism of action of Rifampin?
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Inhibits bacterial RNA synthesis by binding to DNA-dependent RNA polymerase
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How do bacteria develop resistance against rifampin?
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Structural change in the target enzyme, DNA-dependent RNA polymerase
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*Why is it necessary for rifampin to be combined with other antibacterial agents?
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Resistance develops very rapidly to rifampin so must be combined
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What are the adverse effects of Rifampin?
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Hepatitis
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Is rifampin an acid or base?
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Organic base
(Organic bases=aminoglycosides, macrolides, lincosamides, polymyxins, rifampin) |
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Does rifampin have good oral absorption?
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Yes, even though it's a base
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Is rifampin suitable to treat CNS infections?
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Yes, highly lipid soluble and has good distribution into the CNS
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How is rifampin eliminated from the system?
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Metabolism (cytochrome p450 enzyme inducer)
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What is the spectrum of activity of rifampin?
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Gram-positive bacteria and mycobacteria including intracellular organisms.
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What 2 bacteria does rifampin have good activity against?
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Rhodococcus equi (common use)
S. aureus |
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What do vets use to treat MRSA?
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Humans use vancomycin, but want to preserve it so vets use a combination of rifampin and potentiated sulfonamides OR fluoroquinolones
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What is the mechanism of action of fluoroquinolones?
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Alter the structure and function of bacterial DNA by interfering w/ the enzyme DNA gyrase
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What are 2 ways that bacteria develop resistance against fluoroquinolones?
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1) Alteration of A subunits of DNA gyrase
2) Changes in membrane permeability due to increased efflux pump activity or reduction in porin conductance (does this to tetracyclines too!) |
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What does DNA gyrase do?
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Releases the tension in the circular strand of DNA and allows chromosome to physically separate for replication
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What are the adverse effects of fluoroquinolones?
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1) Cartilage damage in young animals, possibly adults
2) GI disturbances |
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Are fluoroquinolones acidic or basic?
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Amphoteric
(Amphoteric=Tetracycline & Fluoroquinolones) |
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Do fluoroquinolones have good oral absorption?
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Yes
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Are fluoroquinolones lipid soluble?
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Moderately lipid soluble-get accumulation in certain cell types
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True or false. Fluoroquinolones are moderately lipid soluble and are well distributed in the CNS.
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False, only distributed into the CNS w/ inflammation.
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How are fluoroquinolones eliminated?
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Metabolism and renal excretion
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What is a specific agent that is a fluoroquinolone?
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Enrofloxacin
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What is the spectrum of activity of enrofloxacin?
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Gram-positive and gram-negative bacteria and mycobacteria including Pseudomonas, mycoplasmas and MRSA
-Not effective against anaerobes |
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What is the mechanism of action of bacitracin?
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Inhibits cell wall synthesis
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What is the spectrum of activity of bacitracin?
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Gram-positive bacteria
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Is bacitracin lipid soluble?
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No, it's a highly polar agent
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What are the adverse effects of bacitracin?
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Nephrotoxicity
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What is the mechanism of action of polymyxin B?
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Disruption of bacterial cell membranes
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What is the spectrum of activity of polymyxin B?
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Gram-negative bacteria
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Is polymyxin B a lipid soluble drug?
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No, highly polar agent
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What are the adverse effects of polymyxin B?
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Nephrotoxicity
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What are the 2 nitrofurans?
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Furazolidone
Nitrofurazone |
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What is the mechanism of action of nitrofurans?
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Inhibit oxidative carboxylation of pyruvate to acetyl CoA, affecting energy metabolism
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What is the spectrum of activity of nitrofurans?
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Gram-negative bacteria, limited gram-positive (not Pseudomonas spp.), some protozoans
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What is the disposition of nitrofurans?
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Moderately lipid soluble, weak acid
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What are the adverse effects of nitrofurans?
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GIT dysfunction
Peripheral neuritis is a problem with systemic administration |
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What are nitrofurans used for?
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Used topically (wounds) and for GI infections (limited)
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Why are nitrofurans banned for use in feed animals?
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Mutagenic
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What is the mechanism of action of metronidazole?
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Disrupts electron transport system; inhibits DNA synthesis and causes DNA degradation
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What is the spectrum of activity of metronidazole?
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Anaerobic gram-negative & gram-positive bacteria, trichomoniasis, amebiasis, giardiasis
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What is the disposition of metronidazole?
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Highly lipid soluble
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What are the adverse effects of metronidazole?
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GI disturbances
Neurological effects Carcinogenesis/mutagenesis |
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Why is metronidazole commonly used?
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Has good activity against anaerobic bacteria
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What antibacterial agent can be used to treat giardiasis, trichomoniasis, amebiasis?
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Metronidazole
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