Antibacterial Agents I Flashcards
How can antimicrobial agents be classified?
1) Mechanism of action 2) Pharmacokinetic parameters 3) Spectrum of antimicrobial activity 4) Adverse reactions/toxicity
What are common targets of antimicrobial drugs?
1) Synthesis or damage to the cell wall 2) Synthesis or damage to cell membrane 3) Modification of synthesis or metabolism of nucleic acids 4) Inhibition or modification of protein synthesis 5) Modification of intermediary metabolism (folate metabolism)
What is selective toxicity?
Selective toxicity is the exertion of toxic effects of the drug on the microbe and not on the host. Biochemical differences between the pathogen target and the host must be discovered and exploited. This leads to the list of common targets of antimicrobial drugs.
What are three mechanisms of resistance to anti-microbial drugs?
1) Natural resistance - a microbe lacks the susceptible target of the drug (e.g. fungi do not have cell walls). 2) Escape - microbe is susceptible to the drug but has sufficient nutrients to overcome drug actions, or there is too little osmotic pressure to lyse the cell. 3) Acquired Resistance - Mutational (chromosome) resistance or plasmid mediated resistance.
How is plasmid mediated resistance achieved?
Plasmid mediated resistance is a clinically important source of multiple drug resistance that can emerge during a single course of treatment. It is achieved through conjugation (sexual transmission), transduction (phage-mediated), or transformation (uptake of naked DNA).
What are the major mechanisms of bacterial resistance to antibiotics?
1) Altered targets or receptors to which the antibiotic cannot bind. 2) Enzymatic destruction or inactivation of the antibiotic. 3) Alternative resistant metabolic pathway. 4) Decreased entry of the antibiotic (natural resistance). 5) Increased efflux (multi drug resistance may be encoded by this single gene)
What is the difference between bactericidal and bacteriostatic agents?
Bactericidal agents actually kill the organisms, while bacteriostatic agents prevent the existing organisms from growing further. These functions are determined by a given antimicrobial’s mechanism of action, in vivo concentration, and the specific microorganism.
What are three bactericidal mechanisms?
1) Inhibition of cell wall synthesis. 2) Disruption of cell membrane function. 3) Interference with DNA function or synthesis.
What are two bacteriostatic mechanisms?
1) Inhibition of protein synthesis (exception: aminoglycosides). 2) Inhibition of intermediary metabolic pathways.
What are four features of bactericidal agents?
Bactericidal agents are preferred in severe infections. They act more quickly and their action is often irreversible with a sustained effect after the drug is eliminated from the blood. They can compensate for patients with an impaired host defense. They are required for treatment of infections in locations inaccessible to the host immune system (CSF, endocarditic vegetations).
What are three significant considerations of the pharmacokinetic distribution of antibiotics in the body?
1) CNS - some drugs cross the BBB readily, while others do only during inflammation or not at all. 2) Fetus - Most drugs given orally (i.e. capable of crossing the gastric mucosal barrier) can also cross the placenta and affect a fetus. 3) Selective distribution (accumulation) - may be beneficial and allow targeting to infections or harmful and cause toxicity.
What are some drugs that have beneficial results of selective distribution?
Clindamycin - bone; Macrolides - pulmonary cells; Tetracyclines - gingival crevicular fluid and sebum; Nitrofurantoin - urine.
What are some drugs that have harmful results of selective distribution?
Aminoglycoside - cells of the inner ear and renal brush border (ototoxicity/nephrotoxicity); Tetracyclines - bind to Ca2+ in developing bone and teeth (abnormal bone growth/discolored teeth in fetus and young children)
What are important points to consider regarding antibiotic metabolism and excretion?
Knowledge of the route of antibiotic elimination is critical to the safe and effective use of antibiotics. Patients with kidney disfunction may be given “renal dosing” whereby doses and frequency are adjusted based on the patient’s renal function. Drugs that require hepatic metabolism are simply avoided in patients with liver dysfunction if possible.
What are some antibiotic effects related to the dosing regimen and duration of antimicrobial activity?
Durations that are too short or doses too low may result in drug resistance or recurrence of infection. Durations that are too long may result in superinfections. Doses too high may result in toxic effects.
