Antibiotics Flashcards
What is the biochemical basis of antimicrobial action (broadly)?
Since organisms need to take up many types of biomolecules to grow and divide, antimicrobial agents interfere with specific processes that are essential for growth and/or division.
What are bacteriocidal antimicrobial agents?
Chemotherapeutic agents capable of causing irreversible damage or death to the organism. The agents are independent of the host’s immune system in their action on the organism. May harm host at high level.
Bacteriostatic
Agents that inhibit the growth and/or reproduction of the infecting agent. These agents are dependent on the host’s immune system for elimination of the microorganism.
MIC
minimal inhibitory concentration - represents the lowest concentration of the antibiotic which prevents the organism from multiplying - not necessarily killing the organism - want trough to be above the MIC
MBC
minimal bacteriocidal concentration - represents the lowest concentration which kills the organism - not relevant with bacteriostatic agents - there are certain conditions where you want the cidal concentration - bone and heart stuff
What are the 5 modes of action of antibiotic drugs?
- Inhibition of cell wall synthesis (most common mechanism - largest class of antibiotics)
- Inhibition of protein synthesis, ribosomal function (second largest class)
- Alteration of cell membranes (antifungal)
- inhibition of nucleic acid synthesis
- Antimetabolite activity, folate synthesis
What are some ideal attributes of antibacterials?
selective target; bactericidal; narrow spectrum (does not kill normal flora); high therapeutic index (ratio of toxic level to therapeutic level); few adverse reactions - toxicity, allergy; various routes of administration - IV, IM, oral; good absorption (cytochrome 450) come are able to absorb things better - absorption and distribution different between children and adults; emergence of resistance is slow
Cell wall synthesis antibiotics - inhibit the linking of NAG and NAM so that the bacteria explode
Glycopeptides: vancomycin, BETA LACTAMS: penicillins, cephalosporins, monobactams, carbapenems
Folic acid metabolism antibiotics
trimethoprim, sulfanamides
Cell membrane antibiotics
polymyxins
DNA, nucleic acid antibiotics
quinolones, rifampin
What are the four antibiotics (inhibitors of cell wall synthesis) that are beta lactams?
Penicillin, cephalosporin, monobactam, carbapenems
Why are the beta-lactams grouped together?
Cidal or Static?
Are they toxic? Expensive? Soluble?
- Share a structural feature; the beta lactam ring
- cidal
- non-toxic, inexpensive, soluble
What to penicillin binding proteins do?
Are a set of transpeptidases that catalyze the final cross-linking reactions of peptidoglycan synthesis - bind to penicillin - b lactam ring inhibits transpeptidease - B lactams are structurally analogous to D- Ala - D- Ala so PBPs react with these antibiotics by cleaving the beta lactam bond and form a stable intermediate that does not react further - acylation of PBPs by beta lactams inactivates the enzyme
- How many different classes of penicillins exist?
- How many different generations of cephalosporins exist?
- what is the most powerful beta lactam?
- six
- four, newer class with activity against MRSA, higher the generation more resistant to destruction
- Carbapenems
What is one type of glycopeptide?
vancomycin - effective against gram positives only, the drugs enter without any problem because peptidoglycan does not act as a barrier for the diffusion of these molecules. Not effective against gram negatives - molecule can not pass through porins - inhibits cell wall synthesis
What are the major antibiotics for the inhibition of protein syntheses?
Tetracyclines, Aminoglycosides (gentamycin, tobramycin), Macrolides (erythromycin, azithromycin, clarithromycin),
Tetracyclines:
- cidal or static?
- What is it used for?
- static - broad spectrum, but resistance is common which limits its use
- Chlamydia, rickettsiae, mycoplasma - not recommended for pregnant women and children because of the toxicity on bones and teeth of fetus
Classification of tetracyclines based on length of activity in the body and absorption from GI tract - doxycline is long acting, has long serum half life - less frequent dosing
Aminoglocosides:
- Method of action
- Cidal or static?
- Bind to the RNA of the 30s ribosomal sub-unit that affects all stages of normal protein synthesis -
- Cidal
Renal and ototoxicity - need to monitor blood levels
Macrolides:
1. Cidal or static?
- static - their spectrum of activity is limited to gram (+) cocci such as streptococci and staphylococci, also active against anaerobes
Anti-metabolites: Folate pathway inhibitors
What is folic acid used for?
Why is folic acid a good target?
- Folic acid is essential for the synthesis of adenine and thymine
- Humans do NOT synthesize folic acid, good selective target
Sulfonamides/ Trimethoprim - folate pathway inhibitors
- Cidal or static?
- what is the mode of action of these drugs?
- Sulfa and trimet are both static, but when used in combination = cidal
- Drug resembles a microbial substrate and competes with that substrate for the limited microbial enzyme. The drug ties up the enzyme and blocks a step in metabolism.
Sulfonamides:
- Do they have good urine solubility?
- What are they used for?
- Yes
2. Acute urinary tract infections, patients allergic to penicillins, otitis media
Fluroquinolones:
What is their mode of action?
Inhibitor of nucleic acid synthesis.
Act by targeting topoisomerases, responsible for cutting one of the chromosomal DNA strands at beginning of supercoiling process
