Lecture 13: Chemotherapeutic Agents and Antibiotics
Terms
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- chemotherapeutic agents
- A chemical that has been sythesized by chemists in a lab or produced by a modification of a preexisting chemical that kills microorganisms.
- antibiotics
- a product of the metabolism of a microorganism
- What is the objective of a selectively toxic drug?
- to kill or inhibit a pathogen while damaging the host as little as possible
- What three things does the degree of selective toxicity depend on?
-
- therapeutic dose
- toxic dose
- therapeutic index - Therapeutic dose
-
drug level required for clinical treatment of a particular infection
need enough of the drug to kill a pathogen so it can't establish disease - toxic dose
-
drug level when undesirable effects are produced
-make extremely sick - Therapeutic index
-
toxic dose/ therapeutic dose
higher therapeutic index, better chemotherapeutic agent - higher therapeutic index, _____ chemotherapeutic agent
- better
- ____ drugs are narrow-spectrum, while ___ are broad-spectrum
-
most- narrow-spectrum
some- broad-spectrum - Most drugs are narrow-spectrum. They treat ____
- only one type of microbe
- ISONIAZID is good for tuberculosis. It won't work for something else like a sinus infection. Is it narrow or broad spectrum?
- narrow
- _____ is a narrow spectrum drug that is good for tuberculosis.
- Isoniazid
- Some drugs are broad-spectrum. Name three different broad-spectrum drugs.
-
Neomycin
Zeocin
Sulfonamides - Nemomycin is effective against what bacteria?
- gram + and -
- Zeocin is a broad-spectrum drug that is _____ AND ____
- anti-bacterial and anti-fungal
- Sulfonamides is a broad-spectrum drug that is _____, _____, and _____
-
anti-bacterial
anti-fungal
anti-protozoal - Bactericidal
- kills target pathogen
- Bacteriostatic
- reversibly inhibits growth of pathogen
- What is the difference between bactericidal and bacteriostatic?
- bactericidal kills. bacteriostatic inhibits.
- Antibiotics can be of what three types?
-
Natural
Synthetic
Semi-synthetic - Natural antibiotics are _____
- produced by some living organism
- Streptomyces is a living organism that makes what three natural antibiotics?
-
Streptomycin
chlortetracycline
erythromycin - Streptomycin, chlortetracycline, and erythromycin are natural antibiotics made by what living organism?
-
streptomyces
*Streptomyces is a bacterium - What living organism makes the natural antibiotic, penicillin?
-
penicillium
*penicillium is a fungus
*penicillin inhibits bacterial growth - Synthetic antibiotics are what?
- manufactured from non-natural products. They are chemotherapeutic agents.
- Give two examples of synthetic antibiotics.
-
sulfonamides
trimethoprim - Semi-synthetic antibiotics are what?
- chemical modification of natural antibiotics
- Give an example of semi-synthetic antibiotics
- penicillin derivatives: ampicillin, carbenicillin, methicillin
- Name three penicillin derivatives
-
ampicillin
carbenicillin
methicillin
* a lot of ppl are allergic to penicillin, so make penicillin derivatives in the lab - What are the 5 mechanisms of antimicrobial action?
-
- protein synthesis
- nucleic acid
- cell wall
- cell membrane
- metabolic reactions - There are 5 things you can target (protein synthesis, nucleic acid, cell wall, cell membrane, metabolic reactions), that kills microbes, but not ____
- but not necessarily the host
- What does polymyxin B disrupt?
-
Cell membrane
*cell membrane is the site of where to attack a microbacterium - Is polymyxin B natural, synthetic, or semi-synthetic?
- natural
- Polymyxin B is a natural antibiotic that comes from ____
- Bacillus
- What is polymyxin B effective against?
- Gram - bacteria (P. aeruginosa)
- Polymyxin B is effective against Gram- bacteria. Give an example
- P. aeruginosa
- What does polymyxin B do?
- Binds cell membrane components, alters membrane permeability (causing cell leakage, death)
- Polymyxin B can be found in ______ and _____
- bacitracin (Gram +) and neomycin (broad spectrum)
- Polymyxin B is only for topical use. If it is ingested, Polymyxin B can cause what?
- numbness in the extremities, kidney damage, respiratory arrest
- Sulfonamides are natural, synthetic, or semi-synthetic?
- synthetic
- Give one type of sulfonamide
- Sulfanilimide
- Sulfanilimide is a structural analog of ____
-
p-aminobenzoic acid (aka PABA)
(-SO2NH2 vs. COOH) - Sulfonamides inhibits _____ production by competing with p-aminobenzoic acid for active site of dihydropterate synthase, an enzyme
- folic acid
- Sulfonamides inhibits folic acid production by competing with _____ for active site of dihydropterate synthase, an enzyme
- p-aminobenzoic acid
- Sulfonamides inhibits folic acid production by competing with --aminobenzoic acid for active site of _____, an enzyme
- dihydropterate synthase
- Folic acid is required for ____
- nucleic acid production
- bacteria make their own ____, but not humans
- folic acid
- Sulfonamides have a high ____, but about 5% of ppl are allergic
-
therapeutic index
*toxic dose/ therapeutic dose
higher therapeutic index, better chemotherapeutic agent - Give two examples of sulfonamides
-
sulfamethoxazole
sulfisoxazole - What two antibiotics inhibits DNA Synthesis?
-
Quinolones
Fluoroquinolones - Give an example of QUINOLONES, which disrupts prokaryotic DNA gyrase (inhibits DNA Synthesis)
- Nalidixic acid
- Nalidixic acid selectively inhibits _____, an enzyme required for DNA replication
- DNA gyrase
- What is Nalidixic acid effective against?
-
only effective against certain types of urinary infections.
*most likely narrow-spectrum - Who is Nalidixic acid bad for? whY?
- Bad for kids & pregnant women because it affects development of cartilage
- Give two types of fluoroquinolones, which inhibits DNA Synthesis
-
Ciprofloxacin
norfloxacin - Fluoroquinolones were developed as improvements over nalidixic acid (an extra F added), because they ____ and ____
-
penetrate tissue better
more broad-spectrum (can treat urinary infections + anthrax + others) - What is a drug that inhibits RNA synthesis?
- Rifampin
- Is Rifampin natural, synthetic, or semi-synthetic?
- semi-synthetic
- Rifampin inhibits DNA-dependent ______ in bacteria
- RNA polymerase, an enzyme
- What three things is Rifampin used for?
-
Tuberculosis
Leprosy
Protection against bacterial meningitis - Rifampin turns bodily secretions ____
- reddish orange
- what four things inhibits cell wall synthesis?
-
Penicillins
Bacitracin
Cephalosporins
isoniazid - What do all penicillins have?
- beta-lactam nucleus
- Penicillins inhibit transpeptidation (linking of polymers w/ amino acid chains) and consequently _____
- cell wall synthesis (results in osmotic lysis)
- Penicillins inhibit _______(linking of polymers w/ amino acid chains) and consequently cell wall synthesis (results in osmotic lysis)
- transpeptidation
- What is a semi-synthetic derivate of Penicillin?
- ampicillin
- What is good about ampicillin compared to penicillin?
- more acid stable
- What are two problems with penicillins?
-
allergic reactions
growing resistance - If you are allergic to penicillin, then you could take _____
- Cephalosporins
- What does Cephalosporins inhibit?
- cell wall synthesis
- Give two examples of cephalosporins
-
cephalexin (Keflex)
cephalothin (Keflin) - Are cephalosporins natural, synthetic, or semi-synthetic?
- Natural, from fungus Cephalosporium
- Cephalosporins are a natural antibiotic from the fungus _____
- Cephalosporium
- Cephalosporins are similar to penicillin in waht way?
-
beta-lactam ring
similar mechanism of action - Cephalosporins have a beta-lactam ring like penicillin, therefore cephalosporins have a similar _____
- mechanism of action
- Cephalosporins are a useful alternative to penicillin in case of ___ or ___
- allergy or resistance
- Bacitracin, another cell wall synthesis inhibitor, interferes with ____, a carrier that transports peptidoglycan subunits to the cell wall
- bactoprenol
- Give four antibiotics that inhibit Protein Synthesis.
-
Tetracyclines
Aminoglycosides
Macrolides
Chloramphenicol - Tetracyclines are narrow or braod-spectrum?
- broad-spectrum (affects Gram - and +)
- What makes up tetracyclines?
- four benzene rings
- Some tetracyclines are natural and are produced from ___
- Streptomyces
- Some tetracyclines are natural and produced from Streptomyces. Give two examples.
-
Chlortetracycline
Oxytetracycline - Some tetracyclines are semi-synthetic. Give four examples.
-
Tetracyline
Doxycycline
Methacycline
Minocycline - Tetracyclines all inhbibit protein synthesis by binding _______
- 30S ribosomal unit
- All inhibit protein synthesis by binding 30S ribosomal unit- inhibits binding of _____ to ____
- tRNA to ribosome
- Who are tetracyclines bad for? why?
- Bad for kids and pregnant women- problems with bone formation (yellow teeth)
- Tetracyclines is the drug of choice for _____ and _____ diseases
- rickettsial and chlamydial diseases
- Aminoglycosides inhibits protien synthesis. They are amino groups bound to ____
- glycosides (carbohydrates)
- What are glycosides?
- carbohydrates
- What three aminoglycosides comes from Streptomyces?
-
Streptomycin
Kanamycin
Neomycin - What aminoglycoside comes from Micromonospora purpurea?
- Gentamicin
- Aminoglycosides prevent reading of ____ by irreversibly binding to ribosome
- mRNA
- Aminoglycosides prevent reading of mRNA by _____
- irreversibly binding to ribosome
- Why are aminoglycosides toxic?
- Deafness, renal damage, loss of balance
- What are macrolides composed of?
- 12-22 carbon lactone ring
- Are macrolides broad-spectrum or narrow?
-
broad-spectrum
(Gram +/-, mycoplasma) - Give four examples of macrolides
-
erythromycin
clindamycin
azithromycin
zithromax - Macrolides inhibit ____
-
peptide chain elongation
(protein synthesis) - Legionnaire's Disease is transmitted by?
-
air
air conditioners
humidifiers
the spray of jacuzzi tubs - What are Macrolides used to treat?
- Legionnaire's Disease
- Chloramphenicol binds ____ and blocks ______ to inhibit protein synthesis
-
ribosome
peptide bond formation - Is Chloramphenicol natural, synthetic, or semi-synthetic?
- natural, from Streptomyces
- Where is Chloramphenicol produced from?
- Streptomyces
- Is Chloramphenicol narrow or broad-spectrum?
- broad-spectrum (bacteria, small bacteria, fungi)
- Chloramphenicol has a low ____: used only in life-threatening situations
- therapeutic index
- Chloramphenicol can cause _____ by preventing hemoglobin from being incorporated into RBC (red blood cell)
- aplastic anemia
- Besides aplastic anemia, what else can chloramphenicol cause?
- gray syndrome
- Gray syndrome is a toxic reaction to chloramphenicol. It is the breakdown of the ___
- cardiovascular system
- What are the two bad side effects of chloramphenicol?
-
Aplastic anemia
Gray syndrome - What are the 6 things that affect bacteria?
-
cell wall
cell membrane
metabolism (folic acid)
DNA synthesis
RNA synthesis
protein synthesis - What are the four mechanisms of resistance?
-
Modification of target
Prevent entrance of drug
prump drug out of cell
chemical modification - Modification of target. Resistance to ______ develops when bacteria alter structure of enzymes used to synthesize folic acid
- sulfonamides
- Resistance to _____ develops when bacteria alter structure of ribosomes
- streptomycin
- Prevent entrance of drug. Mycobacterium has _____ in cell wall
- mycolic acid
- Mycobacterium has mycolic acid in cell wall. Mycolic acid is _____ to most drugs
- impermeable
- Pump drug out of cell. Enzymes such as plasma membrane _____ pumps drugs out of cell.
- translocase
- Pump drug out of cell. Some microbes have ___
- multi-drug resistance pumps
- Inactivation through Chemical Modification. Penicillinase (beta-lactamase) can effect ______- inactivating antibiotic
- hydrolysis of beta-lactam ring
- _________ (beta-lactamse) can effect hydrolysis of beta-lactam ring- inactivating antibiotic
- Penicillinase
- Inactivation through Chemical Modification. Penicillinase (Beta-lactamase) can effect hydrolysis of beta-lactam ring- inactiving antibiotic. This type of resistance can be encoded by ____
-
plasmids.
transferred by conjugation and transformation - Give two reasons as to why microbial drug resistance is increasing
-
indiscriminate use of chemotherapeutics
transmission of R factors among microbes - R factors transferred between _____ through conjugation
- unrelated strains
- What is indiscriminate use? (3 pts)
-
Prescription of antibiotics for viral infections
Low-level use of antibiotics for prevention of infection
inclusion of antibiotics in animal feed - By the process of natural selection, microorganisms that are resistant to a particular drug gradually become ____
- predominant in a population
- What does PPNG stand for?
-
penicillinase-producing Neisseria gonorrhoeae
*No PPNG strains before 1976