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Drugs, Microbes, Host
Dr. David Senchina, Drake University, Medical Microbio notes set 6
65
Microbiology
Undergraduate 2
03/05/2010

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Cards

Term
The central problem of drug design is balancing what things?
Definition
Destruction of the infective agent and doing as little harm as possible to the patient.
Term
Doctrine of Signatures
Definition
A historical pharmaceutical system in which it was believed that plants would indicate which body part they were curative agents of, as a "sign".
Example: Liverwort has liver-shaped leaves, so was assumed to help liver illnesses.
Term
Penicillium spp.
Definition
A species of fungi, discovered by Fleming to have antibacterial effects. Forey was the first to suggest using the fungus to combat human illness.
Term
From what organisms are most modern drugs derived?
Definition
Bacteria
Fungi
Term
How can drugs harvested from organisms be improved upon?
Definition
Selective breeding
Modification of the drug post-collection
Seeking alternative drugs from other organisms
Term
Antibiotic
Definition
A metabolic compound produced by a microorganism with the intent of destroying or inhibiting other organisms.
Term
Natural antibiotic
Definition
An antibiotic that has been taken straight from a microbial producer, with no modification.
Term
Semisynthetic antibiotic
Definition
An antibiotic that has been modified after harvest from an organism.
Term
Synthetic antibiotic
Definition
An antibiotic made in the lab, whose composition is based on designs found in microbial production.
Term
Broad spectrum antibiotic
Definition
An antibiotic that is effective against a diverse range of microbes
Term
Narrow spectrum antibiotic
Definition
An antibiotic that is effective against only a few types of microbe
Term
Why do microbes produce antibiotics?
Definition
The microbes are fighting for real estate and resources. If neighboring species aren't around to take up any room, all the better for their survival.
Term
How do cephalosporin and penicillin inhibit cell wall synthesis?
Definition
They inhibit transpeptidase from accomplishing crosslinking.
Term
How does cycloserine inhibit cell wall synthesis?
Definition
It inhibits peptidoglycan subunit construction.
Term
How does vancomycin inhibit cell wall synthesis?
Definition
It inhibits elongation of peptidoglycan chains.
Term
How does chloroquine interfere with nucleic acids?
Definition
It cross-links the double-helix.
Term
How do nucleotide analogues (like AZT or acyclovir) interfere with nucleic acids?
Definition
They mimic nucleotides, are picked up during elongation, and render the resulting nucleic acid dysfunctional.
Term
Which nucleic acid-associated enzymes do quinolones inhibit?
Definition
They inhibit gyrases.
Term
Which nucleic acid-associated enzymes do rifamycins inhibit?
Definition
They inhibit polymerases.
Term
How does streptomycin interfere with ribosome function?
Definition
It binds to the 30s subunit and causes mRNA to be misread.
Term
How does chloramphenicol interfere with ribosome function?
Definition
It binds to the 50s subunit and stops the formation of peptide bonds between amino acids.
Term
How does erithromycin interfere with ribosome function?
Definition
It binds to the 50s subunit and prevents detachment of the protein or mRNA translocation.
Term
How does tetracycline interfere with ribosome function?
Definition
It inhibits tRNA docking.
Term
How do protease inhibitors mess with proteins?
Definition
Some proteins need to be cleaved into units before they can be packaged and used. Protease inhibitors prevent this from happening.
Term
How does polymyxous disrupt the integrity of the cell membrane?
Definition
It disrupts phospholipid integrity.
Term
How do amphitemicin B and mystatin disrupt integrity of the cell membrane?
Definition
They disrupt embedded molecules, like proteins, sugars, or fats (Mystatin binds to sterols and pushes against them. When enough mystatins have pushed in, they form a pore, which allows outflow of the cell contents.
Term
How do Sulfas and trimethoprim interfere with folic acid synthesis?
Definition
They get into the pteridine synthetase active site and prevent PABA binding.
Term
Pteridine synthetase
Definition
An enzyme that converts PABA to dihydropteroic acid (which is a precursor of folic acid)
Term
Why does the creation of antiviral drugs pose such a big problem?
Definition
Viruses don't have metabolic pathways of their own - they simply hijack ours. So, if we shut down our own pathways, the viruses die, but so do we.
Term
What are the three main modes of activity in antiviral drugs?
Definition
Blocking adsorption (engagement with the cell membrane)
Blocking transcription/translation/replication (example: AZT)
Preventing virion maturation (example: protease inhibitors)
Term
Interferons
Definition
Produced by leukocytes and fibroblasts, they have antiviral and anticancer properties. There are three types: alpha, beta, and gamma.
Term
What are some of the effects of interferons?
Definition
They reduce healing time and side effects from viral infections, prevent or reduce symptoms of chronic viral infection, and slow cancer progress. However, they can also cause dementia.
Term
Beta-lactam compounds
Definition
All have a beta-lactam ring.
Includes penicillin and cephalosporin.
Term
Aminoglycosides
Definition
Are composed of amino sugars and a 6-carbon ring, and are derived from soil bacteria.
Includes gentamycin and streptomycin.
Term
Tetracyclines
Definition
Composed of four circles, derived from Streptomyces spp.
Includes aureomycin, tetracycline, and doxcycline, and both natural and synthetic drugs.
Term
Clindamycin, erythromycin, rifamycin, and vancomycin
Definition
products of Streptomyces spp.
Term
Products of Bacillus
Definition
Bacitracin and polymyxin
Term
Sulfonamides (Sulfas)
Sulfones
Trimethoprim
Oxazolidones
Definition
Synthetics and derivative drugs
Term
What is the concern in the making of antifungal drugs?
Definition
Fungi and humans are both eukaryotic, so they share many of the same pathways.
Term
Macrolide polyenes (Amphotericin B, Nystatin)
Griseofulvin
Azoles
Flucytosine
Definition
Antifungal drugs
Term
Griseofulvin
Definition
Disrupts spindle fibers during mitosis, meaning that the daughter cells will end up with uneven distribution of chromosomes.
Has difficulty differentiating between fungal and liver cells.
Term
Mebendazole and thiabendazole
Piperazine and pyrantel
Niclosamide
Ivermectin
Praziquantel
Definition
Antieukaryotic drugs
Term
Quinine
Definition
The active component of the bark of the cinchona tree, which is used to treat malaria. Today, most quinine is synthetic, because cinchona trees take so much labor, and because we can make better-acting quinine in lab.
Term
Intrinsic drug resistance
Definition
Microbes that produce antimicrobial substances must be resistant to their own products. This isn't a major concern in pharmacy.
Term
Acquired drug resistance
Definition
Drug resistance that comes about through mutations or recombination. It's a major concern in pharmacy.
Term
R factors
Definition
The general name for any plasmid that confers drug resistance. They are mostly transferred through conjugation, but can also be transduced or transformed.
Term
Transposons
Definition
Hypermobile genetic elements that do not have a set position in the genome. They are usually identifiable by their sequence. They can move from chromosome to plasmid or vide versa, or within a type, and in moving, can dirsupt or enhance genes or take pieces of genes with them.
Term
How do humans hasten drug resistance?
Definition
200 million antimicrobial prescriptions per year
Doctors prescribe broad-spectrum drugs more often than narrow (because of time constraints on diagnosis)
Drugs sold OTC with minimal regulation
Hospitals, since they provide so many selective pressures (like drugs and steriliztion) are a breeding ground for especially resistant strains
Drugs in livestock feed cause drug resistance in the anima and in the environment
Term
Mechanisms of drug resistance
Definition
Inactivate the drug
Decrease drug permeability
Increase drug elimination
Change drug receptor
Change the metabolic pattern
Term
How do pathogens inactivate a drug?
Definition
An enzyme acts on the drug, rendering it dysfunctional.
As an example, beta-lactamases cut off penicillin's beta-lactam ring, inactivating it.
Term
How do pathogens decrease drug permeability?
Definition
They change the transport mechanism (i.e. external receptor).
Term
How do pathogens increase drug elimination?
Definition
They use efflux pumps to spit drugs back out once they're in.
Term
How do pathogens change the drug receptor?
Definition
They modify or shield the drug's target.
Examples include changing ribosome structure, changing protein structure, and changing expression of proteins.
Term
How do pathogens change their metabolic pattern?
Definition
They utilize alternative metabolic pathways or simply stop the metabolic activity altogether until the drug is gone. This means that drugs may be able to survive a two-week treatment regimen.
Term
How can physicians combat drug resistance?
Definition
Make accurate, specific diagnoses
Prescribe the right drug for the job
Don't prescribe drugs when they're not needed
Administer multiple drugs simultaneously (because it's less likely pathogens will be able to resist multiple drugs at once)
Term
How can patients combat drug resistance?
Definition
Take correct dosages and don't skip doses
Take medication as directed and at the specified time
Don't whine for drugs inappropriately
Term
How can industry combat drug resistance?
Definition
Change chemical structures of drugs to make them less accessible to pathogens
Make drugs that operate in ways microbes have a hard time circumventing
Focus on short-term, high-dose regimens
Term
Why isn't industry combating drug resistance?
Definition
The economy doesn't favor development of new antibiotics - it's more fiscally sound to make a blood pressure medication that a patient will take for the rest of their life than an antibiotic they'll take for two weeks.
Term
How can the global community combat drug resistance?
Definition
Use drug alternatives - go without if you can, and use vaccines
Better physician and patient education
Reduce antibiotic use in animal feed
Restrict antibiotic use
Increase specificity
Term
What are some novel approaches in drug mechanisms?
Definition
Targeting siderophores
Targeting riboswitches
Pre- and pro-biotics
Lantibiotics
Term
Siderophores
Definition
Mobile iron-hunting unites that pathogens use to collect iron they need.
Term
Riboswitches
Definition
Regulatory proteins within untranslated mRNA, found in all bacteria, that regulate whether the mRNA to which they are attached is translated.
Term
Prebiotics
Definition
Beneficial bacteria cocktails that supplement an already-existing colonies, to help crowd out bad bacteria.
Term
Probiotics
Definition
Microbe cultures that completely flush out and replace the gut flora, to reestablish a beneficial environment.
Term
Lantibiotics
Definition
Short polypeptides that are produced by bacteria as a control measure against other bacteria - they do so by inhibiting enzymes or puncturing cell membranes.
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