Ch. 12: Drugs, Microbes, Host- Elements of Chemotherapy Flashcards
Chemotherapy
any chemical used to treat/prevent disease
set of chemical substances/drugs to treat/prevent disease
Prophylaxis
use of a drug to prevent potential for future infection in a person at risk
ex) condom
Antibiotics
substances produced by the natural metabolic processes of some microorganisms that can inhibit or destroy other microorganisms
~kill microbial infections in a host
Analog
[chemistry] a compound that closely resembles another in structure
Protease
an enzyme which breaks down proteins and peptides.
Resistance (R) factors
plasmids, typically shared among bacteria by conjugation, that provide resistance to the effects of antibiotics
Beta-lactamase
an enzyme secreted by certain bacteria that cleaves the beta-lactam ring of penicillin and cephalosporin, and thus provides for resistance against the antibiotic
MDR bacteria
Multidrug resistant (MDR) — acquired nonsusceptibility to at least one agent in three or more antimicrobial categories.
Antibiogram
test that analyzes the effectiveness of a specific antibiotic on a disease that a patient has
ex) Kirby-Bauer test/ E test/ tube dilution for antibiotic sensitivity
Superinfection
infection caused by microbe resistant to antibiotics; commonly formed as a secondary infection
(candida, yeast infections, c. difficile).
What are the four organisms from which most of our antibiotics are derived?
Penicillium
Streptomyces
Bacillus spp
cephalosporium
most antibiotics are produced by:
bacteria & fungi
[not viruses]
Alexander Fleming
discovered first real [naturally derived] antibiotic in 1928
[penicillin]
draw the beta-lactam ring
beta-lactam antiobiotics act by:
blocking cell wall synthesis
Polymyxins act by:
creating holes in bacterial cell membranes
Substances that are naturally produced by certain microorganisms that can inhibit or destroy other microorganisms are called
antibiotics.
Antibiotics effective against a wide variety of microbial types are termed
broad-spectrum.
Antimicrobics effective against only gram-positive bacteria would be termed
narrow-spectrum drugs.
Penicillins and cephalosporins MOA is:
block cross-linking of peptidoglycan.
Which of the following is LEAST likely to cause allergies?
penicillin
vancomycin
sulfonamides
vancomycin
Sulfonamides MOA:
block folic acid synthesis.
fluoroquinolones MOA is:
they work by inhibiting bacterial DNA replication.
[by targeting DNA gyrase]
Antibiotics that are ___________ include azithromycin and erythromycin.
macrolides
Ampicillin, amoxicillin, mezlocillin, and penicillin all have:
a beta-lactam ring.
Which of the following is the most toxic drug to humans?
ciprofloxacin.
chloramphenicol.
gentamicin.
cephotaxime.
chloramphenicol.
Species of __________ produce polymyxins.
Bacillus
There are fewer antifungal, antiprotozoan, and antihelminth drugs compared to antibacterial drugs because these organisms:
are so similar to human cells that selective drug toxicity is difficult to achieve.
Where is quinine derived from?
a tree
Antivirals that target reverse transcriptase would be used to treat
HIV
An antiviral that is a thymine analog would have an antiviral mode of action that
blocks DNA synthesis.
One of the greatest challenges in development of antivirals is finding drugs that are
selectively toxic for viruses.
The multidrug resistant pumps in many bacterial cell membranes cause
removal of drugs from the cell.
The ____________________ uses an agar surface, seeded with the test bacterium, to which small discs containing a specific concentration of several drugs are placed on the surface.
Kirby-Bauer test
Why has the United States and Europe banned the use of human drugs in animal feeds?
Because it contributes to the growing drug resistance problem.
Penicillinases do what?
destroy penicillin
A superinfection results from
decrease in most normal flora with overgrowth of an unaffected species.
Which antimicrobial is contraindicated for children due to permanent tooth discoloration?
tetracycline
Antibiotics are derived from all the following except
Cephalosporium.
Bacillus.
Streptomyces.
Staphylococcus.
Penicillium.
Staphylococcus.
Aminoglycosides MOA is:
attach to the 30S ribosomal subunit and disrupt protein synthesis.
What are the 2 ways antihelminthic drugs work against the helminth?
1) Paralyze the worm in your intestine; worm is released from the intestinal lining and pooped out
2) block nutrient absorption by tapeworm causing it to starve to death or will release and leave in poop
Acyclovir is used to treat :
genital herpes.
What are the antibiotic resistance genes generally called?
R genes
How long have antibiotics been around?
For millions to billions of years
While trying to start an IV on a patient, Kurt received a needlestick injury and blood exposure involving a patient with AIDS. He was immediately started on three different antiretroviral medications. The advantage of using combined therapy in this circumstance is
this should prevent the emergence of drug-resistant microbes.
Janice has just had hip replacement surgery and her physician has prescribed antibiotics and directed her to take them every time she has a dental appointment. This is an example of antibiotic
prophylaxis.
Albert Alexander :
was the first patient to be treated with injections of penicillin [due to infection after rose thorn scratch; still died]
Which genera produce the widest variety of antibiotics?
streptomyces [1/3 of all types of antibiotics today]
Describe the ways in which antibiotics can destroy a microbe
-target cell wall [lysis] or cell membrane [leak/death]
-affect DNA/RNA = replication/mutations…
-protein production; targeting ribosomes
-metabolic pathway by inhibiting enzyme catalyzed reactions
identify characteristics of the ideal antimicrobial drug
Penicillin
[Structure, MOA]
*Structure: square beta-lactam ring; 5 atom house shape
*Anything that ends with -cillin
MOA: competitive inhibition of enzyme involved in cross-linking of peptidoglycan (blocks cell wall formation)
*Natural source- penicillium
*problems: higher than typical antibiotic resistance in human pathogens & allergies
Cephalosporin
[Structure, MOA]
*Comes from ceopholosporium
*Starts with -ceph, -cef, -kef…
*Structure- 6 atoms- swimming pool shape
No real problems with use [less likely than others]
*MOA: Block cell wall synthesis of peptidoglycan by competitive inhibition of enzymes involved in cross-linking ; beta-lactam drug ; same MOA as penicillin
Vancomycin
[MOA]
*narrow spectrum drug
*Semi-synthetic; comes from streptomyces
*MOA: targets cell wall; prevents cross-linking by causing cell wall to bind to itself
*Very selective; targets peptidoglycan
*Very toxic drug; administered slowly; if too quickly, can cause serious pain
Polymyxins
[MOA]
*Semi-synthetic; Comes from Bacillus polymyxa [only one here from bacillus]; narrow-spectrum
*MOA: Targets bacterial cell membranes; acts as detergent; disrupts cell membrane & causes leaks
*Problem: toxic to kidney bc targets cell membranes [used for antibiotic-resistant UTIs etc..]
Fluoroquinolones
[MOA]
*Usually ends in -floxacin [cipro-, moxi-, nor-…]
*Synthetic [artifically made]; broad-spectrum
*MOA: Target DNA replication by targeting [binding to] DNA gyrase, preventing cell divison
*Side effects may include brain seizures; generally not toxic though
Aminoglycosides
[2 types, structure, MOA]
*Semi-synthetic, usually come from streptomyces or related species
MOA: interfere with protein synthesis [Target 30S ribosomal subunit]; Targets translation; more selectivity; inhibits initiation and translocation and leads to a misreading of mRNA.
2 types
Streptomycin - older [ a little toxic ; SE hearing loss]
Gentamicin - newer [ less toxic]
Streptomycin structure = 6 carbon ring + 2 amino sugars
Tetracyclines
[structure, MOA]
*Broad spectrum
*structure = 4 circles connected to each other
*Come from streptomyces
*MOA: Target 30S ribosomal subunit; Attach to 30S subunit and blocks A site, preventing translation
*Side effects- aesthetic effect on teeth/gum line; also can interfere with fetal bone development; GI issues
Chloramphenicol
[Structure, MOA]
*Look for Cl2 chlorine in structure
*Comes from streptomyces; broad-spectrum
*MOA: Binds to 50S subunit; prevents peptide bond formation [blocks ribozyme activity]
*Toxic to mitochondria [affects bone marrow, causes anemia]
*Not commonly used in hospitals but more for research; immediately halts protein synthesis
Macrolides
[structure, MOA]
*Ex) erythromycin
*Comes from streptomyces
*Structure: like a lobster, 3 circles together and 2 other circles next to it
*MOA: Binds to 50S subunit; inhibits translocation
Sulfonamides
[structure, MOA]
*Totally synthetic [Synthetic; came from dye]; broad-spectrum
*Structure: blue circle connected to 3 other possible shapes; find the aromatic ring and see if the sulfur group and amino group on another side
*MOA: competitive inhibition; targets folate metabolism [enzyme that synthesizes folate]; very selective
[Folate is used to make nucleotides]
*Major problem = allergies
which 2 antibiotics are most commonly associated with allergies?
penicillin & sulfanomides
Polyenes- antifungal
[Structure, MOA]
*Structure: 1 big circle structure
*Come from streptomyces
*MOA: Target fungal cell membranes; targets (binds to) ergosterols causing membrane leaks [doesn’t bind to cholesterol bc mostly selective]
Azoles - antifungal
[MOA]
*Completely synthetic antifungal
*MOA: inhibit ergosterol synthesis
*More synthetic, less side effects then polyenes
Chloroquine
[MOA, example]
-Anti-protozoal; selective
ex) Quinine: comes from cinchona tree bark
*Typical target is protozoa (specifically, malaria)
*MOA: Selectively accumulates in lysosomes of parasites; Parasites consume this, gets into their lysosome, this will change chemical structure which cross links to the parasite’s DNA [destroying its DNA]
*Downside: resistance is developing in plasmodium parasites
Metronidazole
[MOA]
*Antiprotozoal used to treat amoebic infections (amoebic dysentery, giardia..); also an antibiotic
*Completely synthetic, artificial; highly selective
[[[Ends in Azole but different than Azoles]]]
*MOA: Causes DNA double-strand breakage [occurs when it is reduced in lysosome] [similar mechanism to quinine]
Antihelminthic drugs
*kill tapeworms, nematodes…
*Remain and kill things in your intestine
*most common ones work in the intestine
*Work in 2 ways-
1. Paralyze the worm in your intestine; worm is released from the intestinal lining and pooped out
2. block nutrient absorption by tapeworm causing it to starve to death or will release and leave in poop
*Almost no side effects; work well
Antiviral drugs
*know main drugs and the 3 MOA
Inhibiting viral adsorption
Inhibit the nucleic acid synthesis
Or inhibiting proper release
Tamiflu & Relenza MOA
[anti-virals- MOA]
MOA: block proper budding/release from the host cell [useful early in flu infection];
*starting to see some resistance with Tamiflu
Cyclovir
[Anti-viral- MOA]
treats cold sores by herpes virus
MOA: inhibits DNA replication
AZT
[Anti-viral]
works for cells infected with HIV; works well
*MOA: selectively inhibiting HIV’s reverse transcriptase, the enzyme that the virus uses to make a DNA copy of its RNA.
HAART
[Anti-viral]
*highly active anti retro viral therapy- multiple pill cocktail ; entails use of 3+ drugs that work in 2+ different ways
[could be like AZT, protease inhibitors, or can target HIV viral release/fusion/adhesion]
Truvada
[AKA prep: post-exposure prophylaxis]
*Includes 2 different reverse transcriptase inhibitors
*eliminate the risk of HIV; prophylactic
*daily pill; usually used for people that don’t have HIV yet; prevent infections
*can also be used for post-exposure prophylaxis
~few side effects
Interferons
[Anti-viral]
*last resort; naturally occurring molecules produced by the immune system when you have a viral infection
~attacks viruses and cancer
~Derived from human body/gene
*negative side effects- harder to fight off other types of infections
How do bacteria acquire drug resistance?
[5 ways]
- Drug inactivation- R gene makes a protein that is an enzyme that destroys antibiotic (breaks covalent bonds) EX) penecillinase, betalactamase
- Decreasing cell permeability; R gene makes a protein that keeps antibiotic out
- Activation of drug pumps- R gene produces a protein that pumps antibiotic out of the cell using ATP [MDR multi drug resistant pumps]
- Change in drug binding site on target [binding site on target [ribosome] is altered, so drug has no effect]
- Use of alternative metabolic pathways
What contributes to the rise in drug resistance in the population?
[3 categories]
- Use of antibiotics in hospital setting [inappropriate use like doctors prescribing antibiotics w/o proper diagnosis/ when cause is viral infection like a cold]
- Antibiotic use in animal feed
- World-wide drug use [antibiotic use around the world; overuse: antibiotics available without prescription; underuse: not fulfilling full antibiotic course]
How can we limit the increase seen in drug resistance in bacteria?
- Drug usage
-Accurate diagnosis and prescribing, using antiobiogram test
-Make sure patients comply - finish antibiotics
-Combined therapy 2+ drugs that enhance the effectiveness of single antibiotic - Drug research
-Developing shorter-term, higher dose antimicrobials that are cheaper, more effective, and less side effects
-Seeking out new strategies like using bacteriophage therapy - Long-term strategies
-Education of healthcare workers/public
-Only use antimicrobials when absolutely needed
-vaccination
-stop adding antibiotics to animal feed
How can antibiotics harm the person taking them?
1/20 ppl that take antibiotics can have an adverse effect
*Direct damage to human tissue [usually kidney, liver]
*Allergic reactions [mostly with penicillin & sulfanomides]
*Disruption in balance of natural microflora > diarrhea/other sx
*Superinfection
Drugs starting in Cef, Ceph, Kef are:
cephalosporins
drugs ended in floxacin are-
fluoroquinolones
Streptomycin structure is:
6 carbon ring with 2 amino sugars
Tetracyclines are derived from-
streptomyces
identify this
streptomycin (streptomyces)
[aminoglycoside]
identify this
chloramphenicol
Erythromycin is an example of -
a macrolide
identify this
macrolide
identify this
sulfonamide
how is sulfonamide derived?
artificial; from a red dye
Polyenes and azoles target
fungi
[anti-fungals]
identify this
Polyenes
Polyenes are derived from -
streptomyces
Monistat is an example of an-
Azole (antifungal) [miconazole]
The 2 drugs starting with Poly- happen to target:
cell membranes
Polymixins- target bacterial cell membranes
Polyenes- target fungal cell membranes
quinine was found to treat-
Malaria
The downside of chloroquines is-
microbes are starting to develop resistance to it
Metronidazole MOA=
breakage of double DNA strands
Metronidazole targets-
amoebas
cyclovirs are chemicals that mimic ____________
so they can act as ______________
DNA nucleotides
competitive inhibitors and block DNA replication
Most HIV treatment includes-
HAART [3 drugs that work in 2+ different ways]
since HIV rapidly mutates
interferons are derived from
the human body/gene
