Chapter 20 Flashcards
antibiotic
-an antimicrobial drug that is usually produced by bacteria or fungi
Chemotherapeutic agent
a chemical (drug) used to treat a disease
Antimicrobial drugs
chemical that destroys pathogens w/o damaging body tissues
Synthetic drugs
a chemotherapeutic agent made in the laboratory
Paul Ehrlich
- developed concept of chemotherapy
- Salvarsan:
- Syphilis treatment
- Arsenic compound 1st used in early 1900
- dubbed the “magic bullet”
- not as effective as hoped & had extensive side effects
- Salvarsan:
Discovery: Sulfa drugs
- 1930s
- work against gram neg
- some people develop allergies
- were the first effective chemotherapeutic agents
Discovery: Penicillin
- fleming discovered in 1929
- first clinical trails in 1940
- natural penicillin most effective against gram pos and spirochetes
- changed the outcome of wounded soldiers in WWII
Broad spectrum antibiotics
treat a wide range bacterial infections
Narrow spectrum antibiotics
treat a narrow range of bacterial infections, e.g gram neg or gram positives but not both
Superinfection
- growth of a pathogen that has developed resistance
- or growth of normal flora that are usually kept in check by other microbiota, e.g Candida albicans may grow rapidly when the antibiotic kills the normal bacterial flora that keep it in check
bactericidal and bacteriosatic
- bactericidal- kills microbe
- bacteriostatic- inhibits the microbe
antibiotic
an antimicrobial drug that is usually produced by bacteria of fungi
world before antibiotics and vaccines
- people died of blood poisoning- infected wounds
- soldiers died from wound infections and communicable disease
- as many as half of the soldiers who died in WWI died from diseases
- high infant mortality
- Infant mortality 165/1000 live births
- 1900- measles, diphtheria and pertussis were the leading cause of childhood deaths
- Infant mortality went down due to clean water, sewers, better nutrition and feeding supplements
- During second half of the century antibiotics and immunizations made a big difference
inhibition of cell wall synthesis
- antibiotics only affect actively growing cells because they are the ones making new cell wall
- mode of action: prevents cross-linking of the peptidoglycan, thus interfering w/ the cell wall construction of growing cells
ex. Penicillin and synthetic penicillins
injury to plasma membrane
- Polymyxin B
- used as topical drug against gm neg bacteria such as Pseudomonas
- causes changes in permeability of membrane
- Amphotericin B, microonazloe, ketoconazole are anti fungal drugs that affect the plasma membrane
inhibit nucleic acid synthesis
- nucleic acid synthesis refers to-
- DNA replication needed when the cell divides/replicates
- RNA synthesis needed to make proteins (enzymes for metabolism and structural proteins for growth)
- drugs substitute for “real” building blocks for DNA and RNA and stop the synthesis
Inhibit synthesis of essential metabolites: Sulfa Drugs
- Sulfanilamide is similar to a precursor (building block) called PABA which is necessary to make folic acid (a vitamin)
- Sulfanilamide binds with the enzyme that coverts PABA to folic acid and stops the production of folic acid
- Drug only affects those microbes that make own folic acid; some microbes can’t make own folic acid and need to find it in the medium
Antimicrobial
Anti-fungal:
- Azoles: affect plasma membrane
- Amphotericin B
- Griseofulvin: affect cell division
Antiprotozoan
- Metronidazole (Flagyl): Affects anaerobic metabolism; used for trichomonas
- Mefloquine, Chloroquine: Inhibits DNA synthesis; used for malaria
- Artemisinin – malaria
- Ivermectin - helminths
Other antibiotics
Anti-viral
- Amantadine: uncoating step of virus infection; influenza
- Acyclovir: inhibits DNA or RNA synthesis by virus; herpes viruses
- Zidovudine: inhibits RNA synthesis; HIV
-Acyclovir and zidovudine are also called base analogs. This means that they are chemically similar to the bases used to make DNA and RNA: adenine, thymine, uracil, guanine, cytosine. The drug replaces the normal base and stops synthesis of DNA or RNA. [You do not need to know the name of the bases.]
acyclovir
when added to DNA, DNA synthesis stops
Drug activity
- Humans, protozoans, fungi and helminthes (parasitic worms) are made of eukaryotic cells.
- Share basic metabolism
- Antimicrobial drugs that affect the metabolism of a fungus or protozoan may also be toxic to human cells
- Are fewer drugs against eukaryotic cells than prokaryotic cells
- Drugs to treat viruses that infect human cells are also difficult to develop because the virus is inside a human cell and drugs that affect the virus may also be toxic to the human cell
- Pharmaceutical companies study the differences between human cells & metabolism and the metabolism of the fungi, protozoans, helminthes and viruses
- Focus drug development on the differences
- Prokaryotic cells have enough differences from human cells that there are more opportunities for developing antimicrobials
Resistance to Antimicrobial drugs
- Microbes have evolved in response to exposure to antimicrobial drugs: developed resistance
- Pharmaceutical companies have developed several generations of antimicrobial drugs in an attempt to “keep ahead” of the microbes
- Penicillin is a good example of a drug that has been chemically modified
Penicillin Family
- Two types of naturally produced penicillin from the mold Penicillium
- Narrow spectrum of activity: Gram positive bacteria and some spirochetes, e.g. Staphylococcus & Streptococcus
- Susceptible to penicillinase, also called β-lactamases, which cleave the β-lactam ring and inactivate the drug.
Semisynthetic penicillin’s
take the common nucleus of penicillin and modify it by adding a side chain
Purpose of modification: attain a broader spectrum; attain resistance to β-lactamases
Amoxicillin
semisynthethic penicillin
Augmentin
amoxicillin combined with an inhibitor of penicillinase
Choosing best antimicrobial drug
- Microbes differ in their sensitivity to drugs. Even strains of the same species show different sensitivity patterns
- Physicians often must start treatment based on the situation and wait for results from the lab on the specific drug sensitivity for the microbial strain that they are treating
- For some organisms the sensitivity patterns are well known
Disk Diffusion test
-Kirby Bauer Test
0Petri dish with agar medium is inoculated with the test organism so that the organism will grow all over the plate (this is called a lawn)
-Filter paper discs (commercially available) which have been impregnated with a known amount of antibiotic are placed on the agar
-The antibiotic diffuses out of the discs and into the agar
-If the organism is sensitive, it will not grow where the antibiotic has spread into the medium
-The plate is incubated and examined for growth patterns
- Zones with no growth are called “zones of inhibition”
- Zones are measured
- Larger the zone the more sensitive the organism to that antimicrobial drug
- Are charts to look up the size of the zone to determine if this indicates true sensitivity or not
E test
This method uses strips with high concentration of drug at one end and low concentration at the other- graduated concentration in between
Allows determination of the Minimum Inhibitory Concentration (MIC)
Broth Dilution Method
- Serial dilution of the drug so have high concentration at one end of row and low at the other end of row
- Add microbe
- Look for minimum inhibitory concentration (MIC)
- If no growth in any well then is minimum bactericidal concentration (MBC)
Synergism
Some drugs show synergy when used together
The effects of the combination of the two drugs are greater than would be expected by looking at each drug’s effect alone
