Prions & Antimicrobial Drugs
When we change the side chain in the lab what are we doing?
-Broaden the spectrum of the drug so it works on gram negative -Make the drug more tolerant so it can't be destroyed by pH and take orally -Combat resistance
What are the 3 classes of chemotherapy drugs?
1. Antibiotics - naturally produced by bacteria and fungi 2. Synthetic drugs - synthesized in a lab 3. anti-viral drugs
What are the 5 mechanisms of actions for drugs?
1. Inhibit cell wall synthesis(penicillins, cephalosporins, bacitracin, vancomycin) 2. inhibit protein synthesis (chloramphenicol, erythromycin, tetracycline, streptomycin) 3. injure plasma membrane (anti fungals) (polymyxin B) 4. inhibit nucleic acid replication and transcription (anti virals) (quinolones, rifampin) 5. inhibit metabolite synthesis (sulfanilamide, trimethoprim)
What are the 4 mechanisms that bacteria use to become resistant to drugs?
1. They make enzymes that destroy the drug so it no longer works 2. They change or mutate the target that the antibiotics work on 3. They inhibit or change their membrane permeability so the drug can not enter the cell 4. They create pumps that act as efflux pumps to pump the antibiotics out
Antibiotic Resistance can occur in bacteria by what TWO ways that change their genetic information
1. chromosomal mutations 2. R plasmid (resistance factor)
Prokaryotes = 70s ( ___s+___s)
30s + 50s
Eukaryotes = 80s ( __s + __s)
40s + 60s
Mitochondrial have ___s ribosomes
70s
Prokaryotes have ___s ribosomes
70s
Eukaryotes have ___s ribosomes
80s
Prion definition
A protein that can replicate with NO evidence of DNA or RNA or nucleic acids
Antibiotics
A substance that is produced by one microorganism (a bacterium or fungus) which in small amounts will kill or inhibit the growth of another microorganism
What drug targets reverse transcriptase?
AZT
Used to treat genital herpes, chickenpox and shingles.
Acyclovir
who discovered penicillin?
Alexander Fleming
Drugs that inhibit protein synthesis that binds to 30s subunits
Aminoglycosides and Tetracycline
Polymyxin B
Antibacterial drug that injures the plasma membrane
Quinolones and Fluoroquinolones Rifamycins
Antibacterial drugs that inhibit nucleic acids?
Polyenes and Amphotericin B (Imidazoles & Triazoles)
Antifungal drugs that injure the plasma membrane
What microorganisms produce antibiotics?
Bacteria and fungus
ALL penicillins have a 4 ring called the _____
Beta-Lactam ring
Drugs that inhibits protein synthesis that binds to 50s subunits
Chloramphenicol and Macroclides (erythromycin and zithromax)
What drugs bind to the 50s subunits
Chloramphenicol and Macrolides
most common prion infection in humans?
Creuztfeld-Jacob disease
what infectious disease occurs when a spontaneous mutation occurs in a gene on chromosome 20
Creuztfeld-Jacob disease
Aminoglycosides
Drug class that inhibit protein synthesis at 30s subunits
Tetracycline
Drug class that inhibit protein synthesis at 30s subunits
Chloramphenicol
Drug class that inhibits protein synthesis at 50s subunits
Macrolides: examples: erythromycin, used in people allergic to penicillin and zithromax
Drug class that inhibits protein synthesis at 50s subunits
Polyene
Drug class that injures plasma membrane
Trimethoprim and sulfonamides
Drug classes that inhibit metabolites - inhibit folic acid synthesis, analogs of PABA
Selective Toxicity
Drug should only kill/inhibit the pathogen not the host. (Kill the microbe without harming the host )
Azole: drugs that inhibit synthesis of _______
Drugs that Inhibit synthesis of ergosterols
The two types of Macrolides (50s) inhibitors of protein synthesis include _______&_________.
Erythromycin and Zithromax
Example of Macrolides
Erythromycin, Zithromax
Ketoconazole, Miconazole, Amphotericin B, Nystatin
Examples of anti fungal drugs (may be toxic to the host) inhibit ergosterols in plasma membrane of fungi (injury to plasma membrane)
Humans can synthesize PABA. T/F
False
Penicillin V and Penicillin G only affect gram negative bacteria. T/F
False
Penicillin V is given by injection. T/F
False
Penicillins and Cephalosporins are more effective against gram negative organisms. T/F
False
Prions contain DNA and RNA to replicate. T/F
False
Prions contain nucleic acids. T/F
False
There is a cure for prion diseases. T/F
False
The normal protein that every brain contains is called PrP Sc T/F
False - abnormal protein
Penicillin V and Penicillin G are broad spectrum antibiotics. T/F
False, narrow spectrum
Cephalosporins do not have beta lactam rings. T/F
False, they are similar to penicillins an contain a beta lactam ring
You can kill prions with boiling water. T/F
False, they are the hardest particles to destroy
Penicillin _ = sensitive to low pH ( not given orally)
G
Penicillin __ = prototype
G
Penicillins, Cephalosporins, Bacitracin, Vancomycin: What mechanism of action?
Inhibition of cell wall synthesis
Bactrim for UTIs: What mechanism of action?
Inhibition of essential metabolite synthesis
Many of these drugs act as a competitive inhibitor of enzymes: what mechanism of action?
Inhibition of essential metabolite synthesis
Sulfanilamide, Trimethoprim: What mechanism of action?
Inhibition of essential metabolite synthesis
Sulfanilamide: What mechanism of action?
Inhibition of essential metabolite synthesis
anti viral drugs: What mechanism of action?
Inhibition of nucleic acid replication and transcription
Chloramphenicol, Erythromycin, Tetracyclines, Streptomycin: What mechanism of action?
Inhibition of protein synthesis
Aminoglycosides, Tetracyclines, Chloramphenicol, Macrolides: What mechanism of action?
Inhibitors of protein synthesis
Ketoconzole, Miconazole, Amphotericin B, Nystatin: What mechanism of action?
Injury to Plasma Membrane
Majority of anti fungals in this category of drug mechanism of actions
Injury to plasma membrane
Polymyxin B : What mechanisms of action ?
Injury to plasma membrane
Bactericidal
Kill bacteria directly
Examples of zoonotic prion diseases
Mad Cow Disease (Bovine Spongiform Encephalopathy) Scrapie - found in sheep
Prions cause what type of deadly infections?
Neurological
does any drug have 100% selective toxicity?
No, all drugs have some side effects
Sulfanilamide replaces _______
PABA (Paraminobenzoic acid)
What are the 2 natural penicillins called? Penicillin _ & Penicillin _
Penicillin G and Penicillin V
which natural penicillin is acid stable?
Penicillin V
What 2 molds produce antibiotics?
Penicillin and Cephalosporium
Enzyme that is secreted by some microorganisms, MRSA (Methicillin resistant Staphylococcus aureus) is known as
Penicillinase
Enzyme that breaks down β-lactam rings
Penicillinase (β-lactamase)
What drugs that are molds prevent cross linking of peptidoglycan units?
Penicillins and Cephalosporins
Another name for polypeptide antibiotics _____________
Polymyxin B
Polymyxin B
Polypeptide Antibiotic that causes injury plasma membrane
infectious particles that are pieced of protein with no nucleic acids (no RNA, no DNA)
Prions
When bacteria acquire _______ it gains antibiotic resistance against SEVERAL different antibiotics
R plasmid
Grow penicillium so the nucleus is produced then attach R group in the lab OR 2. Tend to have a broader spectrum of activity. These are called ____ Penicillins
Semi-synthetic
All prion diseases cause major neurological infections that are called ______ that turn the brain into a "sponge" appearance with holes
Spongiform Encephalopathy
Bacteriostatic
Stop bacteria from growing but do not kill bacteria
What does AZT do?
Stops the RNA dependent DNA polymerase of HIV Reverse transcriptase Used to treat AIDS patients
What 2 bacterias produce antibiotics?
Streptomyces and Bacillus
Example of a Aminoglycoside
Streptomyin
What drugs bind to the 30s subunits
Tetracyline and Aminoglycosides (Streptomycin)
What is the difference between PrP (c) and PrP (Sc) ?
The normal protein is folded in an alpha helix and the abnormal protein is folded in beta pleated sheet (FOLDED DIFFERENTLY)
How do antifungal drugs work?
They destroy or inhibit ergosterols (injury to the plasma membrane)
Where do penicillins cleave the drug?
They prevent crosslinking of peptidoglycan
How do most bacteria become resistant to penicillin?
They produce an enzyme called Penicillinase or B-lactamase, this enzyme destroys the beta lactam ring - and when the beta-lactam ring is destroyed the drug is then INEFFECTIVE!
5 member ring with N & S atoms
Thiazolidine ring
ALL penicillins have a 5 ring called the _____
Thiazolidine ring
how do prions enter the body?
Through ingestion of contaminated meat or surgical equipments or blood/organ transfusions
AZT is an antiviral
True
Antifungal drugs bind to membrane sterols and disrupt the membrane. T/F
True
Creuztfeld-Jacob occurs from spontaneous mutations or also from contaminated surgeries - usually seen in people in their 50s-60s because it takes a long time to show up. T/F
True
It is best to limit anti fungals as topical creams so they don't cause severe damage to the host. T/F
True
Natural penicillins (Penicillin G and Penicillin V ) are very narrow spectrum antibiotics and only affect gram positive cocci bacteria. T/F
True
Penicillin V and Penicillin G are both susceptible to penicillinase. T/F
True
Penicillin V and Penicillin G only affect gram positive bacteria. T/F
True
Penicillin V is given orally. T/F
True
Penicillins and Cephalosporins are more effective against actively growing cells. T/F
True
Penicillins are bactericidal. T/F
True
Prions can replicate. T/F
True
Selective toxicity is poor in anti viral drugs. T/F
True
antiviral drugs have difficult selective toxicity. T/F
True
the normal protein that every mammal brain contains is called PrP c T/F
True
Many people may have allergic reactions and anaphylactic shock to Penicillins. T/F
True, #1 choice for people who are allergic to penicillin is erythromycin which inhibits protein synthesis (like binding to 50s subunits)
What differentiates the penicillins?
Unique side chain group that differentiates the different penicillins (R group)
what drugs have the best selective toxicity?
antibacterials
What drugs are the worst selective toxicity?
antivirals then antifungals and parasites
Symptoms of a prion infection in humans?
behavioral changes, memory loss, slurred speech, tremors, coma & death
Polypeptide antibiotics - polymxyin B
binds to and alters membrane permeability and causes leakage
Semisynthetic antibiotics are effective against gram positive and gram negative bacteria. Is this an example of a narrow or broad spectrum antibiotic?
broad spectrum
what type of antibiotics can cause super infections such as yeast infections due to killing off normal flora (narrow or broad ) spectrum antibiotics.
broad spectrum antibiotics
Penicillin G is administered ____
by injection
Penicillins and Cephalosporins work by inhibiting _______
cell wall synthesis
When bacteria acquire_______ it usually only gains resistance against ONE antibiotic
chromosomal mutations
Broad spectrum antibiotics
effective against both gram positive and gram negative bacteria
Narrow spectrum antibiotics
effective only against gram negative or gram positive
Fungal cell membranes contain ___
ergosterol
What do sulfonamides interfere with?
folic acid synthesis
Penicillins and Cephalosporins are more effective against what type of bacteria? gram __ bacteria
gram positive bacteria
Penicillins and Cephalosporins work by _______
inhibiting cell wall synthesis by preventing cross linking of peptidoglycan units
What is the most toxic mechanisms of actions for drugs that affects 50s and 30s subunits?
inhibition of protein synthesis
Acyclovir: What mechanism of action?
inhibitors of nucleic acids
What is the #1 cause of antibiotic resistance?
misuse and overuse of antibiotics
Penicillin G is very effective at killing gram positive bacteria but not most gram negative bacteria. Is this an example of a narrow or broad spectrum antibiotic?
narrow spectrum
What are the 2 different types of antibiotics?
natural occurring and semi-synthetic
The majority of anti viral drugs target ______
nucleic acid - destroy RNA or DNA
Antiviral drugs inhibit _______
nucleic acids
Penicillin V is administered ____
orally
Prions stand for _________
proteinaceous infectious particles
Prions are made up of ____ only!
proteins
Animal cell membranes contain ___
sterol
The biggest difference between natural and semi synthetic Penicillins is
their side chains have different components
how do prions replicate if they don't have DNA or RNA?
they convert normal proteins in the brain to an infectious abnormal protein (gene on chromosome 20)
Chemotherapy
use of drugs to treat disease , inhibits growth or kills the pathogen, used internally not externally like disinfectants
Can anti-fungal drugs be toxic to the host?
yes
Is ketoconzole & Miconazole toxic to the host?
yes
