Control of Micro Organisms. 2nd ppt (test 2) Flashcards
Nystatin (a.k.a. mycostatin, achrostatin)
- from Streptomyces bacteria
- binds to sterols (fatty acid in cell membrane) in membrane of fungus and changes permeability (makes them leaky)
- used to treat Candida albicans yeast infections (intestinal, oral, vaginal)
- often combined with broad spectrum antibiotics to prevent Candida overgrowth later
Antifungal Chemotherapeutics.
Nystatin
Amphotericin B
Imidazoles
Amphotericin B
also from Streptomyces
- used for serious fungal infections (including those that become systemic) - binds sterols and degrades (targets cell membrane) - significant side effects (because of the class they are targeting, your cells contain sterols, you get leakiness in your cells and toxicity)
Imidazoles.
- synthetic
- inhibits sterol synthesis (or biosynthetic pathway)
- used topically (ointments) for Candida skin infections and invasive Cryptococossis**
Antiviral chemotherapeutics that block attachment.
most are synthetic
• amantadine (Symmetrel)
• vidarabine (Vira-A)
• enfuvirtide (Fuzeon)
Why don’t antibiotics work against viruses?
don’t grow or metabolize like cells (they also don’t have membranes or cell walls)
What are the 4 primary modes of action of antivirals?
1) inhibit attachment (from targeting and sticking to the cells)
2) disrupt genomic replication (base analogues mimic rungs of DNA or RNA ladder –very similar to DNA – specifically targeting when you are replicating the genome)
3) inhibit viral enzymes (some externally)
4) Interferons (generate antiviral proteins)
What does amantadine (Symmetrel) treat?
most influenza (no longer recommended due to resistance)
What does vidarabine (Vira-a) treat?
herpes zoster (chicken pox, shingles)
What does enfuvirtide (Fuzeon) treat?
HIV 1 (2003) (not HIV2)
What are some example son base analogues (mimic rung on DNA ladder)?
azidothymidine (AZT)
acyclovir (Zovirax)
What does azidothymidine (AZT) treat?
retroviruses (like HIV)
- also called the nonsense molecule (mimics the rung on DNA ladder)
What does acyclovir (Zovirax or valtrex) treat?
ointment for dental herpes or chicken pox
What are some examples of antiviral drugs that inhibit viral enzymes
- protease inhibitors (saquinavier; Invirase)
- Reverse transcriptase inhibitors (nevi rapine; Viramune)
- neuraminidase inhibitor (oseltamivir; Tamiflu)
What is reverse transcriptase needed for?
enzyme needed for replication
What do protease inhibitors (saquinavir; Inverse) treat?
inhibit enzymes that process HIV proteins (needed to reassemble the capsid)
How do reverse transcriptase inhibitor (nevi rapine, Viramune) work?
inhibit the enzymes that converts viral RNA to DNA
How does neuraminidase inhibitor (oseltamivir; Tamil) work?
inhibits spike enzymes that allow penetration and exit from cell; prevents budding of virus
What are interferons?
secreted from cells in response to stimulation by a virus or foreign substance; stimulates the infected cells (remain infected) and those nearby to produce proteins (AVP) that prevent the virus from replicating within them
Describe Interferons (INF) treatment.
- 20 different proteins
- a, b, and g categories
- g forms from tumor cells
- mobilize natural killer cells
- a and b form from virally infected cells (exclusively)
- stimulate Anti-viral Protein (AVP) production which stop viral protein synthesis by binding viral mRNA (blocking protein)
What do g forms of interferon come from?
infected tumor cells
What do a and b forms of interferon come from?
virally infected cells
What does INF-a treat?
hep B, genital warts, leukemia
What is required to develop a drug?
Laboratory testing (in vitro) Animal testing (in vivo) c) Clinical Trials -3 phases each phase increases # of subjects Statistical significance Stringency of test
In vivo.
in life
In vitro.
in a test tube
What is the first phase of clinical trials?
Phase I – aka “safety phase”
- 20 to 100 HEALTHY subjects
- tests different doses
- judges SIDE EFFECTS, BIOAVAILABILITY (how much of the drug is in serum and circulating)
What is the second phase of clinical trials?
Phase II
- approx 500 patients with DISEASE(clinically)
- continues to monitor side effects with (diff.) doses
- COMPARES new drug to control / other drugs
What is the third phase of clinical trials?
- several thousand patients with disease
- tests drug against ESTABLISH METHOD
Triple Blind study.
set-up so that people who analyze the data don’t know – barcodes and randomized. Codes assigned to each sample. Only when the codes are removed they will know at the end who got what. Removes last layer of bias.
How do you establish statistics on efficacy and safety?
triple blind study
How long do trials take?
- trials take 7-15 years on average
- 1/1000 drugs make it to humans
- 1/5000 drugs make it through trials
Superbugs.
resistant bacteria
What do bacteria do to resist antibiotics?
- Destruction of the drug (penicillinase)
- Prevention of drug penetration
- Alteration of the target site (or overproduction)
- Rapid efflux of drug before it can act
What contributes to super bugs?
• Misuse of antibiotics
- Overprescription
- self-medication – can be bought in corner stores over seas. Or even from vets!
- Incomplete antibiotic regimens
- use of antibiotics in livestock
What percent of antibiotics are prescribed for the common cold (virus)?
50%
How many prescriptions of antibiotics in NA/year?
150 million prescription in NA / year
How much of the worldwide use of antibiotics is for animals?
- more than 50% of all antibiotics used worldwide are used in
- animals (Health Canada, 2002)
slide 20 skipped?
slide 20 skipped?
Horizontal gene transfer
sharing resistant genes among bacterial species
What are the 3 major superbugs?
- MRSA (methicillin-resistant Staphylococcus aureus)
- Clostridium difficile (C. difficile)
- VRE (vancomycin resistant enterococcus)
Describe MRSA.
-spread by direct contact – very close proximity to the person – fecal oral route
How many people carry MRSA?
1 in 3 ppl (2billion)
How many cases of MRSA per 1000 admissions in Canada?
5-6 cases
Describe Clostridium difficile (C. difficile).
Gram +ve, sporeforming bacillus
Major cause of colitis** especially after use with broadspectrum antibiotics
Spread by fecal-oral route
Usually nosocomial (in NA)
What is Clostridium difficile (C. difficile) treated with?
- treated with vancomycin + antiprotozoal (metronidazole)
Describes VRE (vancomycin resistant Enterococcus).
Gram +ve cocci
Part of normal flora
Developed by overuse of vancomycin
Spread by fecal-oral route
What is VRE treated with?
Treated with high-dose, combintions (vancomycin, other streptomycin-like antibiotics, chloramphenicol)
What is the prevalence of VRE?
Prevalence remains low in Canada (
What is MDR Klebsiella pneumonia- carbapenemase producing (KPC)?
Gram-ve enterobacillus**
Causes pneumonia and UTIs
Spread by fecal-oral route
What is the last resort antibiotic for MDR Klebsiella pneumonia- carbapenemase producing (KPC)?
Carbapenems are last-resort antibiotics; spread of resistance gene (NDM-1) could be catastrophic**
How can we fight super bugs?
1) Educate front
- line health care professionals
- establish screening techniques
- stop the spread
2) Reduce overmedication
3) Generate new antibiotics (limitation-time)
4) Combination drugs
5) Vaccine development (need an antigen)
6) Alternative drugs
- bacteriophages
- herbs, spice and other drugs?
What is the limitation of generating new antibiotics?
- it takes up to 15 years for drug approval, it takes 4 years for bacteria to show resistance
- not cost effective (research time, market flood, short regiment)
