Emerging Diseases- Slide 17

Geography
Eukaryotic
Has a nucleus and other organelles inside the cell (human)
Antibiotic
bacteria, yeasts, parasites, living cells, usually not viral
Antimicrobial
same as antibiotic
bacteria, yeasts, parasites,
living cells, usually not viral
Antibacteria
bacteria
Antiviral
viral
Antifungal
fungi = yeasts, molds
Drug development
-Exploit differences between pathogens and humans
-Biochemical pathways
-Rigid cell walls (bacteria and yeasts)
Drugs for HIV virus
reverse transcriptase
Drugs for Flu
Nueraminidase inhibitor
What drug is the hardest to develop?
Eukaryotic pathogens (parasites, fungi)
pathogens close to humans
Quinolones
Target DNA replication and unwinding
Inhibit unwinding of DNA
Metronidazole
Target DNA replication and unwinding
binds and distorts DNA
Rifampicin
Target Transcription-Interfere with RNA production from DNA
-Binds RNA polymerase
Target cell membrane
-Lipids in membrane
-Polymyxins- detergent, interacts with cell membrane (polyscporin, bacitracin, neosporin)
Target cell wall
-Interfere with cell wall synthesis
ex: penicillin, Cephalosporins, cephamycins
Therapeutic index
Activity of drug against pathogen vs. activity of drug against human cell

-Best if activity against human cells is 100x to 1000x above activity against pathogen

Bacteriocidal
Kill growing bacteria (don’t kill static cells)
ex: quinolones, penicillins
Bacteriostatic
Inhibit growth
Ex; tetracyclines, macrolides, cholamphenicol
Oral
Drugs that can cross mucosal membranes and enter blood stream
Intravenous
Drugs that cannot cross mucosal membrane and enter blood stream on their own must be given through IV.
Host cell permeability is important for:
Intracellular pathogens whether they can penetrate (macrolides, tetracyclines) or do not penetrate (penicillin)
In vitro
test tube
In vivo
in animals/ humans
Drugs vs. immune systems
-Immune system- major control of pathogens
-drugs- assist immune system in the war
BEST way to treat is restore immune system
Natural Drug development
Screening soil samples and decaying plants for inhibitory microorganisms
ex: penicillin came from common bread mold, Penicillium
Synthetic drug development
Quinolones- Chemically synthesized
Assay development
whole assay
enzyme assay
lead compound
-Compound identified from screen-natural or synthetic
-Shows some activity against pathogen
lead compound
-Compound identified from screen-natural or synthetic
-Shows some activity against pathogen
Rational drug design
-Select a target enzyme
-Determine its structure and shape
-Determine its active site
-Fit small chemicals into the active site
-Test these small chemicals for activity
Drug pipeline
Drug Discovery ->
Preclinical ->
Clinical I, II, II ->
Approval IV ->
Consumers
Three dimensions in drug development (FDA)
Safety
Medical utility
Industrialization
Patent good for
20 years
How many compounds does a certain drug usually start with?
-5-10,000 at start
Cost for drug pipeline
-Basic research- 10s of mil
-Animal models- 10s of mill
-Clinical trials- 100s of mil

A drug needs to generate profit of 0.5 billion above cost of making and marketing drug

Generics
patent expired
How long are drugs normally good for until they become ineffective from resistance?
10 years
Failure of drug in a patient
-Host: immune system, location (brain)
-Drug: cidal/static, oral/IV
-Pathogen: is it susceptible or resistant
Susceptibility testing
how much drug does it take to kill an organism?

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