Antimicrobials Flashcards
What are bacteriostatic drugs?
Cause bacteria to stop growing
What are bactericidal drugs?
Cause bacterial cell death
Drugs that target cell wall synthesis tend to be bactericidal
What are beta-lactam antibiotics?
Inhibit peptidoglycan synthesis (cell wall). Bacterial resistance via beta-lactamases
Penicillin, ampicillin
What are sulfonamides (aka sulfa drugs)? What are some examples?
Inhibit folate synthesis, important for bacterial cell metabolism. Often given with trimethoprim (tetrahydrofolate synthesis inhibitor).
Sulfamethoxazole, sulfacetamide
What are tetracyclines?
Inhibit bacterial protein synthesis (binds to bacterial ribosome)
Tetracycline, Doxacycline
What are Macrolides?
Inhibits bacterial protein synthesis (inhibits peptidyl transferase). Inhibit the enzyme that adds amino acids to protein chains.
Erythromycin
Clarithromycin
What are other mycins?
Antinomycin - polypeptide antibiotic, inhibits transcription
Vanomycin - glycopeptide antibiotic, inhibits Gram + cell wall synthesis
What is antibiotic resistance and how does it evolve?
Antibiotic use + selective pressure = antibiotic resistance
Mutations are random but evolve under selective pressure
Mutation rate approx 1 per 10^10 nucleotides
(S. aureus has a genome size of 2.8^6 nucleotides)
Speed of developing resistance also depends on doubling time/growth rate of microbe.
What are some examples of the mechanisms of antimicrobial resistance?
Drug deactivation Drug altering Drug degredation Drug efflux Compensatory gene expression Etc
Can bacteria develop resistance against natural compounds?
Yes - thoretically? But hasn’t been documented
What are antiviral drugs?
Are typically specialized for viral proteins and processes
What are broad spectrum antivirals and what is their mechanism of action?
Type 1 IFN (interferon) collectively inhibit viral replication by:
antiviral cytokine
Induces inflammation and recruitment of antigen presenting cells
inhibits viral replication and protein synthesis
regulates cell growth
What are oncolytic viruses?
Viruses that kill tumours
Usually modified to take advantage of the interferon pathway
Don’t cause disease because normal cells capable of combating them but the tumour cells either can’t produce interferon or respond to interferon signalling and therefore die.
What are nucleoside inhibitors?
Inhibit integration of nucleoside into DNA or RNA. Not specific for viral nucleic acid. Must be engineered to be specific for virally infected cells.
Acyclovir, gancyclovir, calacyclovir (anti-herpetics). Prodrugs activated by viral thymidine kinase enzyme
NRTIs (antiretrovials) - recognized specifically by RT enzyme
What are virus specific drugs?
Inhibit unique viral processes or proteins. Viral specificity achieved because drugs don’t interfere with normal cellular processes
Our bodies don’t have these processes or proteins so only targets virus.
What are examples of mechanisms of action of antiviral drugs?
M2 proton pump inhibitor - influenza M2 is required for acidification of the virus containing endosome following entry
HIV protease inhibitors - specific for viral protease. Important for virus lifecycle.
What are antifungal medications and how do they work?
Generally inhibit fungal cell wall synthesis - fungus specific
What are examples of antifungal drugs?
Polyene drugs competitively inhibits sterol synthesis
Axoles inhibit enzymes responsible for sterol synthesis
What are antiparasitic medications?
Generally inhibit parasitic metabolism, many mechanisms of action unknown
What are anti-folates?
Inhibit inhibit folic acid metabolism
Affect metabolism of pathogen and host cells
chemotherapy drugs
trimethoprim, pyrimethamine
What are imidazoles and imidazole derivatives?
Effective against many protozoal and helminthic infections
mechanism still unclear
What are antihelminthics?
Cause expulsion of worms by a variety of proposed mechanisms
Praziquantel
Mebandazole
Antimicrobial classification
Is not mutually exclusive - can have multiple mechanisms of action
ex. Mitronidazole is a imidazole derivative: antifungal, antibiotic, antiprotozoal
Who discovered penicillin?
Alexander fleming 1928
WWII Howard Florey and Ernst Chain isolated the active compound penicillin. Used to treat most bacterial infectious affecting soldiers. Widespread usage and misusage has led to emergence of penicillin resistance: bacterial beta-lactamases. 2nd and 3rd gen antibiotics resist beta-lactamases. Bacterial evolution leads growing resistance against 2nd and 3rd generation beta lactams
What was penicillin isolated from?
A fungus
What is isolated from chincona bark?
Quinine
Used as antimalarials
What is isolated from wormwood?
Artemisin
First line treatment for malaria
What is isolated from willow bark?
Salicylic acid
Anti-pyretic
What are the advantages of natural products over antimicrobial drugs for the treatment of infectious disease?
Occurs within the other compounds of the plant/microbe
etc??
What are emerging infections?
Includes new pathogens, drug-resistant pathogens, and bioweapons
What are the factors influencing emergence/re-emergence?
Human activity Microbial adaptation (environment, drug), antibiotic usage (human, industrial) climate change dam and irrigation systems bioterrorism public health infrastructure
eamples: syphilis, multi-drug resistant TB, in Alberta measles.
Where does increased antibiotic use come from?
Industrial process: agriculture, water/irrigation systems, commercial use
Allopathic medical practice: necessary evil, patient education, miseducation, and pressure, short term goals.
Where does antibiotic misuse come from?
Industrial processes: agriculture, water/irrigation systems, commercial use
Allopathic medical practice: compliance and complacency
What are some examples of drug resistant infections?
MRSA, VRSA (staph aureus) Vancomycin-resistant enterococci multidrug resistance TB HIV influenza A N. gonorrheae N. meningitidis Candida sp. P. falciparum (STIs hugely emerging drug resistant)
