Intro to Antibacterial Drugs Flashcards
What is a substance produced by micro-organisms to kill other micro-organisms or to protect from toxins produced by other micro-organisms?
antibiotics
What are the three ways that antibiotics are made?
- micro-organisms
2, precursor by microogranisms - semi-synthetic - synthetic
What type of antibiotics are from natural products and modified for pharmokinetic properities?
semi-synthetic antibiotics
“___” refers to life destroys life amongst lower species.
Antibiosis
Who noted that anthrax bacilli grew rapidly when introduced into sterile urine but failed to multiply and died if “common” bacteria were introduced at the same time?
pasteur and joubert (1877)
Explain the “magic bullet” theory by Paul Ehrlich? What did this lead to?
Chemotherapy - chemicals can kill bacteria.
Chemical affinity for human tissues which exert action against microbes - Salvarsan for syphillis (1909)
Led to the discovery of red dye with antibacterial action - Prontosil.
Sulfanilamide was found in ___ and kills streptococci. Penicillin was discovered in ___ and mass produced in ___.
1936; 1928; 1941
T/F. Most of the over 150 drugs in clinical use are semi-synthetic.
True.
What are the desirable pharmacologic properties of IDEAL antibacterial Drugs?
- Stability: PEN G (benzyl penicillin -1st- not suitable for stomach acid) vs PEN V (Phenoxy-benzyl penicillin - 1st semi-synthetic - stable in stomach)
- Solubility: sulfonamides - crystalluria (stay hydrated)
- Diffusibility - cross BBB if lipophilic (tetracyclines bind Ca2+ and stain teeth)
- Slow Excretion - protein binding/drug combinations
- High/Large Therapeutic Index - Selective
[TD50/ED/50] = higher ratio = safer/more selective
Explain how vancomycin is bacteriostatic and bactericidial.
- Cidal: vancomycin inhibits cell wall synthesis
- Static: increase resistance (need higher doses)
___ temporarily decreases most likely pathogens below critical level required to cause infection. Under what conditions is this given?
Prophylaxis
- prevent epidemic meningitis, bacterial endocarditis
- prosthetics
- transplants
- surgery (perioperative): gun shot wound, burns, colon surgery, other surgeries
T/F. One quarter to one half of antibacterial drug use is for empiric therapy.
False, One quarter to one half of antibacterial drug use is for prophylaxis.
What type of therapy is the initiation of treatment before etiology of infection is known with agents known to be effective against the most likely pathogen acquired (suspected from source of infection)?
empiric therapy
What does pathogen directed therapy involved?
identification of bacterial species (gram stain - crystal violet)
Gram ___ bac have many lactamases and a thick peptidoglycan of 50-100 layers. Gram ___ bacteria have few lactamases and a thin peptidoglycan of 1-2 layers.
postive; negative
Explain intrinsic mechanism of resistance vs acquired resistance.
Intrinsic - vancomycin is a large cyclic glycoprotein that is too big to get thru porin structure, therefore it is not effective against gram (-) bacteria
Acquired - Ciprofloxacin can kill gram (-) bacteria by using its porin to enter the cells. Acquired resistance is based on changes in the porin structure
How do you determine the antibiotic sensitivity?
Susceptibility-guided therapy
1. MIC (minimum inhibitory concentration) - lowest concentration of drug which completely inhibits growth for 24hrs
2. MBC (minimum bactericidal concentration) - lowest concentration of which no growth after transfer to no Ab medium
3. Disk Diffusion Assays (qualitative test) and E-test (quantitative test)
DDA - determines which Ab is best
E-test - pre-determined strip reads out MIC
T/F. Once sensitivity profile is known, choose effective drugs with the broadest spectrum of activity in order to avoid emergence of resistance micro-organisms.
False, Once sensitivity profile is known, choose effective drugs with the NARROWEST spectrum of activity in order to avoid emergence of resistance micro-organisms.
T/F. A consideration for antibacterial drug selection is the location of the infection because many agents don’t cross the BBB making it difficult to treat CNS infections.
True.
What are the pharmacokinetics of antibiotics?
[ADME + T] A: Absorption D: Distribution M: Metabolism - (prodrugs cause drug-drug interactions based on cyt p450 activation or inactivation) E: Excretion (ex: Penicillins for UTIs T: Toxicity
What are the three toxic side effects?
- nephrotoxicity
- ototoxicity
- hypersensitivity
What are anti-biograms?
antibiotic susceptibility data (resistance bacterial strains) reported in individual hospitals and/or medical centers
- emergence of different resistance strains in different locales (hospitals) depending on clinical use and/or natural selection
- resistance can determine 1) choice of drug 2) how much drug and 3) drug combinations
T/F. One consideration for antibacterial drug selection is virulence strains.
True, Group A Streptococcus killed Jim Henson of pneumonia
What host factors should be considered for antibacterial drug selection?
- patient age - distribution, renal, hepatic function vary
- allergy history - penicillin
- food, hydration effections on P-K, absorption, solubility, renal function - Ca2+ limits ciprofloxacin absorption by chelation (don’t take with milk)
- hepatic function
- pharmacogenetics - fast vs slow metabolism - acetylation of isoniazid: slow metabolizers lead to peripheral neuropathies
- pregnancy status - some agents are teratogenic (tetracyclines)
- immune status
