Introduction to Antimicrobial Drugs Flashcards
How many cells are there in the human body and how many of those are human cells?
- Approx 100 trillion
- 1 in 10 are human
What amount of my total body weight is microbes?
1-3 lbs of your total body weight
How many bacterial genes are there vs. human genes?
3.3 million bacterial genes
22,000 human genes
For every Human Gene in your body there are how many microbial genes?
360
Define Antibiotic
A low molecular substance produced by a microorganism that inhibits or kills other microorganisms while (ideally) causing little or no damage to itself
Define Antimicrobial
Any substance of natural (ie, penicillin and alkaloids), semisynthetic (ie, methicillin and amoxicillin) or synthetic (ie, sulfonamides and quinolones) origin that kills or inhibits the growth of microorganisms while (ideally) causing little or no damage to the host
T/F all Antimicrobials are antibiotics
FALSE, but all antibiotics are antimicrobials
What is the broadest classification for antibiotics?
Which microorganisms the drugs are active against
Name 5 broad classifications for antibiotics
- Antiviral
- Antibacterial
- Antifungal (antimycotic)
- Antiprotozoal
- Antihelmintc
What are 4 ways that an antibiotic can be classified even further?
- The class and spectrum of microorganisms it effects:
- Bacterostatic vs. Bacterocidal
- Broad vs. Narrow Spectrum
- The biochemical pathway or target on the microorganism with which it interferes
- Chemical structure of the pharmacophore
- Pattern of activity (Type I, II, III)
- Type I: more concentration dependent
- Type II: More time dependent
- Type III: time dependency effects after the drug is removed
T/F A drug’s “spectrum of action” is synonymous with its “useful theraputic range”
FALSE
What type of drugs are active against a wide range of microorganisms?
Broad Spectrum
Describe the functional activity of Narrow spectrum antimicrobials
They have limited activity and are primarily only useful against particular species of microorganisms
What is something that may change the spectra of activity?
The acquisition of resistance genes
Give an example of an antimicrobial that is effective against all microbes.
Trick question, there isn’t one
What are some important clinical considerations before prescribing an antimicrobial therapy?
- Don’t use AMTs casually
- Is it really an infection? Is it benign and self-limiting?
- Is it a pathogen that calls for an antibacterial drug?
- Does patient’s health, medications or conditions put them at higher risk
- Don’t guess, Culture and test
- Is there an effective drug?
- Will the route get enough of the drug to the site of infection?
Define Spectrum of Action
The variety of pathogens against which an antibody has an effect
Define Useful Theraputic Range (index)
Ratio of toxicity to efficacy. The larger it is the safer the drug
**refers to either the dosage range or blood plasma or serum concentration usually expected to achieve desired therapeutic effects.
Name 5 questions to ask before deciding on the appropriate antimicrobial drug?
- Is it the MOST EFFECTIVE and LEAST TOXIC?
- Does it have the NARROWEST SPECTRUM?
- Is it the LEAST EXPENSIVE?
- Will it EXACERBATE the patient’s existing pathologies?
- Does it take into account the patient’s IMMUNE STATUS?
T/F Treatment should be started alone before the collection of specimens and before cultures have been started
FALSE
What are some exceptions to collecting specimens and starting cultures before treatment?
If the infection:
- Is recognizable by characteristic signs/symptoms?
- Can it be assessed by rapid test
- Culture to confirm
What doe MIC stand for and what is it?
Minimum Inhibitory Concentration
It is the lowest concentration of an antibiotic that will inhibit the growth of a bacterial strain
What is the Disc Diffusion test?
Antibiotic diffuses out of a disk placed on the surface of the agar. If bacteria are sensitive to the antibiotic, then a zone of growth inhibition forms around the disk after incubation.
**The Zone size depends on several factors and two methods area available to control this process, comparative disk testing (both test and control organism on same plate), and standardized disk testing
What does MBC stand for and what is it?
Minimum Bacterial Concentration
It is the lowest concentration of an antibiotic that will kill a bacterial strain
What is a Broth Dilution Test?
Determines both the MIC and MBC
How do the MIC and MBC values differ in Bactericidal and Bacteristatic drugs?
Bactericidal antibiotics usually have very similar MIC and MBC values
Bacteristatic antibiotics have much higher (if any) MBC than MIC values
What is the difference between Prophylactic and a Definitive Antimicrobial Treatment?
Successful identification of the infective pathogen
What is Prophylactic Treatment?
medication or a treatment designed and used to prevent a disease from occurring.
**Treatment in the absence of infection
What is Definitive Treatment?
The treatment plan for a disease or disorder that has been chosen as the best one for a patient after all other choices have been considered.
**Pathogen has been isolated
Define Pharmacokinetics
The relationship of the time course of drug absorption, distribution, metabolism, and excretion (ADME)
**What the body does to the drug
Define Pharmacodynamics
The relationship of the drug concentration at the site of action and the resulting effects, including the time course and intensity of therapeutic and adverse effects
**What the drug does to the body (efficacy, toxicity)
What is important to keep in mind about the comparison between MIC and plasma concentrations?
That although MIC is compared to plasma concentrations, these concentrations may or may not reflect drug concentration at the site of infection
What effects can the site of infection have on the ATM?
Pus or hemoglobin at the site of infection can bind to and thus inactivate some AMTs
What are the 2 goals of ATM doses?
- Achieve a bactericidal concentration at the site
2. Discourage emergence of resistant bacteriai
What phase of bacterial growth is most sensitive to antimicrobial intervention?
Log phase
Define Bactericidal and Bacteriostatic
Bactericidal: Antibiotics kill bacteria
Bacteriostatic: antibiotics stop bacteria from growing or reproducing
What are 3 pharmacodynamic (PD?) properties of antibiotics that best describe activity?
- Concentration dependence
- Time-Dependence
- Time-dependence with persistent effects
What does PAE stand for and what does it mean?
- Persistent Post-Antibiotic Effect
- Providing suppression of bacterial growth following antibiotic exposure. (Delayed regrowth of the bacteria after complete removal of an antibiotic allow less frequent dosing than with agents with no PAE)
What are the goals of therapy for Type I, II, and III drugs respectively?
- Maximize concentrations
- Maximize duration of exposure
- Maximize amount of a drug
What are the key rules for treating serious infections?
- Begin treatment ASAP (should still culture)
- use the safest effective drug
- use the largest reasonable dose
- Monitor the plasma concentration of antibiotic if it is needed to guide dose or to avoid toxicity
- Mus continue treatment at least two days past apparent “cure” but some infections require much longer.
- CNS infections (site with limited drug access): 6-8 weeks
- Malaria: 8-10 weeks
- TB: 6-12 months
Why is selectivity a valuable thing in a drug?
- It means selective toxicity towards the pathogen rather than the host
- When selectivity is high, the risk of adverse effects are reduced
What defines ideal Antimicrobial therapy?
Its specificity of action in host vs. bacteria
Many, but not all adverse effects are ___-__________
Dose-Dependent
What are the two categories for adverse effects of a drug?
- Adverse effects ANALOGOUS to antimicrobial action
- an effect on human cells resulting from the same mechanism as the antimicrobial effect
- Adverse effects INDEPENDENT of antimicrobial action
- Irritation, allergy, etc.
Describe importance and factors of absorption of a drug
- Absorption critically determines the compound’s bioavailability
- Route of administration is an important consideration
What are some factors regarding distribution of a drug?
- Will it pass the blood-brain-barrier?
- Is it lipid soluble or water soluble?
- Is there systemic inflammation?
- In cases of CNS inflammation, brain capillaries ares o leaky dose-adjustment may be required
- Some antibiotics leave the brain by active transport via choroid plexus
Describe Metabolism of a drug
- Usual routes of clearance are through the liver and kidneys
- Drugs begin to break down to metabolites as soon as they enter the body usually via liver redox enzymes, termed Cyt. P450 enzymes
- Metabolites may also be pharmacologically active, sometimes more so than the parent drug
- Inactivation can happen by bacterial enzymes
Describe the excretion of a drug
- Low potency drugs are often used for UTI’s since they concentrate in urine because their resorption is so low
- Other UTI drugs concentrate by active transport into urine
Name the 4 broad mechanisms of action for ATMs
Inhibition of:
- Cell wall synthesis and cell membrane function/permeability
- Protein synthesis
- Inhibits 50s and 30s ribosomal subunits
- Metabolic pathways
- Folic acid
- Nucleic acid synthesis
- DNA
- RNA
Why would you use combination therapy?
- For treatment of inherently mixed infections
- To improve efficacy
- For initial empiric therapy of uncharacterized serious infection
- To enable use of lower drug concentrations
- To delay emergence of resistance by avoiding the selection of naturally occurring drug-resistance mutants
**Combinations are effective so long as they are not antagonistic, not all combinations increase efficacy
What is a superinfection?
The overgrowth of pathogens resulting from use of antimicrobial drugs
**The larger the disruption of the microbiome, the greater the opportunity for pathogens to overgrow
When was the last time that a new class of antibiotics was introduced?
1987
What types of drugs would qualify a drug under the GAIN act?
Drugs that treat:
- Drug-resistant infections Gram + pathogens
- Multidrug resistant Gram - bacteria
- Multidrug resistant TB
- Any other WHO defined drug-resistant public health threat
Name 6 patient-related factors to consider before prescribing Antimicrobial drugs
- Age
- Sex (pregnant, lactating)
- Weight, allergies
- Genetic factors
- Renal and hepatic function
- Concurrent medications
What determines the rate of effect of a drug?
- Length of time necessary to kill bacteria
2. effect of increasing concentrations
