Module G Flashcards
List the 4 classifications of antibiotic agents
- Cell wall synthesis inhibitors
- Protein synthesis inhibitors
- Nucleic acid synthesis inhibitors (antifolates, quinolones, etc.)
- Cell membrane synthesis inhibitors
Compare and contrast the actions of bacteri/fungicidal and bacteri/fungistatic agents
both types of agents are antimicrobial and inhibit the cellular processes of bacteria or fungi
bacteri/fungicidal agents kill the susceptible organisms and reduce the number of organisms in the body
bacteri/fungistatic agents inhibit growth of susceptible organisms so that their number remains constant after administration.
Explain why administration of bactericidal agent is usually preferable to a bacteristatic agent
Bactericidal agents kill the susceptible pathogen and rapidly reduce its numbers in the body. This leads to a more rapid resolution of symptoms, less dependence on immune function, and a lower likelihood of the pathogen developing resistance
Describe the advantages of narrow-spectrum drugs over broad spectrum, and explain when broad-spectrum drugs would be preferred
Narrow-spectrum drugs act on fewer microbes and are less likely to disturb the normally bodily flora, so they generally have fewer adverse effects.
Broad-spectrum drugs are preferable when there is a serious infection where the pathogenic organism haas not yet been identified.
Describe the metric used to define microbial sensitivity to a drug
Minimum Inhibitory Concentration (MIC) is the minimum concentration of a drug required to inhibit growth of a pathogen in a nutrient medium. The lower the MIC, the more sensitive the pathogen is to the drug
Describe the ways in which pathogens become resistant to drugs
- Innate resistance already exists when the pathogen is first exposed to the drug. ex: gram negative bacteria tend to be resistant to penicillins
- Acquired immunity can be through mutation/selection or transferrable resistance
- Mutation occurs randomly and is more likely to confer resistance to inappropriately managed infections (drug concentration too low, therapy terminated early, therapy too long).
- Transferrable resistance occurs when microbes exchange plasmids containing resistance-conferring genes. This leads to multidrug resistance
Describe factors important in selection of antimicrobial therapy
- Host Factors: Allergies, pregnancy, renal/hepatic failure, age
- Microbial Factors: If the organism is known, an appropriate narrow-spectrum antibiotic should be used. Empiric therapy may be initiated based o an educated guess of the pathogenic organism (based on knowing what organisms tend to cause which infections). Broad-spectrum antibiotics may be preferred in serious infections where the causative organism is unknown
- Pharmacokinetic factors: A drug should be selected that promotes compliance (easy dosing) and that maximizes concentration in the effected tissues
Describe combination drug therapy and compare its benefits to monotherapy
combination drug therapy is treatment with multiple antimicrobials. It is useful in mixed infections (more than one pathogen), in empiric therapy, or to take advantage of drug interactions (additive, synergistic, indifferent)
Monotherapy with a narrow-spectrum drug is preferred when the causative organism is known because it is less expensive and less likely to produce adverse reactions
Describe prophylactic use of antimicrobials
- not common any more because injudicious use of antimicrobials contributes to resistance-formation
- is used to prevent infections during invasive procedures
- is used to prevent disease transmission (malaria, TB, meningococcal infections
The structural difference between gram-positive and gram-negative bacteria is:
the presence of an outer trilaminar membrane in gram-negative bacteria. Lipopolysaccharrides in this outer membrane act as endotoxins
List the 4 classes of Beta-lactam antibiotics
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
The first type of antibiotic that was isolated and used to treat systemic bacterial infections is
Penicillins
Group the penicillins according to efficacy spectrum
Penicillin G and V are narrow-spectrum. Amoxycillin and ampicillin are extended-spectrum, having some activity against gram-negative (in addition to gram-positive) bacteria
Describe the most common form of resistance to penicillins
most commonly due to expression of penicillinase/beta-lactamase which cleaves the lactam ring
Describe the MOA of beta-lactam drugs
Penicillins bind to PBPs (penicillin binding proteins) irreversibly, inhibitng the cell’s ability to produce peptidoglycans for cell wall formation, causing cell death
The most common adverse reaction to penicillins is
allergic/anaphylactic reactions
Describe the role of beta-lactamase inhibitors in antimicrobial therapy and give an example
beta-lactamse inhibitors like clavulinic acid inhibit penicillinase/beta-lactamse and prevent the breakdown of the lactam ring, protecting the drugs from inactivation by resistant bacteria. They are often given as a mixed formulation with a beta-lactam drug and are especially useful against staphylococci (MRSA)
The largest and most widely used group of antibiotics is:
cephalosporins
Describe advantages of cephalosporins over penicillins
cephalosporins are less susceptible to degradation by beta-lactamase and have a broader spectrum (effective against both gram-positive and gram-negative bacteria).
Compare first-generation to later-generation cephalosporins
later generation cephalosporins generally are more effective against gram-negative bacteria and are less susceptible to beta-lactamase activity
Cephalosporins generally _____ (can / can not) be used in patients with mild allergic reactions to penicillins
Can
cephalosporins should be avoided in patients with confirmed anaphylactic reactions to penicillins
common adverse effects of cephalosporins are
- generally safe
- hypersensitivity reactions may occur, and there may be cross-sensitivity with penicillins
- may cause bleeding due to platelet dysfunction
Describe characteristics of carbepenem antibiotics
- beta-lactam antiobiotics
- broad spectrum against gram positive and gram negative bacteria
- resistant to many beta-lactamases
- IV-only
- generally used for serious, systemic, and multi-drug resistant infections
- may be combined with cilastin to extend duration of action
what is cilastin used for in antibiotic therapy
extends duration of action of some carbepenem antibiotics
patients that are allergic to penicillins ___ (may / may not) be treated with carbepenems
may not!
contrast this to cephalosporins which often can be administered to patients with mild penicillin allergies
Name a bacterial cell wall synthesis inhibitor that is not a beta-lactam
vancomycin
Describe the use of vancomycin in antibiotic therapy
- very effective against many gram-positive and some gram-negative bacteria
- Useful in treatment of antibiotic resistant bacteria (MRSA)
- most useful in treatment of skin infections
- Generally IV only
what is the significance of vancomycin resistance?
bacteria that are resistant to vancomycin are often resistant to all other common forms of antibiotics
Name three common classes of antibiotics that target bacterial protein synthesis
aminoglycosides, tetracyclines, and macrolides
Decribe the general mechanism of action of aminoglycosides and explain why they are bacterioselective in their action
aminoglycosides bind to the 30s ribosomal subunit and cause an incorrect amino acid insertion, leading to inhibition of protein formation. They do not interact with human ribosomes which have a 40s subunit instead of a 30s subunit
What class of bacteria are must susceptible to treatment with aminoglycosides
gram negative aerobic organisms
streptomycin is the first-line treatment for TB
What routes are available for administration of aminoglycosides
IV or topical
List common adverse effects of aminoglycoside (streptomycin, gentamycin, etc.) administration
ototoxicity and nephrotoxicity
Describe the spectrum and general clinical uses of tetracyclines
broad-spectrum bacteriostatic antibiotics
Generally used to manage infections by small pathogens (rickettsia, mycoplasma pneumonia, lyme disease spirochetes). May be used to treat severe acne
Common adverse reactions to tetracyclines include:
- discolouration of teeth
- increased skin sensitivity to light
- nephrotoxicity
- hepatotoxicity
Explain a reason why tetracycline resistance is increasing worldwide
heavy prophylactic use in agriculture
Describe common clinical uses of macrolides (erythromycin, azithromycin)
used in management of gram-positive upper respiratory infections and community acquired pneumonias
Explain why a patient with COPD may be prescribed macrolides
macrolides may be prescribed prophylactically if the patient is at risk of acute COPD exacerbation due to pneumonia
Describe common clinical uses of clindamycin and its classification as an antimicrobial
clindamycin is a uniquely-structured protein-synthesis inhibitor that does not belong to the tetracyclines, aminoglycosides, or macrolides.
It is important in the mangement of MRSA and penicillin-resistant bacteria
also useful in mangement of C. Perfrigens, the cause of gas gangrene.
Name the two main categories of nucleic acid sythesis inhibitors
Antifolates and fluoroquinolones
What are the two classes of antifolate antibiotics? How are they related?
sulfonamides (sulfa drugs) and trimethoprim
both classes inhibit folate metabolism, but at different steps in the pathway. They are often given together to produce a synergistic effects
What are the two classes of antifolate drugs and what are the most common adverse reactions to these drugs?
sulfonamides (sulfa drugs) and trimethoprim
the most common adverse effect is allergic reaction. Sulfa drugs can cause life-threatening skin reactions
What are two major advantages of fluoroquinolones?
- they have good broad-spectrum bactericidal activity
- they are well absorbed orally and can often be given once-a-day
fluoroquinolones can be identified by their generic names ending in:
-floxacin
ex: ciprofloxacin, levofloxacin, moxifloxacin
Describe how fluoroquinolones are commonly used and give an example of the class
- commonly used in empiric therapy due to their broad-spectrum efficacy and convenient pharmacokinetics
- Generally reserved for serious infections that are resistant to other drugs
- useful in UTI mangement due to high urine concentration
why should fluoroquinolones only be used in adult patients
due to the potential adverse effects of tendonitis and tendon rupture
Describe first and second line TB therapy
- 1st line: PIRE (Pyrazinamide, Isoniazid, Rifampin, Ethambutol)
- 2nd line: fluoroquinolones (cipro), amikacin, streptomycin
Describe difficulties with effectively treating TB
- Often present with long periods of inactivity encased in granulomatous tissue, hindering antimicrobial access to microbes
- Frequently incompletely eradicated so resistance rates are high
- Requires a long duration (6-9 months) of treatment to fully eradicate pathogen from body
Describe strategies for effectively managing TB
- aggressive management is required to kill bacteria rapidly
- Combination therapy is essential
- Patient isolation to limit disease transmission
- Therapy must continue long after signs disappear to ensure total eradication of pathogen
- DOT (directly observed therapy) is used to ensure compliance
Describe drug resistance in TB
drug resistant TB strains are grouped as MDR-TB and XDR-TB
MDR-TB (multi-drug resistant) strains are resistant to at least rifampin and isoniazid
XDR-TB (extreme-drug resistant) strains are resistant toisoniazid and rifampin as well as second-line drugs (fluoroquinolones, streptomycin, etc.)
List the three types of fungal infection
- superficial
- subcutaneous
- systemic
Most fungal infections are ___________, and predominantly occur in immunocompromised or debilitated patients
opportunistic
Most antifungal medications are effective against fungi and __________
protozoa
The prototype antifungal is _________, and is most often used for severe infections due to its toxicity
amphoteracin B
Compare nystatin to amphoteracin B for antifungal treatment
nystatin is only used for superficial infections whereas amphoteracin B is used for serious or systemic infections. Amphoteracin has higher toxicity than nystatin
Pentamidine is primarily used to treat:
pneumocystis pneumonia in HIV patients
The organism that is targeted by pentamidine is classified as a
fungus; pneumocystis carinii was previously believed to be a protozoan, but is now classified as a fungus
pentamidine may be given by which routes
parenterally or inhalational
antiviral therapy should be initiated _______ (before / after) signs of infection are present
before
briefly describe how antivirals that are used against Herpes viruses have their effect, and give examples
they generally act as nucleoside analogues, causing errors in viral replication. Examples are acyclovir and famciclovir
HIV is calssified as a ________
retrovirus
Define HAART and describe components of HAART
HAART = Highly Active AntiRetroviral Therapy
Usually composed of several NRTIs (nucleoside reverse transcriptase inhibtors) combined with a NNRTI
Describe how NRTIs like zidovudine or aziothymidine have their effect in HAART
they mimic viral nucleosides and terminate nucleic acid synthesis
NRTIs used in HAART have the common ending:
-dine
ex: zidovudine, aziothymidine
How do NNRTI protease inhibitors have their effect in HAART
they inhibit the action of HIV-1 protease which interferes with virion production. They are generally combined with 2 or more NRTIs
How is Tamivir used clinically?
used in treatment of influenza A and B to treat and prevent viral spreading. Usual care for influenza is prophylactic by influenza vaccine
Which forms of hepatitis can be treated by antiviral therapy?
Hepatitis B and C
Why are trimethoprim and sulfamethoxazole given together as combination therapy, and what infection are they specifically indicated for?
The two antifolates have synergistic effects if given together, turning them from bacteriostatic to bactericidal.
They are used to treat pneumocystis carinii pneumonia (PCP)
