Pharm II exam Flashcards
definitive therapy
Once microbiology results have helped to identify the etiologic pathogen and/or antimicrobial susceptibility data are available, every attempt should be made to narrow the antibiotic spectrum. This is a critically important component of antibiotic therapy because it can reduce cost and toxicity and prevent the emergence of antimicrobial resistance in the community.
empiric therapy
Because microbiological results do not become available for 24 to 72 hours, initial therapy for infection is often empiric and guided by the clinical presentation. A common approach is to use broad-spectrum antimicrobial agents as initial empiric therapy with the intent to cover multiple possible pathogens commonly associated with the specific clinical syndrome.
normal flora
The normal flora are bacteria which are found in or on our bodies on a semi- permanent basis without causing disease.
colonization
The presence of bacteria on a body surface (like on the skin, mouth, intestines or airway) without causing disease in the person.
infection
The invasion and multiplication of microorganisms such as bacteria, viruses, and parasites that are not normally present within the body. An infection may cause no symptoms and be subclinical, or it may cause symptoms and be clinically apparent. An infection may remain localized, or it may spread through the blood or lymphatic vessels to become systemic (bodywide). Microorganisms that live naturally in the body are not considered infections. For example, bacteria that normally live within the mouth and intestine are not infections.
superinfection
- – a new infection occurring in a patient having a preexisting infection, such as bacterial superinfection in viral respiratory disease or infection of a chronic hepatitis B carrier with hepatitis D virus.
- –an infection following a previous infection, especially when caused by microorganisms that are resistant or have become resistant to the antibiotics used earlier
bactericidal
kill bacteria at drug serum levels achievable in the patient (more aggressive antimicrobial action)
bacteriostatic
bacteriostatic drugs arrest the growth and replication of bacteria at serum or urine levels achievable in the patient, thus limiting the spread of infection until the body’s immune system attacks, immobilizes, and eliminates the pathogen. If the drug is removed before the immune system has scavenged the organisms, enough viable organisms may remain to begin a second cycle of infection.
MIC
minimum inhibitory concentration - the lowest concentration of antibiotic that inhibits bacterial growth
MBC
minimum bactericidal concentration - the lowest concentration of antibiotic that kils 99.9% of bacteria
susceptible
The “susceptible” category implies that isolates are inhibited by the usually achievable concentrations of antimicrobial agent when the recommended dosage is used for the site of infection.
resistant
The “resistant” category implies that isolates are not inhibited by the usually achieveable concentrations of the agent with normal dosage schedules, and clinical efficacy of the agent against the isolate has not been reliably shown in treatment studies.
intermediate susceptibility
The “intermediate” category includes isolates with antimicrobial MICs that approach usually attainable blood and tissue levels and for which response rates may be lower than for susceptible isolates. The intermediate category implies clinical efficacy in body sites where the drugs are physiologically concentrated (e.g. quinolones and beta-lactams in urine) or when a higher than normal dosage of a drug can be used (e.g. betalactams).
sites with special accessibility factors to antibiotics (or lack of accessibility)
CNS: blood-brain barrier has tile-like endothelial cells with tight junctions; impede entry of all but small, lipophilic molecules. Note that when the brain becomes inflamed (e.g. meningitis), local permeability increases and some antibiotics can then enter the CSF in therapeutic amounts.
Prostate, vitreous body of eye: very difficult to get antibiotics here in therapeutic amounts
Which antibiotics are lipid-soluble and can penetrate into the CNS?
cloramphenicol
metronidazole
What are the patient factors that influence selection of antibiotic therapy? (6)
Immune system: antibiotics reduce the bacterial load but the host’s immune system must ultimately clear the infection - immunosuppressed individuals usually require higher-than-usual doses to eliminate infective organisms
Renal dysfunction: poor kidney function increases accumulation of antibiotics that would otherwise be eliminated
Hepatic dysfunction: erythromycin and tetracycline are concentrated or eliminated by the liver; use caution
Poor perfusion: decreased circulation to an area reduces the amount of antibiotic that reaches that area (e.g. diabetics/lower limbs)
Age: newborns have poorly developed renal/hepatic systems -> toxicity
Pregnancy: many antibiotics cross the placenta
Lactation: many antibiotics are present in breast milk
Name 3 anti-infectives that inhibit the CYP450 system.
Erythromycin
Sulfamethoxazole-Trimethoprim
indinavir/saquinavir
Cross-sensitivity/allergy risks between the beta-lactam antibiotics
- –Up to 10% of people with reaction (rash, anaphylaxis) to penicillin will have reaction to cephalosporin
- –Cross-reactivity is sometimes due to the beta-lactam ring, sometimes due to side chain moieties
- –Ampicillin and amoxicillin share side chains with cephalosporins, but not penicillin
Reasons for antibiotic failure
- Drug resistance
- Hypersensitivity
- Direct toxicity
- Superinfections
- Premature stoppage of administration
- Not the right drug
- Failure to reach MIC/MBC
Name 2 synergistic drug combinations and explain why they are synergistic.
Penicillins + clavulanic acid: penicillins have a beta lactam ring, and bacteria have beta lactamases. Clavulanic acid binds and inactivates the beta lactamases, which enables the pencillin to be more effective.
Aminoglycoside + vancomycin or penicillin: Vanco & penicillin create a leaky cell wall, which makes it easier for the AGs to get in to where the protein is being synthesized and interrupt it.
How do nucleoside analogs work to treat viral infection?
Nucleoside analogs are incorporated into a growing nucleic acid strand, but since they lack a 3’ OH, no further elongation will be possible, because all nucleic acid synthesis requires a 3’ OH site for adding the NEXT nucleotide.
Name 3 nucleoside analogs and what they treat.
acyclovir - Herpes simplex, varicella zoster
valacyclovir - prodrug of acyclovir
ribavirin - children with RSV
How do protease inhibitors work to treat viral infection?
In the late stages of viral assembly, viral proteases cleave polyproteins into viral proteins. Protease inhibitors prevent this cleavage and therefore inhibit the production of new infectious virus particles.
Name 2 protease inhibitors and what they treat.
indinavir - HIV
saquinavir - HIV
