AMDs Flashcards
6 groups of AMDs
Beta-lactams, aminoglycosides, tetracyclines, sulfonamides, macrolides, fluoroquinolones
Bacteriostatic to bactericidal
Can become bactericidal at high enough concentrations
Time-dependent AMDs
Efficacy is associated with the length of time the drug concentration stays above the MIC
Concentration-dependent AMDs
Efficacy depends on peak concentration
Relationship between resistance and use
Positive
Classes of antimicrobial sensitivity
Good, variable, moderate, resistance
Are bacteria the same level of sensitivity to all drugs
No!
AMD mechanisms
Damage membrane s inhibit cell wall synthesis, inhibit protein synthesis, inhibit folic acid synthesis, damage DNA
Serial dilution
Keep diluting drug concentration by 50% and then seed with standard amount of bacteria → let grow and assess for cloudiness of tubes
MIC
Concentration where there’s no visible growth but some bacteria may be alive
MBC
Concentration that sterilized the tube
Kirby-bauer test
Paper discs have different drugs and are placed on bacterial lawn to see zone of inhibition
Culture and sensitivity testing
Done for life-threatening infections, but takes a long time
Considerations when selecting drugs
Bacterial sensitivity, bacteriostatic versus bactericidal, adverse effects, distribution, and cost
Diseases w/ special considerations
Osteomyelitis, foreign bodies, abscess, intracellular pathogens, obstructed areas, immunodeficiency
Prophylactic uses of AMDs
High risk of infection after trauma, immune or anatomical defects, surgery
AMDs during surgery
Want to have adequate levels at the time of incision
Criteria for selecting AMDs
Spectrum, mechanism, adverse effects, distribution and elimination, line, cost, route of admin
Health Canada AMD drug categories
1,2,3, 4
Category 1
Very high importance to human health; life and death situation
Category 2
High importance; some alternatives available;drug of choice for serious infections
Category 3
Medium importance; not preferred for serious infections
Category 4
Low importance; not used in humans
Beta-lactams
Penicillins and cephalosporins
Beta-lactam ring
In beta-lactams, gives activity, susceptible to temperature changes
Beta-lactamases/penicillinases
Enzymes from some bacteria that destroy beta-lactams
Beta-lactam mechanism
Bind to and inactivate the transpeptidase enzyme that builds the cell wall → cell lysis
Types of penicillin
Narrow spectrum, penicillinase resistant, extended spectrum
Narrow-spectrum penicillin
Penicillin G
Penicillinase-resistant penicillin
Dicloxacillin
Extended spectrum penicillins
Ampicillin, amoxicillin
Targets of penicillin G
Gram positive aerobes, anaerobes
Pk of penicillin G
Not acid stable so it has to be given parenterally
Target of dicloxacillin
Penicillinase-producing staphylococci
Pk of dicloxacillin
Acid stable so it can be given orally!
Targets of amoxicillin
Gram positive aerobes, gram negative aerobes, and anaerobes
Pk of amoxicillin
Acid stable with a very high oral bioavailability
Potentiated penicillin
Amoxicillin plus clavulanic acid to resist penicillinases; make the penicillin second line treatment
Distribution of penicillins
Everywhere except CNS and prostate
Elimination of penicillins
Excreted unchanged in urine, mostly by active secretion
Resistance against penicillins
Gram-negative cell wall, acquired penicillinases
Adverse effects of penicillins
Hypersensitivity (don’t use topically), seizures
Cephalosporins
Type of beta-lactam with very similar mechanism of action, distribution, elimination, and adverse effects to penicillins
Are cephalosporins sensitive to penicillinases?
No, but they are sensitive to beta-lactamases
Cephalosporin generations
1,2,3,4
1st generation cephalosporins spectrum and acid stability
Identical spectrum to amoxicillin, not acid stable (most)
3rd generation cephalosporins spectrum
Less effective against gram positive aerobes and anaerobes, but more effective against gram negative aerobes; some can readily cross the BBB
Aminoglycosides uses
Systemic administration for dangerous gram-negative aerobes, or topical use
Most commonly used aminoglycoside
Gentamicin - highly ionized so isn’t absorbed orally or topically
Aminoglycoside mechanism of action
Irreversibly inhibit protein synthesis and cause production of wrong peptides that produce poring → lysis
Spectrum of aminoglycosides
Gram-negative aerobes, staph, mycoplasma
Types of resistance against aminoglycosides
Structural (entry requires oxygen-dependent transport so anaerobes are resistant), aminoglycosidases
Main adverse effects of aminoglycosides
Mephrotoxicity and ototoxicity
Nephrotoxicity from aminoglycosides
Every patient will have some renal damage but it usually isn’t a problem unless they are dehydrated, have renal disease, or are elderly
Washout period
Give single dose of aminoglycosides and let concentrations fall over the day
Ototoxicity from aminoglycosides
Damage to cranial nerve 8 and hair cells that can cause permanent, high-frequency hearing loss but the vestibular system is okay
Susceptibility to ototoxicity
Inherited susceptibility for severe hearing loss, most people will just have a little
Tetracycline mechanism of action
Reversible inhibit bacterial protein synthesis (bacteriostatic)
Tetracycline spectrum
Basically all atypical bacteria
Atypical bacterial infections
Rickettsia, chlamydia, mycoplasma
Tetracycline distribution
Water-soluble don’t readily enter cells or CNS, lipid-soluble (doxycycline) enters cells
Doxycycline
Lipid-soluble tetracycline important for intracellular pathogens
Tetracycline elimination
Water-soluble are excreted in urine and metabolized in liver, lipid-soluble are entirely metabolized in liver and secreted in bile
Resistance to tetracyclines
Efflux pump; can be overwhelmed by high topical doses
Adverse effects of tetracyclines
Renal damage, photosensitivity, incorporation into teeth and bones
What line are tetracyclines?
First!
Effectiveness of sulfonamides alone
Largely ineffective
Diaminopyrimidine inhibitors
Trimethoprim (TM)
Potentiated sulfonamides
Trimethoprim plus sulfonamides (TMS or co-trimoxazole)
Are sulfonamides bactericidal or bacteriostatic
Bactericidal
Mechanism of action of sulfonamides
Competitively Inhibit dihydropteroate synthetase, which helps synthesize folic acid from PABA
Mechanism of action of trimethoprim
Competitively inhibit dihydrofolate reductase, which helps synthesize topic acid later in the pathway
Why potentate sulfonamides are more effective
You competitively inhibit 2 of the enzymes in the pathway and resistance to both of these enzymes is less common
Why sulfonamides are ineffective with pus
Pus has a lot of PABA so they will be outcompeted
Spectrum of sulfonamides
Atypical bacteria; can also be used against lower UTI infections
Distribution of sulfonamides
To all tissues
Elimination of sulfonamides
Some excreted unchanged in urine, some metabolized in liver; metabolites accumulate in kidneys
Resistance to sulfonamides
Can acquire different dihydropteroate synthetase or dihydrofolate reductase enzymes
Adverse effects of sulfonamides
Hypersensitivity and renal damage
Most recent class of AMDs
Fluoroquinolones
Most common fluoroquinolone
Ciprofloxacin
Fluoroquinolone mechanism of action
Damage DNA by inhibiting DNA gyrases and topoisomerases
Spectrum of fluoroquinolones
Gram negative aerobes, staph, and some atypical (no anaerobes)
Pharmacokinetics of fluoroquinolones
Oral bioavailability ~100%, very long half-life, concentrates in lung, renal excretion
Adverse effects of fluoroquinolones
Severe cartilage damage, tendon rupture, reduction of seizure threshold, phototoxicity
Resistance to fluoroquinolones
Mutations in DNA gyrases and topoisomerases that stop fluoroquinolones from binding
Fluoroquinolone line
Only second
Macrolides mechanism of action
Inhibit protein synthesis reversibly
Pharmacokinetics of macrolides
Penetrate cells easily, concentrate in lung, older have very short half-life while newer have very long, erythromycin can inhibit p450 enzymes
Erythromycin
Oldest macrolide
Spectrum of erythromycin
Closest to broad spectrum: gram positive aerobes, anaerobes, some gram negative aerobes, some atypical
Spectrum of newer macrolides
Mostly gram negative aerobes, somewhat affects everything else (good for community-acquired bacterial pneumonia)
Macrolide resistance
Very effective macrolide efflux pump
Adverse effects of macrolides
Tissue irritation, vomiting because erythromycin stimulates motilin receptors
Divalent cations
Inhibit oral absorption of tetracyclines
Spectrum of chloramphenicol
Broad
Routes of admin of chloramphenicol
Basically all
Distribution of chloramphenicol
All except prostate
What tissue chloramphenicol penetrates best
Cornea
Major adverse effect of chloramphenicol
Fatal aplastic anemia
Mechanism of action of chloramphenicol
Inhibits protein synthesis (bacteriostatic)
When to use chloramphenicol
In fatal or crippling infections where there are no other options
