Pharmacology Antimicrobials

Pharmacokinetics
Influence of body on the drug
ADME
Absorption
Distribution
Metabolism
Excretion
***Time vs. plasma concentration

Pharmacodynamics
Drug action on the body/organism
Interaction with specific receptors
Anti-infectives target living cells other than our own (bacteria, protozoa, etc.)
***Plasma concentration vs. drug effect

Time vs. plasma concentration
Pharmacokinetics, ADME, influence of the body on the drug

Plasma concentration vs. effect
Pharmacodynamics, drug action on the body/organism

Cmax
Maximum concentration achieved by a drug in plasma
Peak on time vs. concentration graph (PK)

T 1/2
Half-life: time taken for the concentration of a drug to decrease to half

Vd
Apparent volume of distribution (based on how well the drug distributes, not based on an actual volume)

Cl
Clearance: amount of fluid clearance of a drug per unit time

Minimum inhibitory concentration
96-well plate
Two-fold serial dilution of the antibiotic
Incubated over night
MIC = lowest dilution that inhibits the growth (well is clear, not turbid)
Doesn’t indicate time***

Bacteriostatic vs bactericidal
Can’t determine by mechanism
Depends on achievable dose within a patient

Total drug vs free drug
Drug bound to plasma proteins isn’t functional

Pharmacokinetic parameters
Time vs. concentration
Peak serum level (Cmax)
Trough level (Cmin)
Area Under the serum concentration time Curve (AUC)

fCmax:MIC
***Concentration-dependent
Cmax divided by MIC
PK/PD index

fT>MIC
***Time-dependent
Time above MIC
Percentage of a dosage interval in which the serum level exceeds the MIC
PK/PD index

fAUC:MIC
***Concentration/Time-dependent
AUC / MIC
PK/PD index

Pharmacodynamic parameters
Time-dependence
Concentration-dependence
Persistent effects (includes PAE)

PAE
Persistent Antibiotic Effect: persistent suppression of bacterial growth following antibiotic exposure

Concentration-dependent ABX
Cmax:MIC
Killing of bacteria increases as concentration increases
Optimal killing at 8-10x the MIC
PAE occurs
Goal: maximize concentration (w/ safety in mind)
Aminoglycosides, daptomycin, fluoroquinolones

Time-dependent ABX
Time-dependent ABX
T>MIC
Killing of bacteria determined by length of time above MIC
No PAE
Goal: maximize TIME of exposure
Beta-lactams

Aminoglycosides ABX type?
Concentration-dependent
Cmax:MIC
Higher dose once daily gentamicin maximizes efficacy but does not increase toxicity

Daptomycin ABX type?
Concentration-dependent
Cmax:MIC

Fluoroquinolones ABX type?
Concentration-dependent
Cmax:MIC

Beta-lactams ABX type?
Time-dependent
T>MIC
Maximize T>MIC by increasing dose, duration of infusion, continuous infusion, frequency
For bactericidal effects, T>MIC:
-Cephalosporins 60-70%
-Penicillins 50%
-Carbapenems 40%

Time and concentration-dependent ABX
Time and concentration-dependent ABX
AUC/MIC
Killing determined by mixed properties
Moderate PAE
Goal: maximized total amount of drug/exposure
Vancomycin, tetracyclines, clindamycin
Target higher trough values

Vancomycin ABX type?
Time and concentration-dependent
AUC/MIC
Target higher trough values

Tetracyclines ABX type?
Time and concentration-dependent
AUC/MIC
Target higher trough values

Clindamycin
Time and concentration-dependent
AUC/MIC
Target higher trough values

PK/PD considerations for obese patients
Altered Vd
Altered glomerular filtration rate

PK/PD considerations for critically ill patients
Increased Vd b/c vasodilation, increased permeability, and IV fluids
Higher fraction of unbound drug
Augmented renal clearance

Antimicrobial stewardship
Multidisciplinary program that promotes the appropriate use of antimicrobials (including ABX), improves pt outcomes, reduces microbial resistance, and decreases the spread of infections cause by multidrug-resistant organisms

Make sure you know the learning objectives. Describe the pharmacokinetic parameters: clearance, apparent volume of distribution, bioavailability, and half-life. Explain how plasma drug concentration is dependent on the route and schedule of drug administration. Explain how plasma drug concentration in …

aka Biodisposition; The effects of biologic systems on drugs. It deals w/ the Absorption, Distribution, & Elimination of Drugs. Loading & Maintenance Doses can be calculated. What is Pharmacokinetics? What processes are involved? What can be calculated in Pharmacokinetics? The …

Define Half-Life t½ means half life – The time it takes for blood levels of drug to decrease to half of what it was at equilibrium. If maximum level is 16 mg and the half life is 2 hours, after …

What is CL (clearance) proportional to in first order kinetics? CL = kel * Vd Proportional to: elimination rate constant and the volume of distribution Meaning: as the rate of elimination goes up, the amount of clearance goes up as …

What is the equation for volume of distribution? Vd = Dose/Co Vd = volume of distribution Co = Conc. of drug in plasma at time zero. What is the equation for half-life of a drug? t1/2 = 0.7 x Vd/Cl …

Absorption refers to the movement of drug into the bloodstream, with the rate dependent on the physical characteristics of the drug and its formation. Refers to the passage of drug molecules from the site of administration into the circulation. Active …

David from Healtheappointments:

Hi there, would you like to get such a paper? How about receiving a customized one? Check it out https://goo.gl/chNgQy