PHAR 6124

The following objectives are intended to be used as a general guide for focusing your studying for the midquarter examination. This is not all-inclusive but can be used as a general reference. Supplemental study guide materials may be distributed later in the course to augment this guide.

Please remember that you are responsible for mechanisms of action and resistance covered in-depth in Dr. Remmel's class.

This study guide is NOT intended to replace your notes, readings, lecture handouts. The purpose of this study guide is to assist you in focusing your studying efforts only.

PHARMACODYNAMICS

Understand:

Pharmacokinetics vs. Pharmacodynamics

Concentration-dependent killing vs. concentration-independent killing

Know which drugs are concentration-dependent killers and concentration-independent killers

MICs, MBCs, SITs, SBTs

Bacteriostatic

Bactericidal

Tolerance

Synergy

Antagonism

Importance of pharmacodynamic outcome predictors (best predictors for each antibiotic class)

AMINOGLYCOSIDES

Gentamicin, Tobramycin, Amikacin, Streptomycin

Concentration-dependent killing

Conventional dosing

Single daily dosing (rationale, Hartford Nomogram)

Know average half-life (approx. 2 hours), volume of distribution (0.25-0.35 L/kg)

Understand peak and trough levels (what levels are you trying to achieve)

Post-antibiotic effect

Toxicity: ototoxicity, nephrotoxicity

Complete computer tutorial modules 1 and 2

Dosing:

	Conventional dosing
	Single daily dosing

Pharmacokinetics:

Know how to calculate:

	LBW, dosing weight
	Creatinine clearance

Know how to determine:

	Predicted half-life based on population based data
	Determine appropriate starting dose, regimen for a patient

Aminoglycoside levels:

	Understand significance of 1st dose levels, 2nd dose levels, and steady-state levels
	Using logarithmic graph paper, determine patient-specific half-life
	Determine other patient-specific parameters: volume of distribution
	Recommend new dose, regimen based on desired peak/trough levels and patient data

Complete modules (AGI, AGII, AG kinetics tutorial, AG study guide, AG study guide 2)

MICROBIOLOGY

Understand chemical tests used to identify organisms:

Catalase

Coagulase

Indole

Glucose fermentation

Bile-Esculin test

6.5% sodium chloride

Oxidase test

Understand:

	E test
	MIC/MBC testing
	Exponential growth (bacterial curve growth)
	Stationary growth

Gram Positive:

Understand/Memorize flow chart

	Aerobic/anaerobic/facultative
	Cocci: Staphylococcus, Streptococcus, Enterococcus
	Bacilli: Listeria, Clostridium
	Differentiate types of hemolysis

Gram Negative:

Understand/memorize flow chart

	Aerobic/anaerobic/facultative
	Cocci: Neisseria, Moraxella
	Bacilli: Enterobacteriaceae group, Pseudomonas, Helicobacter pylori, Stenotrophomonas

Complete microbiology module

VANCOMYCIN

Understand:

Spectrum:

Gram positive

Pharmacokinetics:

	No oral absorption
	Expected half-life
	Volume of distribution
	Elimination: renal
	Concentration independent killer
	Biexponential decay
	One compartment vs. multicompartment modeling

Pharmacodynamics:

	Bactericidal/bacteriostatic
	Synergy with aminoglycosides/rifampin

Appropriate use: (CDC recommendations)

	MRSA/MRSE (present or suspected)
	PCN allergy
	PCN-resistant Strep. pneumoniae

Adverse Effects:

	Nephrotoxicity
	Ototoxicity
	Phlebitis
	Red Man Syndrome

Dosing/Monitoring:

10 mg/kg/dose (interval based on renal function)

Peak/trough levels:

Usually only monitor trough levels (5 to 10 mcg/mL)

Dosing in renal dysfunction/failure (increased half-life)

CDP controversy

Resistance:

	Vancomycin resistance enterococcus (VRE)
	Plasmid mediated
	Transfer to Staphylococcus (VISA/GISA)
	(See BACTERIAL RESISTANCE Lecture)

Complete vancomycin module

BACTERIAL RESISTANCE

Understand:

Different mechanisms of resistance

	Influx alterations: porin channel modification
	Environmental changes
	Transport changes
	Enzyme production: beta-lactamases
	Chromosomal vs. plasmid mediated
	Target alteration: penicillin binding alteration

Beta-Lactamases:

Mechanism of resistance

Chromosomally mediated, plasmid mediated

Induction: What organisms can be induced to produce beta-lactamases

Classification schemes: Richmond Sykes (esp. Type I/Type IIIs)

	H. influenzae: beta-lactamase producers (> 90%)
	Moraxella catarrhalis: beta-lactamase producers (> 90%)

Specific Antibiotic Destruction:

Aminoglycosides

Adenylation/Acetylation/Phosphorylation

Macrolides

	50s ribosome alteration
	Resistance to one, means resistance to all

Cephalosporins

Beta-lactamases

Penicillins

Penicillinases

Fluoroquinolones

DNA gyrase alteration

TMP/SMX

Metabolic bypass (folic acid)

Vancomycin

Metabolic bypass

Penicillin binding alteration:

PCN resistance Strep. pneumoniae

	Sensitive MIC less than or equal to 0.6 mg/L/ Nonsusceptible MIC 0.12 to 1.0 mg/L/Resistant greater than or equal to 2mg/L
	Prevalence
	Drugs of choice based on sensitivities

MRSA/MRSE

PBP-2

Enterococcus:

Mechanisms of resistance:

PBP (approx. 98%)

Tolerance

Beta-lactamase production: PCN resistance (approx. 2%)

High level gentamicin, streptomycin resistance

Vancomycin resistance (alteration of amino acid)

E. faecium > (vanco/ampicillin) resistance than E. faecalis

Van A, Van B, Van C

	Van A: high level resistance vanco/teicoplanin; transferable/inducible/transposon
	Van B: Moderate vanco resistance/susceptible teicoplanin; Chromosomal/transferable
	Van C: Low level resistance vanco/susceptible teicoplanin

Therapeutic options based on mode of resistance

H. fluenzae

	Mechanisms of resistance
	Prevalence

M. catarrhalis

	Mechanisms of resistance
	Prevalence

MACROLIDES (not lectured on, but may be included in the midquarter) (Erythromycin, Azithromycin, Clarithromycin, Dirithromycin, Roxithromycin)

Understand:

	Spectrum: Strep/H. flu/M. catarrhalis/H. pylori/Gr. A. Strep/Chlamydia/Legionella/Mycoplasma/ Mycobacterium
	Mechanism of action: binds 50s ribosome
	Bacteriostatic antibiotics