Tdm!!!!

Front 1

Coefficient Variation

Back 1

precision within a run and between runs of samples (ideally < 10%)

Front 2

Correlation Coefficient

Back 2

fit of linearity of measured v. actual concentrations (ideally > 0.95)

Front 3

Sensitivity

Back 3

the lowest value that may be precisely and accurately measures (+)

Front 4

CrCl Dose Adjustment

Back 4

< 60 modest, < 30 moderate, < 15 significant

Front 5

CrCl Calculation

Back 5

Urine collection, Cockcroft-Gault in adults, Schwartz in pediatrics, Jelliffe-Jelliffe in rapidly declining renal funx

Front 6

CrCl in Special Populations

Back 6

Decreased muscle mass (obesity, elderly) minimum set at 1 mg/dL

Front 7

Aminoglycoside Mechanism

Back 7

Bind 30S ribosomal subunit. PAE. Bactericidal G- and synergistic G+ (enterococcus and S. aureus)

Front 8

AG PK

Back 8

Concentration-dependent. Cmax correlated with efficacy. Measure pk 1 h after infusion

Front 9

AG Toxicity

Back 9

Indicated by troughs. Nephro: reversible, non-oliguric, monitor SCr, esp. in elderly, CHF, dehydration, RF, and concomitant nephrotoxins. Oto: irreversible, initially high frequency, monitor for hearing loss

Front 10

AG Vd

Back 10

Fluid status extremely important. ~0.3 normally, 0.2-0.25 in elderly or dehydrated, 0.35-0.5 in CHF

Front 11

EID vs. TD

Back 11

High peaks and low troughs. Cheap, convenient, rapid outcomes, reduced toxicity. Levels measured after 8-10 h and plotted on Hartford nomogram

Front 12

Vancomycin PK

Back 12

Time-dependent (AUC/MIC)

Front 13

Vanco Dosing

Back 13

15-20 mg/kg using ABW rounded to 250 mg increment. Dosing interval determined using CrCl via Matzke nomogram

Front 14

Vanco Dose Adjustment

Back 14

SS trough most practical marker of efficacy - draw within 30 mins of 4th dose. Goal: 10-20; pneumonia, bacteremia, endocarditis, osteomyelitis, meningitis 15-20. Adjust interval (4 h) or dose (100 or 250 mg)

Front 15

Vanco Toxicity

Back 15

Nephro associated with high troughs. Oto questionable, requires monitoring with concomitant ototoxins for N/V, HA, vertigo, nystagmus. Redman syndrome

Front 16

Theophylline PK

Back 16

Cl = 0.04, Vd = 0.5, t1/2 = 8 h

Front 17

Theo Dosage Forms

Back 17

Aminophylline S = 0.8, po dosing q 6 h. Theo po dosing bid, avail. as 100, 200, 300 mg tabs

Front 18

Theo Dosing

Back 18

LD (if needed) empirically 5 mg/kg. With prior exposure: (Vd * Cp) / (S * F). MD = 0.6 mg/kg/h OR using CL

Front 19

Theo Monitoring

Back 19

Therapeutic range: 5-15 mg/L. Check at 24 h and again at SS (~48 h). Linear adjustment

Front 20

Best Time to Collect Drug Sample

Back 20

Cmin - 30 mins before dose (AM)

Front 21

Fluctuation

Back 21

Greater for short half-lives (rapid metabolism [pediatrics], obese, burn pts)

Front 22

Minimizing Fluctuation

Back 22

ER DFs, more frequent dosing. Appropriate for drugs with short half-lives, rapid metabolism, NTI drugs, dose-related side effects

Front 23

Delayed Release

Back 23

Same elimination and similar absorption with delay. Increase BA and decrease AEs (esp GI)

Front 24

Phenytoin Dosing

Back 24

Loading dose (if needed) = 18 mg/kg. Vd = 0.7 L/kg. With prior exposure: Vd * desired change in Cp. Max. po 600 mg/dose. MD = 4-5 mg/kg/d, 5-15 in children

Front 25

Pheny Monitoring

Back 25

Therapeutic range: 10-20 mg/L. Monitor after 14 days at the earliest. Fospheny 1.5:1. Sodium pheny S = 0.9

Front 26

Pheny Metabolism

Back 26

Primarily 2C9, secondarily 2C19

Front 27

Pheny Adjustment

Back 27

Privitera < 7 warrants 100 mg/d increase, 7-12 increase 50 mg, > 12 no more than 30 mg increase. Graves-Cloyd appropriate when one dose-conc pair is available. Graphing preferred when possible

Front 28

Protein Binding Problem Populations

Back 28

Hypoalbuminemia (< 3.4 - malnutriiton, burns, elderly), RF, pregnancy, neonates, critical care, multiple highly protein-bound drugs

Front 29

Normalization of Pheny Concs

Back 29

RF: C/(0.1 * Alb + 0.1) and hypoalbuminemia C/(0.25 * Alb + 0.1)

Front 30

Child-Pugh

Back 30

A: 5-6, mild. B: 7-9, moderate. C: 10-15, severe

Front 31

Hepatic Decline

Back 31

Protein synthesis declines before detoxification

Front 32

Time Course of Induction/Inhibition

Back 32

Mechanism: alter amt or affinity for substrate. Half-life: max fx achieved at SS. Time of initiation and discontinuation

Front 33

1A2 Polymorphisms

Back 33

*1C Japanese. *1F increased activity in British and German (~30%)

Front 34

2C9 Polymorphisms

Back 34

*2 Euro (15%) and AAs (1%). *3 Euro (5%), Asians (2-4%), AAs (2%) - more profound

Front 35

2C19 Polymorphisms

Back 35

*22 Japanese (20%) and Whites (2-5%). *3 Vanatu (15%). *17 increased activity in Swedes + Ethiopians (20%), Jap (1%), Chinese (<1%)

Front 36

2D6 Polymorphisms

Back 36

*2xn ultra-rapid in Ethiopians + Saudis (10-15%), Whites (1-5%), Asians (< 1%). *10 Asian (10-51%), AA (5%), Whites (1-2%). *41 AA (10%), Whites (10%), Jap (3%) - codeine allergy

Front 37

TPMT

Back 37

Mutations more common in White, Ghana, Kenyan, AA pts. Less common in SW Asians, Japanese, Han

Front 38

Warfarin Metabolism

Back 38

S-isomer (active) 2C9* vs. R-isomer 3A4 > 1A2

Front 39

Warfarin Dosing and Patient Factors

Back 39

5-10 mg. Higher requirements for male, young, overweight, smokers. Lower requirements for liver disease and interacting medications (amiodarone, statins, TMP/SMZ, azoles). Blacks > Whites > Hispanics + Asians

Front 40

Monitoring

Back 40

Baseline prior. Inpatient daily or outpatient 2-3x/wk upon initiation. Then once weekly. Every 2 weeks. Every 4 weeks. Every 12 weeks if trustworthy. Within 7-10 days after dose change

Front 41

Supratherapeutic

Back 41

Decrease dose if > 3.5. Consider holding doses at 4.5. Phytonadione with active bleeding or at 10

Front 42

Subtherapeutic

Back 42

Increase dose if < 1.5. Consider LMWH or bolus

Front 43

Drug Interactions

Back 43

ABs, Antifungals, APAP, antiinflammatories, antiplatelets, antidepressants, amiodarone, alternative therapies. Preemptive dose reduction for amiodarone, TMP/SMZ, metronidazole. Inducers: pheny, carbamaze, phenobarb, rifampin, nafcillin, dicloxicillin, St. J. Vit K in MV

Front 44

Dietary Interactions

Back 44

Reduced dietary intake and some fruits increase INR

Front 45

Condition Interactions

Back 45

Liver disease, HF, hyperthyroidism, fever, diarrhea increase INR. Fever and stress -> variability

Front 46

Lifestyle Interactions

Back 46

Tobacco chronically increases INR. MJ and alcohol acutely increase INR

Front 47

Bioequivalency Studies Required For

Back 47

New products in comparison to brand only. For one strength. For NTI drugs. For BCS classes II-IV

Front 48

BCS Classes

Back 48

in vitro solubility + permeability. Class I high sol (< 250 mL) high perm (> 90%). Class II low sol high perm. Class III high sol low perm. Class IV low sol low perm

Front 49

PK Considerations

Back 49

Geometric mean and 90% CI must fall within 80-125% for Cmax and AUC

Front 50

NTI Drugs

Back 50

Reference variability < 10%: 90-111.11% range