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T/F: Active Absorption of most drugs are unchanged as patients get older
False - Passive absorption... not active
In terms of Drug Distribution, a Decrease in Muscle Mass can lead to __________________________
Decreased Vd for Water soluble drugs
In terms of Drug Distribution, a Decrease in Total body water can lead to __________________________
Decreased Vd for Water soluble drugs
In terms of Drug Distribution, an Increase in Body fat can lead to __________________________
Increased Vd for Fat soluble drugs
Decreased albumin = ______________________ free fraction = ______________________ drug to act on receptors
Increased; More
T/F: No dosing changes are needed when titrating Albumin to effect
True
In older patients, Bioavailability ___________________
Increases
T/F: Phase 2 Reaction activity are generally preserved with aging
True
Decreased renal mass & blood flow = ____________________ renal excretion of drugs
Decrease
Dose standardization for Pediatrics
Amoung per kg or per BSA
Gastric emptying and intestinal motility matures by ______________
4 months old
Neonates have ______________ pH compared to adults
higher
(acid labile drug would have greater bioavailability)
The ratio of TBSA:BM in infants is _____________ than adults
greater
Premature Infants have _____________ Total Body water % compared to Adults
higher
Premature Infants have _____________ Albumin Level compared to Adults
Lower
Drug distribution in neonates is directly related to ___________________________
gestational age
Pediatrics have ____________ Vd than adults
Higher
Neonates have ______________________ Metabolism until aged 1-5 where it ______________________. After puberty, it then ______________________
Decreased; Increases; Decreases
___________________________ have higher metabolism of theophylline (caffeine) than adults
Younger Children (peaks at 1-9 years)
By _______________, GFR of a child expectedly reaches above 100 mL/min
6 months
For Penicillins, Adults rely on _____________________ for elimination whereas Neonates ________________ is the major pathway for elimination
Tubular Secretion; GFR
Agents with Black Box warnings in kids
Atomoxetine,
Codeine,
Tramadol
(CYP2D6)
Children receiving Atomoxetine should have a dose ______________ to prevent _______________ who are ___________________________ for CYP2D6.
Decrease; Toxicity; Poor metabolizers
Codeine and Tramadol are a concern for Children who are __________________________.
Ultra-rapid metabolizers
Carboplatin is dosed based on
AUC
Agents that increase toxicity and reduce metabolism of Carboplatin
Fluorouracil,
Irinotecan,
Mercaptopurine,
Thioguanine
Calvert Equation
(CrCl/GFR + 25) * Target AUC
High dose = Methotrexate > ______________ gram/m2 IV
0.5
What agent is required for all patients receiving High Dose therapy of Methotexate?
Leucovorin
___________________________ is to be used only when Methotrexate level is > 1 mcmol/L plus evidence of delayed methotrexate clearance and kidney injury
Glucarpidase
Use sodium bicarbonate-based IV fluids and ensure alkalization of urine ______________ infusing methotrexate to prevent precipitation and to promote excretion of drug
before
Leucovorin dose adjustments are made based on ___________________________
methotrexate levels and creatinine trend
Busulfan pharmacokinetic analysis and subsequent dose adjustments help optimize dose to ______________________________________
maximize efficacy and minimize toxicity
In obesity, Delayed gastric emptying results in
Lower Cmax
In obesity, Absorption of oral med is increased with a fatty meal results in
Higher Cmax
T/F: IM injections administered instead of SubQ results in Higher Cmax
False - impact is unknown
A __________________ Vd implies the drug is distributed extensively to tissue
high
A __________________ Vd implies the drug is concentrated in the plasma
low
In obesity, Lipophilic medications are associated with higher Vd, which usually requires ___________________
TBW dosing
In obesity, Hydrophilic medications are associated with lower Vd, which usually requires ___________________
IBW or ABW (if TBW > 120% IBW)
In obesity, Aminoglycosides are primarily distributed through ECF... we should use ____________________
IBW/ABW (Decreased Vd if based on TBW)
In obesity, Vancomycin are primarily distributed through the tissues... we should use ____________________
TBW
Depleting Agents (lyses T cells)
Thymoglobulin, Alemtuzumab
Non-Depleting Agents (inhibits T cells)
Basiliximab
Primary Maintenance Immunosuppressants
Calcineurin Inhibitors,
Antimetabolites,
Corticosteroids
Adjuvant Maintenance Immunosuppressants
mTOR inhibitors,
Costimulation Blockers
Calcineurin Inhibitors
Tacrolimus, Cyclosporine
Tacrolimus Trough Goals Post Transplant
1-90 days:
90-365 days:
> 365 days:
1-90 days: 8-10 ng/mL
90-365 days: 6-8 ng/mL
> 365 days: 5-7 ng/mL
Antimetabolites
Mycophenolate,
Azathioprine
Mycophenolate is inhibited by
Cyclosporine (MRP2 transport protein inhibitor)
Azathioprine is an _______________________ inhibitor
Xanthine Oxidase (leads to myelosuppression and hepatotoxicity)
Azathioprine should test for _____________________ before administration
TPMT Deficiency
T/F: Mycophenolate is teratogenic and interacts with birth control
True
mTOR Inhibitors
Sirolimus, Everolimus
How should Antimetabolites be dosed?
based on side effects
How should Calcineurin Inhibitors be based on?
Based on Levels
mTOR inhibitors should be based on
Trough levels
Enzyme Inducers _________________ drug concentrations
Decrease
Enzyme Inhibitors _________________ drug concentrations
Increase
BBW of mTOR inhibitors?
Increased hepatic artery thrombosis or renal artery thrombosis
Costimulation blockers
Belatacept
When immunosuppressant agent may be used in Epstein Barr Virus positive patients only?
Costimulation Blockers (Belatacept)
SLED, EDD, PD, iHD are all examples of ______________________ therapy
Intermittent Renal Replacement Therapy
CVVH, CVVHD, CVVHDF, SCUF are all examples of ______________________ therapy
Continuous Renal Replacement Therapy
Which types of Dialysis are primarily seen in Inpatient or Outpatient?
iHD,
PD
(Everything else in ICU)
Which type of Dialysis is Simpler?
IRRT
Which type of Dialysis is Adjustable?
CRRT
Which type of Dialysis can lead to Hypotension/Electrolyte changes?
IRRT
Which type of Dialysis requires anticoagulant and can lead to Hypothermia?
CRRT
Drug Characteristics that ImpactDialysis Removal
Molecular Weight (Large molecules less cleared by dialysis),
Vd (Large Vd not easily removed),
Protein Binding (more bound, less cleared by dialysis),
Renal vs Non-Renal Clearance (<25% renal elimination may have little effect by dialysis)
Which Type of Dialysis is most effective?
CVVHDF
(CVVHDF > CVVHD > CVVH > PIRRT >= iHD)
Low flux
Smaller Pores
High Flux
Larger Surface area and pore size
- can lead to removal of larger drug molecules
Diffusion results in the movement of solutes from ____________________________
high to low concentration
Which Renal Replacement Therapies use Diffusion
iHD,
CVVHD,
PIRRT
Which Renal Replacement Therapies use Convection (Hemofiltration)
CVVH
Which type of Renal Replacement Therapy provides better removal of larger solutes?
Convection (CVVH does this)
Vancomycin is dependent on
AUC/MIC (should be 400 when treating MRSA)
Vanc dosing Goals for Non-invasive (blood infections)
Trough 4-5 times MIC
no lower than 10 mcg/mL
Vanc dosing Goals for Invasive (CNS, Lung, Bone infections)
8-10 times MIC
AUC/MIC 400 for MRSA
Nephrotoxicity Levels of Vanc
Troughs > 15 mcg/mL,
AUC > 800
When to Change the dose ONLY (no change in int)
Both Peak and Trough are Low (increase dose) or HIGH (decrease dose)
If Trough Low and Peak Normal
Shorten interval
If Trough High and Peak Normal
Lengthen Interval
If Trough High and Peak Low
Lengthen Interval and Increase dose
If Trough Low and Peak High
Shorten Interval and Decrease dose
Anti-Xa Therapeutic Levels
0.3-0.7 U/mL
Dalteparin Class
Low Molecular Weight Heparin
Enoxaparin Class
Low Molecular Weight Heparin
Dabigatran Class
Direct Thrombin Inhibitor
Argatroban Class
Direct Thrombin Inhibitor
Bivalirudin Class
Direct Thrombin Inhibitor
Apixaban Class
Anti-Xa
Rivaroxaban Class
Anti-Xa
Edoxaban Class
Anti-Xa
Fondaparinux class
Anti-Xa
Warfarin Class
Vitamin K Antagonist
Reversal Agent for Unfractionated Heparin
Protamine Sulfate
Low Molecular Weight Heparin Target Peak
0.5-1.1 IU/mL
Reversal Agent for Low Molecular Weight Heparin
Protamine Sulfate