P2 Clinical Science Foundations Exam 2 Part I

Front 1

Maintenance dose always depends on

Back 1

CL

Front 2

Css=

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Ro/CL

Front 3

Ave Css with conronic dosing always =

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(Dose*F*S/(t))/(CL)

Front 4

Maintenance dose=

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Css*CL*(t)

Front 5

Maintanace dsoe are also useful for Sustained release formulation=

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Css*Cl*t

Front 6

When the 1/2 life is 3 times greater than or equal to tau, then

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Css=Ro/Cl Cmax Min Cmin and Css are all the same

Front 7

Always pick a frequency around

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1/2 life

Front 8

How can a dose regimen be developed

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by targeting Cmax and Cmin

Front 9

How do you calculate the dosage interval

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t= ln(Cmax/Cmin)/K

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How do you determine what dose do be given

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CmaxSS=dose/V/(1-e-kt)

Front 11

What are 2 ways to calculate the loading dose

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1. Loading dose= maintance dose/(1-e-kt)
2. Loading dose= Css X Vol

Front 12

First dose Cmax =

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Dose(F)(S)/V

Front 13

SSCmax=

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Cmax/(1-e-kt)

Front 14

When we use first dose PK to predict SS PK we assume

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constant linear PK,

Front 15

Most often this is true, expect for

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auto-induction metabolism or saturable elimination

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Examples where constant linear PK does not work

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carbamezepine

Front 17

Not all patients have same PK--what factors affect CL and V

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age, lean body weight, obesity, genetics, administered drugs, genetics

Front 18

Volume tells us the "size of the tank" and it influences that time it takes

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to FILL the tank, and the time it takes to empty the tank

Front 19

Volume does NOT influence what

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AUC and Css

Front 20

Volume only inlfuences the SHAPE of the PK profile b/c

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it influences the TIME it takes to fill the tank and EMPTY The tank

Front 21

CL tells us what

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maintence dose will KEEP the tank full thus AUC and Css

Front 22

CL and Volume both affects

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Ke ,and half life

Front 23

CL only affects

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CSS, AUC and maintenece dose

Front 24

Volume only effects

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Loading dose (Conc Css desired * Volume

Front 25

CL is the funadmental DRUG removal process, and determinant of CSS and AUC, CL is most important for

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DOSE changes

Front 26

How does Renal CL in elderly change

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CL decreases in elderly

Front 27

If CL decreases in elderly, then what changes

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1/2 Life
AUC
Css
Mainence dose

Front 28

CL does not affect

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Volume or loading dose

Front 29

Liver function changes with aging as less predictable

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YES

Front 30

What happens to PHase I and Phase II enzymes in elderly

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Phase 1 enzymes activity decreases
Phase II realtively preserved

Front 31

What happens to the EXTENT of absroption in the elderly for drugs that undergo HIGH first-pass extraction

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MAY BE HIGHER

Front 32

The elederly may have increases drug sensititvty to what drugs

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benzodiazepines, warfarin, oral hypoglycemics, and anticholinergic drugs

Front 33

Why is the RATE of absroption either slower or smae in elderly

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the % of body weight lean muscle mass goes DOWN, and % fat does up so VD can icnrease or decrease

Front 34

Drugs taht distrbutes in lean muscle in elderly may have

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LOWER volume distribution

Front 35

If the drug distrubtes into fat in the elderly than what

Back 35

VD may increase

Front 36

What changes are predictable in the elderly

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CL-slow in elderly espically for renall eliminated drugs

Front 37

What changes are NOT predictable in elderly

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Hepatic CL, absroption and Volume distribution less predictable

Front 38

Lean body weight is usally

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postivielty correlated with CL as lean weight increases so does CL, and so does Volume

Front 39

The physiological basis is the liver/kideny are proptionally sized to the LEAN mass of the person, example

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large LEAN adult have 2lbs kidney
small LEAN adult 1 lbs kdineys

Front 40

What is the difference in maintenace doses between a pt with higer lean body weight, compared to lower lean body weight

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Higher lean body weight needs higher dose b/c has faster clearnace

Front 41

Lean body weight positively correclates with BOTH

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CL and Volume
larger lean weight, larger the Volume and CL

Front 42

Obesity is generally defined as >30%, and a BMI >

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30 is defined as obses

Front 43

Morbid obesity is defined as

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195% of ideal body weight (2x ideal body weieght

Front 44

Organ mass slight increase in obesity, but NOT proprtional to weight, how is renal clearnace affected

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Increased
GFR increase
Tubular secretion increases
Blood flow same
Reabsroption decrease
--overal renal clearnace increases

Front 45

The liver can be inflamed with fat so heapatic CL can be

Back 45

increased or decreases

Front 46

What is changes in phase I of obestity in liver

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CYP2E! is increase and 3A is decreases

Front 47

What is changes of Phase II in obesity

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Increases sulfation and increased glucuronidation

Front 48

Is absoprtion rate changed in obesity

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NO

Front 49

Overall how is volume affected in obesity

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VOLUME Is increase in obesity

Front 50

Drugs that distribute into fat may have

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much higher Volume in obesity (not universal cyclosporine)

Front 51

Why do drugs that distrubte into extraceullar water may also have increased Volume b/c

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there is genrally more extraceullar water in obesity

Front 52

Given that obese pts have a 3 fold large Volume what PK parameters would be changed

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T-1/2
Cmax Bolus (Co)
Loading dose
TIME to reach SS increased in obese

Front 53

Which is more pronounch in obesity CL or Volume

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Volume

Front 54

B/c Volume is more pronouched in Obesity, what are need for changes in

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loading doses and TIME to reach SS

Front 55

Some PK profiles have 2 phases called

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Alpha phase
Beta Phase

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What is the alpha phase AKA

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distriubtion phase

Front 57

What happens during the alpha phase

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STEEP DECLINE drug transfer from the vasculature into the tissue until equilibrium is reached

Front 58

What is the beta phase AKA

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terminal decline distribution is at equilibrium

Front 59

The beta phase is analaougs to

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one-compartment model

Front 60

We can use 1 comparemtne model except for drugs where significant elimination occurs during

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the dsitrubiton phase (methoorexate, lidocain, lithium

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When do we obtain blood samples in 2 compartment drugs

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AFTER disbution

Front 62

What is Vi

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is the inital volume immediately after distribution in smaller compartment and reaches rapid equilibrium

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Once equilibrium is reqch in Vi, then it distrbutes to Vt, which is

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is the tissue volume into which the drug distrubtes during the alpha phase

Front 64

What is the calculation for Loading dose in 2 compartment model

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Vi+Vt

Front 65

If the entiere loading dose is given during the Vi, what does this mean

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conc will be very HIGH

Front 66

If the entire loading dose is given during VI, conc will be very high this is bad for some drugs werhe the

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"effect side is in the VI tissue

Front 67

Digoxin is a 2 comparmen t drug where its effect site is the in tissue Vt, how can we administer the loading dose

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can be given during VI, but will be very high but does not cause toxicity b/c the conc has not eqiulbrated with the tissues

Front 68

Lidocaine is a 2 compartment drugs its effect site is in the Vi, how can we adminsiter the loading dose

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loadin dose will beed to be delivered SLOWLY or in small increments to ALLOW for distribution so levels will not get to high in Vi

Front 69

Drugs usually bind to proteins

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reversibly

Front 70

Reversible drug-protein binding implies that the forces that lead to the binding are

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hydrogen bonding or van der Wasl forces

Front 71

What are 2 main plasma proteins

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Albumin and A1 Acid glycoprotein

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Where are albumin and Alpha 1 acid glycoprotein synthesized

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by the liver

Front 73

What does Albumin maintain in the blood

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osmotic pressure of the blood

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What does albumin transport

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endogenous and exogenous substances (FFAs, biliruin, hormones, typrophan)

Front 75

What is most common plasma protein for acidic drug binding

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Albumin

Front 76

Clinically yo may encoutner conditions with albumin

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the REDUCE albumin, and reduced DRUG binding (seen in End stage renal and liver disease)

Front 77

Alpha 1 Acid Glycoprotien always transport substance in the blood but binds

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pirmarily basic drugs

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A1 Acid glycoprtoein is also an acute-phase reactant that

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increases with inflammation and trauma by 5x

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A1 Acid Glycoproin is NOT a common clinial lab like albumin, but clinically yo may encounter conditioants that

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increase AAH conc with increase binding

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Both endounesou and exogenous compounds can also bind to RBC's or

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erthrocytes

Front 81

Cyclosporine therapetic range for serum/plasma vs whole blood

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serum plasma 50-125ng/ml
whole bood 150-400

Front 82

Total plasma concenterations are measured clinicaly which is

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bound drug PLUS free drug

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The free plasma conc are considered

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pharamcologically acid

Front 84

Fraction unbound (FU)=

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unbound/(total)

Front 85

Total conc are indreict measure of free conc. when do we WORRY about varaiblity in protein binding

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Narrow Therapetic range
drug is highly protein bound

Front 86

Why dont we worry about protein binding if drug has WIDE therapeutic index

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b/c small to moderate varailbity in FU will not result in bid changes to cause toxicity or loss of effect

Front 87

Why dont we worry about small to moderate protein binding if FU is already

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big or >30%

Front 88

IN GENERAL If there is recued binding the TOTAL conc will decrease, but

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FREE conc will remain the same

Front 89

Typically with reduced bidning the total conc decreases, and fraction unbound INCREASES this is true for

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Low E drugs and High E drugs given ORALLY

Front 90

CL of low E and High E drugs given PO are rate limited by

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CLint X Fu,
so as fu so do clearance

Front 91

High E drugs given IV are ratelimited by

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BLOW flow to liver only

Front 92

For Low extraction drugs IV the higher the fraction unbound, the higer

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the CLearnace, and the higher the clearance the lower the Css(total) so Css unbound remains the same

Front 93

For Low extraction drugs ORAL the higer the FU the higher

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the CL, and the HIGHER the CL, the Lower the Total conc of drug so Fraction unbound remains the same

Front 94

As you increase Fraction unbound you Increase Cl, so what happens to Css (total)

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decreases---do the Css unbound remains the same

Front 95

ONLY exception to rule is HIGH extraction DRUGS IV, b.c

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CL is dependent on blood flow so Css (total) stays the same, but Css fraction unbound increases

Front 96

What are factors that increase VOLUME

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Decrease plasma protein binding
Increased tissue bidnign
Large tissue mass

Front 97

What are factors that decrease VOLUME

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Increased plasma protein binding
Decreases tissue binding
Small tissue mass

Front 98

Renal failure may decrease digoxin binding in tissue what would this do to digoxin loading loas

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Decreased Vd
so Decrease Loading dose

Front 99

Low extraction ratio drugs E<30% are rate liminted by

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FU X Clint

Front 100

High extraction ratio drug >70 are rate limited by

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Blood flow, so a change in FU will not affect CL

Front 101

Low extraction druat have a

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HIGH F or bioavailability

Front 102

F (bioavailability is =

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Q/ (CLint * fu)

Front 103

Unbound conc are only signifgant High Protein bound drugs with Narrow therapetic ranges and

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have high extraction ratio and IV