PK Exam 1 Considerations

Square root of height times ABW divided by 3600

What is the Mosteller BSA equation?

Is not

The kinetics of chemotherapy in obese patients (is/is not) significant enough to warrant a change in the way we dose.

Actual

Is actual, ideal, or adjusted body weight typically used in dosing chemotherapy, even in obesity?

GFR

The Calvert equation (AUC dosing) is used for carboplatin because the renal clearance of the drug is directly related to ____. This dosing allows for individualized dosing within patient's TI.

Increase, increase

As the target AUC increase, the carboplatin dose will (increase/decrease). As GFR increases, the carboplatin dose will (increase/decrease).

Toxicity, undertreatment

Without using the Calvert equation for carboplatin dosing to account for GFR, the dose may be too high, risking ____, or it may be too low, risking ____.

Overdosing, subtherapeutic

AUC dosing in carboplatin prevents ____ in patients with impaired renal function. AUC dosing also avoids ____ dosing in patients with high renal clearance.

125 ml/min

What is the maximum GFR that avoids toxicity from overdosing and estimates normal renal function?

900, 600, 300

Carboplatin target AUC of 6 max dose is ____. Target AUC 4 max dose is ____. Target AUC 2 max dose is ____.

Adjusted, overdose

For carboplatin doses, consider using ____ body weight for overweight patients (BMI > 25) to avoid (undertreatment/overdose).

45.5 or 50 + 2.3 x (each inch over 5')

Adjusted body weight equation and CCG equation use IBW. What is the equation for that?

1.5, overdose, 10, undertreatment

Carboplatin dosing should always be recalculated if patients SCr > ____ x ULN because it could lead to (undertreatment/overdose). It should also be recalculated if there is a ____% weight change because it could lead to (undertreatment/overdose).

0.7

What is the minimum SCr used in CrCl to calculate carboplatin dose?

Actual

When dosing carboplatin, if the actual (total) body weight is less than the ideal body weight, which weight do you use?

Decrease, increase, decrease, decreased, decrease, increase, decrease

Renal dysfunction ADME changes:

1. GI absorption may (increase/decrease) due to uremia

2. Vd may (increase/decrease) due to edema

3. Plasma protein binding may (increase/decrease) due to (increased/decreased) albumin

4. Hepatic clearance may (increase/decrease)

5. Free drug available for hepatic metabolism may (increase/decrease)

6. Excretion may (increase/decrease)

Both, increase, decrease, decrease, both, increased

Hepatic dysfunction ADME changes:

1. GI absorption may (increase/decrease/both)

2. Vd may (increase/decrease) due to ascites or (increase/decrease) due to sarcopenia

3. (Increase/decrease) in plasma protein binding due to decreased albumin

4. First-pass may (increase/decrease/both)

5. Impaired biliary excretion may lead to (increased/decreased) serum drug [ ]

Renal, hepatic

(Renal/hepatic) dose adjustments are available in PI while (renal/hepatic) dose adjustments are rare in PI.

GFR

Equations such as CKD-EPI (more accurate) and MDRD estimate ____ which approximates total clearance.

Good

MDRD doesn't perform well in patients with really (good/bad) renal function.

CrCl, GFR

Cockcroft-Gault is used to estimate ____ which correlates approximately with ____.

Elderly, weight, was not

Cockcroft-Gault is more inaccurate in the ____ (underestimation) and those at extremes of ____ (overestimation). The population used to develop is (was/was not) very diverse, so it is not the most accurate.

De-indexed

When using an eGFR equation like CKD-EPI for drug dosing, the result should be ____-____ because low or high BSA will affect the results.

Actual BW, adjusted BW, ideal BW

For CCG, if actual BW < ideal BW, use ____. If actual BW > 1.2 x ideal BW, use ____. Otherwise, use ____.

IBW + [(ABW - IBW) x 0.4]

What is the equation for adjusted BW?

Clinical judgement

When dosing in renal and hepatic impairment, nothing replaces ____ ____ and consideration of the patient as whole.

0, overdose

When SCr doubles in 24 hours, true GFR is expected to be close to ____ mL/min, likely causing an (underdose/overdose).

120, underdose

eCrCl underestimates GFR when SCr is falling. True GFR may be close to ____ mL/min, likely causing an (underdose/overdose).

Initial

Liver dysfunction cannot be clearly calculated, but the Child-Pugh score can provide information that may help guide ____ dosing in patients.

Max adult dose

Most institutions use mg/kg dosing until kid is up to 50kg, not surpassing what dose?

Low, elevated, low, 24 hours

Premature neonates have (low/high) gastric acid secretion, resulting in (reduced/elevated) pH. Full term neonates have (low/high) gastric acid secretion at birth, resulting in pH from 6-8 that declines to 1-3 within ____ ____ of birth.

Stability, ionization, absorption

The change in pH (elevated) in neonates directly affects both the ____ and the degree of ____ of a drug. This influences drug available for ____.

Better, lower

Due to the pH elevations in neonates, acid-labile drugs (broken down by acid) like penicillin G are (better/worse) absorbed. This may result in a (lower/higher) dosing per kg.

Decreased, higher

Due to pH elevations in neonates, weak organic acid drugs like phenobarbital have (increased/decreased) BA. This may result in (lower/higher) dosing per kg.

Increased, decreased, rate

There is (increased/decreased) gastric emptying in the first week of life, but overall (increased/decreased) during infancy. Gastric emptying determines the ____ of drug absorption.

Onset, stack, toxicity

Due to peds delayed gastric emptying and delayed absorption, there can be delayed ____ and/or adverse effects. It is important not to ____ dosing with sedation/pain meds and BP meds because it can lead to ____.

1/2, formula

PO/gastric route should only be used in neonates once they are able to tolerate ____ to full feeds. (Formula/breastmilk) takes twice the time to transit the stomach compared to the other.

Decreased, amount, increased

Infants have (increased/decreased) GI motility until they are about 4 months old. This means that the ____ of drug absorbed may be (increased/decreased).

Rate, amount

Gastric emptying corresponds with (amount/rate) of drug absorption while GI motility corresponds with the (amount/rate) of drug absorption.

Decreased

Neonates have decreased pancreatic enzymes (amylase, lipase, protease) and bile salts which leads to (increased/decreased) absorption of lipid-soluble drugs.

Decrease

Neonates GI blood flow and surface area is decreased, which will (increase/decrease) absorption.

Increased, thinner, perfusion

Percutaneous absorption is (increased/decreased) in neonates and infants due to (thinner/thicker) stratum corneum, greater ____ and hydration, and larger ratio of BSA to body mass.

Perfusion, contractions, is not

Premature neonates have poor ____ to muscles, peripheral vasomotor instability, and insufficient muscular ____, so IM absorption is altered. IM (is/is not) recommended except in an emergency.

Reliable, if there is a tear in rectum the bacteria in the tear will be introduced to the system

Rectal absorption in neonates is usually (reliable/unreliable). Suppositories however are not good for IC patients like preemies. Why is this?

Higher, more, wider

Infants have a (lower/higher) water content than adults. To get the same [ ], you have to give (less/more) mg/kg of the drug to the infant because there is (narrower/wider) distribution.

Decreased, capacity, affinity, competition, free

Binding of drugs to plasma proteins is decreased in newborns due to (increased/decreased) plasma protein [ ], lower binding ____ of protein, decreased ____ of proteins for drug binding, and ____ for certain binding sites. All of this leads to more ____ drug, so possibly higher effect.

Quality, quantity

Protein binding in newborn distribution is a ____ and ____ problem.

Free, bilirubin, ceftriaxone and sulfamethoxazole

In newborns, ____ levels for highly protein bound meds should be checked. Medications that compete with ____ for albumin binding sites should be avoided in neonates to avoid kernicterus. What two drugs are these?

Immature

Both metabolism and elimination are (immature/mature) at birth.

Chloramphenicol, gray baby

Glucuronidation matures at ~3 years of age. Because of this, accumulation will occur when giving infants ____ if doses are not reduced. This results in ____ ____ syndrome from toxic levels.

APAP

Sulfation matures to adult levels at birth. Because of this, ____ is safe in infants and they are less susceptible to toxicity.

Theophylline

Methylation is present in infants but not in adults, so ____ is metabolized to caffeine.

Gasping syndrome, preservatives, midazolam

Alcohol dehydrogenase does not mature until 5 years old, so ____ ____ can occur from accumulation of benzyl alcohol ____ in neonates. What is a drug example of this?

Age

Due to the differences in renal elimination throughout development, treatment regimens should be individualized in an ____-appropriate fashion for renally excreted drugs.

Decreased, increased, decreased, decreased

In kidney disease, absorption either remains the same or is ____, distribution is ____, metabolism is ____, and clearance is ____.

Diffusion, convection

The main method of drug removal by dialysis is ____, especially for small molecules. For larger solute, ____ is the method of removal.

25

Dose adjustments are needed if dialysis clearance accounts for ____% or more of total drug clearance.

Intermittent, diffusion, intermediate

Hemodialysis (HD) is (intermittent/continuous). It is used in ESKD and AKI. Its primary method of drug removal is (diffusion/convection), and it has the (most/intermediate/least) efficiency.

Continuously, convection, diffusion, most

Continuous RRT (CRRT) is (intermittently/continuously) used in the ICU for AKI. Its primary method of drug removal is ____ but it may add ____. It has the (most/intermediate/least) efficiency.

Continuous, diffusion, least

Peritoneal dialysis (PD) is (intermittent/continuous) and used for ESKD. Its primary method of drug removal is (diffusion/convection). It has the (most/intermediate/least) efficiency.

Less, more, less

Drug factors affect drug removal by dialysis. If there is wide distribution into the tissues, it will be (more/less) cleared. If it is mostly distributed in the vascular, there will be (more/less) clearance. If it is highly protein bound, (more/less) of it will be removed.

Do not, SCr

With KRT, (do/do not) adjust drug doses based on estimates of renal function (CrCl, GFR). These equations assume stable ____ and do not apply with RRT.

5000, 80, 1

Criteria for drug removal by hemodialysis:

1. MW < ____ g/mol

2. Protein binding < ____%

3. Vd < ____ L/kg

Maintenance, post-HD, after

When dosing drugs with PD target Cmin > MIC (time-dependent, b-lactams), patient is given intermittent ____ dose until HD. After dialysis, a ____-____ dose is given to replace drug lost by HD. Schedule doses that are due on HD days (before/after) HD.

Loading, peak

When dosing concentration-dependent drugs (aminoglycosides), a ____ dose is given. Remaining renal function will eliminate some of this before HD, then a post-HD dose will be given to get [ ] back to the ____.

5000, unbound

CRRT criteria for drug removal:

MW < ____ g/mol

Only ____ drugs removed

Output

CRRT ____ is important for drug dosing and will be given on the drug order. It ranges from 1-2 L/hour and affects how much drug is cleared.

Adds

If Cl CRRTmax > 25% of patient's residual clearance, CRRT (adds/removes) significantly to the drug's elimination and requires dose adjustments.

Decrease, increase, decrease

If CRRT is interrupted, clearance will (increase/decrease) while t1/2 and Css ave will (increase/decrease). May need to (increase/decrease) the dose.

Increase, decrease, increase

If CRRT output is increased, clearance will (increase/decrease) while t1/2 and Css ave will (increase/decrease). May need to (increase/decrease) the dose.

Inverse

Peritoneal dialysis (PD) generally has limited drug clearance. There is a (direct/inverse) relationship between PD drug clearance and MW, Vd, and extent of protein binding.

Increased, increased

PD variables affecting drug clearance:

1. Volume of dialysate - more fluid means (increased/decreased) drug clearance

2. Dwell time - more dwell time/increased exchanges means (increased/decreased) drug clearance

Will not

High MW drug removal (will/will not) be affected by shorter dwell times/increased exchanges.

10-15

Drug dosing recommendations for patients on PD typically follow drug recommendations for patients with CrCl ____-____ mL/min.

ABX

Patients with PD catheters are at high risk of peritoneal infections, so ____ can be added to dialysate fluid for treatment (using process in reverse).

18.5, 18.5, 25, 25, 30, 30, 35, 35, 40, 40

BMI classifications:

Underweight BMI < ____

Healthy BMI ____ to < ____

Overweight BMI ____ to < ____

Obesity class 1 BMI ____ to < ____

Obesity class 2 BMI ____ to < ____

Obesity class 3 BMI >/= ____

Stays the same, increase, increase, increase

PK changes in obesity:

Absorption may (increase/decrease/stays the same)

Distribution may (Increase/decrease/stays the same)

Metabolism may (Increase/decrease/stays the same)

Clearance may (Increase/decrease/stays the same)

Increased, 2

In obesity, highly lipophilic meds with have an (increased/decreased) Vd. Highly lipophilic meds are those with a log p > ____.

Hepatic, renal

(Renal/hepatic) elimination and metabolism may either increase or stay the same in obesity, while (renal/hepatic) elimination and metabolism will increase.

No

If the patient's weight doubles, will the Vd and Cl double?

Is not, underestimate, lean, total

BMI (is/is not) routinely used for drug dosing. IBW may (underestimate/overestimate) dosing in obesity. ____ body weight accounts for fat in cells, marrow, and CNS but is complicated to calculate. ____ body weight for dosing assumes PK increases linearly with weight.

Higher

Highly lipophilic and high Vd drugs favor (lower/higher) dosing weights.

Lower

Small Vd and hydrophilic drugs favor (lower/higher) dosing weights.

Titrating, frequent, capping

When dosing in obesity, consider ____ to effect, small and ____ doses, or ____ the dose.

De-indexed

If using eGFR to estimate renal function in obesity, the values need to be ____-____ to true BSA.

Adjusted BW

When using CrCl to estimate renal function in obesity, what is the most accurate body weight to be used?

Decreased, gastric emptying, N/V, decreased

Drug absorption is (increased/decreased) in pregnancy. Increased progesterone levels delay ____ ____. ____/____ also impacts absorption. It is also impacted by physiologic changes like (increased/decreased) sphincter tone and expanding uterus.

Increased, increased, fat

Drug distribution is (increased/decreased) in pregnancy due to a (increase/decrease) in TBW and ECF and increased ____ stores.

Decreases, less

Serum protein [ ] (increases/decreases) in pregnancy due to (less/more) albumin and a1 acid glycoprotein to bind drug.

Acidic, basic

Albumin binds to (basic/acidic) drugs and a1 acid glycoprotein binds to (basic/acidic) drugs.

Lower

In pregnancy, increased Vd and decreased serum protein [ ] (raise/lower) peak drug [ ] achievable.

2C19 and 1A2

Pregnancy increases the activity of most CYP450s, but decreases the activity of which two CYPs?

Increases

In pregnancy, GFR (increases/decreases) by ~50%, but begins to return to normal the last 3 weeks of pregnancy.

Junction between mom and baby, its own

What is the syncytiotrophoblast? Does it have its own UGTs and CYPs or use the mom's?

Passive

Placental drug passage is predominantly (active/passive) diffusion.

Large, ionized, non-lipophilic, high

Transplacental drug passage - preferred characteristics:

(Small/large) molecular weight

(Ionized/non-ionized) drugs

(Lipophilic/non-lipophilic) drugs

(Low/high) protein bound drugs

Increased, total

During pregnancy, free phenytoin levels will be (increased/decreased). Because of this, ____ phenytoin levels must be adjusted.

Keppra and Lamictal

What are two safer options than phenytoin in pregnancy?

Contraindicated, LMWH

Warfarin is (not recommended/contraindicated) during pregnancy except in high risk patients with a mechanical heart valve. Instead of warfarin, what is the recommended anticoagulant in pregnancy?

Weight, anti-Xa

When using LMWH in pregnancy, use ____-based dosing and possibly monitor ____-____ levels.

Large, more, less, high

Lactation drug passage - preferred characteristics:

(Small/large) molecular weight

(More/less) ionized drugs

(More/less) lipid solubility

(Low/high) protein bound drugs