Mod 13 and 15 Flashcards PDTI

On IBW, which of the following statements are true or false?

-ABW tried to overcome the limitation of IBW for obese patients

-ABW is frequently used for amino glycoside dose calculation

-General rule, if the ABW is greater than 30 percent of of the IBW use the ABW!

all true

True or false: obese patients have a higher percentage of body fat

-the effect of body weight on volume of distribution depends on the lipophilicity of a drug

both true

Difference in pharmacokinetics of hydrophilic drugs vs lipophilic drugs (Vd etc)

Hydrophilic: low Vd

-eliminated by kidneys

-lower intracellular and tissue penetration

Lipophilic: generally high vd

-eliminated by the liver

-high intracellular and tissue penetration

For a lipophilic drug, what effect does obesity have on clearance and vd?

increase in vd and variable effect on drug clearance

For a hydrophilic drug, what effect does obesity have on clearance and vd?

little effect on vd and higher clearance unless renal impairment

for a lipophilic drug, what is the dosing in obesity?

total body weight

for a hydrophilic drug, what is the dosing in obesity?

adjusted

Why the use of total body weight to calculate the volume of distribution and dose in obesity for hydrophilic drugs may lead to toxicity?

-Hydrophilic drugs do not have affinity for fat tissue, they do not penetrate deep in the tissue and therefore, distribution will be low•

-If we calculate volume of distribution based on total body weight, it will be higher than the observed one as no much change is expected with respect to normal body weight subjects•

-In this case, ideal body weight or adjusted body weight(depending on the drug) should be use to calculate the distribution

The following plot shows diazepam (very lipohilic) distribution in normal weight, obese, and control.. which statements are true?

-since the drug is very lipophilic it has a high affinity for fat so it can easily cross membranes and it will penetrate deep into the tissues

-Vd in obese people will be high, leading to lower plasma concentrations but will remain in the body for longer time

Which of the following weights must be used to calculate the dose ofaminoglycosides in obese patients?

adjusted body weight

Obesity changes the fat contain of the body but can also:

increase cardiac output, organ mass, lean body mass, blood volume, adipose mass tissue, cause changes in plasma/tissue binding. ALL CAUSE SIGNIFICANT CHANGES IN DISTRIBUTION

when do the most dramatic changes in maturation, and drug PK/PD occur?

during the first 1-2 years

In neonates, an increase in oral bioavailability is expected for phenobarbital (acidic drug) due to a higher gastric pH in this special population

false

T or F: Newborns have higher protein binding and volume of distribution that is why they have lower peak concentration compared to adults

False

Which of the following statements are true:

I. Infants have reduced skeletal-muscle blood flow

II. Frequent feeding with milk doesn't influence gastric pH

III. Infants have slower gastric emptying than adults

IV. 4 to 6 months old infants already develop the same metabolic capacity as adults

1 and 3 are true

T or F: Chronological age (number of years lived by a person) may not correlate properly with the physiological or biological age, and as a consequence, a 65 years old individual may have 75 years old body function

true

Chronological Categories: Young old:

Middle Old:

Oldest old:

65-74

74-84

85 and older

Drug X in a new highly lipid-soluble drug. Considering changes in body composition in older adults (> 65 years) with respect to younger adults, what changes in the distribution of Drug X are expected in elderly subjects?

Distribution of Drug X in the elderly population will increase due to the higher percentage of body fat

What method is used to evaluate renal function from serum creatinine in children?

Schwartz method

Absorption in patients with renal impairment patients can be altered

II. Plasma protein binding of many acidic drugs decrease in renal impairment

III. Renal dysfunction can affect drug volume of distribution

IV. Renal dysfunction can alter drug metabolism in the liver

V. There can be accumulation of active/toxic metabolites in renal impaired patients

all of them are true

When the fraction excreted by the kidney is lower than 0.3 no dosage adjustment is required

II. When the fraction excreted by the kidney is higher than 0.3 dosage adjustment is most likely required in patients with CrCl<30 mL/min

III. When the fraction excreted approaches 1, dosage adjustment will probably be needed when the CrCl<50 mL/min

IV. When fraction excreted is <0.3, dosage adjustment may still be necessary since metabolizing enzymes and transporters are often changed in renal disease.

2, 3, 4 are true

The C-G formula is recommended by the National Kidney Foundation for dosing medications?

true

The MDRD/CKD-EPI formula is recommended by the National KidneyFoundation for evaluating renal disease progression

true

Adjusted body weight in obesity =Ideal Body Weight + 0.4 (ActualBody Weight - Ideal Body Weight)?

true

Adjusted body weight in obesity is used for calculating Vd of lipophilic drugs?

False TBW is recommended

Distribution of lipophilic drugs in the obese have a decreased Vd?

False

Drug Vd in obesity depends on the physico-chemical characteristicsof a drug?

true

Indicate if the following statement is true or false: "Patients should avoid grapefruit products for 72 hours before taking a drug that could have an interaction"

True

What is a competitive inhibitor?

Competitive inhibitor compete with the substrate for the same site of the enzyme

Consequence: increase of the Km

What is a non-competitive inhibitor?

Inhibitor binds to a different same site of the enzyme inactivating the enzyme

Consequence: decrease in Vmax

• The following statements are true or false?

• An estimated one third of adults in the western world use alternative therapies, including herbs.

• ~70% patients do not reveal their herbal use to their physicians.

• ~25% of Americans taking prescription medication also take a dietary supplements.

All trrue

What may happen when a drug is given together with an inhibitor of the same metabolic pathway?

Higher concentrations of the drug

Higher therapeutic response / adverse events

What may happen to active metabolite when given with an inhibitor? (assume that the drug is 100%eliminated by this pathway)?

Lower concentration of active metabolite

Inferior therapeutic outcome

What is a pharmacodynamics DDI?

One drug affects the effect of the other drug not related with changes in the pharmacokinetics

What are examples of Drug-Food interaction?

Milk, vitamins, alcohol, juices,....A common drug-food interaction is when a medication interacts with substancesc ontained in grapefruit juice

Are all the DDI undesired?

No, sometimes the co administration of two drugs that interact is beneficial. Ritonavir-boosted therapy and the combined administration of penicillin and probenecid are examples of beneficial Drug-Drug interactions.

Why elderly patients are usually at risk of DDI?

Usually elderly patients take many drugs to treat different conditions and comorbidities

Which cytochrome is moreprevalent and thereforeinvolved in many DDI?

CYP 3A4

What happen when a drug is given with an inducer of its metabolic pathways?

Inducers can increase the enzyme expression level through various mechanisms, and therefore, the victim drug is metabolized faster:

Lower plasma concentration and possible treatment failure

What is the most common mechanism of DDIs?

enzyme inhibition

Select the correct statement(s) concerning a two-compartment body model.

I. For a two-compartment-body model drug, the rate constant describing the elimination of the drug from the central compartment (K10, quantifying urinary and/or metabolic elimination) is larger number than beta.

II. The bi-exponential concentration time-profile, is due to the fact that K10 changes over time.

III. Vdc is smaller than Vdss.

IV. Let us assume that the toxicity of aminoglycosides is related to the drug-concentration in a deep peripheral compartment into which the drug enters and leaves very slowly. Drug toxicity will be observed immediately after an i.v. bolus of this aminoglycoside

one and 3 are true