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Pharmacology 785 > Pharmacokinetic Concepts > Flashcards

Pharmacokinetic Concepts Flashcards

1
Q

What are some pharmacokinetic parameters

A

Half-life, clearance

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2
Q

What can pharmacokinetic parameters be used to predict?

A

Drug dose, dose intervals, dosing in renal impairment

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3
Q

What is the prime goal of any drug therapy?

A

To achieve the desired beneficial effects with minimal adverse effects.
The choice of a drug will be governed by the effect desired (pharmacodynamics)
The dose of a drug, route, formulations, frequency will be determined by the pharmacokinetic characteristics (pharmacokinetic)

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4
Q

Why is plasma concentrations used?

A

Proxy of drug concentrations. It is not feasible to routinely measure drug concentrations in other tissues/organs

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5
Q

How do we determine the amount of drug to give a patient to achieve the plasma concentration that will provide the optimum therapeutic effect but minimal toxocity?

A

By application of basic pharmacokinetic principles to our clinical reasoning

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6
Q

What is the therapeutic window?

A

The concentration of a drug where therapeutic benefits are gained from a drug within a window below which there is no therapeutic benefit and above which there are harmful effects (toxicity).

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7
Q

What happens to the therapeutic window of a drug between IV and oral doses?

A

Therapeutic window is the same but there are different absorption and elimination profiles for IV and oral delivery

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8
Q

What is oral bioavaliability?

A

Is the proportion of an administered dose of a drug which reaches the systemic circulation intact.
For IV the proportion is 100%.

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9
Q

What is a margin of safety?

A

The difference between effective dose and toxic dose

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10
Q

What is bioequivalent?

A

Different brands of drugs should be similar to the innovator brand.

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11
Q

What is the bioavailability calculation from IV to oral?

A

IV drug / Oral bioavailability

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12
Q

What is the bioavailability calculation from oral to IV?

A

IV drug x Oral bioavailability

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13
Q

What is cMax?

A

Maximum plasma concentration

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14
Q

What is Tmax?

A

Time to reach maximum plasma concentration

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15
Q

What is volume of distributoin?

A

The apparent volume that the drug would distribute to if it was found in the body in the same concentration as is found in the plasma after a single dose. Expressed as volume/L.
Gives us an idea of how readily the drug distributes from the plasma.

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16
Q

What is the volume of distribution (Vd) calculation?

A

Vd (L) = amount (dose) of drug given (mg) / Concentration of drug in plasma (mg/L)

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17
Q

What does a high Vd mean?

A

Wide distribution to the various organs and tissues

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18
Q

What does a low Vd mean?

A

The drug is restricted to the plasma and ECF - poor distributed

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19
Q

How does age affect Vd?

A

Vd is based on normal population values, these will change with age due to less body water and disease states

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20
Q

What is clearance?

A

Measures the ability of the body to eliminate the drug.
It is expressed as volume/unit of time (e.g. mL/min) and represents the volume of blood completely cleared of the drug per unit of time

21
Q

What is total clearance?

A

Is a combination of all routes of elimination i.e. CI (total) = CI (renal) + CI (hepatic) + CI (other sites)

22
Q

What is the Clearance calculation?

A

Vd / renal clearanceL/min = xminutes

23
Q

How do you assess kidney function?

A

Clearance of drugs is affected by organ function especially kidneys.
Kidney function is estimated using the glomerular filtration rate (GFR) mL/min

24
Q

At what GFR is kidney failure?

A

0-15mL/min

25
Q

At what GFR is kidney disease?

A

15-60mL/min

26
Q

At what GFR is normal kidney function?

A

60-120mL/min

27
Q

What is the most common measure to estimate GFR?

A

Creatinine clearance (ClCr)

28
Q

What is creatinine?

A

It is a waste metabolite produced by muscles from the breakdown of a compound called creatine and is produced at a relatively constant rate related to muscle mass. It is completely filtered by the kidney and not reabsorbed through the nephron.

29
Q

How is eGFR calculated?

A

Uses serum creatinine, gender, ethnicity, & age to calculate eGFR. Is is reported in mL/min/1.73m2 i.e. body surface area of 1.73m2.

30
Q

What are some limitations to the use of eGFR?

A

Extremes of body size, high protein diet, under 18 years, ethnicity factors not yet calculated for other ethnic groups.

31
Q

What is half-life?

A

It is the time taken for the concentration of the drug in the plasma to increase (accumulate) or decrease (elimination) by 50% (half)

32
Q

What is the half life dependent on?

A

volume of distribution and clearance

33
Q

What is the half life calculation?

A

t1/2 = 0.693 Vd / Cl

34
Q

What does the half life determine?

A

Half life determines the time to reach constant effective concentrations in the plasma and the appropriate dosing interval to maintain that concentration

35
Q

What is steady state (Css)?

A

When the amount of drug entering the blood

36
Q

What is steady state (Css)?

A

When the amount of drug entering the bloodstream (absorption) is equal to the mount of drug being eliminated (metabolism & excretion) from the bloodstream

37
Q

How is Css determined?

A

By the half-life of the drug and is generally attained after approximately 4 half lives when repeated doses are given

38
Q

What is the loading dose used for?

A

May be given to quickly attain Css, particularly if the drug has a long half-life

39
Q

What is the therapeutic window?

A

This is the range of concentration at which the drug is therapeutically effective with the minimum unwanted side effects

40
Q

What is the calculation for therapeutic index?

A

minimum toxic dose / minimum effective concentration

41
Q

What is ED50?

A

Is the effective dose in 50% of the population

42
Q

What is TD50?

A

Is the toxic dose in 50% of the population

43
Q

What is target concentration?

A

This will be a concentration within the therapeutic window . It makes no sense to under dose, could e seen as potentially as harmful as over dosing

44
Q

What is minimum effective concentration?

A

The minimum concentration at which a therapeutic response (pharmacodynamic effect) is obtained

45
Q

What is the maximum recommended concentration (or minimum toxic concentration)

A

The maximum effective concentration above which toxic/unwanted side effects occur

46
Q

What is the loading dose equation?

A

LD = volume of distribution x TC / Bioavailability

47
Q

What is the maintenance dose concentration?

A

MD = clearance x TC / Bioavailability

48
Q

What is therapeutic drug monitoring?

A

Sampling of drugs to ensure they are within the therapeutic index. Especially drugs with a narrow therapeutic index e.g. gentamicin, vancomycin, lithium, amiodarone, clozapine

Pharmacology 785 (9 decks)

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