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FPP > Pharmakokinetics > Flashcards

Pharmakokinetics Flashcards

1
Q

Definition of Pharmacokinetics

A

what the body does to the drug

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2
Q

Definition of pharmacodynamics

A

what the drug does to the body

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3
Q

PK/PD definition

A

relation between pharmacokinetic and pharmacodynamic

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4
Q

what are the 2 primary measures

A
  1. CLEARANCE
  2. VOLUME OF DISTRIBUTION
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5
Q

clearance is the only parameter that determines what?

A

Clearance (Cl) is the only parameter that determines maintenance dose rate required to achieve a target plasma concentration (and therefore effect) at stetheady state

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6
Q

what is volume of distribution

A

Volume of distribution (Vd) is an essential determinant of drug half-life, as t1/2 = 0.693 * Vd/Cl.

What this means is that for 2 drugs with the same clearance, but different voluymes of distribution, the bigger volume with have a longer half-life.

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7
Q

what is bioavailability

A

Fraction of unchanged drug reaching the systemic circulation (F).

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8
Q

what does systemic circulation (F) depend on in intravenous dosing?

A

f = 100%

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9
Q

what does systemic circulation (F) depend on in oral dosing?

A

F depends on Absorption and Clearance

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10
Q

what are 2 types of in vivo PK experiments

A

IV bolus dose
oral dose

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11
Q

where is an intravenous bolus administered

A

plasma compartment

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12
Q

where is oral dosing administered

A

Dosed into the gastro-intestinal tract

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13
Q

what is Absorption

A

The Process by which a drug moves from the site of administration to the site of action

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14
Q

what is absorption quantified by

A

Quantified by the Absorption rate constant (A First Order Process)

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15
Q

what 3 unique properties does oral absorption require

A

Water Soluble in the gut

Lipophilic for membrane permeation

Water soluble in plasma

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16
Q

what is distribution

A

is the process by which a drug moves from the bloodstream into the peripheral tissues

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17
Q

what is distribution driven by

A

Driven by the relative affinity of binding for blood and tissue compartments

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18
Q

what is distribution quantified by

A

Quantified by the Volume of Distribution (Vd)

“The ratio between the amount of drug in the body and the amount in the plasma”

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19
Q

what 2 ways can calculate volume of distribution

A
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20
Q

metabolism definition

A

Metabolism is the irreversible chemical alteration of a drug by a biological system

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21
Q

Drug Metabolism can happen in most organs and is covered by 2 Phases:

what are the 3 phase 1 reactions and what is its aim

A

Introduces a new chemical group via:
Oxidation Reactions
Reduction Reactions
Hydrolysis Reactions

Aim: To produce Inactive metabolites

22
Q

Drug Metabolism can happen in most organs and is covered by 2 Phases:

what are the 3 phase 2 reactions and what is its aim

A

Conjugates the molecule with charged chemical species via:
Glucouronidation
Acylation
Sulfation

Aim: To decrease lipophilicity and increase solubility for enhanced excretion

23
Q

what is excretion

A

Excretion is the irreversible elimination of a drug from the systemic circulation and Clearance can be used to define excretion

24
Q

what are the 2 routes that make up drug excretion

A

Renal Excretion – Into the Urine

Hepatic Excretion – Into the Bile (Faeces)

25
Q

what are 3 other excretion routes

A

Sweat
Milk
Saliva

26
Q

what is half life

A

Half life (t1/2): This is the time taken for the plasma concentration of a drug to decline by 50%

27
Q

what are the two phases of metabolism?

A

Phase 1 → drug is inactivated

Phase 2 → making drug more susceptible for elimination

27
Q

what must we do to out curve before calculating the elimination rate constant (k)?

A

what must we do to out curve before calculating the elimination rate constant (k)?

28
Q

how do we calculate the half life of a drug?

A

On a first order monoexponential decline curve, the half-life can be estimated anywhere on the curve

29
Q

the slope of the line in a galf life graph is equal to what

A

Slope of the line = Elimination rate constant (k)

30
Q

what 2 ways lets you calculate the slope of the line

A
31
Q

what is the most important primary measure of PK

A

Clearance is the most Important Primary Measure of PK

32
Q

what effect does low clearance have on the theraputic effect

A
33
Q

Why is Clearance important?

A

Clearance is the ONLY parameter that determines the maintenance dose rate required to achieve a target plasma concentration (and therefore effect) at steady state

34
Q

what are 2 ways of calculating total clearance

A
35
Q

what is the main organ for drug clearance

A

liver

36
Q

What affects the hepatic clearance?

A

Enzymatic activity in the liver

Hepatic blood flow (Rate Limiting Step

37
Q

what is maximum hepatic clearance equal to?

A

Maximum hepatic clearance is equal to liver blood flow (Q)

Therefore, if the total blood clearance is greater than liver blood flow (Q), there must be extra-hepatic clearance

38
Q

how do we calculate hepatic clearance?

A

Hepatic clearance = liver blood flow X Extraction ratio

39
Q

what 2 things determines the clearance by each organ

A

Extraction ratio and Blood flow for each organ determines the clearance by each organ

40
Q

what is whole body clearance

A

Whole body clearance is the sum of all organ clearances

41
Q

What is the bioavailability of a drug?

A

fraction of unchanged drug that reaches the systemic circulation

42
Q

for IV dosing, f must equal what

A

F must always equal 1 (100%)

43
Q

For Oral Dosing, Bioavailability depends on what 2 things:

A

Absorption from the Gut
Clearance

44
Q

Bioavailability is calculated using dose-adjusted AUCs of oral and iv dosing by:

A
45
Q

Why can a drug be 100% absorbed but still have zero bioavailability?

A

first pass effect

46
Q

*key equation to remember

Relationship between half-life (t1/2) in hours and the elimination rate constant (k) (hours-1)

A

t1/2 = 0.693 / k

47
Q

*key equation to remember

Volume of distribution (Vd, Units: mL, L)

A

𝑉𝑑=𝐷𝑜𝑠𝑒 𝐴/𝐴0

48
Q

*key equation to remember

Whole Body Clearance (Cl, Units: mL.min-1, L.h-1)

A

𝐶𝐿=𝑘 ∗𝑉𝑑

𝐶𝑙=𝑑𝑜𝑠𝑒 ∗𝐹 /𝐴𝑈𝐶

49
Q

*key equation to remember

Oral Bioavailability (F, Units: %)

A
50
Q

describe where the following would be on a pharmacokinetics graph:

safety window
toxicity level
minimum effective concentration
theraputic window

A

FPP (9 decks)

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