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ME2019 PART 2 > Drug Distribution > Flashcards

Drug Distribution Flashcards

1
Q

What needs to happen to a drug once it has been absorbed?

A

Needs to be distributed to the tissue

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2
Q

What is drug distribution?

A

Refers to the reversible transfer of a drug between the blood and the extra-vascular fluids and tissues of the body

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3
Q

What is tissue distribution impacted by?

A

Plasma protein binding

Tissue perfusion

Membrane characteristics (blood brain barrier, blood-testis/ovary barrier)

Transport mechanisms

Diseases and other drugs

Eliminations

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4
Q

What do many drugs bind to?

A

Proteins such as albumin or alpha1-glycoprotein

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5
Q

When is the drug biologically active?

A

When it is unbound

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6
Q

What can drugs binding to proteins be described as?

A

Reversible

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7
Q

What is the amount of drug bound changed by?

A

Renal failure

Hypaalbuminaemia

Pregnancy

Other drugs

Saturability of binding

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8
Q

What does a small change in the amount of unbound drug lead to?

A

A massive change in the drug action, for example:

A drug that is 96% bound changes to 92%, so the amount of active drug has doubled

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9
Q

What is the therapeutic range?

A

Concentration of drug to achieve the desired therapeutic effect

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10
Q

What is the ability to achieve the therapeutic range affected by?

A

Volume of distribution

Clearance

Half life

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11
Q

What is apparent volume of distribution (Vd)?

A

Volume of plasma that would be necassary to account for the total amount of drug in a patient’s body, if that drug was present throughout the body at the same concentration as found in the plasma (expressed as L/kg)

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12
Q

What is the apparent volume of distribution (Vd) expressed as?

A

L/kg

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13
Q

What is a formula that describes the apparent volume of distribution?

A

Vd = (total amount of drug in the body) / (drug blood plasma concentration)

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14
Q

What does it mean if a drug has a high volume of distribution?

A

It will go to the tissue

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15
Q

What does it mean if a drug has a low volume of distribution?

A

It will stay in the plasma

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16
Q

If the drug spread through every membrane what would the volume of distribution be (Vd)?

A

42L (because there are 42L of fluid in the average body)

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17
Q

What would the volume of distribution be if the blood cannot penetrate cells?

A

12L

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18
Q

What would the volume of distribution be if the drug is highly protein bound?

A

3L

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19
Q

What is clearance (Cl)?

A

Theoretical volume from which a drug is completely removed over a period of time (measure in units of time ml/min)

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20
Q

What is clearance expressed as?

A

ml/min

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21
Q

What are the two kinds of clearance?

A

Hepatic clearance

Renal clearance

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22
Q

What is clearance a measure of?

A

Elimination

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23
Q

What does clearance depend on?

A

Concentration and urin flow rate for renal clearance

Metabolism and bilary excretion for hepatic clearance

24
Q

What is half life (t1/2)?

A

Time taken for the drug concentration in the blood to decline to half of the current value

25
Q

What does half life depend on?

A

Volume of distribution

Rate of clearance

26
Q

How many half lifes does it generally take to clear a drug?

A

5

27
Q

What does prolongation of half life increase?

A

Drug toxicity

28
Q

What could prolongation of half life be due to?

A

Reduction in clearance

Large volume of distribution

29
Q

What does knowledge of a drugs half life allow?

A

Us to work out how often a drug needs to be administered

30
Q

How are most drugs given to achieve their therapeutic effect?

A

Chronically

31
Q

When is the steady state of a drug normally obtained?

A

After 4 half lifes

32
Q

What is time to the steady state independant of?

A

Dosage

33
Q

What is proportional to a drugs dosage?

A

Steady state concentration

34
Q

What are fluctuations in concentration proportionate to?

A

Dosage and half life

35
Q

What is drug elimination?

A

Removal of active drug from the body

36
Q

What does drug elimination determine?

A

The length of action of the drug

37
Q

What are the 2 parts of drug elimination?

A

Drug metabolism

Drug excretion

38
Q

Where does drug metabolism usually occur?

A

In the liver

39
Q

Where does drug excretion normally occur?

A

Usually in the kidney, but also in bilary systems, lungs and milk

40
Q

What are the 3 mechanisms that the kidneys use for excretion?

A

Glomerular filtration

Passive tubular reabsorption

Active tubular secretion

41
Q

Why is renal damage important for causing drug toxicity?

A

The kidneys are important for excretion

42
Q

How much fluid does glomerular filtration filter per day?

A

190L

43
Q

What drug are filtered by glomerular filtration?

A

All unbound drugs as long as their size, charge or shape are not excessively large

44
Q

What do factors that affect glomerular filtration reduce?

A

Clearance of the drug

45
Q

What happens during tubular reabsorption?

A

1) As filtrate moves down the renal tubule any drug present is concentrated
2) Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation

46
Q

Where does passive tubular reabsorption occur?

A

Distal tubule and collecting duct

47
Q

What kinds of drugs are reabsorbed in passive tubular reabsorption?

A

Only unionised drugs such as weak acids

48
Q

What can passive tubular reabsorption be affected by?

A

Renal failure

49
Q

What happens to acidic/basic compounds?

A

They are actively secreted into the proximal tubule by active tubular secretion

50
Q

What is active tubular secretion the most important system for?

A

Eliminating protein bound cationic and anionic drugs

51
Q

How much bile does the liver secrete per day?

A

1L

52
Q

What are the two ways that drugs can be secreted into the bile?

A

Actively or passively

53
Q

What happens to many drugs from the bile?

A

They are reabsorbed into circulation which continues until the drug is metabolised in the liver or excreted by the kidneys

54
Q

What is drugs being reabsorbed from the bile into circulation known as?

A

Entero-hepatic circulation

55
Q

What does metabolism in the liver lead to?

A

Conjugation of the drug, the conjugated drug not being reabsorbed from the intestine

56
Q

What doesn’t happen to the conjugated drug proced during metabolism in the liver?

A

It is not reabsorbed from the intestine

57
Q

What does damage to the liver reduce?

A

The rates of conjugation and bilary secretion and so allows the build up or reabsorption of the drug resulting in toxicity

ME2019 PART 2 (45 decks)

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