Drug Distribution Flashcards

1
Q

What affects tissue distribution?

A
  • Plasma protein binding (the degree to which the drug is bound to it)
  • Tissue perfusion
  • Membrane characteristics
  • Transport mechanisms
  • Disease and other drugs
  • Elimination
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2
Q

How does plasma protein affect tissue distribution?

A
  • The amount of bound drug can be affected by:
    • Renal failure
    • Pregnancy
    • Hypoalbuminaemia
    • Other drugs
    • Satruation
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3
Q

In plasma protein binding, what part is biologically active?

A

The unbound drug only

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4
Q

When is plasma protein important?

A
  • The drug must be more than 90% bound and the tissue distribution small.
  • I.e. if the drug is 96% protein bound then only 4% of the drug is free and available for action. If the unbound level changes to 6% then plasma levels of free drug will increase by 50%
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5
Q

Define volume distribution

A

The theoretical volume that is necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma.

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6
Q

The greater the Volume distribution…

A

the greater the ability of the drug to diffuse into and through membranes

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7
Q

Define clearance

A

The theoritical volume from which a drug is completely removed over a period of time

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8
Q

What is clearance dependent on?

A

-Concentration, urine flow rate for renal clearance, metabolism, biliary excretion for hepatic clearance

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9
Q

Define drug elimination

A

The removal of active drugs and metabolites from the body

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10
Q

What is drug elimination made up of?

A
  • Drug metabolism (usually in the liver)

- Drug excretion (usually kidney but also gut and lung)

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11
Q

What are the three principle mechanisms of drug excretion?

A
  • Glomerular filtration
  • Active tubular secretion
  • Passive tubular reabsorption
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12
Q

How are many drugs distributed around the body?

A
  • Many drugs bind to proteins in the plasma such as albumin, lipoproteins or alpha1-glycoprotein
  • Binding is reversible
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13
Q

What happens in glomerular filtration?

A
  • The glomerulus is a cluster of capillaries around the end of a kidney tubule
  • Filters 190l of fluid a day
  • All unbound drugs will be filtered at the glomerulus as long as their molecular size, charge or shape are not excessively large
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14
Q

What happens in active tubular secretion?

A
  • acidic and basic compounds are actively secreted into the proximal tubule
  • Most importnat system for eliminating protein bound cationic and anionic drugs
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15
Q

What are the drugs present in Passive Tubular Reabsorption?

A
  • As the filtrate moves down the renal tubule, any drug that is present is concentrated.
  • Only UN-IONISED such as weak acids are reabsorbed
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16
Q

What does Passive Tubular Reabsorption allow?

A

-Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation

17
Q

Where does Passive Tubular Reabsorption occur?

A

-distal tubule and collecting duct

18
Q

Why is the distribution of drug not uniform throughout the body?

A

the different tissues receive the drug from plasma at different rates and different extents.

19
Q

What is distribution half life?

A

the time taken for 50% of the drug present in plasma to distribute outside the bloodstream.

20
Q

What are barriers to drug distribution?

A
  • blood brain barrier
  • placenta
  • testis
21
Q

What are barriers to drug distribution?

A
  • blood brain barrier
  • placenta
  • testis
22
Q

How are drugs secreted into the bile?

A

-drugs may be passively or actively secreted into the bile
-biliary secretion accounts for 5-95% of drug elimation
-

23
Q

What may happen in Biliary Secretion of drugs?

A
  • many drugs are then reabsorbed from the bole into the blood circulation. This is called Enter-Hepatic Circulation.
  • it continues until the drug is metabolised in the liver or excreted by the kidneys
24
Q

What are the four stages of drugs within the body?

A

Absorption, distribution, metabolism, excretion

25
Q

Where are drugs easily and less easily distributed?

A
  • easily distributed to the kidney, liver and heart

- distributed in small quantities through less perfused tissues like muscle and fat