Drug Distribution Flashcards

1
Q

What does drug distribution refer to?

A

The Reversible Transfer of a Drug between the Blood and the Extra Vascular Fluids and Tissues of the body (for example, fat, muscle, and brain tissue).

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2
Q

What does tissue distribution depend on?

A
Plasma protein binding
Tissue perfusion
Membrane characteristics
Blood-brain barrier
Blood-testes/ovary barrier
Lipid soluble drugs
Actively transported
Transport mechanisms
Diseases and other drugs (esp renal failure, liver disease, obesity)
Elimination
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3
Q

What can be said about an unbound drug (not bound to plasma protein)?

A

Only unbound drug is biologically active.

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4
Q

What can change the amount of bound drug?

A
Renal failure
Hypoalbuminaemia
Pregnancy
Other drugs
Saturability of binding
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5
Q

When does protein binding matter?

A

When there is a very large percentage of the drug that is bound to plasma proteins - a small increase in unbound level has a massive percentage change of the free drug level (4% to 6% means a 50% increase in free drug levels)

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6
Q

What are the parameters of the therapeutic range?

A

volume of distribution, clearance and half-life

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7
Q

What is the volume of distribution?

A

The volume in which the amount of drug would be uniformly distributed to produce the observed blood concentration.

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8
Q

What does a greater Vd indicate?

A

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

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9
Q

What is the Vd in theory

A

42L (in equal distribution in the body)

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10
Q

What is the definition of clearance?

A

The theoretical volume of fluid from which a drug is completely removed over a period of time.

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11
Q

What is the measurement of clearance?

A

Measured in units of time (ml/min)

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12
Q

What does clearance depend on?

A

Dependent on concentration and urine flow rate for renal clearance.
Dependent on metabolism and biliary excretion for hepatic clearance.

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13
Q

What is the definition of half life?

A

The time taken for the drug concentration in the blood to decline to half of the current value.

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14
Q

What is half life dependant on?

A

Volume of distribution and rate of clearance.

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15
Q

What is the result of prolongation of the half life of a drug?

A

Will increase the toxicity of a drug.

Due to reduction in clearance
Due to a large volume of distribution (amiodarone)

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16
Q

How many doses are usually required before plasma levels of a drug stabilise?

A

4-5 half-lives

17
Q

What is drug elimination?

A

Removal of active drugs and metabolites from the body

18
Q

What are the two components of drug elimination?

A

Metabolism (usually in the liver)

Excretion (kidney, biliary system/gut, lung, milk)

19
Q

What are the three main mechanisms for drug excretion by the kidney?

A

Glomerular filtration
Passive tubular reabsorption
Active tubular secretion

20
Q

What is renal damage often a cause of?

A

Drug toxicity

21
Q

What system is important for the elimination of protein bound cationic and anionic drugs?

A

Active tubular secretion

22
Q

What kind of drugs are passively reabsorbed from the renal tubule into the circulation?

A

Un-ionised drugs

At this point they are concentrated and the diffusion occurs at the distal tubule and the collecting duct

23
Q

What accounts for 5%-95% of drug elimination?

A

Biliary secretion

24
Q

What is the entero-hepatic circulation?

A

The reabsorption of drugs from the bile to the circulation

25
Q

When does the reabsorption of drugs from the bile to the circulation stop?

A

When the drug has been completely excreted by the kidney or metabolised by the liver

26
Q

What is conjugation of a drug? Often caused by the metabolism of the liver

A

The combination of toxic substances formed by drugs with glucaronic or suphuric acid in the liver - It is a means by which the biological activity of a certain chemical is terminated and the substance is made ready for excretion

27
Q

Is the conjugated drug reabsorbed by the small intestine?

A

NO

28
Q

What may happen after damage to the liver?

A

Reduce rates of conjugation and biliary secretion and so allow the build up or reabsorption of the drug with resultant toxicity