WEEK 2 Flashcards by Monet Freeman

What does drug distribution refer too?

Drug distribution refers to the movement of a drug to and from the blood and various tissues of the body (for example, fat, muscle, and brain tissue) and the relative proportions of drug in the different sites.

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The transfer of drug between blood and tissues takes place largely in the … bed.

capillary

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T or F
Once absorbed, most drugs distribute evenly throughout the body

False!

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T or F
Once absorbed water-soluble drugs tend to stay within the plasma water and the fluid that surrounds cells (interstitial water).

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Lipid-soluble drugs can enter the … space and are also able to cross the … cell wall and enter the … space.

interstital
lipophilic
intracellular

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… drugs tend to concentrate in fatty tissues within the body.

Fat-soluble

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T or F
Some drugs may concentrate mainly in only one small part of the body

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Iodine concentrates mainly in the … gland

thyroid

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T or F
Drug distribution is an irreversible process

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T or F
Drugs can move in both directions, that is into the tissues and also back out to the capillary blood.

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The exchange of drug molecules across a biological barrier often continues until …

the free drug concentration on both sides of the barrier is the same.

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Drug in the … is exposed to the eliminating organs of the body and removed.

plasma

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Some drugs, such as those that accumulate in …., may leave the tissues so slowly that that drug continues to circulate in the bloodstream for days after a person has stopped taking the medication.

fatty tissues

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Drug distribution in the body is dependant on many factors including:

Tissue blood flow
Physiochemical properties of the drug (water solubility/lipophilicity, molecular weight, pKa and acid/base balance)
Membrane transports (e.g. P-glycoprotein)
Plasma and tissue protein binding

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T or F
Blood flow to different parts of the body is equal

False!

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Which organs of the body receive the greatest supply of blood?

The most vitally important such as the heart, kidney, liver, lungs and brain.

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What organ of the body receives the least supply of blood compared to other organs?

Adipose tissue (fat)

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T or F
Tissues within the body that have good blood supply will have medications delivered more slowly to them.

False!
Tissues within the body that have good blood supply will have medications delivered more
QUICKLY to them.

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T or F
Tissue perfusion has a major effect on the rate of distribution of drugs.

True. Although other factors such as drug properties and drug membrane permeability play a greater role in the extent of drug distribution.

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T or F
Drug membrane permeability plays a greater role than tissue perfusion in drug distribution.

T or F
Tissue perfusion plays a greater role than drug properties in drug distribution.

Lipid soluble drugs tend to concentrate in … tissues.

fatty

T or F
Lipid soluble drugs can more easily cross cell membranes than water soluble drugs.

Water soluble drugs in some cases may cross the cell membrane via … proteins.

transporter

T or F Water-soluble drugs, tend to stay in intracellular spaces

F Water-soluble drugs, tend to stay in extracellular spaces

T or F The molecular size of a drug may limit its penetration to various tissues.

T (Typically this is only the case with very large drug molecules.)

T or F Heparin tends to be confined to the systemic circulation as it is too large to cross the capillary wall.

Drugs that are ....... and ........ will exist in an equilibrium mixture of the ionised (charged) and unionised (uncharged) form.

weak acids and weak bases

T or F Intracellular fluids are typically more acidic (pH~7.2) than extracellular fluids (pH~7.4).

T or F The position of drugs equilibrium depends on the pH of the fluid they are in.

T or F Weak bases are more ionised in extracellular fluid and tend to remain more in these spaces.

F Weak acids are more ionised in extracellular fluid and tend to remain more in these spaces.

Are drugs that are weak acids (such as salicylic acid and some of the NSAIDs) more or less likely to move into the intracellular fluid?

Drugs that are weak acids such as salicylic acid and some of the NSAIDs are LESS likely to move into the intracellular fluid and for this reason tend to have smaller volumes of distribution.

Why do weak acids tend to have smaller volumes of distribution in comparison to other drugs?

Because they are LESS likely to move into the intracellular fluid.

Are weak bases more ionised in intracellular or extracellular fluids?

Weak bases are more ionised in intracellular fluids and may concentrate in these spaces.

Increased ionisation of the weak base as it enters the intracellular fluid space means ...

it is less readily able to diffuse back across the lipophilic cell membrane and return to the circulation.

Why do weak bases tend to have a larger volume of distribution?

Increased ionisation of the weak base as it enters the intracellular fluid space means it is less readily able to diffuse back across the lipophilic cell membrane and return to the circulation.

Name some membrane transporters located at different tissue barriers within the body

- Blood brain barrier - Gastrointestinal tract - Renal tubules - Biliary tract - Placenta

T or F Considering where a drug distributes to may influence therapy selection.

To readily penetrate the brain what properties must a drug have?

- Fairly small - lipid soluble OR must be picked up by a carrier-mediated transport mechanism in the central nervous system.

T or F Extracellular bacterial pathogens are more likely than intracellular bacterial pathogens to invade and replicate within host body cells.

F Extracellular bacterial pathogens, are LESS likely/able to invade host body cells, instead they proliferate in the extracellular environment which is enriched with body fluids.

The major determinate of a drugs volume distribution is ...

the relative strength of its binding to tissue components in the body as compared with plasma proteins and blood cells.

If a drug is very tightly bound by tissues and very little is in the blood will it appear to have a large or small volume of distribution?

the drug will appear to be dissolved in a large volume and its volume of distribution will be large.

T or F Volume of distribution has physiological meaning for certain drugs, but not others.

When is a maintenance dose usually given?

At the time of the second dose (time of loading dose + dose interval)

What are some assumptions that are inherit to non-compartmental analysis?

1. That there is no error in the assay 2. That the time of the dose and sampling times were exact 3. That the sampling times were taken at times that are appropriate to provide these summary measures

Why is it that the lower the Cmax value the higher the Tmax value for a given drug dose?

the longer it takes for drug absorption to reach its peak, the more time there is for the drug to be eliminated, so the lower the maximum concentration will be.

T or F During NCA we estimate AUC numerically by using the trapezoidal rule.

T or F AUMC will always be smaller than AUC.

F AUMC will always be larger than AUC.