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MD3001 - Cardiology Pharmacology > Drug distribution > Flashcards

Drug distribution Flashcards

1
Q

What is drug distribution?

A

Movement of a drug to/from blood and tissues of the body

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2
Q

Factors that affect drug distribution

A
  • Cardiac output and blood flow
  • Plasma protein binding
  • Lipid solubility
  • Degree of drug ionisation
  • pH of compartments
  • Capillary permeability
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3
Q

List in order the level of blood flow to the tissues in the body

A
  1. Kidneys
  2. Liver
  3. Heart
  4. Brain
  5. Skeletal muscle
  6. Fat
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4
Q

What does initial rate of distribution depend on?

A

blood flow

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5
Q

What is the predominate plasma binding protein?

A

Albumin

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6
Q

What binds to albumin?

A
  • Lipid-soluble drugs bind non-specifically
  • Weak acids bind to a specific saturable site
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7
Q

What does hyperalbuminemia cause and how does it affect free drug levels?

A

Dehydration

Decreases free drugs levels

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8
Q

What does hypoalbuminemia cause and how does it affect free drug levels?

A

Causes:

  • Burns
  • Renal disease
  • hepatic disease
  • malnutrition

Increases free drug levels

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9
Q

What affects the albumin conc in the blood?

A
  • pH
  • Temperature
  • Drug interaction
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10
Q

Describe lipophilic drugs

A

soluble in fats and non-polar substance

Rate of distribtuoon is dependent on the rate of delivery to tissues (blood flow)

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11
Q

Describe hydrophilic druhs

A

highly soluble in aqueous, polar media

Rate of distribution is dependent on diffusion characteristics of the drug

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12
Q

List some drugs that are bases

A
  • Amphetamine
  • Atropine
  • Noradrenaline
  • Coedine
  • Diazepam
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13
Q

List some drugs that are acids

A
  • Paracetamol (weak)
  • Phenytoin
  • Warfarin
  • Aspirin
  • Penicillins (strong)
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14
Q

What does the ratio of ionised-unionised drug depend on?

A

pH

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15
Q

Describe the lipid solubility of ionised drugs

A

low lipid solubility meaning they will not diffuse across the cell membrane

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16
Q

What type of drug as a fast rate of diffusion?

A

lipophobic

17
Q

What are the 3 types of capillaries

A

Continuous, discontinuous, fenestrated

18
Q

What is an example of a functional and physical barrier in the body that will only let certain drugs through?

A

Blood Brain Barrier

19
Q

What type of drugs can move through the BBB without a specific transport mechanism?

A

lipophilic e.g. beta-blocker

20
Q

Explain how the plcaenta is a specialised physical barrier

A
  • Tight endothelial cell junctions in maternal and fetal capillaries
  • Partially protective, except with:
    • lipid soluble drugs
    • unionised forms of weak acids and bases

**Drug is less likely to leave the fetal circulation and be eliminated from the mother in these cases

21
Q

What does understanding the amount of fluid in each compartment of the body allow?

A

helps understand where blood is likely to go and with it drugs depending on their chemical properties

22
Q

Breakdown of fluid in an adult body

A
  • Extracellular flui = 15L
    • Plasma = 3
    • Interstitial fluid = 12
  • Intracellular fluids = 27L
  • Total = 42L
23
Q

What is contained the the EXC fluid?

A

Large, water soluble molecules

24
Q

What is contained within the plasma?

A

Highly plasma-bound molecules

Highly charged molecules

Very large molecules (e.g. heparin)

25
Q

What is the volume of distribution?

A

the theoretical volume required to acount fo thee amount of drug in the body

Can indicate where the the body the drug is contained

26
Q

Vd =

A

total amount of drug in the body

_____________________________

blood plasma concentration of drug

27
Q

Explain single compartment model of distribution

A
  • Assumes rapid mixing of drug in plasma
  • ASsumes drug in plasma is in rapid equilibirum with drug in extravascular tissues
28
Q

What is the mechanism of excretion in two compartment model of distribution

A

Drug must travle back into the central compartment to be metabolised and excreted

e.g. bisophosphonates (peripheral compartment = bone)

29
Q

What does Vd vary with?

A
  • Height
  • Weight
  • Age
  • Fluid accumulation
    • Ascites
    • Oedema
    • Pleural effusion
  • Accumulation of fat

MD3001 - Cardiology Pharmacology (8 decks)

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