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MD3001 > drug distribution > Flashcards

drug distribution Flashcards

1
Q

what are factors affect distribution?

A
  • cardiac output and blood flow
  • plasma protein binding
  • lipid solubility
  • degree of ionisation
  • pH of compartments
  • capillary permeability
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2
Q

what is drug distribution?

A
  • movement of a drug to or from the blood and the tissues of the body
  • understanding where the drug is moving
  • helps us to understand the relative proportions of a drug in tissues and predict the response or risk.
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3
Q

why do the kidneys have the greatest exposure to drugs?

A

because they are exposed to the greatest amount of blood flow

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4
Q

why is there a high probability that drugs will be distributed to the kidneys and not to the skeletal muscle?

A

because 20% of total cardiac output will go to the kidneys and skeletal muscle
- kidneys = 450ml/min/100g of tissue
- skeletal muscle = 3ml/min/100g
this is because the kidneys are a lot smaller than the skeletal muscle
resulting in the kidneys being exposed to high conc of any drug in plasma

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5
Q

albumin function?

A
  • it is a globular protein that helps to prevent fluid from leaking out of the blood vessels into tissue
  • (helps to generate osmotic forces that pulls fluid into capillaries)
  • predominate plasma binding protein (40g/L)
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6
Q

how do lipid soluble drugs bind to albumin?

A

non specifically

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7
Q

how to weak acids bind to albumin?

A

they bind specifically at a saturable site.
- competition for the binding site
- limited occupancy
- effects the degree of free drug

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8
Q

what happens if there are multiple weak acids competing for the limited binding sites?

A

this will lead to a drug being displaced which can then be exerted from the body or raise the free drug conc leading to side effects.

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9
Q

what will lipophilic drugs bind to to get around the body?

A

albumin

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10
Q

what does the degree of distribution and ability to cross a membrane depend on?

A

how ionised/ unionised a drug is in the plasma/different compartments with differing pH levels.

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11
Q

what can influence how much albumin is in the blood?

A

disease state
- therefore, effecting the amount of free drug and should be considered when prescribing a sick patient.

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12
Q

2 ways you can have depleted albumin?

how does this effect the levels of free drug?

A

1- lack of kidney function (supposed to filter it out of the urine so it stays in the blood)
2- lack of liver function (its made here)

increases the levels of free drug.

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13
Q

cause and effect of hyperalbuinemia?

A

(high albumin)
cause = dehydration
effect = decreased free drug levels.

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14
Q

4 causes of hypoalbuminemia and what is the effect of each?

A

(low albumin)
cause =
1- burns
2- renal disease
3- hepatic disease
4- malnutrition

all will cause increased levels of free drug

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15
Q

what are 3 other factors that will effect albumin binding?

A
  • pH
  • temperature
  • drug interactions
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16
Q

relate hydrophilic drugs to their rate of distribution?

A

hydrophilic drugs are highly soluble in aqueous, polar media.
the rate of distribution will be dependent on diffusion characteristics of the drug.

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17
Q

relate lipophilic drugs to their rate of distribution?

A

lipophilic drugs are soluble in fats and non-polar solutions
the rate of distribution dependent on the rate of delivery to tissue (eg blood flow)

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18
Q

why are some drugs contraindicated in pregnancy?

A

due to the difference in pH between maternal and feral circulating blood.
if the drug gets into feral circulation it may become more ionised and not move out which could be toxic to the foetus.

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19
Q

what does partition influence?

A

the conc of the drug that accumulates on either side of the membrane.

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20
Q

what does the ionised:unionised ratio depend on?

A

pH

21
Q

do ionised drugs have high or low lipid solubility?

A

low lipid solubility.
therefore ionised drugs will not diffuse across the membrane

22
Q

examples of strong to weak acid drugs?

A

strong:
penicillins
aspirin
warfarin
phenytoin
paracetamol

23
Q

examples of strong to weak base drugs?

A

strong:
amphetamine
atropine
noradrenaline
codeine
diazepam

24
Q

what 3 factors will effect the diffusion of hydrophilic and lipophilic drugs across capillaries?

A
  • surface area
  • time
  • type of capillary
25
Q

how does the surface area of the capillary effect the ability of the 2 different types of drugs to diffuse?

A

a greater surface area of capillary will lead to greater concentration of drug diffusion across the capillaries into the tissues

26
Q

how does the time effect the ability of the 2 different types of drugs to diffuse?

A

greater time spent in capillaries will led to greater concentration of drug diffusion across the capillaries into the tissues
- this is for both hydrophilic and lipophilic

27
Q

how does the type of capillary effect the ability of the 2 different types of drugs to diffuse?

A
  • lipophilic drug can rapidly get across capillaries
  • large hydrophilic drugs can get across all capillaries but their size will impact they rate at which they diffuse.
  • in continuous caplarries, small hydrophilic drugs will slowly defuse, while large hydrophilic drugs diffuse extremely slow
28
Q

least permeable to most permeable capillary?

A

least:
continuous
fenestrated
sinusoid

29
Q

function of the BBB?

A
  • physical and functional barrier
  • prevents things from getting into the CNS from the blood due to the arrangement of tight junctions, glial cells, astrocytes etc…
30
Q

why is it hard to get substances across the BBB and what properties do drugs have to have to be able to get across?

A
  • it is difficult because the BBB has a lack of expression of transport proteins
  • the substances that get across have to be very lipophilic or transported via special mechanisms
31
Q

how do drugs get into the CNS and what is an example?

A

you need drugs with specific characteristics that will increase the permeability of the BBB.
Eg) bacterial meningitis
it causes inflammation which will change the permeability of the BBB which allows drugs to move across

32
Q

describe the specialised barrier of the placenta?

A
  • tight endothelial cell junctions in maternal and fatal capillaries
  • partially protective except from:
  • lipid soluble drugs
  • unionised forms of weak acids and bases
33
Q

how does chronic abscesses act as specialised barrier/compartment?

A

because of the lack of blood supply (avascular tissue compartment)
- also unfavourable pH

34
Q

how do lung infections act as a specialised barrier/compartment?

A

because it has a local low PO2 and high CO2 which causes vasoconstriction
- low o2 = vasoconstriction = no blood flow = harder to get drug there.

35
Q

what is the total body water for a 70kg adult?

A

42 L

36
Q

what is the volume of ECF and ICF in the body?

A

ECF= 15 L
ICF = 27 L

37
Q

what is the volume of plasma and interstitial fluid in the body?

A

plasma = 3L
interstitial fluid = 12L

38
Q

calculation for the Css?

A

the rate of drug administered (K0)
/
volume of plasma cleared of drug per unit time (CL)

39
Q

time taken to reach Css depends on what?

A

elimination half life (t1/2)

40
Q

what does t1/2 directly depend on?

A

the volume of distribution (Vd) and inversely on the clearance (CL) of drug from the body.

41
Q

calculation for t1/2?

A

In2x Vd
/ CL

42
Q

calculation for the Vd of a drug?

A

the total amount of drug in the body
/
blood plasma conc of the drug

43
Q

what is Vd?

A

the theoretical volume required to account for the amount of drug in the body
- units are in Litres or sometimes L/kg of body weight.

44
Q

what does single compartment model of distribution assume?

A
  • assumes rapid mixing of drug in plasma
  • assumes drug in the plasma is in rapid equilibrium with the drug in extravascular tissue.
45
Q

what will Vd vary with?

A
  • height
  • weight
  • age
  • fluid accumulation (ascites, oedema, pleural effusion)
  • accumulation of fat
46
Q

how do you calculate the total amount of drug in the body?

A

A= C x Vd

C= blood plasma conc of drug
Vd = apparent volume of distribution

47
Q

describe the single compartment model of distribution?

A
  • drug has been injected into a single compartment, distributed evenly and rapidly, forming a single well stirred compartment
  • this model assumes the drug in the plasma is in rapid equilibrium with the drug in extravascular tissue
  • if the drug can get into the interstitial space from the plasma but it is in an equal equilibrium, then this would be a well-stirred compartment that makes up the extracellular fluid
  • to be excreted or metabolised, drugs will have to move back to their main compartment
48
Q

describe the two compartment model of distribution?

A

sometimes, drug is distributed from the central compartment into poorly perfused peripheral tissue, where they will accumulate (equilibrium Is not equal and favours moving into the peripheral tissue)
- drugs moving to another compartment will increase the apparent volume of distribution massively, which increases half life and increases the length of time the drug stays active for.
- drugs will stay active for longer for poorly perfused tissue as it will take them a long Tim to move back to the central compartment to be removed by the kidneys/liver

MD3001 (56 decks)

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