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Pharmacokinetics Flashcards

(50 cards)

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1
Q

Window of therapeutic index?

A

Safer is window is as big as possible
If above window then TOXIC
If lower doesn’t meet effective concentration

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2
Q

ADME

A
  1. Absorption
  2. Distribution
  3. Metabolism
  4. Excretion
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3
Q

Compliance

A

Patients willingness to take drugs

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4
Q

Routes of drug administration

A
  • Enteral (oral rectal)
  • Parenteral (subcutaneous/ intramuscular/ intravenous)
  • Percutaneous (inhalation/ Sublingual/ topical)
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5
Q

Absorption depends on:

A

Route of administration
Blood flow at site of administration
Drug solubility
Active vs passive diffusion
Dose of drug

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6
Q

What is bioavailability

A

Fraction of the total dose administered that reaches the plasma

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7
Q

Does drug diffuse directly to target organs?

A

No. Drug randomly diffuses.

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8
Q

Chemical properties of a drug:

A

Chemical nature
Molecular weight
Solubility
Partition coefficient

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9
Q

What affects the absorption of drugs from gastrointestinal tract :

A
  • formulation of drug
  • stability of drug (digestive enzymes)
  • time available for absorption (tansit time, diarrhoea)
  • lipid solubility
  • interaction with food
  • conc of drug
  • blood flow
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10
Q

Pharmaceutical interventions influencing absorption:

A
  • particle size (dry powder inhaler)
  • coating of tablets
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11
Q

What is enteric coating of tablets?

A

Slow-release
Solid core around it and water diffuses in and releases drug

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12
Q

Factors affecting transdermal (through skin) absorption:

A
  • lipid solubility
  • formulation
  • skin thickness
  • hydration
  • blood flow
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13
Q

Pinocytosis?

A

Facilitated diffusion and active transport

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14
Q

Lipophilicity?

A

Strongly decides whether a compound an pass through membrane

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15
Q

Distribution depends on:

A
  • lipid solubility
  • diffusion barriers
  • tissue binding
  • plasma protein binding (albumin)
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16
Q

One compartment model?

A

Assume the body is one whole compartment

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17
Q

Pharmacokinetics view of the body (specific properties):

A
  • how many membranes
  • pH value
  • circulation
  • size of surface area
  • any diffusion barriers
  • any inactivating enzymes
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18
Q

Special highly regulated diffusion barriers?

A
  1. Blood brain barrier
  2. Placenta
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19
Q

AVD

A

Apparent volume of distribution

The notional volume of fluid required to dilute
the absorbed dose to the concentration found in plasma

How extensively a drug is distributed in the body

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20
Q

What is the AVD of drug that is heavily plasma protein bound?

A

Low ~ 6 litres

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21
Q

AVD if drug heavily tissue bound?

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A

High ~ More than 70 litres
Bcs concentration of drug in the blood is lower

AVD= drug mass/ conc

22
Q

Two compartment model?

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A

Central and periphery compartments
The central compartment (compartment 1) consists of the plasma and tissues where the distribution of the drug is practically instantaneous. The peripheral compartment (compartment 2) consists of tissues where the distribution of the drug is slower.

23
Q

Ion trapping?

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A

Many drugs exist in eqm btw ionised and unionised forms
Only unionised form is lipid soluble and infuses through membranes
Charged molecules can’t diffuse back out so traps them

24
Q

Protonisable groups?

25
Where will drugs tend to accumulate?
In area where ionisation is favoured
26
Where weak acidic drugs absorbed and accumulate
Tend to be well absorbed from acidic environments and accumulate in basic environments
27
Where Basic drugs absorbed and accumulate
Well Absorb from basic environments and accumulate in acidic environments
28
Why are basic drugs secreted into the stomach?
Because of ion trapping pH is acidic in stomach And basic drugs accumulate in acidic environments
29
Were are acidic drugs excreted?
In urine
30
First pass metabolism?
Drug gets metabolised at a specific location in the body that results in reduced concentration of the active drug upon reaching site of action
31
Which administrative route has a high first pass metabolism effect?
Orally
32
How does plasma protein binding affect distribution of drug?
Unbound drugs free to diffuse into tissue Med with low plasma protein binding distributed readily Med with high binding has a longer duration of action
33
Where does metabolism occur?
Liver (first pass metabolism) Kidney Skin/ lungs Microbiome
34
Why is knowledge of first pass metabolism important ?
Can assist the prescriber when deciding on doses and dose schedules to ensure correct dosing by correct route for optimum effect
35
In bio transformation is there reduction and oxidation of drugs?
No. Mainly oxidation (via cytochrome p450 enzymes) - addition of hydroxyl groups conjugation (attaching small polar molecules on drugs) - addition of small polar groups
36
What does metabolism do to drug?
Usually inactivates drug but can activate them too
37
Ways of Excretion of drugs?
1. Kidney - into urine 2. Liver - into bile, enterohepatic circulation 3. Lungs - exhalation 4. Saliva, sweat, milk
38
What bodily fluids are usually used for drug analytics
Urine Saliva Blood
39
Preclinical outcomes of studying pharmacokinetics
- Select drugs with max potential for reaching target - Select appropriate route of administration to deliver drug - Blood levels relate to efficacy/ toxicity so an select safe doses - decide Frequency and duration of dosing
40
What drugs have high volumes of distribution
Lipophillic Basic drugs
41
What drug is heavily plasma protein bound?
Acidic drugs
42
What drug is heavily tissue bound?
Basic drugs
43
What is the definition of pharmacokinetics
Study of the movement of drugs in the body
44
What does it mean if AVD is high
Less drug stays in blood (vascular space) More drugs absorbed into organ systems
45
What does it mean if AVD is low
More drug stays in vascular space
46
Distribution in two compartment models
Distribution takes time Not instantaneous like one compartment model
47
AVD of two compartment model
AVD becomes larger until eqm is reached and as drug distributes further
48
Why has two compartment model got a bi exponential decline
Initially decline is plasma drug conc due to elimination and distribution (steep) Later decline in plasma drug conc due ONLY to elimination (slower)
49
What is the AVD for one compartment model
Constant from beginning
50
Why is one compartment model mono exponential
Decline in plasma drug corn is ONLY due to elimination

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