PHAR232 - pharmacokinetics wk 5 Flashcards

You may prefer our related Brainscape-certified flashcards:
1
Q

What is pharmacokinetics?

A

Pharmacokinetics is the study of how the body absorbs, distributes, metabolizes, and eliminates drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 4 key areas of pharmacokinetics?

A

The four main processes of pharmacokinetics are:

Absorption: This is the process by which drugs enter the bloodstream from the digestive tract, skin, or other tissues.

Distribution: This is the process by which drugs are transported throughout the body.

Metabolism: This is the process by which drugs are broken down by the liver and other organs.

Excretion: This is the process by which drugs are excreted from the body, typically through the kidneys or liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are tissue reservoirs?

A

A place where a drug can hide e.g. fat cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Where is the major site for metabolic biotransformation?

A

The liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the primary organ for excretion?

A

Kidney function
CV intergrity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

When you age do you lose plasma protein?

A

Yes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What’s the role of pharmacokinetics in research?

A
  • Invsestigate implications for developing foetus
  • Designing safe and effective doses
  • Amelioration of disease
  • Inter-species variability (animals vary massively)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the accronym for the basis of Pharmacokinetics?

A

L=Liberation= release of drug from formulation

A = Absorption - update of drug into circulation

D = Distribution - Movement of drug between body compartments

M = Metabolism - effect of ENZYMES on drug

E = Excretion - Removal of unchanged drug or metabolite from body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the addition term for ‘metabolism + excretion’?

A

Elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the additional term for ‘Distribution + elimination’?

A

Disposition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

The are the key family of liver metabolic enzymes?

A

CYP450 family

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What phase of detoxification does CYP450 enzymes convert drugs/metabolites to?

A

Phase I

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Is the metabolite (offspring) the same as the drug (parent)?

A

No e.g. if 100% of the drug was metabolised, there is no more DRUG. The drug no longer exists.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How do you evaluate systemic drug exposure?

A
  • Circulation: Plasma, serum, whole blood
  • Products: milk, urine, saliva, exhaled air
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

UNDERSTAND MORE ABOUT PLASMA DRUG CONCENTRATIONS

A

WHAT MATTERS IS THE FREE-UNBOUND DRUG IN PLASMA

Bound to plasma protein = CANNOT EXERT AN EFFECT

Measurement of plasma concentration = bound & unbound

MUST KNOW KINETICS and how much is bound and effective concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are disadvantages of plasma drug concentration evaluation?

A
  1. Measurement of plasma concentration = bound & unbound drug
  2. Assumes good integrity of circulation (atherosclerosis etc)
  3. Assumes homogenous distribution of drug e.g equilibrium of drug between plasma & tissues (intereference)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

UNDERSTAND MORE ABOUT COMPARISON OF PLASMA & WHOLE BLOOD CONCENTRATIONS FOR DRUG EVALUATIONS

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What is the exposure-time profile determined by?

A
  • Rate of drug administration
  • Dose administered at this rate
  • Distribution
  • Rate of elemination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What does Cmax stand for?

A

Maximum concentration of drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does tMax stand for?

A

Time of maximum concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What does AUC stand for?

A

Area under the curve

(exposure)

22
Q

If a curve is steep in an exposure-time profile, what does this mean?

A

It’s the rate of absorption

23
Q

What does the half-life of a drug mean?

A

The half-life of a drug is the time it takes for half of the drug to be eliminated from the body.

E.g 50%, 50%, 50%, 50%

24
Q

Can you only clear what the system sees as a free-drug instead of a bound drug?

A

Yes

25
Q

What is clearance (CL)?

A

Quanity of blood that has drg removed from it over a period of time e.g.
Uniters = volume per unit time = ml/min or L/hr etc.

Relates to ORGAN doing the clearance

26
Q

What is volume of dristribution (Vd = V)?

A

a THEORETIC VOLUME - NOT AN ACTUAL

BODY DISTRIBUTION and ASSOCIATION with cellular proteins

27
Q

Vd = V example

it’s an IDEA, of the ease with which the drug distributes, and the extent to which it MIGHT be found in tissues.

Reflects the POTENTIAL ability of the drug to DISTRIBUTE TO THE TISSUES

A

Cmax = maximum concentration

= How QUICKLY the drug is being absorbed vs how QUICKLY the drug is being eleminated

If absorbing SLOWLY you would be ELIMINATING as you absorb

28
Q

Does the time to maximum concentration change with a higher dose?

A

No

29
Q

LOOK AT

Exposure is the same in both A & B charts
PEAK IS DIFFERENT
And that can make a difference in toxicity

E.g. slow release vs rapid release drugs

A
30
Q

What does Area under the curve represent? (AUC)

A

Index of total systemic exposure to drug

31
Q

How do you determine the AUC?

A
  • Use the curve data points to add up the INDIVIDUAL PIECES
    e.g. difference between red dots in the attached
    Then ADD them up
32
Q

Trapezoid rule

A
33
Q

Where is usually the Y and X axis on a chart?

A

Y-axis: vertical axis, left side of a chart,

x-axis: horizontal axis , bottom.

34
Q
A
35
Q

First pass metabolism

A

First pass metabolism:
- Gut lumen
- Gut wall
- Portal vein
- Liver
- Metabolism
- Biliary excretion
- Faeces

36
Q
A
37
Q

Disposition = what combination?

A

Distribution + elemination

38
Q

What is disposition influenced by?

A
  • Organ blood flow
  • Organ size
  • Binding of drug to blood proteins & tissues
  • Membrane transport
39
Q

What regulates penetration of a drug?

A

Surface area x permeability of the membrane

e.g. size, proteins, concentration gradient, lipophilic?? etc
(plasma vs tissue gradient)

40
Q

Disposition to the tissue cycles

A
41
Q

What is a common error when thinking about ELIMINATION?

A

ERROR: That elimination ONLY refers to excretion

FACT: ELIMINATION = metabolism + excretion

42
Q

How would the evaluation of a drugs metabolism be recognised in urine?

A
  1. % of drug UNCHANGES IN URINE
  2. % of METABOLITES in urine
43
Q

What does pKa stand for?

A

pKa stands for “acid dissociation constant” or “dissociation constant of an acid.

50% of the molecule is IONISED & 50% of the molecule is UN-IONISED

44
Q

What’s the difference between ionised and un-ionised drugs?

A

Un-ionised: cross membranes
Ionised drugs: do not cross membranes

e.g. un-ionised drugs are more potent as they have more exposure to cytosol

45
Q

Is a weak base ionised or unionised?

A

Mostly unionised

46
Q

The lower the pKa value, the more ionized or unionised the base will be?

A

ionized

47
Q

What pH level or above does it need to be ionised?

A

11 - 14 pH scale

48
Q
A
49
Q

What are the 3 ways that you discover and develop new drugs?

A
  • Drug modification (build on excisting drugs)
  • Natural product chemistry
  • Ethnopharmacology (indigenous groups and asking what they use for ancient traditions)
50
Q
A
51
Q
A