Pharmacokinetics Flashcards
1
Q
Define pharmacokinetics. (1)
A
- The study of the fate of drugs from time of administration to time of elimination
2
Q
ADME (4)
A
- Absorption
- Distribution
- Metabolism
- Elimination
3
Q
Absorption (1)
A
- how the drug enters the body and systemic circulation
4
Q
Distribution (1)
A
- how the drug is distributed between circulatory system and tissues
5
Q
Metabolism (1)
A
- irreversible modification of the drug inside the body
6
Q
Elimination (1)
A
- how the drug or its metabolites leave the body
7
Q
Define pharmacodynamics (1)
A
- the branch of pharmacology concerned with the effects of drugs and mechanism of their action
8
Q
What is the aim of pharmacokinetics? (5)
A
- To assess drug behaviour via mathematical methods
- Requires the use of model systems – compartmental models
- Biological system – interconnecting compartments
- A compartment = a group of tissues with similar blood flow & drug affinity
- Model allows relationship to be expressed as equations
9
Q
Compartment models (6)
A
- Compartments communicate via reversible processes
- Rate constants are used to measure rate of entry/exit of drug
- Distribution of drug is rapid & homogenous within a compartment
- Each drug molecule has equal chance of leaving
- All models are based on a central compartment = plasma + highly perfused tissues (liver and kidneys)
- Elimination occurs only from the central compartment
10
Q
Define clearance (1)
A
- volume of blood in a specific region of the body cleared of the drug per unit time
11
Q
Define half-life (1)
A
- the time it takes for plasma concentration of a drug to drop by half
12
Q
Define rate of elimination (1)
A
- describes the fraction of drug eliminated per unit of time
13
Q
Define bioavailability (2)
A
- fraction of drug entering the general circulation
- amount of drug entering general circulation ÷ dose administered
14
Q
Calculate apparent volume of distribution (Vd) (1)
A
- Vd = Dose (D) ÷ Drug concentration in plasma (Cp)
15
Q
Calculate clearance (CL) (1)
A
- CL = rate of elimination from entire body (kel) ÷ drug concentration in plasma (Cp)
16
Q
Calculate half-life (T1/2) (1)
A
- T1/2 = 0.693 (or ln2) ÷ rate of elimination (kel)
17
Q
Calculate rate of elimination (kel) (1)
A
- kel = 0.693 (or ln2) ÷ half-life (t1/2)
18
Q
IV bolus kinetics (3)
A
- Inject whole dose at a time/time 0
- Elimination starts immediately
- Elimination is a first order process – for a given time, concentration is halved (i.e., 100%, 50%, 25%, 12.5% etc.)
19
Q
IV Infusion kinetics (4)
A
- Injection of a drug at a steady state
- Initial increase in plasma concentration due to positive difference between rate of infusion and rate of elimination
- As Cp increases over time, the rate of elimination increases
- Eventually a steady state concentration is reached
20
Q
Oral administration kinetics (4)
A
- Balance between absorption and elimination
- Cp (t) reaches a maximum drug concentration (Cmax) after a particular time (tmax)
- Elimination starts as soon as drug enters the plasma. Since Cp (t) initially rises due to absorption, rate of elimination increases with increasing Cp (t)
- Once all of the drug is absorbed, elimination becomes dominant
21
Q
How does the calculation of the PK parameters help in rational drug design? (4)
A
- PK parameters (ADME) provide info on what type of modification to the drug would be needed to improve PK properties
- Inactivation due to metabolism/elimination: ‘stabilise’ the drug, i.e., improve its half-life by modifying relevant chemical group in the drug molecule
- Poor uptake: if it will not pass cell membranes it may be too water soluble; reduce the polarity i.e., redesign drug molecule to be more hydrophobic
- Are its metabolites toxic or safe (or more therapeutically active)
