Pharmacology Flashcards
ADME Lectures + Drugs for Diabetes
- Briefly describe the differences between pharmacoKINETICS and pharmacoDYNAMICS
KINETICS - “What the body does to the drug” - describes relationship bw the DOSE and the [unbound drug] at the site of action (drug receptor, DR), and the TIME COURSE of [drug] in the body.
DYNAMICS - “What the drug does to the body” - describes relationship bw [unbound drug] at receptor and the drug RESPONSE (ultimately the therapeutic effect).
i.e. PK - Time course of drug concentration in the body
PD - Concentration-effect relationship
- What does Drug DISPOSITION describe?
A broad term that covers all the processes by which the body handles foreign chemicals including drugs.
These are Absorption, Distribution, Metabolism & Excretion - abbreviated as ADME.
(usually just refers to M&E)
- Why are pharmacokinetics/pharmacodynamics (PK/PD) important for clinical pharmacology?
Clinical PCOL applies PK/PD principals to the individual patient, thus providing the means of prescribing the right dose and thereby optimising the therapeutic effect & minimising adverse effects.
- What is the fundamental parameter known as CLEARANCE (CL)?
Describes the efficiency of elimination (irreversible) of a drug from the body (systemic circulation).
Defined as ‘the volume of blood cleared of drug per unit time’, its units are thus VOLUME per TIME, usually L/hr or mL/min.
It is a constant characteristic of a particular drug AND a particular patient. Thus, it’s the proportionality constant bw plasma drug concentration and elimination rate (ER = CL*C).
- What is the fundamental parameter that describes the relationship bw the drug conc. in the accessibly body fluid (blood) and the drug in the tissues of the body at the site of action?
Volume of Distribution (V, or Vd)
- What is the elimination rate constant known as?
The HALF-LIFE.
It is determined by both the CL and Vd of a drug.
- Define ‘Steady State’
The situation at which the rate of drug administration is equal to the rate of drug elimination so that the amount of drug in the body, and therefore the plasma drug concentration, remains constant.
At steady state,
ELIMINATION RATE = MAINTENANCE DOSE RATE (DR)
- If Clearance (CL) is the constant relating [plasma drug] (C) to the rate at which the drug is eliminated from the body, i.e:
Elimination rate (mg/hr) = CL (L/hr) * C (mg/L)
Then, how can the maintenance dose rate (DR) required to achieve a target steady state plasma drug concentration be calculated?
Since at steady state:
Elimination Rate = DR (mg/hr)
Then by the relationship of CL to plasma drug concentration (C) and Elimination Rate:
DR = CL*Css
where Css is the Steady State Drug Concentration.
- What is the mathematical relationship bw PLASMA DRUG CONCENTRATION and CLEARANCE?
For a given dose rate, the plasma drug concentration is INVERSELY PROPORTIONAL to clearance.
For example, if the clearance is reduced by half, the steady state concentration will double.
(see fig. 1.1, extra notes)
- Vd = total amount of drug in body (A) / plasma drug concentration (C).
If a drug has a plasma conc. of 10 mg/L when there’s 1000 mg of drug in the body, what is the volume of distribution?
Briefly describe how this is determined in the body.
100 L.
That is, dissolving 1000 mg of drug in an imaginary volume of 100 L would give a concentration of 10 mg/L.
If volume of distribution is an ‘imaginary’ volume, what’s it determined by? The major determinant is the relative strength of binding of the drug to tissue components as compared with plasma proteins.
If a drug is v tightly bound by tissues & not by blood, most of the drug in the body will be held in the tissues and v little in the plasma, so that the drug will appear to be dissolved in a large volume and Vd will be large. E.g. lipid-soluble bases such as imipramine (2100L) & chlorpromazine.
- What are the main determinants of Volume of Distribution, Vd?
The relative strength of binding of the drug to tissue components as compared with plasma proteins,
i.e. the ratio of the fraction of drug UNBOUND in the PLASMA to the fraction UNBOUND in the TISSUES (fu/fu_T).
Vd = plasma volume + fu/fu_T * tissue volume
Molecular size an also have a major impact on Vd, e.g. therapeutic mAbs & IgG are excluded from cells due to their large molecular size, and will have a Vd similar to plasma volume in the body (low, IgG 5 L).
- If a drug is tightly bound to plasma proteins and not to tissues:
a) Vd will be large (greater than blood volume)
b) Vd will be very close to blood volume
b) Vd will be very close to blood volume
e. g. this is the case for Warfarin, with a Vd of 8L.
- What factor determines the drug concentration at steady state during continuous administration?
a) Half-life
b) Clearance
c) Volume of Distribution
d) Dose Rate
b) Clearance
