Pharmacodynamics 3 (DONE)

Question 1

Factors affecting tissue equilibrium

Answer 1

Approach to equilibrium and loss of drug from tissue takes longer the poorer the perfusion and the greater the partitioning into the tissue
Applies equally to both perfusion and permeability limited drugs- permeability rate limitation takes longer than perfusion rate limitation
At equilibrium, unbound concentration in tissue should be same as plasma but: pH gradient across cell membrane, active transport, maintenance of sink conditions in eliminating organ

Question 2

Extent of distribution within tissues

Answer 2

Multiple equilibria within plasma when drugs bind various proteins
Distribution within tissue also involves multiple equilibria- phospholipids and adipose

Question 3

Relating response to exposure- delays

Answer 3

Site of action generally lies outside vasculature

Delays often exist between drug administration and response, obscures relationship

Question 4

PD modelling

Answer 4

Relate plasma concentration to response when constant concentration (constant drug input)
Incorporation of the time course of drug movement between plasma and site of effect, predicts effect-site concentrations that can be related to response

Question 5

Population pharmacodynamics

Answer 5

Describes the variability in (PD) within a population- failure to respond to treatment even when systemic exposure is within range
Distinct from population PK
NB inter-individual variability generally larger than intra-individual variability

Question 6

Gender, age and PD

Answer 6

Gender specific examples: male/female contraceptives, BPH, cancers e.g. breast, prostatic
Age specific examples: digoxin- children tolerate higher unbound concentration, benzodiazepines- increase sensitivity in elderly, anaesthesia- systemic exposure of desflurane reduced in elderly

Question 7

Examples of polymorphisms affecting PK

Answer 7

Receptor expression- Tetrazumab (Herceptin) and HER2
Affinity for receptor: Gefitinib (Iressa) and EGFR-TK; B2 adrenoceptor
Warfarin- vitamin K epoxide reductase, polymorphism in subunit 1 associated with high response or resistance

Question 8

Why do we not measure concentration at the site of action?

Answer 8

Ethical and technical issues, response due to integration of multiple effects at numerous sites