Pharmacodynamics 3 (DONE) Flashcards Preview

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Flashcards in Pharmacodynamics 3 (DONE) Deck (8):

Factors affecting tissue equilibrium

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


Extent of distribution within tissues

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


Relating response to exposure- delays

Site of action generally lies outside vasculature
Delays often exist between drug administration and response, obscures relationship


PD modelling

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


Population pharmacodynamics

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


Gender, age and PD

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


Examples of polymorphisms affecting PK

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


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

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