Page 130 - TNFlipTest

CP8 Clinical Pharmacology
Pharmacodynamics
Toronto Notes 2019
AGONIST BINDING
Agonist
Receptor
BINDING
Elicited effect
REVERSIBLE BINDING
IRREVERSIBLE BINDING
ALLOSTERIC CHANGE
ANTAGONIST BINDING
1) Competitive reversible binding
Agonist Antagonist
Receptor
2) Competitive irreversible binding
Increased concentration of agonist overcomes antagonist binding competition
Agonist cannot bind receptor which is irreversibly blocked by antagonist
Antagonist bound to alternative site prevents agonist from binding to receptor
Agonist Antagonist
Figure 8. Mechanism of agonists and antagonists
Receptor
Antagonist binding
3) Non-competitive irreversible binding
Agonist Antagonist
Receptor
Antagonist binding
Antagonist binding
Effectiveness and Safety
Effectiveness
The two most clinically relevant properties of any drug are effectiveness and safety
Drugs with a narrow TI have a high likelihood of causing toxicity and need close therapeutic monitoring
• ED50 (effective dose): the dose of a drug needed to cause a therapeutic effect in 50% of a test population of subjects
Safety
• LD50 (lethal dose): the dose of a drug needed to cause death in 50% of a test population of subjects • TD50 (toxic dose): the dose needed to cause a harmful effect in 50% of a test population of subjects
Therapeutic Indices
Therapeutic Index: TD50/ED50
• reflectsthe“marginofsafety”foradrug–thelikelihoodofatherapeuticdosetocauseserioustoxicity or death
• thelargertheTI,thesaferadrug
• common drugs with a narrow TI that require therapeutic drug monitoring include: digoxin,
theophylline, warfarin, lithium, and cyclosporine • factorsthatcanchangetheTI
■ presence of interacting drugs ■ changes in drug ADME
Certain Safety Factor: TD1/ED99
• >1translatestoadoseeffectiveinatleast99%ofthepopulationandtoxicinlessthan1%ofthe population
© Adrian Yen 2006