Drug Interaction

Pharmacokinetic (most common)
1. Two drugs compete for the same mechanism of absorption, distribution, metabolism or excretion (ADME)
2. Results in a change in one or both drugs concentration at the site of their action when both agents are taken
3. Typically involves Cytochrome P450, UGT, P-Glycoprotein or OATP
4. Often drug dosage changes and monitoring are sufficient for low to moderate risk interactions
Pharmacodynamic
1. One drug directly blocks or exacerbates another drugs activity without modifying drug concentrations
2. Offending drug, typically must be stopped (drug dosage modifications typically do not resolve interaction)

Altered Drug Absorption
1. Drug absorption is inhibited by a second agent
2. Gastrointestinal absorption may be affected by altered pH (e.g. Antacids), ion or chemical binding (e.g. Doxycycline) or gi motility
Altered Drug Metabolism
1. See Drug Metabolism
2. Cytochrome P450 metabolism my be inhibited (increasing Drug Activity) or induced (decreasing Drug Activity)
Plasma Protein Binding Competition
1. Two drugs may compete for plasma Protein binding sites, with one with lower affinity displaced, resulting in increased serum drug levels
Altered Drug Excretion
1. Renal excretion may be decreased for a drug that competes for specific carrier Protein facilitated transport resulting in increased drug levels

Additive Drug Interactions (1 + 1 = 2)
1. Effect is equal to what would be expected from the combination of the 2 individual drugs
Synergistic Drug Interactions (1 + 1 = 3)
1. Effect is greater than what would be expected from the additive effects of the 2 individual drugs
Potentiated Drug Interactions (0 + 1 = 2)
1. Drug which normally does not have clinical effect, potentiates a second drug to greater effect
Antagonistic Drug Interactions (1 + 1 = 0)
1. One drug inhibits the effect of a second drug