II. Types: General
- Pharmacokinetic (most common)
- Two drugs compete for the same mechanism of absorption, distribution, metabolism or excretion (ADME)
- Results in a change in one or both drugs concentration at the site of their action when both agents are taken
- Typically involves Cytochrome P450, UGT, P-Glycoprotein or OATP
- Often drug dosage changes and monitoring are sufficient for low to moderate risk interactions
- Pharmacodynamic
- One drug directly blocks or exacerbates another drugs activity without modifying drug concentrations
- Offending drug, typically must be stopped (drug dosage modifications typically do not resolve interaction)
III. Types: Pharmacokinetic Interaction Mechanisms
- Altered Drug Absorption
- Drug absorption is inhibited by a second agent
- Gastrointestinal absorption may be affected by altered pH (e.g. Antacids), ion or chemical binding (e.g. Doxycycline) or gi motility
- Altered Drug Metabolism
- See Drug Metabolism
- Cytochrome P450 metabolism my be inhibited (increasing Drug Activity) or induced (decreasing Drug Activity)
- Plasma Protein Binding Competition
- Two drugs may compete for plasma Protein binding sites, with one with lower affinity displaced, resulting in increased serum drug levels
- Altered Drug Excretion
- Renal excretion may be decreased for a drug that competes for specific carrier Protein facilitated transport resulting in increased drug levels
IV. Types: Drug Interactions
- Additive Drug Interactions (1 + 1 = 2)
- Effect is equal to what would be expected from the combination of the 2 individual drugs
- Synergistic Drug Interactions (1 + 1 = 3)
- Effect is greater than what would be expected from the additive effects of the 2 individual drugs
- Potentiated Drug Interactions (0 + 1 = 2)
- Drug which normally does not have clinical effect, potentiates a second drug to greater effect
-
Antagonistic Drug Interactions (1 + 1 = 0)
- One drug inhibits the effect of a second drug
V. Causes: Food Interactions
- See Antibiotic Food Interactions
- See Grapefruit Interactions
VI. Causes: Common Serious Drug-Drug Interactions
- Drugs with numerous interactions
- Specific important drug-Drug Interactions
- Phosphodiesterase Inhibitor (e.g. Viagra) and Nitroglycerin (Hypotension)
- Beta Blockers and Clonidine (Hypertensive Crisis)
- ACE Inhibitors and Potassium supplements, Potassium-Sparing Diuretics or Septra (Hyperkalemia)
- Drug-Induced Syndromes (exacerbated by combinations of agents)
VII. References
- Olson (2020) Pharmacology, Medmaster, Miami, p. 1-12
- Asher (2017) Am Fam Physician 96(2): 101-7 [PubMed]