Intro to Pharm Sciences Drug Interactions Flashcards
Drug-Drug interaction
Addition of another drug increases or decreases the effect from the therapy
Can also cause adverse effects, can be worse when using narrow therapeutic index
Pharmaceutical DI
When drugs are incompatible due to their physiochemical properties
Pharmacokinetic DI
When one drug alters the plasma concentration of another drug by affecting:
Absorption
Distribution
Metabolism
Excretion
Pharmacological DI
When one drug alters the pharmacological effect of another drug due to:
Antagonistic (1+1=0)
Additive (1+1=2)
Synergistic (1+1=3)
Why does physiochemical incompatibility happen?
Occurs when drugs that are incompatible are administered together
Example: Lantus (Long-acting) mixed with a short acting insulin product
Absorption - Chelation
Formation of an insoluble complex or salt that is poorly absorbed
Certain drug structures allow them to bind metal ions
Most of the metal ions found in antacids, laxatives, milk, and multivitamin products
Common for tetracyclines and fluoroquinolones to form insoluble complexes
Problem and solution for Chelation
Problem: Reduced therapeutic effect
Solution: Separate the administration of the agents by two hours
Absorption - Adsorption
Non-specific binding of a drug to the surface of other solid
Adsorption –> Decreased free drug concentration –> Decreased absorption –> Decreased efficacy
Examples: Antacids, anti-diarrheal
Problem and solution for Adsorption
Problem: Reduced therapeutic effect
Solution: Separate the administration of the agents by two hours
Absorption - Changes in Gastric pH
Change in gastric pH –> Change in the ratio of weak acidic and basic drugs in GI tract –> Alter drug dissolution and absorption
Example: Antacids, H2-receptor blockers and proton-pump inhibitors
Absorption - Changes in GI Motility (Slow)
The slower the drug moves through the small intestine, the slower the rate of absorption
Drugs that decrease GI motility –> Slow down the drug movement towards intestine –> Delayed absorption
Example: Anti-diarrheals, Opioid analgesics, and anticholinergics
Net effect: Slow onset of therapeutic effects
Absorption - Changes in GI Motility (Fast)
The faster the drug moves through the small intestine, reduces the extent of absorption
Drugs that increase GI motility –> Speed up drug movement through intestine –> Reduced extent of absorption
Example: Laxatives
Net effect: Less therapeutic effect
Absorption - Changes in intestinal flora
Intestinal bacteria are responsible for metabolism and deconjugation of certain drugs
Oral contraceptives undergo enterohepatic cycling
Secreted in the bile to the small intestine as glucuronide conjugate
That is cleaved by gut bacteria and the free drug is absorbed
Antibiotics kill bacterial flora –> Reduce drug recycling –> Decrease plasma drug concentration –> Less therapeutic efficacy
Pharmacokinetic Distribution and Displacement
Displacement of one drug by another from plasma protein binding site –> Altered plasma protein binding of the displaced drug
3 elements must be present for displacement to be significant:
1. Both drugs are highly protein-bound
2. At least one of the drugs has a narrow therapeutic index
3. The patient has impaired renal or hepatic function
Pharmacokinetic Metabolism Induction
CYP450 Induction:
When one drug increases the metabolism of another drug by inducing CYP450 synthesis
CYP induction –> Greater drug metabolism –> Less plasma drug concentration –> Less therapeutic effect
