Drug-Drug interactions (Lecture 19) Flashcards
Official definition of drug-drug interactions
Drug interactions occur when there is an alteration in the clinical effects of a drug when taken at the same time or in relative temporal relation with one or more other drug properties
What % of prolonged hospital stay is caused by DDI (probs not that important to know)
7%
What are the types of PD interactions -> increasing in effects of drug
Duplication (Same drug in 2 different products)
Additive effects (1+1 =2) -> Diff drug but has the same effects
Synergistic effects -> 1+1 > 2, drugs increase the effect of one another
What are the types of PD interactions -> decreasing effects of drugs
Antagonistic effects (Fentanyl and Naloxone)
How can DDI increase toxicity
1 drug -> Slightly toxic
2 drugs combined -> Toxic effects increased
What is ion exchange binding?
Drugs with opposite charges are attracted to each other, cannot be absorbed when paired, can also cause drugs to stick to tubings
Example for ion exchange binding
Heparin OD -> Heparin is neg charge so give Protamine sulfate (Postivie charge) -> They bind together, reducing effects of heparin
What is dissolution effects?
Therapeutic agent may dissolve in material that isn’t absorbable
Example for dissolution effects
Reduction in absorption of fat-soluble vitamins when taken with mineral oil (cannot be absorbed)
What is complexation effects
Some antibiotics form complexes with metal ions when taken with antacids
How does mucosal damage effect drug absorption?
Drugs like NSAIDS (Ibuprofen), can damage mucosal layer, increasing drug absorption for other drugs
How can increasing GI affect absorption
Increasing rate of GI motility -> Rapid onset of action -> But less amount of drug absorbed (Increase Tmax, decrease Cmax)
How can decreasing GI affect absorption
Decreasing GI motility -> Slower onset of action -> But more amount of drug absorbed (Decrease Tmax, Increase Cmax)
How can altering gut bacteria affect absorption?
Antibiotics can kill helpful bacterial in the gut reducing their metabolism -> e.g. decreased digoxin metabolism -> Increased concentration
How can altering the gastric pH change absorption?
Antacids, H2 receptor antagonists, PPI can raise pH in stomach -> Decreased acidic drug absorption, increased basic drug
What can propafenone + digoxin cause
Propafenone -> Blocks MDR1(p-gp) receptor (efflux) -> Increasing Digoxin conc -> Possible toxicity
How can fruit juices cause DDI
Fruit juice inhibit OATPs (influx) -> Decrease absorptio of antihistamine (Fexofenadine)
How can albumin competition cause DDI (and how its not)
Albumin binding competition may increase free drug concentration of drugs -> increased effects temporarily -> BUT ELIMINATION ALSO INCREASES SO USUALLY NOT A PERMANENT ISSUE
Loperamide + Quinidine
Quinidine is a p-gp inhibitor -> Loperamide can’t be effluxed out of Brain -> Sedative effects
Terfenadine + Erythromycin
Terfenadine is not converted to Fexofenadine due to Erythromycin blocking CYP3A4, thus toxicity
Phenytoin + Warfarin (IN context of metabolism)
Phenytoin induces CYP2C9/10, needs a higher dose of warfarin
Probenicid + Penicillin
Prevents drug secretion (Prevent renal excretion)
Cyclosporine + St. Johns Wort
St. Johns Wort induces CYP3A4 and pg-p, thus decreasing cyclosporine (immunosuppressant for organ transplant), thus making them fail
