1What are drug-drug interactions?
can occur whenever a patient takes more than one drug
some interactions are intended, some are not
patients often taken > than one drug
multiple drugs to treat one disorder, multiple disorders requiring different drugs
over-the-counter medications, caffeine, nicotine, alcohol may contribute to drug interactions
2Intensification of effects from drug-drug interactions
increased therapeutic effects
increased adverse effects
3Reduction of effects from drug-drug interactions
decreased therapeutic effects
decreased adverse effects
4What are the four basic mechanisms drugs can interact?
1. direct chemical or physical interaction
2. pharmacokinetic interaction
3. pharmacodynamic interaction
4. combined toxicity
5Direct chemical and physical interaction
never combine drugs in the same container without establishing compatibility
most common in intravenous solution, if they cause precipitation -> do not mix
may cause issues if chemicals are mixed together
6What are the pharmacokinetic interactions for drug-drug?
altered absorption
altered distribution
altered renal excretion
altered metabolism
cytochrome P450 (CYP) group of enzymes
7What causes altered absorption?
elevated gastric pH
laxatives
drugs that depress peristalsis
drugs that induce vomiting
absorbent drugs
drugs that reduce regional blood flow
8What causes altered distribution?
competition for protein binding
alteration of extracellular pH
9What causes altered renal excretion?
drugs can alter: filtration, reabsoprtion, active secretion
10What causes altered metabolism?
most important and most complex mechanism in which drugs interact
cytochrome P450 (CYP) group of enzymes
11What interactions can happen with reduced or increased PGP (p-glycoproteins)?
intestinal epitheliun: affects absorption
placenta: affects drug export fro placental cells to maternal blood
blood-brain barrier: affects drug export from the cells of brain capillaries into the blood
liver: affects drug export from liver into bile
kidney tubules: affects drug export from renal tubular cells into the urine
12Pharmacodynamic interactions: at the receptor site
almost always inhibitory (antagonist/ agonist)
13Pharmacodynamic interactions: at separate sites
may be potentiative (morphine and diazepam)
or inhibitory (hydrochlorothiazide and spironolactone
14Pharmacodynamic interactions: combined toxicity
drugs with overlapping toxicities should not be used together
15Drug-Food interactions
impact of food on: drug absorption, decreased absorption, rate
extenet of absorption (occasionally)
increased absorption: without food, not enough is absorbed
16What is the concern with grapefruit juice? **important**
grapefruit juice effect (not occuring with other citrus fruits or juices) impacts certain set P450 enzymes and causes issues with metabolism of drugs
can make moreor less effective
can increase the drug's blood levels
17Drug-food interactions with drug toxicity
monoamine oxidase inhibitors (MAOIs) and tyramine-containing foods
psych drug -> cheese and wine impact
18Drug-food interactions with drug action ???
warfarin and foods rich in vitamin K
19Timing of drug administration
some drugs are better tolerated on an empty stomach- could be 1 hour before a meal or 2 hours after
others should be taken with food, especially for nausea
20Drug-herb interaction
some drugs can interact with herbal preparations
interactions w herb medicines can occur with prescription medications
21John's Wart **important**
induces drug-metabolizing enzymes and reduces the blood levels of many drugs
very popular herbal medication