Drug Interactions Flashcards
Drugs can interact with…
Other drugs
Disease States
Food and Drinks
Alcohol
What is a Drug-Drug Interaction
Whenever one drugs affects the PK,PD,efficacy or toxicity of another drug
Object drug is…
Drug affected by the interaction
Precipitant drug is…
drug causing the interaction
Antagonistic effect?
one drug lessens effects of another
Additive effect?
both drugs result in an increased effect
Synergistic effect?
both drugs result in an increased effect more than just the addition of both
Idiosyncratic effect?
Response is unexpected from the known effects of either drug
Pharmacodynamic MOA drug interaction
one drug induces change in patients response to drug without altering drugs PK
Pharmacodynamic MOA drug interaction
one drug alters rate or extent of ADME of another drug
Examples of Additive effects
Additive anticholinergic effects
ACE-I and Spironolactone
Combo of drugs that prolong QT interval
Examples of Antagonistic effects
NSAID inhibit antihypertensive effects of ACE-I
PK absorption
Inhibition:
Precipitant drug impairs bioavailability of object drug, resulting in decreased therapeutic effect of object drug
Common percipients
Binding agents (Cholestyramine)
Cations (Al,Mg,Fe)
Altered stomach pH
Caution: Rate vs Extent
Most important plasma proteins for PK distribution
Albumin
Alpha-1-acid glycoprotein
Lipoproteins
Biggest portion of Drug-Drug interactions?
Metabolism
What do all CYP450 have?
Central Heme Unit
CYP450: Those with Wild Type alleles..
Extensive metabolizers
CYP450: Those with nonfunctional or missing alleles…
Poor metabolizers
CYP450: Those with alleles with repeated gene copies….
Ultra Rapid metabolizers
Co-admin of CYP450 inhibitors can…
convert EM to PM
Where do issues come with CYP450 metabolism and potential for drug interactions?
When drug has an affinity to 1 particular CYP enzyme instead of a variety of them.
(in gut) P-gp info
transports drug molecules out of cells. tries to keep drug from getting into plasma, sends back to intestinal lumen
net effect is decrease drug in systemic circulation
found in intestines/liver/kidney
(in gut) P-gp inhibition will result in….
increased bioavailability and drug effect
(in gut) P-gp induction will result in…
decreased bioavailability and drug effect
(Liver/Kidney) P-gp inhibition will result in…
decrease metabolism/excretion
Increase drug effect
(Liver/Kidney) P-gp induction will result in…
increase metabolism/excretion
Decrease drug effect
(Liver/Kidney) P-gp info
acts to increase excretion of drug by transporting molecules into bile and urine
Phase I enzyme?
Flavin monooxygenases
Phase II enzymes?
UGTs
Drugs that are strong inhibitors or inducers of drug metabolizing enzymes or transporters?
Clarithromycin
Carbamazepine
Drugs with serious dose dependent adverse effects or narrow TI
Statins Calcium Channel Blockers Methotrexate Oral anticoagulants Antipsychotics Opioids
