Lecture 15 Drug interactions Flashcards
When does a drug interaction occur?
When the effects of one drug are altered by another drug, food, herbal remedy or by some chemical agent these can be beneficial but are most often harmful leading either toxicity or loss of therapeutic effect
What are examples of drug interactions being beneficial?
Probenecid can reduce renal clearance of ampicillin and methotrexate
Cyclosporin can act with a CYP3A4 inhibitor (such as ketoconazole) to double its bioavailability
HIV protease inhibitors such as indinavir have greater bioavailability with the addition of ritonavir
What are the two classes which drug interactions can be divided into?
Pharmacodynamic where the drugs have actions on the same receptor or physiological system
Pharmacokinetic where one drug effects the ADME of another
What two classes can Pharmacodynamic interactions be divided into?
Synergistic or antagonist
What is an example of an antagonist pharmacodynamics drug interaction?
Naloxone can be used to reverse respiratory depression or coma caused by overdose of morphine or heroin by competing for the same receptor
What are examples of synergistic pharmacodynamics interactions?
Taking alcohol with drugs that act on the central nervous system
Combinations of anti-cancer or anti-viral drugs
What are the two most common effects of pharmacokinetic drug interactions?
There is an increase in the drug concentration at the site of action leading to exaggerated or toxic response
There is a decrease in drug conc. At the site of action causing reduced or loss of drug responsiveness
What is an example of a pharmacokinetic drug interaction that affect drug absorption?
Some antibiotics such as tetracycline forms insoluble complexes with metal ions present in milk and antacids in the stomach/intestines this can result in a 75% reduction in the amount of the antibiotic that gets into the body
What are drugs that affect renal function or clearance?
Probenecid or diuretics which tend to increase the excretion of other drugs
What are drugs which influence active transport of other drugs?
P-glycoprotein is an ATP dependent drug efflux pump which has significant overlap with CYP3A4 substrates and inhibitors and inducers
What drugs are likely to have clinically significant pharmacokinetic drug interactions?
Drugs with a steep dose-response curve
Drugs with a low toxic/therapeutic ratio such as anticoagulants, anticonvulsants, cardioactive drugs, immunosuppresants, oral contraceptives
What are examples of herbal-drug interactions?
These are not well-documented as there is little economic interest, few legal requirements and patients can often lie
However St. John’s wort (treatment for mild depression) has been documented to cause organ rejection when used with cyclosporine, decreased conc of indinavir causing therapeutic failure as it is a potent CYP3A4,1A2,2C9 inducer
What are the drug-herbal interactions which involve warfarin?
It is metabolised by CYP2C9
And has interactions reported with garlic, ginko, biloba, ginseng, glucosamine and cranberry juice which typicallylead to increased response hemorrhage and death
