Drug Interactions Flashcards
What can drug interactions do?
Reduce therapeutic effects
Increase therapeutic effects
Inc or reduce toxicity
What are common outlets for drug therapy?
Hypertension
Heart failure
Pain
Cancer
What are the goals of combination drug therapy?
Enhance desired therapeutic results
Dec drug induced toxicity
What are some classifications of drug interactions?
Pharmacokinetic (delivery of a drug to site of action altered by second drug)
Pharmacodynamic (response of the drug target is modified by a second drug)
Where do pharmacokinetic interactions take place?
GI, plasma, liver, kidney
Where do pharmacodynamic interactions take place?
Target organ
What interaction can occur in the GI tract?
Interactions can reduce the entry of drugs into the systemic circulation
What are some drugs that reduce systemic entry to the GI tract?
Aluminum containing medicines
Sucralfate reduced absorption to Ciprofloxacin and Azithromycin
omepazole (raise stomach PH)
What are some interactions that happen before administration?
Phenytoin is precipitates dextrose solution
Amphotericin precipitates in saline
What is protein bumping?
Interactions in serum that can cause an increased amount of free drug
What does metabolism of biotranformation refer to?
Disapperance of a drug when it changed chemically into another compound - a metabolite
What is the basic chemical process for a drug being metabolized?
Converting of a nonpolar, lipid-soluble compound to a more polar form that is more water soluble and can be readily excreted in the urine
What is the spectrum of cosequences of drug metabolism?
Inactive products (majority) Active metabolites Similar to parent drug New action Toxic metabolites
What are prodrugs (drugs in less actiev or inactive form) administered for?
Absorption
Overcome potential destruction by stomach acid
Minimize expose to high reactive chemical species
Allow for selective generation of active metabolites at target in vivo
What is cytochrome P450 (mixed function oxidases)?
A group of enzymes that are hemoproteins
What is Phase I of drug metabolism?
Oxidation (P450 dependent)
Oxidations (P450 independent)
Reduction
Hydrolyses
What is Phase II of drug metabolism?
Conjugation to -OH, -NH2 and -SH functions on drug molecule
Subgroups added
What are some phase I reactions?
Function to convert lipophilic molecules to more polar molecules bu introducing (unmasking) a polar functional group (OH, NH2, SH)
Most frequently involved in drug metabolism are catalyzed my microsomal mixed function oxidases
What are drug interactions due to hepatic metabolism?
Due to interaction at phase I enzymes
P450 common
What are the most common and important CYP450?
CYP3A4 (30%)
CYP2C9 (20%)
CYP1A2 (15%)
What is the Cytochrom P450 nomenclature for CYP2D6?
CYP = cytochrome P450 2 = genetic family D = genetic subfamily 6 = specific gene
What is CYP3A4 responsible for in terms of metabolism?
Most calcium channel blockers Benzos HIV PIs HMG-CoA reductase inhibitors Cyclosporine Non-sedating antihistamines Cisapride
Where would CYP3A4 be found?
GI tract and liver
What is the main form of CYP inhibitors?
Through competition for the same isozyme
What are some drugs which are CYP3A4 inhibitors?
Ketoconazole Itraconazole Fluconazle Cimetidine Grape fruit juice Amiodarone Ritonavir
What are some CYP3A inducers?
Carbamazepine
Rifampin
Phenobarital
Phenytoin
What is the action of cytochrome P450 2D6?
Catalyzes primary metabolism of codeine, B-blockers and trucyclic antidepressants
What is CYP2D6 inhibited by?
Fluoxetine
What does CYP2C9 primarily metabolize?
Most NSAIDS (COX-2)
S-warfarin (active)
Phenytoin
What is CYP2C9 inhibited by?
Fluconazole
Which CYP is induced by smoking tobacco?
CYP1A2
What does CYP1A2 primarily catalyze in metabolism?
Theophylline
Imipramine
Propranolol
Clozapine
What inhibits CYP1A2?
Many fluorquiolone antibiotics
Fluvoxamine
Cimetidine
