Exam 1: DDI Flashcards
DDI: What is the object drug?
Drug AFFECTED by the interaction
DDI: What is the precipitant drug?
Drug CAUSING the interaction
Results of DDI: What is antagonistic effect?
One drug lessens effect of another
Results of DDI: What is additive effect?
Both drugs result in an increased effect
Results of DDI: What is synergistic effect?
Both drugs result in an increased effect more than just the addition of both
Results of DDI: What is idiosyncratic effect?
Response is unexpected from the known effects of either agent
DDI: T/F Asymptomatic DDIs occur regularly
True
DDI: T/F: DDIs resulting in obvious adverse outcomes occur regularly
False – they occur occasionally
Pharmacodynamic interactions: Additive effects – 3 examples
- additive anticholinergic effects
- ACEI and spironolactone
- Combinations of drugs that prolong the QT interval on ECG
Pharmacodynamic interactions: Antagonistic effects – 1 example
NSAID inhibiting antihypertensive effect of ACEI
PK: Absorption: Common inhibition precipitants
Binding agents (cholestyramine, colestipol)
Cations (aluminum, magnesium, iron)
altered stomach pH
PK: Distribution: Important plasma proteins
Albumin
Alpha-1-acid glycoprotein
Lipoproteins
PK: Distribution: Displacement of highly protein bound drugs example: Warfarin
If warfarin is displaced, there is more free drug, INR goes up, bleeding risk
PK: Metabolism: What is phase I reactions
Oxidation (CYP450)
PK: Metabolism: what is phase 2 reactions?
Conjugation (glucuronidation, sulfation)
P450 nomenclature: CYP3A4 – what is the family
CYP3
P450 nomenclature: CYP3A4 – what is the sub family
CYP3A
P450 nomenclature: CYP3A4 – what is the single gene/protein
CYP3A4
P450: Activity can be inhibited
Drugs that inhibit P450 may slow down the inherent activity or prevent metabolism of other drugs at the site of action
P450: Activity can be induced
Exogenous compounds can stimulate SYNTHESIS of more P450 (as opposed to stimulation)
P450: Genetic polymorphism: What is extensive metabolizers (EM)?
Those with the average “wild type” alleles
P450: Genetic polymorphism: What are poor metabolizers (PM)?
Those with non-functional or missing alleles
P450: Genetic polymorphism: What are ultra rapid metabolizers (UM)?
Those with alleles with repeated gene copies
P450: T/F Co-administration of P450 inhibitors may “convert” EMs to PMs
True
P450: T/F There are less than 40 P450 enzymes found in humans
False – there is AT LEAST 40
P450: What are the 6 P450 enzymes responsible for ~90% of all drug metabolism?
1A2, 2C9, 2C19, 2D6, 2E1, 3A4
P450: What are minor but clinically relevant P450s?
2A6, 2B6, 2C8
P450: Where are these enzymes found?
Found on smooth ER of hepatocytes, luminal epithelium of sm. intestine, other tissues
P450: Which P450 isozyme is not inducible?
2D6
P450: Which P450 does not show genetic polymorphism but may have a close functional relationship with P-gp?
3A4
P-gp: What is the function of P-gp?
Transports drug molecules OUT of cells (ex. in the gut: transports drug back into gut lumen preventing systemic absorption)
P-gp: What is the net effect of P-gp?
Decrease of drug in the systemic circulation
P-gp: What happens when you INHIBIT P-gp?
Increased bioavailability and drug effect
P-gp: What happens when you INDUCE P-gp?
Decreased bioavailability and drug effect
P-gp: What are other drug metabolizing enzymes?
- Flavin monooxygenases (phase 1)
- P-gp (transporter function)
- UGTs (Phase 2)
What are 2 drugs that are strong inhibitors/inducers to be alert for?
Clarithromycin and carbamazepine
What are some drugs that have dose dependent AEs or narrow therapeutic index?
Statins, CCB, methotrexate, oral anticoagulants, antipsychotics, opioids
