DDIs Flashcards
(22 cards)
Concurrent use of ALPHA-1 ADRENERGIC BLOCKERS and BETA-ADRENERGIC BLOCKERS (two drugs that are antagonists acting on separate receptors in the sympathetic nervous system to prevent hypertension) might result in what effect?
Exaggerated hypotensive response due to additive effect
What is a possible DDI between an ACE inhibitor (that acts on prostaglandins to decrease BP) and an NSIAD?
NSAIDs act by decreasing prostaglandins, so they remove the targets for ACE inhibitors–leading to decreased effectiveness in preventing hypertension
Combining aspirin with clopidogrel (anti-platelet) may have what effect?
aspirin irreversibly binds to platelets to inhibit them, so there would be an increased risk of bleeding due to an additive effect.
Oral contraceptives commonly have DDIs with what agents?
antibiotics (ex. amoxicillin) will decrease the effectiveness of OCs
Mixing potassium tablets with some anti-hypertensives may lead to what effect?
hyperkalemia (may lead to arrhythmia via electrical activity)
Why is digoxin a very tricky drug?
it has a very small therapeutic window, and when it is mixed with other drugs, this window can be altered, increasing its serum concentration and is LIFE THREATENING
What are the 4 main areas of concern with DDIs?
- Patient coagulation Status
- Drugs that relate to heart
- Drugs that affect the CNS
- Hepatic Toxicity
What anticoagulant has a narrow therapeutic window?
warfarin (hemorrhage or thrombosis)
What antidepressant has a narrow therapeutic window?
doxepin (excessive sedation, tachyarrhythmias)
What bronchodilator has a narrow therapeutic window?
theophylline (CNS toxicity)
What immunosuppressives have narrow therapeutic windows?
Cyclosporine (nephrotoxicity, HTN, hyperlipidemia)
Methotrexate (pancytopenia, hepatotoxicity)
What inotropic agent has a narrow therapeutic window?
Digoxin (cardiac tachyarrhythmias, AV block)
List mechanisms of PHARMACOKINETIC chemical interactions.
Biotransformation
Distribution
Absorption
Excretion
List mechanisms of PHARMACODYNAMIC chemical interactions.
Receptor
Non-receptor
Explain how a drug induces CYP metabolism.
When a drug enters the cell, it binds to the PXR which forms a complex with RXR. This complex binds to DNA upstream of target genes and recruits a coactivator to bind to TATA box binding protein and activates transcription by RNA polymerase II. Target genes for PXR include CYP3A4.
Name a drug that induces its own metabolism by inducing CYP.
atorvastatin
Name a CYP3A4 inducer that can interfere with OCs and warfarin.
Rifampin
How does ranitidine affect absorption?
(H2 receptor antagonist, raises GI pH) leads to increase in absorption of basic drugs (ex. tirazolam) in the stomach
How does cholestyramine affect absorption? What drug?
bile-acid sequestrants ike cholestyramine leads to significantly reduced serum concentrations of propranolol and may diminish its effect for a given dose.
What leads to toxicity in drugs that are highly protein-bound in plasma?
In overdose, these drugs have enhanced toxicity if protein binding sites become saturated, if patient has physiological state that leads to hypo-albuminemia, or if the drug is displaced from the plasma protein by another drug
What chemotherapy drugs have the same target and will form a complex that enhances binding?
methotrexate and fluorouracil
What chemotherapy drugs bind to two different binding sites of the same target protein, enhancing the interactions of each other?
cisplatin and cyclophosphamide
