Drug-Drug Interactions Flashcards
Lag time for IV drug
None
3 Areas of concern when thinking about drug-drug interactions
Coagulation, Heart, CNS
Action of Deferasirox
Chelating Agent
Adverse effects of Warfarin
Hemorrhage
AE’s of Cyclosporine
Renal, HTN, Hyperlipidemia
AE’s of Digoxin
Cardiac Tachyarrhythmias, AV block
AE’s of Doxepin
Excessive sedation, Tachyarrhythmias
AE’s of Methotrexate
Pancytopenia, Liver
AE’s of Theophylline
CNS Tox
Agonist of Histamine H2 receptor would affect GI pH how
Raise GI pH –> Increase absoprtion of basic drugs
Antibiotics generally __ the effects of Warfarin
Increase
Anticoagulant w/ Narrow TI
Warfarin –> Hemorrhage
Antidepressant w/ Narrow TI
Doxepin –> Sedation, Tachyarrhythmias
Azole with no effect on CYP3A4
Fluconazole
Azole with strong inhibition of CYP3A4
Voriconazole
Bile sequestrant –> Bind drugs (eg Propanolo) –> Decrease absorption
Cholestyramine
Both irreversible and Quasi-Irreversible CYP inhibitor are caused by
Formation of Reactive Metabolites
Both irreversible and Quasi-Irreversible CYP inhibitor require
At least 1 cycle of CYP catalytic process
Bronchodilator w/ Narrow TI
Theophylline –> CNS toxicity
Cisplatin + Cyclophosphamide both
form DNA adducts at diff sites
CYP effect of Fluoxetine, Paroxetine
CYP2D6 strong inhibition
CYP inhibitor potency determined by
Lipophilicity and Strength of bonds
Ergotamine + Caffeine =
Increased Ergotamine uptake
Erythromycin effect on CYP
Strong inhibitor of 3A4 and 1A2
Function of Chelating Agent
Administered to bind serum iron and heavy metals to facilitate renal elimination
Immunosuppressives w/ Narrow TI
Cyclosporine –> Renal, HTN; MTX –> Panctyopenia, Liver tox
Importance of Atorvastatin
Binds PXR and RXR –> Upregulate CYP3A4
Important PXR target
CPY3A4
Inotropic Agents w/ Narrow TI
Digoxin –> Tachyarrythmias, AV Block
Macrolide with no inhibition of CYP3A4
Azithromycin
Macrolide with strong CYP inhibition
Erythromycin
Many potent reversible CYP inhibitors contain
Nitrogen
Methotrexate + Fluorouracil =
5-FU solidifies action of MTX
Most common herbal products have effects on __ activity
CYP
Most common type of CYP inhibition
Reversible
Niacin + Simvastatin =
Decrease LDL cholesterol
Non-specific beta-adrenergic blocker used to treat HTN
Propanolol
Peak drug effect usually occurs when
Drug level in plasma reaches highest point
Propanolo and Salmeterol both act on
Beta-2 Adrenergic receptors, but in diff organs
Propanolol + Salmeterol =
Antagonism
Propanolol is used to treat
HTN (non-specific beta-adrenergic blocker)
Raising GI pH increases absorption of
basic drugs
Result of Rifampin added to Cyclosporine
Cyclo levels decline due to CYP induction –> Loss of transplant
Result of Rifampin added to Hormonal Contraceptives
HC levels decline due to CYP induction –> Preg
Result of Rifampin added to Tacrolimus
Tacro levels decline due to CYP induction –> Loss of transplant
Result of Rifampin added to Warfarin
Warfarin levels decline due to CYP induction –> Thrombosis
Reversible CYP inhibition is result of
Competition at active site, probably only involves first step
Role of Cholestyramine in Drug Drug Interactions
Bile sequestrant –> Bind drugs (eg Propanolo) –> Decrease absorption
Role of Clarithromycin in Drug Drug Interaxn
Weak CYP3A4 inhibitor
Role of Erythromycin in Drug Drug Interactions
Strong CYP3A4 and 1A2 inhibitor
Role of Fluoxetine/Paroxetine in Drug Drug Interaction
Strong 2D6 inhibitor
Role of Itraconazole in Drug Drug Interaxn
Weak CYP3A4 inhibitor
Role of Ranitidine in Drug Drug Interactions
Agonist of Histamine H2 receptors –> Raises GI pH –> Increase absoprtion of basic drugs
Role of Voriconazole in Drug Drug Interaction
Strong CYP3A4 inhibitor
Salmeterol + Fluticasone =
Synergistic T cell activation and Apoptosis induction
Salmeterol is used to produce
bronchodilation by activating beta-2 adrenergic receptors in bronchial SM of lung
SSIR + Triptans =
Serotonin Syndrome
SSRI + Tramadol =
Serotonin Syndrome, Seizures
SSRI with strong inhibition of CYP2D6
Fluoxetine, Paroxetine
Statin drugs in high concentrations cause
Breakdown of muscle (Rhabdomyolysis) –> Pain, Renal Failure
Statins that are CYP3A4 substrates
Atorvastatin, Lovastatin, Simvastatin
Sulfamethoxazole + Trimethoprim both target the
DHFR pathway
The effects of the body on a drug
Pharmacokinetic
The effects of the drug on the body
Pharmacodynamic
Three examples of drugs affected by Rifampin CYP3A4 induction
Warfarin, HC’s, Cyclosporine/Tacrolimus
Voriconazole effect on CYP3A4
Strong inhibitor
What do Aspirin, Barbituates, Phenytoin, Sulfonamides, Valproic Acid, and Warfarin have in commone
Highly protein-bound in plasma
What drug would reduce absoprtion of Propanolol
Cholestyramine (bile sequestrant)
What would increase Triazoloam absorption
Increase stomach pH (Ranitidine)
Who are especially susceptible to effects of drug-drug interaction
Women, old, young