Term
Decreased Delivery to site of Action
Decreased GI absorption |
|
Definition
- Binding
- Cholestyramine + levothyroxine → ↓ levothyroxine absorption
- Antacids (Ca, Al, Mg) + tetracycline → chelate formation with ↓ tetracycline absorption
- ferrous sulfate + tetracycline → ↓ tetracycline absorption
- Altered gut motility-no example given
- Altered pH gastrointestinal fluid
- cimetidine (or ranitidine) + ketoconazole → ↓ ketoconazole abs
- May be due to decreased ketoconazole dissolution at ↑ pH
- cimetidine should be given 2 hrs after ketaconazole
- fluconazole + cimetidine (oral) → ↓ fluconazole abs
- fluconazole + cimetidine (IV) → fluconazole abs does not change
|
|
|
Term
Decreased delivery to site of action
Decreased transport to cellular site of action |
|
Definition
- tricyclic antidepressents + guanethidine → ↓ guanethidine uptake by sympathetic nerve endings → ↓ anti-hypertensive effects
- ephedrine, amphetamines, phenothiazines have similar effect
|
|
|
Term
Decreased delivery to site of action
Enhanced Elimination |
|
Definition
- Enzyme Stimulation
- Examples of INDUCERS of CYP inculde phenobarbital, carbamazepine, phenytoin, rifampin, St, Johns Wart
- Phenobarbital + warfarin → ↓ anticoagulant effect (↓ plasma levels of warfarin)
- Interactions with St. Johns Wart
- Induction of CYP enzymes; can also induce P-glycoprotein transporter
- St. Johns wart + (indinavir or cyclosporine via CYP or digoxin via p-glycoprotein) → ↓ plasma drug concentration
- Increased renal elimination
- alkalinization of urine + phenobarbital → ↑ excretion of drug
- acidification of urine + amphetamines → ↑ excretion of drug
|
|
|
Term
Increased Delivery to Site of Action
|
|
Definition
- Increased Absorption-no example given
- Decreased plasma protein binding-no example given
- Decreased Elination
- Inhibition of p-glycoprotein
|
|
|
Term
Increased Delivery to Site of Action
Decreased Elimation |
|
Definition
- Inhibition of Xanthine Oxidase
- allopurinol + azathioprine (6-MP) → ↑ toxicity due to increased levels of MP
- This occurs in both IV and oral forms according to package insert
- Inhibition of CYP enzymes
- Examples of inhibitors of CYP include amiodarone, erythromycin, ketoconazole, grapefruit juice
- amiodarone + warfarin → ↓ warfarin elimination → ↑ warfarin plasma levels
- Ketoconazole + terfenadine (Seldane) → ↓ terfenadine elimination → ventricular arrhythmia
- Ketoconazole blocks the conversion of terfenadine → fexofenadine (not active)
- Grapefruit juice + felodipine → ↑ plasma felodipine concentration
- Inhibition of monoamine oxidase
- MAO inhibitor + tyramine → hypertension
- MAO inhibitor + selective serotonin reuptake inhbitor → serotonin syndrome
|
|
|
Term
Increased Delivery to Site of Action
Decreased Renal Excretion |
|
Definition
- Prodenecid + penicillin → ↓ penicillin excretion
- Thiazide diuretic + lithium → ↓ lithium excretion
|
|
|
Term
Increased Delivery to Site of Action
Inhibition of P-glycoprotein |
|
Definition
- quinidine + digoxin → ↓ digoxin clearance
- Quinidine reduces the clearance of digoxin; inhibition of P-glycoprotein-mediated digoxin transport has been implicated
|
|
|
