Pharmacokinetics III: Drug Interactions & Individual Variation to Drug Responses Flashcards
What are Drug Interactions?
A change in the magnitude or duration of response of one drug due to presence of a second drug
Are drug interactions chemical or physiological interactions?
Physiological
What is a rare example of a chemical interaction between two drugs?
Thiopental + Suxamethonium = Precipitate
What are the TWO potentially dangerous effects of drug interactions?
- Additive - Drug B BOOSTS Drug A effects
- Negating Effect - Drug B DECREASES Drug A effect
What is the equation for the Therapeutic Index for a drug?
What are the some pharmacodynamic considerations for drugs with NARROW therapeutic ranges?
- Small REDUCTION in drug plasma -> Loss of efficacy
- Small INCREASE in drug plasma -> Toxicity
What is a pharmacokinetic consideration if the concentration-response for a drug is STEEP?
Small change in drug plasma -> Big change in effect
Where do Pharmacodynamic Drug Interactions occur?
At the receptor
How is gastrointestinal absorption affected by drugs that inhibit gastric emptying?
Slowed absorption
How is gastrointestinal absorption affected by drugs that speed up gastric emptying?
Accelerated absorption
Which drug do Ca2+ and Fe2+ form insoluble complexes with in the GI tract?
Tetracycline
Which TWO drugs does Colestyramine (bile acid-binding resin) bind in the GI tract?
Warfarin and Digoxin
What effect does complex formation in the GI tract cause?
- DECREASED drug absorbance
- DECREASED drug plasma concentrations
What happens to the levels of free drugs in the plasma with concurrent administration of two drugs with high binding to plasma proteins?
INCREASED free drug levels for both drugs
What is Enzyme Induction?
Increase in enzyme activity caused by a foreign compound (inducer)
Does Enzyme Induction occur slowly or fast?
Slowly
TRUE OR FALSE:
Enzyme Induction requires a single exposure to the inducer?
False.
Requires repeated / prolonged exposure
What are the THREE roles of Enzyme Induction in drug interactions?
- Accelerates clearance
- Reduces drug action
- Increases formation of toxic metabolites
What inducer enhances the metabolism of Barbiturates, Estradiol, Phenytoin, and Quinine?
Barbiturates
What inducer enhances the metabolism of Dexamethasone, Digitoxin, and Theophylline?
Phenytoin
What inducer enhances the metabolism of Anticoagulants, and Oral Contraceptives?
Rifampicin
What is Enzyme Inhibition?
Decreased enzyme activity caused by a foreign compound
Does Enzyme Inhibitions occur slowly or fast?
Fast
What are the THREE roles of Enzyme Inhibition in drug interactions?
- Requires on a single dose
- Impairs drug clearance
- Prolongs drug action
What inhibitor inhibits the metabolism of Diazepam and Warfarin?
Cimetidine
What inhibitor inhibits the metabolism of Antipyrine, Ethanol, Phenytoin, and Warfarin?
Disulfiram
What inhibitor inhibits the metabolism of Methanol?
Ethanol
How does Hepatic blood flow affect the rate of drug metabolism?
Reduced hepatic blood flow = Reduced metabolism
Which types of drugs are particularly susceptible to changes in hepatic blood flow?
First-Pass metabolism drugs
What are the THREE main mechanisms of renal excretion?
- DECREASED protein binding would INCREASE filtration and elimination
- Inhibition of tubular secretion
- Alter urine flow and/or urine pH
