Flashcards in Pharmacokinetics and Pharmacodynamics II Deck (25)
What tissues/compartments are drugs with low volumes of distribution (4-8L) distributed to?
Which tissues/ compartments are drugs with medium volumes of distribution distributed to?
Which tissues/ compartments are drugs with high volumes of distribution distributed to?
All tissues (p.227)
Describe the molecular properties of a drug that has a low volume of distribution.
Large/charged molecules; plasma protein bound (p.227)
Describe the molecular properties of a drug that has a medium volume of distribution.
Small hydrophilic molecules (p.227)
Describe the molecular properties of a drug that has a large volume of distribution.
Small lipophilic molecules, especially if bound to tissue protein (p.227)
How many half lives does it take a drug infused at constant rate to reach steady state?
4-5 half lives (p.227)
What is the equation for determining the half life of a drug?
T(1/2) = (0.7 x Vd)/ CL (p.227)
What is clearance?
Relationship of the rate of elimination of a drug to its plasma concentration; may be impaired with cardiac, hepatic, or renal dysfunction (p.227)
What is the equation for determining the clearance of a drug?
CL= (rate of elimination of drug)/ (plasma drug concentration) = (Vd x Ke) where Ke is an elimination constant (p.227)
How do you calculate loading dose?
LD= Cp x (Vd/F) (Where Cp= target plasma concentration) (p.227)
How do you calculate maintenance dose?
MD= Cp x (CL/F) (p.227)
How do maintenance and loading doses change in a patient with renal or liver disease?
Maintenance dose decreases; loading dose is unchanged (p.227)
What determines time to steady state of a drug? What factors are independent of this?
Dependent primarily on half life; independent of dosing frequency or size (p.227)
Describe the properties of a zero-order elimination of drugs.
Rate elimination is constant regardless of Cp; a constant AMOUNT of drug is eliminated per unit of time and Cp thus decreases linearly with time. Capacity-limited elimination (p.228)
Name three drugs that are eliminated by zero-order elimination.
Phenytoin, Ethanol, Aspirin (at high or toxic concentrations) (p.228)
Describe the properties of a first-order elimination of drugs.
Rate of elimination is directly proportional to the drug concentration with a constant FRACTION of drug eliminated per unit of time. Cp decreases exponentially with time. Flow dependent elimination (p.228)
How do you trap a weak acid in urine?
Trapped in basic environments. Use bicarbonate to treat overdoses of phenobarbital, methotrexate, aspirin, etc. (p.228)
How do you trap a weak base in urine?
Acidify the urine. Use ammonium chloride to trap amphetamines, etc. (p.228)
What is involved in phase I of drug metabolism?
Reduction, oxidation, hydrolysis with cytochrome P-450 usually yields slightly polar, water-soluble metabolites that are often still active (p.228)
How is drug metabolism impaired in geriatric patients?
Geriatric patients often lose phase I of drug metabolism (p.228)
What is involved in phase II of drug metabolism?
Conjugation (Glucuronidation, Acetylation, Sulfation) usually yields very polar, inactive metabolites (renally excreted) (p.228)
What changes in drug metabolism occur in patients who are slow acetylators?
Decreased Phase II metabolism- greater side effects from certain drugs due to decreased rate of metabolism (p.228)
What is the principle difference between the metabolites produced in Phase I vs. Phase II drug metabolism?
Phase I: slightly polar, water soluble metabolites; Phase II: very polar, inactive metabolites (p.228)