Unit 1 Pharmacokinetic Principles Flashcards
Discuss the pharmacokinetic principles of Distribution.
- Factors influencing drug distribution
- Volume of Distribution
- Loading Dose
What are the factors that influence drug distribution?
- Blood flow to the area of action
- membrane permeability
- Plasma protein binding
Give an example how blood flow to the area of action can influence drug distribution.
Blood Brain Barrier
Prostate
Give an example how membrane permeability can influence drug distribution.
Lipophilic drugs readily cross the BBB (vs hydrophilic)
Give an example how plasma protein binding can influence drug distribution.
higher protein binding decreases unbound or “free” drug in the blood; only unbound drug can exert pharmacologic effect
A drug that is protein bound or unbound has the best chance of crossing the BBB?
Unbound
Bound or unbound proteins are less active?
Bound
Phenytoin is a 90% protein bound drug; 10% is free or unbound. What percentage is going to cross the BBB?
Unbound/free = 10%; need to give a high enough does to equal that 10%.
Vd
Volume of distribution
The apparent volume into which a drug distributes in the body at equilibrium.
Vd (volume of distribution)
the volume that would be required to contain the administered dose if that dose was evenly distributed in blood or plasma
Vd
Vd = __________ divided by ____________
amount in body (mg) / plasma drug concentration (mg/L)
An initial dose that is larger than subsequent doses for the purpose of achieving therapeutic drug concentrations more rapidly
Loading Dose
Loading dose = ________ x ___________
LD = Vd x Cp
Where are most drugs primarily metabolized?
Liver
What does metabolism do to drugs?
process makes the drug more water soluble to be eliminated.
List the factors that influence metabolism.
- Hepatic dysfunction (in liver)
- Severe CHF (decrease blood flow via liver)
- Advanced age (slower metabolism)
Metabolism slows down at what age?
65yrs
Phase I Reactions, Phase II Reactions, Prodrugs, and Active metabolites all would be classified under what pharmacokinetic principle?
Metabolism
When a drug is oxidized or reduced to more polar form?
Phase I Reaction
A Phase 1 Reaction makes a drug more water soluble or less water soluble?
More polar = more water soluble
Cytochrome P450 system is a Phase 1 Reaction or Phase 2 Reaction?
Phase I Reaction
What organ contains most of cytochrome P450?
liver
List the organs where cytochrome P450 is located.
liver, intestines, skin, kidneys, brain, lungs
A dug metabolized by Cytochrome P450 system is and inducer, inhibitor, or substrate?
Substrate
Hydrophilic or lipophilic drugs are mostly metabolized by Cytochrome P450?
lipophilic
Drug that causes more rapid metabolism of substrate drugs? Substrate, Inducer, Inhibitor, prodrug, or active metabolite?
Inducer
Give an example of a drug inducer.
chronic EtOH
Drug that causes slower metabolism of substrate drugs? Substrate, Inducer, Inhibitor, prodrug, or active metabolite?
Inhibitor
Give an example of a drug inhibitor.
Cimitidine
What is a Phase II Reaction?
Polar group is conjugated to the drug
A phase II reaction will do what to polarity?
increase polarity
The goal of metabolism is to make a drug more soluble or insoluble?
water soluble
Describe the term prodrug.
inactive substance metabolized to an active substance w/in the body
Give an example of a prodrug.
Prednisone metabolized & changes to prednisolone
Codeine to morphine
Fosphenytoin to phenytoin
A prodrug has pharmacological activity? T or F?
False
A metabolite that also has therapeutic activity.
Active metabolite
Metabolites can be active or inactive?
They can function as both!
Describe how elimination is a pharmacokinetic principle.
Drugs are excreted from the body after being metabolized to a more polar form; others are excreted unchanged, usually in the urine
How are drugs eliminated?
Via Filtration, secretion, and reabsorption
Term: Drugs diffuse from blood to nephron
Filtration
Drugs best travel through the nephron in what form and become eliminated?
Small, unbound, nonionized, lipid soluble
Explain how drug travel from high concentration to low concentration during filtration.
They diffuse from blood to the nephron (small, unbound, non-ionized, lipid soluble
When do some drugs go through active transport during the elimination process? Term.
Secretion: Drug into the nephron
Term:
Drugs reabsorbed into the blood stream by diffusion from the nephron tubule (small, non-ionized)
Reabsorption
List factors that influence elimination.
Renal dysfunction; Heart Failure exacerbation, diabetes, uncontrolled HTN, decrease age
Explain half life (t 1/2)
the time it takes the plasma concentration of a drug to decrease by 50% after a given dose
Give an example of 2 anticoagulants with different half-life.
Heparin = 1.5hrs; Warfarin = 40 hrs
The time from 10 hours to 5 hrs is 1 Half-life. At what point does the following half occur?
At 2.5 hrs.
How is t 1/2 related to dosing frequency?
The longer the t 1/2, the longer the dosing interval.
How is Vd related to t 1/2?
A. No relationship
B The smaller the Vd, the shorter the t 1/2
C. The larger the Vd, the shorter the t 1/2
B. The smaller the Vd, the shorter the t 1/2
Describe Steady State
absorption = elimination; the drug in the body is in a state of homeostasis; generally reached in 5 half-lives.
Heparin’s t 1/2 is 1.5 hrs. Warfarin’s t 1/2 is 40 hrs. What is there steady state?
Heparin = 7.5 hours later Warfarin = 200 hrs (8 days)
The dose of drug that attempts to maintain a steady state plasma concentration in the therapeutic range.
Maintenance Dose
Term: What drugs do to the body.
Pharmacodynamics
The component of a cell or organism that interest w/ a drug and initiates the chain of biochemical events leading to the drug’s observed effects
Receptor
What type of receptor alters the physiology of a cell by binding to plasma membrane or intracellular receptors
Agonist
