Pharmacokinetics Flashcards
Pharmacokinetics
Factors that contribute to controlling concentration of a drug at an action site
Absorption (bioavailability)
Distribution
Metabolism (/clearance)
Bioavailaibiilty
Fraction or % of a drug that enters the circulation after the first pass effect
Bioavailable dose
mg or mg/kg of a drug that enters the circulation after first pass effect
Factors for deciding the appropriate route of administration
Prospects for compliance
Speed of absorption
Potential for therapeutic effects with local delivery
Enteral routes
Entering via intestine
Parenteral routes
Entering outside the intestine
Oral administration
Pros - convenient, safe, economical, higher compliance, can induce vomiting if overdose
Cons - first pass effect, irregular absorption due to pH/food, not practice if patient is vomiting
Advantage of sublingual administration
Avoids first pass effect
Rectal administration
Pros - can be used for vomiting patient or where oral impractical
Cons - absorption can be irregular, slower (typically)
Intravenous administration
Pros - instantaneous, Endothelia more tolerant of irritating solutions
Cons - toxicity?, not readily reversible, requires expertise, repeat injection —> lose patency of veins
Subcutaneous administration
Can be manipulated for fast or slow administration
Common for vaccines
Intramuscular injection
Often slow
Can be painful
Instantaneous administration
IV
Inhalation
Nasal
Slow administration
Rectal
transdermal
IM
Other routes of administration
Intrathecal, intraocular, intraosseous
Factors affecting bioavailability
Route of administration
Physicochemical properties of drug
Physiology of patient
Methods of crossing membranes
Passive diffusion (lipid soluble)
Carrier-mediated transport (charged/polar molecules)
Weak acids will be absorbed …
In an acidic environment
Weak bases will be absorbed …
In a basic environment
Factors that affect distribution
Rate of absorption (charge, lipophilicity, pH, amount in circulation, surface area of compartment)
pH gradients
Weak acids will accumulate in …
Basic compartments
Weak bases will accumulate in …
Acidic compartments
Volume of distribution
Hypothetical/apparent volume of plasma into which a drug distributes if drug were only distributed in plasma
= Bioavailabile dose / concentration of drug in plasma
Volume of distribution > 0.6 L/kg indicates
Drug accumulated in non-aqueous environment (fat, organs)
Volume of distribution «_space;0.6 L/kg indicates…
Drug is being accumulated in blood compartments; does not have access to non-plasma compartments
Majority of drugs are metabolized by …
First order kinetics
First order kinetics
Rate of metabolism is proportional to concentration of drug
(I.e. the same amount of drug is metabolized over a given interval)
No saturation effect
Clearance
Metabolism + elimination
Volume of plasma that is cleared of a drug per unit time (normalized to body weight - ml/min per kg)
Two compartment pharmacokinetic model
A drug may enter a particular compartment quickly —> then redistribute to other areas of the body - this results in an initial rate, followed by a secondary rate
Starts out step —> quickly leaves central compartment (most heavily perfused) —> redistributes —> clears more slowly from the system (peripheral compartment)
Change in concentration = some of two first order decay processes
Repeated administration of a drug
Four doses required to reach steady state
Peak/troughs average over plateau concentration
To avoid the ramp up to the plateau concentration of a drug
Administer a loading dose (initial high dose)
When an enzyme system is saturated elimination follows…
Zero-order kinetics
Zero order kinetics
Same amount of drug is eliminated in any time interval (as opposed to same fraction under normal conditions)
Common example = alcohol
Factors that may impact pharmacokinetics
Age
Weight
Disease states
Drug-drug interactions
Polymorphisms
Species
