U3.1 PHARMACOKINETICS Flashcards
What the body can do to the drug
Pharmacokinetics
Dose-concentration relationship
Pharmacokinetics
Effects of the biologic system on drugs
Pharmacokinetics
T/F Pharmacodynamics deals with the processes of absorption, distribution, [metabolism], and elimination [or excretion] of drugs
F
Concentration of a drug at the receptor site [in contrast to drug concentrations that are more rapidly measured, eg, blood]
Effective Drug Concentration
The amount of drug waiting to associate with its receptor
Effective Drug Concentration
T/F Not all of the drug that the patient takes in would take effect
T
3 contributors to plasma concentration
- Rate of input of the drug by absorption
- Rate of distribution to peripheral tissue
- Rate of elimination, or loss, from the body
2 basic parameters of pharmacokinetics
- Volume Distribution (Vd)
- Clearance (CL)
measure of the apparent space in the body available to contain the drug
Volume distribution
measure of the apparent space in the body available to contain the drug
Volume distribution
measure of the ability of the body to eliminate the drug
Clearance
related the amount of drug in the body to the concentration of drug (C) in blood of plasma
Volume distribution
T/F Initial distribution is in the liver, kidney and brain
T
T/F Distribution is faster in muscle, viscera, fat and skin
F
T/F Distribution happens in the interstitial and intracellular fluids
T
Amount of drug in the body to the plasma/serum concentration
Volume Distribution
distribute your
drug inside the tissues
Intracellular
distribute drug outside the cells
Extracellular
T/F When a drug is avidly bound in peripheral tissues, its concentration in plasma may drop to very low values even if the total amount in the body is large
T
↑ Vd = distributed in ___
peripheral tissue
Relationship of Vd to plasma volume
When a drug is completely retained in the plasma compartment
Volume of distribution (Vd) = plasma volume
Rate of elimination compared to drug concentration (C)
Clearance (CL)
Depends on the drug and the organs of elimination in the patient
Clearance (CL)
2 major sites of drug elimination
Liver & Kidney
↑ Vd = ___ plasma concentration
↓ plasma concentration
↑ Vd = distributed to ____ e.g. urine, brain
tissues
↓ Vd = stays in the _____ e.g. septicemia
blood
T/F In clearance, drugs are eliminated with first-order kinetics
T
T/F Clearance is constant and can be calculated via area under the curve (AUC)
T
First Order = ___ drug concentration, ___ elimination
↑ drug concentration, ↑ elimination
T/F CL = rate of elimination / plasma concentration
T
T/F Continuous elimination half-life makes the initial concentration smaller & smaller; thus slowing down elimination.
T
Clearance : 2 Types of Elimination
- Capacity-Limited Elimination
- Flow-Dependent Elimination
T/F During capacity-limited elimination, clearance does not remain constant but will vary depending on the concentration of drug that is achieved
T
T/F Most drug elimination pathways by metabolism will not become saturated if the dose and therefore the concentration are high
enough.
F; it will become saturated
Type of elimination
Some drugs are cleared very readily by the organ of elimination
Flow-Dependent Elimination
Type of elimination
When blood flow to an organ does not limit elimination, the relation between elimination rate and concentration (C) is expressed mathematically in equation
Capacity-Limited Elimination
Type of elimination
Most of the drug in the blood perfusing the organ is eliminated on the first pass of the drug through the organ.
Flow-Dependen elimination
T/F For Flow-Dependent elimination, the elimination of these drugs will thus depend primarily on the rate of drug delivery to the organ of elimination.
T
Flow Dependent Elimination
main determinant of drug delivery
Blood flow to the organ
Flow Dependent Elimination
important for extensively bound drugs that are highly extracted
plasma protein binding and blood cell partitioning
Time it takes for the amount of concentration of a drug to fall to 50% of an earlier measurement
Half-Life T1/2
T/F Drugs eliminated by first-order kinetics are constant
T
Determines the rate at which blood concentration rises during a constant infusion and falls after administration is stopped.
Half-Life T1/2
T/F Drug accumulation happens when repeated drug doses will be accumulated until dosing stops
T
inversely proportional to the fraction of
dose lost in each dosing interval
Accumulation
drug administration = elimination
Steady State Concentration
Dose in = Dose Out
Steady State Concentration
of Half lives for the drug to have a steady state
4
Fraction of the administered dose of the drug that reaches the systemic circulation
Bioavailability
Equal to the amount absorbed over the amount administered
Bioavailability
Bioavailability
Unity or 100%
Intravenous administration
Bioavailability
< 100%
First-pass elimination by the liver.
Oral administration
T/F Drugs are more absorbed in the small intestines because it has a larger surface area.
T
Liver immediately metabolizes and makes it water soluble to make it easier to be excreted via kidneys.
First pass metabolism
Routes with low bioavailability
Sublingual, Rectal, Inhalation or nasal, Transdermal patches
T/F Bioavailability is dependent on extent of absorption, first-pass effect, rate of elimination and site of administration.
F; extent of absorption, first-pass effect, rate of absoprtion and site of administration
Bioavailability route
100% BA; most rapid onset
Intravenous (IV)
Bioavailability route
75 to < 100; Large volumes often feasible, may be painful
Intramuscular (IM)
Bioavailability route
75 to < 100; Smaller volumes than IM, may be painful
Subcutaneous (SC)
Bioavailability route
5 to <100; Most convenient; 1st-pass effect may be important
Oral (PO)
Bioavailability route
30 to <100; Less first-pass effect than oral
Rectal (PR)
Bioavailability route
5 to <100; Often very rapid onset
Inhalation
Bioavailability route
80 to ≤100; Usually very slow absorption, lack of first-pass effect
Transdermal
Bioavailability route
Prolonged duration of action
Transdermal
Determined by the site of administration & drug formulation
Rate of Absorption
Type of drug absorption
Rate is independent of the
amount of drug remaining in the gut.
Zero-order drug absorption
Type of drug absorption
When the rate of absorption is proportional to the concentration.
First-order drug absorption
T/F Systemic clearance is not affected by bioavailability
T
T/F During Oral administration, concentration of drug
metabolites will be increased compared to IV
administration
T
Alternative Routes
direct access to systemic but not portal veins
Sublingual Absorption & Transdermal Route
Alternative Route
drain into inferior vena cava, bypassing the liver
Lower rectum suppositories
Alternative Route
bypass first-pass effect by inhalation to lungs
Non-gastrointestinal (“parental”) routes
Time Course of Drug Effects
Instantaneous effect
Immediate Effect
Time Course of Drug Effects
Directly related to concentration
Immediate Effect
Time Course of Drug Effects
Due to distributional delay
Delayed Effect
Time Course of Drug Effects
Delayed expression of the physiologic substance needed for the effect.
Delayed Effect
Time Course of Drug Effects
slow turnover of a physiologic substance that is involved in the expression of the drug effect
Delayed Effect
Time Course of Drug Effects
Constant infusion
Cumulative Effects
Time Course of Drug Effects
Aminoglycosides cause renal toxicity if given constantly.
Cumulative Effects
Time Course of Drug Effects
Intermittent dosing only.
Cumulative Effects
Fraction of the drug removed from the perfusing blood during passage to the organ
Extraction ratio
Measure of the elimination of the drug by that organ.
Extraction
↑ hepatic extraction, __ first-pass effect
↑ first-pass effect
Drugs are eliminated unchanged or as metabolites
Excretion
Polar compounds are more efficiently eliminated
Excretion
The concentration wherein you see the desired
therapeutic effects of the drug
Target Concentration
T/F Target concentration will also depend on the specific
therapeutic objective
T
Plan for drug administration over a period
Dosage Regimens
Achievement of therapeutic levels of the drug in the body without exceeding the minimum toxic concentration
Dosage Regimens
Dose needed to maintain a steady state of concentration
Maintenance Dose
Maintain plasma concentration within a specified range
over long periods of therapy
Maintenance Dose
Most important parameter in defining rational drug dosage
Clearance
For drugs with long half-lives and longer time to reach a steady state
Loading Dose
Given to promptly raise the concentration of the drug to the target concentration
Loading Dose
Important factor to consider in loading dose
Volume of distribution
↑ volume of distribution, __ loading dose
↑ loading dose
4 Pharmacokinetic Variables
- absorption
- clearance
- volume of distribution
- half life
Pharmacokinetic Variable
Compliance of patient is important.
Absorption
Pharmacokinetic Variables
Variations in bioavailability are usually due to variations in metabolism
Absorption
Pharmacokinetic Variables
Most important parameter in designing dosage regimen.
Clearance
Pharmacokinetic Variables
may be anticipated when there is major impairment of the function of the kidney, liver, or heart
Abnormal clearance
Pharmacokinetic Variables
Good indicator of renal function
Creatinine Clearance
Pharmacokinetic Variables
↑ Vd = ____
↓ Vd = ____
↑ Vd = tissues, body waters, extracellular accumulation of body fluids
↓ Vd = plasma
Pharmacokinetic Variables
Dependent on clearance and volume of distribution
Half-life
2 Pharmacodynamic Variables
- Maximum Effect
- Sensitivity
Pharmacodynamic Variables
No more increase in effect even if the concentration is
increasing
Maximum effect
Pharmacodynamic Variables
Increased, exaggerated response to small doses
Sensitivity
Pharmacodynamic Variables
EC50, the concentration required to produce 50%
of maximum effect
Sensitivity
More highly protein bound drug will displace the less protein bound drug
Plasma binding proteins
Acidic drugs bind to ____
albumin
Basic drugs bind to ____
α1-Acid glycoprotein
Average total amount of drug in the body does not change over multiple dosing intervals
Steady State Concentration
Safe opeing between the MEC and MTC of the drug
Therapeutic Window
used to determine the range of plasma levels that is acceptable when designing a dosing regimen
Therapeutic Window
Peak and Through Concentrations
determines the desired trough levels of a drug given intermittently
MEC : Minimum effective concentration
Peak and Through Concentrations
determines the permissible peak plasma concentrations
MTC : minimum toxic concentration
Most appropriate time to measure drug concentration
2 hours
T/F With maintenance dose drugs, you’ve already reached the steady state concentration
T
First Order kinetics
↑ drug concentration, ____ rate of elimination
↑ rate of elimination
↑ Vd = distributed to tissues, ____ half-life
↑ longer half-life
↓ Vd = stays in the blood, ____ half-life
↓ shorter half-life
↑ drug accumulation, ____fraction of the dose lost in each interval
↓ fraction of the dose lost in each interval
↓ affinity drugs = ____ plasma concentration
↑ plasma concentration