Pharmacology – Ch. 3 – Pharmacokinetics

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aka Biodisposition; The effects of biologic systems on drugs. It deals w/ the Absorption, Distribution, & Elimination of Drugs. Loading & Maintenance Doses can be calculated.
What is Pharmacokinetics? What processes are involved? What can be calculated in Pharmacokinetics?

The concentration of a drug AT THE RECEPTOR SITE (in contrast to drug concentrations that are more readily measured like in the blood)
What is Effective Drug Concentration?

Vd = (Amount of Drug in the Body) / (Plasma Drug Concentration) in Volume Units; The higher the Vd, the more the drug has been distributed to the tissues as opposed to free flowing in the plasma
What is the Volume of Distribution (Vd)?

CL = (Rate of Elimination of Drug) / (Plasma Drug Concentration) in Volume per Unit Time
What is Clearance (CL)?

CONSTANT (the ratio of elimination to plasma concentration is the same regardless of plasma concentration)
What is the Clearance of Drugs that are eliminated w/ 1st Order Kinetics?

1) Type of Drug; 2) Condition of Organs of Elimination (Liver, Kidney, etc); Clearance is often Flow-Limited because the clearance of a drug is sometimes very effectively extracted by an organ (the blood is completely cleared of the drug as it passes thru the organ); In these conditions, blood flow thru the eliminating organ is more important
What 2 things is Clearance dependent on? How is Clearance often Flow-Limited?

1) Ethanol; 2) Aspirin; 3) Phenytoin
Majority of Drugs follow 1st Order Kinetics. Which 3 important drugs do NOT follow this?

t1/2 = (.7 x Vd) / (CL); The time required for the amount of drug to fall to 50% of an earlier measurement; derived from Vd & Clearance; CONSTANT for 1st order kinetics
What is Half-Life? What is the Half-Life of drugs following 1st Order Kinetics?

The fraction (or %) of drug concentration/dose that reaches the Systemic Circulation; Unity or 100%
What is Bioavailability? Bioavailability of IV administered drugs?

Incomplete Absorption (expulsion of drug by intestinal transporters by intestine), 1st Pass Metabolism, & Any Distribution into Other Tissues that occurs before the drug enters the systemic circulation
What factors REDUCE Bioavailability of drugs administered other ways besides IV?

It is the Area Under the Plasma Concentration Curve (or AUC); (AUCroute) / (AUCiv); AUC is the graphic area under a plot of Drug Conc. versus Time after a single dose
How is Bioavailability measured on a graph curve? What is AUC?

The elimination of drug that occurs after administration but before it enters the systemic circulation; Ex: during passage thru Gut Wall, Portal Circulation, or Liver for an orally administered drug)
What is the 1st Pass Effect?

The fraction of the drug removed from the perfusing blood during its passage thru the organ; Drugs that have a high hepatic extraction ratio have a large 1st pass effect so the bioavailability of these drugs after oral administration will be low
What is Extraction Ratio?

Oral administration
What route of administration has a large 1st pass effect & therefore low bioavailability?

A plan for drug administration over a period of time. An appropriate regimen results in the achievement of therapeutic levels of the drug in the blood w/o exceeding the minimum toxic concentration;
What is a Dosage Regimen?

Maintenance: To maintain the plasma concentration w/in a specified range over long periods of therapy; Loading Dose: Necessary to achieve the target plasma level Rapidly and the volume of distribution is large; it is used to “Load” the volume of distribution w/ the drug
When are Maintenance Doses given? Loading Doses?

Dosing Rate = (Clearance x Desired Plasma Concentration) / (Bioavailability); Vd is not involved
What is Maintenance Dose? Which parameter is not involved?

Loading Dose = (Vd x Desired Plasma Concentration) / (Bioavailability); Clearance is not involved
What is Loading Dose? Which parameter is not involved?

The safe range b/t the minimum therapeutic concentration (Trough) & the minimum toxic concentration of the drug (Peak)
What is the Therapeutic Window? What are the Trough & Peak concentrations of a drug?

Renal Disease or Reduced Cardiac Output, sometimes Liver Disease; Corrected Dose = (Average Dose) x (Patient’s Creatinine Clearance / 100mL/min)
Which conditions normally reduces the clearance of drugs? What is the formula for the corrected dose needed for patient’s where the elimination of their drugs is altered by disease?

The condition in which the average total amount of drug in the body does NOT change over multiple dosing cycles (ex: The condition in which the rate of drug elimination = The rate of Administration)
What is Steady State?

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