Basics of Anesthesia 5th ed Chapter 5 Basic Pharmacology Flashcards
Pharmacokinetics
Describes the absorption, distribution, metabolism and excretion of drugs
Pharmacodynamics
Describes the responsiveness of receptors to drugs and the mechanisms by which these effects occur.
What the body does to the drug.
Pharmacokinetics
What the drug does to the body.
Pharmacodynamics
The components of the cell that interact with drugs to initiate a sequence of events leading to pharmacologic effects
Receptors
How are drug effects terminated? Name 3 ways.
Metabolism
Excretion
Redistribution to inactive sites
3 ways that understanding dose-response relationships of a drug can be adventageous
Allows comparision with other drugs
Determines the influence of altered physiologic states on a drug
Allows consideration of new approaches to drug administration (ie: computer driven infusion pumps, patient controlled analgesia
The most pharmacologically active form of a drug is usually
A. The ionized portion
B. The non-ionized portion
The Non-ionized, lipid soluble form
Which is pharmacologically active, lipid soluble or water soluble drugs?
Usually lipid soluble. They cross membranes more easily.
Water soluble drugs are usually
A. Ionized
B. Non-ionized
ionized and inactive
Our bodies frequently metabolize lipid soluble drugs to the ionized water soluble form for excretion through the urine.
The degree of ionization of a drug is a function of what 2 factors?
pH and pKa
What do you know about a drug when the pH of the environment and the pKa of the drug are equal?
The drug will be 50% ionized and 50% unionized.
How do small changes in pH effect the degree of ionization of a drug?
Small pH changes can result in large changes in degree of ionization.
What type of drugs tend to be highly ionized at alkaline pH?
Acidic drugs
Name a drug classification that is acidic.
Barbiturates
Basic drugs are highly ionized in what pH range?
Acidic pH ranges
Does lipid versus water solubility influence absorption and elimination characteristics of drugs?
Yes
The rate at which a drug leaves its site of administration is called:
Absorption
Name 3 ways drugs can cross cell membranes.
Simple diffusion
Facilitated diffusion (carrier mediated transport)
Active transport
Is simple diffusion a uni- or bi- directional process?
Bidirectional
What determines the rate of drug transfer across a cell membrance with simple diffusion?
The concentration gradient
What 2 types of drugs diffuse passively across cell membranes?
Highly lipid soluble drugs
Small molecular weight drugs
How do large molecular weight drugs get across membranes?
Carrier mediated or active transport
Which requires energy, simple diffusion, carrier mediated transport and/or active transport
Active transport requires ATP
Which are usually better absorbed, liquids/crystalloids, solids, or colloids?
Why?
Liquids/crystalloids
Because they are more soluble in membranes
What kinds of things change the rate at which a drug is absorbed?
Solubility - High lipid solubility increases drug absorption
Concentration gradient - the higher the gradient, the faster the rate of absorption
Heat/Cold - Heat increases rate of absorption, Cold decreases it
Vasodilation increases absorption, vasoconstriction decreases absorption
Degree of ionization of the drug - unionized portion is absorbed more quickly
Route of administraiton - IV route absorbed quickest, administration in highly vascular tissues increases absorption
Which will be more rapidly absorbed fromt he stomach, an acid or a basic drug?
Acid
More of an acid drug will be in the unionized form when it is placed in acidotic tissue.
Which will be more rapidly absorbed form the small intestine, an acid or a basic drug?
Basic
The Environment is more alkaline in the small intestine. A higher amount of a basic drug will be in the unionized form in a basic environment.
What is meant by the “first pass hepatic effect?”
Drugs absorbed from the small intestine enter the portal venous system. This carries the drug through the liver before it circulates thorugh the systemic circulation. Some of the drug is metabolized in the liver before it reaches the central circulation.
Why do drugs like propranolol and lidocaine require much higher dosage when given PO as opposed to IV?
These drugs undergo first pass hepatic metabolism when given PO.
Complete this chart
Characteristic Nonionized Ionized
Pharmacologic effect
Solubility
Cross lipid barriers
Renal excretion
Hepatic metabolism
Characteristic Nonionized Ionized
Pharmacologic effect Active Inactive
Solubility Lipids Water
Cross lipid barriers Yes No
Renal excretion No Yes
Hepatic metabolism Yes No
What three factors influence absorption of a drug?
Route of delivery
Bioavailabilty
The possibility of first-pass metabolism
Which of the following is not relevant when a drug is administered IV?
Absorption
Distribution
Metabolism
Elimination
Absorption
What is meant by “drug distribution?”
Instantaneous distribution of the drug into the blood volume (+ dilution) and partitioning the drug into peripheral compartments.
What is meant by “drug clearance?”
Removal of the drug, typically through hepatic metabolism, renal elimination or exhalation.
Which is absorbed more quickly, drugs given through the sublingual/buccal mucosa or drugs given PO?
Drugs given sublinqual or through the buccal mucosa because they do not undergo first pass hepatic metabolism and the absorption is not influenced by the presence of food.
Characterize the speed of absorption for a drug given through the inhalation route.
The drug will be absorbed into the blood stream rapidly.
How is the effect of a local anesthetic injected into subcutaneous tissue terminated?
The drug is picked up by capillaried in the area of the injection and carried through the central circulation to its point of metabolism.
What are the advantages and disadvantages to using the skin as a route of drug administration?
The skin presents a considerable barrier to absorption but it does provide a depot for drugs which allows for continued drug delivery even after the drug (patch) has been removed.
The rate of transfer of a drug from the depot (stomach, lung, nerve bundle, transdermal patch) to the central circulation is directly proportional to ________.
the concentration gradient between the depot and th systemic circulation.
How does rapid and/or slow absorption effect peak plasma concentrations?
Rapid absorption leads to high peaks and slow absorption leads to smaller peaks.
Local anesthetics used for nerve blocks are at higher risk of producing systemic toxicity if injected into an area where drug absorption is faster or slower?
Faster
What is meant by “distribution.”
Distribution dilutes the drug from the highly concentrated solution injected into the body to the highly dilute concentration in the plasma. It is a process of mixing, initially with the blood, and then with the tissues of the body.
What is the formula for calculating volume of distribution?
Solume = Dose(amount)/Concentration
What is the “central volume of distribution.”
It is the apparent volume immediately (actually 1/2 minute) after injecting a bolus of drug into the body.
What is meant by central volume?
The blood and tissue that the drug has had time to mix with during the first 1/2 minute or so after injecting it.
Typically it is the blood in the heart and great vessels as well as drug uptken by the lungs.
What is the formula for determining the dose of a drug that should be adinistered to obtain a given concentration?
Dose = Desired concentraiton x volume
Are anesthetic drugs primarily water soluble or lipid soluble?
Lipid soluble
Because anesthetic drugs are highly fat soluble, how much of tehm is distributed into peripheral tissues?
A considerable amount of lipid soluble anesthetic drugs are distributed into peripheral tissues.
What is meant by the “peripheral compartment?”
The peripheral tissues in which highly fat soluble anesthetic drugs distribute.
The size of the peripheral volumes of distribution relates to the _____?
Solubility of the drug in the tissue, relative to the solubility in blood (or plasma).
If a drug is highly soluble in a tissue, then it will have a large or small peripheral volume of distribution?
Large
What is the peripheral volume of distribution of propofol?
> 1000L
What are the four main tissue compartments of the body?
Vessel rich group (brain and most organs)
Muscle group
Fat group
Vessel-poor group (skin, cartilage, ligaments)
What is clearance?
The process that removes drug from a tissue.
What is systemic clearance?
Permanent removal of drug from the body.
What is intercompartmental clearance?
The movement of drug from one tissue to another.
What is the difference between systemic clearance and intercompartmental clearance?
Systemic clearanceis the permanent removal of drug from the body.
Intercompartmental clearance refers to movement of drug from one tissue to another.
What are the units of clearance?
Clearance has units of flow; the volume “cleared” per unit of time (liters/minute)
Compare hepatic clearance of propofol to hepaticl clearance of fentanyl.
The liver metabolizes almost all of the propofol th.at enters it through the hepatic artery and portal vein. So propofol’s clearance = hepatic blood flow
The liver clears only about half of the fentanyl that enters via the hepatic artery or portal veins.
So, fentanyl’s clearance is half of liver blood flow.
If the kidneys remove every molecule that enters the kidney then renal clearance would equal . . .
Renal blood flow
If the kidneys only remove every molecule that is filtered at teh glomerulus, then plasma clearance is equal to
glomerular filtration rate
