Passage of drugs form an area of higher concentration to an area of lower concentration until the drug molecules are equally distributed
equilibrium
same affect
agonist
opposite
antagonist
able to reverse drugs effect
Competitive antagonism
AKA Reversible antagonism/Surmountable
antagonism
Drug doesn’t have ability to change or even have an effect on a drug
Noncompetitive/Irreversible/Insurmountable
Something that helps another antagonist
partial antagonist:
Ex: Drug A helps to lower BP 25%, Drug B helps lower the BP 15%..they work together and help one another do the same job
Compounds used as drugs that combine with ions in an environment to produce their effects
chelator
Ex: EDTA combines with calcium in the blood and prevents the clotting mechanism from turning the sample into a clot
Value that provides an approx. of the extent to how a drug is distributed throughout the body
volume of distribution
Movement of a drug from the blood to the tissue (brain), back to the blood and then to a
second tissue (fat)
redistribution
Transport System is backed up and is continuously occupied with drug molecules that can’t move across the membrane yet
saturation
Increased rate of metabolism of the drug
induced metabolism
Active form of the drug is more rapidly converted to a less active form shortening its life in the body
A drug that combines with its receptor and produces a specific effect on the cell
intrinsic activity
Alkaline Environment
Basic Environmental pH
Amount of a drug admin. At one time
Drug Dose
First part of the renal nephron
bowmans capsule
area of the nephron where some of the drug molecules may move from the filtrate and go back into circulation>>Reabsorption
loop of henle
Active part that contains active trans. Mechanisms for moving electrolytes, glucose and some drug molecules and essential molecules back and forth among urine
proximal convoluted tube
drug molecules actively transported from the peritubular capillaries into the urine
active secretion
Tuft of capillaries in the kidney. Pressure here forces water and small molecules from the blood into the bowman’s capsule
glomerulus
point where a t.i.d. admin. Drug reaches its peak and trough concentrations that are the same from dose to dose
steady state
drug that combines with a receptor and causes a cell to prod. A physiologic change
agonist
Movement of a drug molecule from an injection site to the systemic circulation
absorption
Molecular process where drugs move through fluid
passive diffusion
conversion of a drug from active to inactive form by the liver
biotransformation
study of how a drug moves into, through and out the body
pharmacokinetics
study of how the drug prod. Its effect on the body
pharmacodynamics
dissolving of a drug
dissolution
A more hydrophilic/eliminated drug
metabolite
hepatic effect in which some PO administered drugs do not make it to systemic circulation because they are removed by the liver
first-pass effect
in a dosage regimen, the instructions "b.i.d." would be what component
dose interval
movement of a drug molecule from an injection site to the systemic circulation
absorption
movement of a drug molecule into a compartment where it changes from a lipophilic state to a hydrophilic state and remains in that compartment
ion trapping
molecular process by which drugs move through fluid
passive diffusion
form of a drug molecule that cannot readily penetrate a cell membrane
ionized or hydrophilic
movement of drug molecules across a cellular membrane by using a carrier molecule and not requiring any energy expenditure by the cell
facilitated diffusion (NOT active transport)
type of drug (not drug molecule form) that becomes more ionized as the environmental pH becomes more acidic
alkaline or basic drug
route of administration that typically reaches a peak almost as quickly as the IV route of administration
IM
a smaller dose of a drug administered to keep drug concentrations in the therapeutic range after an initial, large dose of drug
maintenance dose
movement of a drug from systemic circulation out of the body
elimination or excretion
movement of a drug from the flood into the brain would be an example of this movement of drugs in pharmacokinetics
distribution
where the first-pass effect occurs
liver
conversion of a drug from active to inactive form by the liver
metabolism or biotransformation
movement of drug from a tissue back to the blood and then to a second tissue
redistribution (distribution is going from blood to tissue)
movement of drug from the intestinal tract, to the liver, to the blood and tissue, back to the liver, to the intestinal tract, and then reabsorbed back from the gastrointestinal tract to the liver
enterohepatic circulation
the point at which a t.i.d. administered drug achieves peak and trough concentrations that are the same from dose to dose
steady state
route of administration in which a drug is injected into the layers of the skin
intradermal
a drug that combines with a receptor and causes a cell to produce a physiologic change
agonist
the recommended total daily dose for a drug is 480 mg. what are the equivalent total daily doses for the following dosage intervals? from a practical point of view, which schedule provides the greatest chance for client compliance?
? mg q12h
? mg t.i.d.
? mg 18h
? mg q24h
? mg q4h
? mg q.i.d.
240 mg q12h
160 mg q8h
80 mg q4h
160 mg t.i.d.
480 mg q24h
120 mg q.i.d.
which one of the following drugs is absorbed in the greatest amount?
B. 200 x 0.4 = 80
rank the following injection routes in order of the most superficial to the most deep:
intramuscular, intradermal, subcutaneous
intradermal
subcutaneous
intramuscular
if you were injecting a drug IP, in what body area would you inject it?
abdominal or peritoneal cavity
drugs move through the body by a variety of mechanisms, including diffusion and active transport. which mechanism of drug movement is described by the following:
a local anesthetic injected subcutaneously produces a spreading feeling of numbness in the skin.
passive diffusion through extracellular fluid between cells
drugs move through the body by a variety of mechanisms, including
diffusion and active transport. which mechanism of drug movement is
described by the following:
large drug molecules are taken up by macrophage scavenger cells in the alveoli of the lungs
phagocytosis or pinocytosis because it is a large molecule
drugs move through the body by a variety of mechanisms, including
diffusion and active transport. which mechanism of drug movement is
described by the following:
the cells of the renal tubules accumulate concentrations of aminoglycoside antibiotic that greatly exceed drug concentrations in the plasma
active transport: able to accumulate drug in spite of the concentration gradient
drugs move through the body by a variety of mechanisms, including
diffusion and active transport. which mechanism of drug movement is
described by the following:
a hydrophilic drug that moves down a concentration gradient into a cell
facilitated diffusion: moves along a concentration gradient so no cellular energy is being expended, and because it is hydrophilic it is not likely to passively diffuse through the lipid cellular membrane; thus it needs a carrier to get through the membrane
will ionized drug molecules dissolve more readily in water or fat? which passes through membranes better - ionized molecules or nonionized molecules?
ionized molecules dissolve in water
nonionized molecules pass through membranes
which is the more acidic environment: a pH of 3 or a pH of 7?
pH of 3
drug A is an acid drug. is it more likely to be in the lipophilic or hydrophilic form when placed in a very acidic environment, such as the stomach?
acid drugs in acidic environments are more likely nonionized and therefore liphophilic
drug B exists in the ratios of nonionized molecules to ionized molecules at the following pH environments:
pH 4, 1: 100
pH 5, 1: 10
pH 6, 1: 1
pH 7, 10: 1
what is the pKa?
based on how drug B reacts as the pH becomes more alkaline or acidic, determine if drug B is an acid drug or basic drug.
pKa = 6
This drug becomes more ionized in more acidic environments and more nonionized in alkaline environments. That would make the drug an alkaline, or basic, drug
indicate a predominance of drug molecules in the ionized form or nonionized form:
acid drug pKa 3 placed in liquid pH 6
ionized
indicate a predominance of drug molecules in the ionized form or nonionized form:
acid drug pKa2 placed in liquid pH 9
ionized
indicate a predominance of drug molecules in the ionized form or nonionized form:
acid drug pKa 5 placed in liquid pH 2
nonionized
indicate a predominance of drug molecules in the ionized form or nonionized form:
acid drug pKa 7 placed in liquid pH 5
nonionized
indicate a predominance of drug molecules in the ionized form or nonionized form:
acid drug pKa 7 placed in liquid pH 7
1/2 in ionized form and 1/2 in the nonionized form
indicate a predominance of drug molecules in the ionized form or nonionized form:
alkaline drug pKa 6 placed in liquid pH 9
nonionized
indicate a predominance of drug molecules in the ionized form or nonionized form:
alkaline drug pKa 9 placed in liquid pH 8
ionized
ionizedindicate a predominance of drug molecules in the ionized form or nonionized form:
alkaline drug pKa 5 placed in liquid pH 2
indicate a predominance of drug molecules in the ionized form or nonionized form:
alkaline drug pKa 5 placed in liquid pH 8
nonionized
rank the following drugs with 1 being most rapidly absorbed and 4 being slowest to be absorbed from a subcutaneous tissue site with a pH of 7.4
basic drug, pKa 5.4
acid drug, pKa 8.4
acid drug pKa 6.4
basic drug pKa 9.4
with SQ, drug most in ionized state will most rapidly diffuse to capillary and enter systemic circulation.
Fastest - basic drug, pKa 9.4
Second - acid drug, pKa 6.4
Third - acid drug, pKa 8.4
Fourth - basic drug, pKa 5.4
for the situation, state whether the dose should be increased or decreased to compensate for the condition and still achieve therapeutic concentrations in the body.
half-life for a drug is extended
decrease dose: it takes longer for the drug concentrations to drop by 1/2
for the situation, state whether the dose should be increased or decreased to compensate for the condition and still achieve therapeutic concentrations in the body.
the metabolism of a drug has been accelerated by exposure to phenobarbital
increase dose: the drug is being converted to a metabolite (presumably an inactive metabolite) at a quicker rate
for the situation, state whether the dose should be increased or decreased to compensate for the condition and still achieve therapeutic concentrations in the body.
a hypoproteinemic animal is given a drug that is normally highly protein bound
decrease dose: less protein in the blood for binding means more drug molecules in the free form and available to distribute to tissues to produce a greater effect
or the situation, state whether the dose should be increased or decreased to compensate for the condition and still achieve therapeutic concentrations in the body.
the volume of distribution for a drug is decreased
decrease dose: with the drug distributed to fewer tissues and hence less diluted by the volume of tissue fluid, the amounts of drug in the tissues will become more concentrated. Decrease dose to prevent concentration from exceeding therapeutic range
always looks for two concentrations that are one half to one fourth of each other. In this problem there is 160 microgram/mL at 1 hour after dose and 40 at 5 hours after dose. 160 divided by 2 is 80 and 80 divided by 2 is 40. Thus the concentrations went through two half-lives to go from 160 to 40. How long did that take? The elapsed interval between the two samples is 4 hours. Thus if 4 hours is 2 half-lives, then 1 half-life must be 2 hours. Therefore no matter at what concentration we start on this dose curve, 2 hours later the concentration will be half of what it was.
If the half-life is 2 hours and the concentration at 2 hours after injection is shown as 100, then 2 hours later at 4 hours after injection the concentration will be one half. At 4 hours after injection the concentration will be 100 divided by 2 = 50 microgram/mL
40 microgram/mL at 5 hours after injection will be half again 2 hours later at 7 hours after injection. At 7 hours after injection the concentration will be 20 microgram/mL.
what is the estimated peak concentration that occurred shortly after the IV bolus was given?
The estimated peak concentration occurring immediately after the completion of the IV bolus push should theoretically be double what it is at 2 hours after injection because this drug has a 2-hour half-life. Thus, the peak concentration at 0 hours after injection is estimated at 100 x 2 is 200 microgram/mL
how long would it take multiple maintenance doses to reach a steady state for this drug?
Steady state = 5 x the half-life.
5 x 2 hours = 10 hours to reach steady state
True or False:
if the metabolism of a drug has been induced, the dose of the drug should be decreased to compensate.
False
If metabolism has been induced, it has been sped up. The drug is being broken down quicker and therefore inactivated more rapidly. The dose needs to be increased. This is the explanation for why tolerance develops to drugs such as barbiturates, alcohol, and opioid/narcotics.
True or False:
excretion of a drug by the liver is called biliary excretion.
true
True or False:
the neutralization of stomach acid by Tums or Rolaids is a non-receptor-mediated action.
true
True or False:
an agonist would typically have little or no intrinsic activity on a receptor to which it binds.
false
An antagonist is a drug molecule that occupes a receptor site without producing an effect. In so doing, the antagonist blocks the agonist from occupying the receptor site and therefore reverses the agonist's effect.
True or False:
if the Vd of a drug increases, the concentration of the drug decreases.
true
if Vd increases there is more volume of fluid into which the drug is dissolved and therefore the drug is more distributed.
If a drug is in hydrophilic form when given subcutaneously, how is it able to enter the capillaries? Can it also exit the capillaries? Can it exit from all capillaries in the body?
Capillaries have openings called fenestrations through which drug molecules can enter. Drug molecules can leave through fenestrations to go from system circulation to tissues. The capillaries in the brain, prostate, and glove of the eye do not have fenestrations and therefore the only way a drug can get into these areas from systemic circulation is if the drug is in a lipophilic state.
The veterinarian asks you to administer four drugs. Each has a different route of administration. Drug A must be given PO, drub B must be given IV, drug C must be given SC, and drug D must be given IM. Assuming these drugs are given to normal animals, where should each of these drugs be administered, and which drug will reach its peak plasma concentration the fastest, second fastest, and slowest?
PO meas per os, so it is given by mouth. IV - intravenously, so it is placed within the veins. SQ = subcutaneously so it goes in the tissue beneath the skin. IM goes into the deep belly of a muscle. Obviously the IV drug will reach it speak in the plasma first because all of the drug, if given as a bolus, is placed immediately into the blood (no absorption phase). IM, in muscle that is well perfused and usually moving, is almost as quick to reach its peak concentrations. SQ and PO will be much more variable in their onset of peak concentration because of the various factors that influence their absorption.
The veterinarian is reviewing a brochure for a new drug that says "Our drug reaches concentrations of 40 mg/mL within 2 hours of administration." The veterinarian comments that the drug concentration by itself does not indicate how effective the drug is. What is the reason for this comment, and what information is necessary to better assess the usefulness of this new drug?
The veterinarian is correct in his statement. The value of 40 microgram/mL within 2 hours sounds impressive, but if the bottom end of the therapeutic range is 40 microgram/mL, the drug will still be in the subtherapeutic range after 2 hours. Or, if the toxic range starts at 20, at 2 hours this animal is going to be very ill. Without knowing what the therapeutic range is for this drug, this single concentration value is worthless.
A dosage regimen specifies 15 mg/kg IV for the loading dose followed by a maintenance dose of 5 mg/kg q12h PO. What is the advantage of using a loading dose?
The loading dose is a large dose given initially to establish concentrations within the therapeutic range (or at least close to it). Once therapeutic drug concentrations in the body are established, the smaller maintenance dose will keep the drug concentrations there. The advantage of using the loading dose is that therapeutic concentrations are established very quickly. If just a maintenance dose is used, it may take hours or even days for the drug to gradually accumulate to its steady state within the therapeutic range.
Digoxin is a cardiac drug with a narrow therapeutic index. (Highest concentrations in the therapeutic range are close to the lowest effective concentrations.) Considering the plasma drug concentration curves for various routes of administration, why is IV administration not recommended for drugs with a narrow therapeutic range?
IV bolus administration results in very high initial concentrations within the plasma shortly after the bolus is administered. Unfortunately, if these high concentrations are above the therapeutic range, these high initial concentrations may result in the animal showing toxic signs until plasma concentrations decrease. For a drug like digoxin that has a narrow therapeutic index there is not much difference between plasma concentrations of drug that provide benefit and those plasma concentrations that cause toxicity. Thus is would be safer to use a route of administration that has less prominent swings in peaks, such as the PO or SQ route. Digoxin is usually used PO in veterinary medicine.
The veterinarian wants to lengthen the dosage interval from the 50 mg q6h PO being given now to 100 mg q12h PO. What will happen to the amount of swing between the peak concentration and the trough concentration when the interval is switched from 16h to q12h? Why might this be of concern?
In this situation the drug is being administered as the same total daily dose amount. But because more drug is being administered at one time with the 100 mg q12h dosage regimen, higher concentrations at the peak are going to be achieved. And because the 100 mga12h regimen goes longer between doses, the concentrations are going to be allowed to drop for a longer period, resulting in trough concentrations lower than with the 50 mg q6h dosage regimen. Thus with the 100 mg dosage regimen, the greater swings in concentrations from peak to trough may result in periods when the concentrations exceed the therapeutic range (toxicity) or drop below the therapeutic range (subtherapeutic).
A drug's package insert states that the drug can be given as an IV bolus or by IV infusion. What is the difference in these methods of administration? How do the systemic concentrations achieved differ?
An IV bolus or push means that the whole amount of the drug is being delivered within a few seconds. An IV infusion means that the drug is being dripped into the animal over minutes to hours. A major difference between these two is that the bolus will result in very high concentrations in the blood until it gets a chance to distribute to the body. During that time it is possible that the high concentrations can result in toxic signs. The IV infusion has no prominent peak concentration but shows slowing increasing concentrations over time.
A new drug's package insert has a caution statement that says "Do not give this drug extravascularly." What does this mean? How would you be able to tell if you had injected it extravascularly? What might be the hazard of giving such a drug extravascularly?
Do not let the drug leak or get out of the vasculature. Some drugs can be extremely irritating to tissues if deposited outside the vein. In some cases, the tissue can die and slough off. If you administer a drug intravenously and it goes extravascularly, you should be able to notice a distension of the tissue surrounding the injected site.With irritating drugs there will also likely be a pain response from the animal. If you do not detect the extravascular administration, the next day you may find that the injection site is warm, sensitive, and swollen.
If a drug is given in aerosol form, where would you expect the largest drug concentration to be immediately after administration?
Aeorsol drugs are meant to be administered by a nebulizer into the respiratory tract. The highest concentrations will be lining the inside lumen of the trachea, bronchi, and bronchioles in the respiratory tree. This is the goal with antibiotics administered by aerosol nebulization to combat bacterial infections brought into the lungs by air.
Why would an animal respond to injection of a drug directly into the carotid artery with severe central nervous system signs, whereas an IV injection of the same drug into the jugular vein in the same general area in the neck results in no adverse effects?
An intracarotid injection would send the concentrated drug directly to the brain. There are several drugs used in horses that will produce a violent reaction if inadvertently given in the carotid artery instead of the jugular vein.
Why do facilitated diffusion and active transport have maximal rates at which they can transport drug molecules across a membrane and passive diffusion does not?
Facilitated diffusion and active transport are processes that use special proteins located within the cell membrane to move drugs across the membrane. There are a finite number of these proteins present. Therefore, if all the available proteins are occupied with transporting drug molecules across the membrane, the transport process is operating at its maximal speed. Passive diffusion, because it does not require special proteins to get across the membrane, is not limited to the maximal rate that a carrier system can operate.
You are tired of fighting with a nasty stallion during his IM injections every 8 hours. Why not put the medication in a slurry and give it PO or sneak it into some sweet molasses for him to eat on his own?
SQ and IM administered drugs are placed into extracellular fluid and therefore need to be hydrophilic drugs so they can readily dissolve and move away from the site of administration toward the capillaries between loosely packed cells by passive diffusion. There are no membranes for these drugs to penetrate when given by SQ or IM route of administration. Unfortunately in the GI tract the cells lining the lumen of the gut are very tightly packed together so that there are no extracellular gaps; hydrophilic drugs cannot get through the GI cellular membranes and hence are poorly absorbed. Thus will this horse might consume the drug in the appropriate dose, if the drug is mostly in the hydrophilic state in the lumen of the GI tract, it will not be absorbed.
Which would be more readily absorbed from the stomach (pH of 2 to 3): an acid drug or an alkaline drug, both with a similar pKa?
Acid drugs in general become more lipophilic as they are placed in increasingly acidic environments. Alkaline drugs become more ionized in this same situation. And because the GI tract requires drugs to be in the lipophilic form to be absorbed, acidic drugs are more likely to be absorbed from the GI tract at a pH of 2 or 3.
Aspirin causes stomach upset in people and animals a few hours after being taken PO because of the ion trapping phenomenon. Aspirin is an acidic drug. How does it get trapped and accumulate within cells lining the stomach lumen?
Acid drugs in the liphophilic form in the stomach pH of 2 or 3 will enter a more alkaline environment of pH = 7.4 when they move through the cell membrane into the cell's cytoplasm. This more alkaline pH will result in more of the nonionized molecules becoming ionized and thus trapped within the confines of the cellular membrane.
An animal has ingested a poison that is normally excreted by the kidneys. The poson is primarily an acid compound with a pKa of 6. To increase the rate of elimination of this drug, should the urine be acidified or alkalinized?
Remember that reabsorption from the kidney tubules back into systemic circulation is by passive diffusion and requires a drug molecule to more through the renal tubular cell membrane. Thus a lipophilic drug is reabsorbed from the renal tubules but a hydrophilic drug remains in the tubules and excreted with the urine. Because this a poison, the drug needs to be in the hydrophilic form so it will be excreted and not reenter the body to do more damage. This poison is an acid type compound. Any time the pH of its environment is more alkaline, an acid drug is going to become more ionized. Therefore a urinary alkalizer should be used to make the drug molecules more hydrophilic within the renal tubules and be less reabsorbed.
The manufacturer or an antibiotic claims that the enteric coating on the product enhances the drug's effectiveness compared with products without enteric coating. How might this be possible?
Eneteric coatings are designed to protect the drug from the gastric acid environment. If a drug is broken down or inactivated by the extreme acidity of the stomach, the enteric coating might allow more active drug to make it to the duodenum where it can be absorbed.
A cat with pylorospasm (contraction of the muscles surrounding the outflow tract from the stomach, which delays passage of stomach contents into the intestine) is given an alkaline drug with a pKa of 6. What effect would pylorospasm have on the rate of drug absorption or the amount of drug absorbed?
Pylorospasm would slow the gastric emptying. If the drug was not inactivated in the stomach, the only difference would be a delayed onset of the drug's activity (assuming not much of the drug is absorbed from the stomach because it is a basic drug). If the drug is degraded by the acidic stomach environment, then both a delay of onset plus a reduced amount of intact drug present to be absorbed would occur.
Why would an orally administered antibiotic tablet not be well absorbed in an animal with diarrhea?
If the intestinal transit time was shortened a tablet might not have enough time to physically break down in size small enough to be absorbed before it is moved through the small intestine into the colon, which does not abosrb drugs as readily as the small intestine.
Why are some toxic materials not very toxic when ingested but are extremely lethal if accidentally injected?
Same concept that a highly hydrophilic compound will not be absorbed into the body from the GI tract and thus will not have an effect on the body overall. If injected or absorbed across mucous membranes or damaged skin, it can gain access to systemic circulation and cause its damage. Another reason why a PO drug might be ineffective is that even if it is absorbed across the gut wall, it might be taken out by the liver and not reach systemic circulation in significant concentrations.
Why are drugs injected subcutaneously absorbed more slowly on a cold day than on a hot day?
In cold conditions the body protects itself from heat loss by causing vasoconstriction of blood vessels near the surface of the body. This vasoconstriction reduces perfusion of the superficial tissues and thus means a drug injected SQ has to diffuse a lot further to find an open capillary and be absorbed.
Diabetic animals are often overweight. Why should you be careful not to accidentally inject insulin (for control of diabetes mellitus) into the fat?
Fat is poorly perfused tissue. Therefore any drug injected into a fat pad will be very poorly absorbed, or have significantly delayed absorption, and will have a reduced effect upon the body.
Why are many antibiotics effective for infections at other body sites often not effective against bacterial infections involving the brain?
Blood-brain barrier of tight-junctioned capillaries and glial cells means the drugs must be in the lipophilic form to get into the brain from the blood. To get around the blood-brain barrier, some drugs are injected directly into the cerebrospinal fluid surrounding the spinal cord. This fluid will then transport the injected drug into the brain.
You inject an appropriate dose of thiopental IV into a thin dog and the animal stops breathing, reacting as though it received an overdose. The veterinarian looks over your shoulder and says, "Don't worry, the redistribution will take care of it." What is the significance of that comment?
Redistribution is the movement of drug from tissue A back into the blood and then to tissue B. In this case, the anesthetic thiopental is diffusing back into the blood from the brain and then into the fat tissue. As concentrations drop in the brain, the animal starts to breathe and may actually start to wake up.
A very thin dog with chronic liver disease has low plasma protein levels. The dog requires treatment with a drug that is highly protein bound. Considering the dog's poor body condition and low plasma protein levels, should the standard drug dose be increased or decreased?
Decreased. With fewer than normal numbers of protein molecules floating around in the blood, there are fewer sites for the administered drug to be tied up. With more of the administered drug in the free form, and therefore capable of distributing to tissues, a normal dose will end up delivering higher concentrations of drug molecules to the tissues and possibly producing an overdose. The dose should be decreased
Which drug would probably better penetrate tissues: drug A, with a Vd of 1L, or drug B, with a Vd of 3L? If equal amounts of drug A and drug B were given to an animal, which would be present in greater concentrations in the plasma?
Drug B has the greater distribution as reflected by the total volume of fluid in which it is dissolved. If drugs A and B are given in the same amounts, drub B would be diluted and thus have lower concentrations (even though those concentrations are distributed to a larger number of organs or tissues).
Digoxin is a cardiac drug with an apparent volume of distribution that seems to exceed the total volume of water possible within an animal's body. For example, in an animal with a body water volume of 3L, the volume of distribution for digoxin may be 4L. How is this possible? (Remember that digoxin selectively binds to sites in skeletal and cardiac muscle in high concentrations.)
Volume of distribution is usually called the apparent Vd because it is always an approximation based on what the concentration of drug is within the plasma only. In the case of digoxin, so much of the drug moves out of the plasma into the skeletal and cardiac muscle that concentrations within the plasma are very low. It would therefore appear from looking at plasma concentrations that digoxin is diluted in a very large volume of fluid. In fact, it is simply that the drug is being bound to sites outside of the plasma.
In an animal with an increased volume of distribution as a result of ascites, would systemic drug concentrations resulting from a standard dose likely by higher or lower than normal?
Lower concentrations. More fluid in the body to dilute the drug, thus lower concentrations.
A dog is hospitalized because of insecticide poisoning. The veterinarian is concerned and says, "We can't use an antidote to reverse the effect because the insecticide is a noncompetitive agonist." What is the significance of that comment?
An antagonist to the insecticide would probably be ineffective because the insecticide has combined with a receptor in such a way that an antagonist will not be able to readily replace it at the receptor site. This is in contrast to a competitive agonist/antagonist situation in which simply by giving more antagonist, the effect of the agonist can be reversed.
What effect would a partial narcotic agonist/partial narcotic antagonist such as butorphanol have on an animal if it was given after administration of a strong narcotic such as hydromorphone? How would this effect be different than that of a true narcotic antagonist such as naloxone?
Butorphanol has intrinsic narcotic activity when it combines with narcotic receptors, but its sedation and pain relief effect is much weaker than that of hydromorphone. Therefore, if butophanol replaces hydromorphone at the opiod receptors, the animal's degree of narcosis and analgesia will be decreased, but no totally eliminated. With the use of a true antagonist like naloxone that has little or not intrinsic activity, the narcosis and analgesia of hydromorphone would be completely reversed.
How can a chelating drug produce its physiologic effect when placed in a cell-free test tube of serum or within the lumen of the intestine where no cells, and hence no cellular receptors, are present for the drug to attach to?
A chelator is an example of a non-receptor-mediated drug activity in which the effect for which the drug is intended does not require a cellular receptor. In this case, there is a direct chemical reaction between the chelator drug and ions that produces its effect.
Why must veterinary professionals be concerned about using hepatically biotransformed drugs in young animals and cats? Should they have similar concerns about administering drugs that are excreted unchanged through the kidneys?
Cats have a limited ability to conjugate glucuronide and other compounds with drugs, and thus drugs that depend on this process for normal metabolism will be metabolized at a slower rate. Young animals have immature livers that are not able to biotransform drugs as readily as older animals and therefore heptically biotransformed drugs must be used with caution in very young animals. Because the kidney does not have to mature and because the cat's kidneys are just as efficient as any other species' kidneys, this same concern does not necessarily apply to drugs that are exclusively renally excreted.
A dog is being treated with phenobarbital to control epileptic seizures. Why must the dosage be adjusted 2 to 3 weeks after therapy begins? Is the dose likely to be increased or decreased at that time and why?
Phenobarbital induces its own metabolism, meaning that the liver metabolism of phenobarbital speeds up. Because the phenobarbital is broken down quicker, the concentrations of drug in the body decrease more rapidly and thus less drug accumulates between dosages. Thus an increase in drug dose will be necessary to compensate for the more rapid metabolism caused by induced phenobarbital metabolism.
What effect would decreased renal perfusion have on blood concentrations of a drug excreted through the kidneys?
Decreased blood flow to the kidney means less drug delivered to the kidney and subsequently less drug excreted by the kidney.
A particular dose of penicillin is quite effective against a specific bacterium when it is found in the urine. When the same bacterial strain is found in other tissues in the body, however, the same dose of penicillin is not nearly as effective. Based on what you know about penicillin from this chapter and how it is eliminated, explain why this could occur.
Penicillin is actively secreted into the renal tubule lumen and thus can achieve concentrations in the urine that may be much higher than those in the plasma. Thus the bacteria are killed in the urine by the higher concentrations attained through active secretion.
An animal has ingested a poison, and the veterinarian gives it activated charcoal repeatedly for several hours by a stomach tube because of enterhepatic circulation. Why must the charcoal be given repeatedly rather than only once or twice?
Enterohepatic circulation means that the poison is excreted by the liver, dumped into the intestine, and then reabsorbed back into the body where it can continue to cause damage. The activated charcoal, which is added to give the poison something to stick to in order to decrease its absorption, must be given as long as the poison is being excreted back into the intestinal tract. Otherwise the poison will have a much longer effect on the body.
The veterinarian comments, "These fluids will increase drug clearance." What is the significance of that comment?
Clearance is a measure of how quickly a drug is removed from the blood. Rapid clearance means rapid movement out of the blood and presumably from the body.
Why is a loading dose more necessary with a drug that has a long half0life than with a dug that has a short half-life?
This question has to do with the time to reach steady state (5x half-life). Until steady state is achieved, the drug concentrations are climbing upward. A drug with a long half-life, such as phenobarbital, will not achieve steady-state concentrations for days as opposed to a drug like penicillin, which has a half-life of approximately 2 hours and thus would be at steady state by 10 hours after the first administration of the drug. Because phenobarbital is slowly increasing over days, it may be present in very low concentrations during the first few hours (or days) after the drug is begun and not have therapeutic concentrations. There it might benefit from administration of a loading dose to establish therapeutic concentrations much faster.
Which food animal drug would require a longer withdrawal time: drug A, with a half-life of 30 minutes, or drug B, with a half-life of 5 hours?
Theoretically the withdrawal time should be shorter for drug A because its half-life is so rapid and that means the drug is leaving the blood at a faster rate (and it is assumed that it is leaving the body when it is leaving the blood). Several other factors may enter into the withdrawal time, such as how long it takes for the drug to leave the body tissues (not just the blood) or if lower concentrations of residues are required of one drug or the other in order for the meat or food products (eggs and milk) to be considered safe for human consumption.
