GENERAL PHARMACOLOGY OF DOGS
Pharmacology is the study of the uptake and use of drugs by the body.
It comprises...
(1) pharmacodynamics, the study of the responses elicited by drugs in
the body and the mechanisms by which these occur;
(2) pharmacokinetics, the
study of factors determining the degree and length of duration of drug activity in the body; and
(3) pharmacotherapeutics, the study of the rational clinical
use of drugs.
Many drugs have not been studied in animals, and their use should not be
taken lightly. It always is inappropriate to assume a drug will work the same
way in domestic animals that it does in humans. Sir William Osler, a renowned
physician from the turn of the last century, reminds us, “Remember how much
you do not know. Do not pour strange medicines into your patient.”
For a drug to be prescribed for you by a veterinarian, the Food and Drug
Administration (FDA) requires that a valid veterinarian-client-patient relationship exist. Standards for this relationship include the following.
• The veterinarian is responsible for diagnosis, knowledge, experience, and any
laboratory tests (including pathology and necropsy requests and reports).
• The veterinarian agrees to keep accurate records and to report to the client
regularly.
• The veterinarian has seen and examined the patient in question.
• The client agrees to follow the veterinarian’s recommendations.
• The patient is seen by the veterinarian on a regular basis (frequency of visits
may be mandated by law).
How drugs are taken up, distributed, and removed from the body depends
on how they are administered, if they will dissolve (are soluble) in water or fat,
whether they bind to proteins in the body once they have been administered,
and whether they are broken down or remain intact as a chemical.
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GENERAL PHARMACOLOGY OF DOGS |
A. ADMINISTRATION
Drugs can be administered locally or throughout the body (systemically). Local
routes of administration are intended to concentrate the drug where the effect
is needed and to minimize movement of drug into parts of the body where it
is not needed or might be toxic. With any local drug administration, some of
the drug will be absorbed into the bloodstream and distributed throughout the
body. Local routes of administration of drugs include the following:
• Transdermal—Topical drug is rubbed into the skin, usually in the form of a
lotion, or is absorbed through the skin from a patch. Administration of medications into the ear canal is also a transdermal administration.
• Ophthalmic—The drug is infused directly into the eye. Although the drug is
applied to the corneal surface of the eye, which has no blood vessels, drug is
absorbed quickly through the eye and moves into the general circulation.
• Local anesthesia—Anesthetic agent is infused into the area to be numbed.
Novocain used before human dentistry is an example of local anesthesia.
Systemic drug administration is more commonly used. In this technique
drug is supplied to the body as a whole and is expected to reach effective concentrations in the tissue of choice by being absorbed into and delivered by the
circulatory system. Examples of systemic routes of drug administration include the following:
1. Oral—This is the most common route of drug administration.
Compounds ingested must be able to survive digestion and passage through
the intestinal tract. For this reason many drugs that are proteins are difficult to administer orally because the body treats them like any other protein.
Breakdown of the drug within the intestinal tract must occur to some extent to allow its absorption from the intestinal tract, similar to what happens
with nutrients after digestion of food.
Drugs taken up from the gastrointestinal (GI) tract usually pass through the liver, where further breakdown
often occurs.
This process of chemical change in the liver is called biotransformation. The drug may become more active after passage through the
liver, or it may be inactivated and sent to the feces or urine for excretion .
Drugs to be administered orally must not be irritating to the
GI tract.
Aspirin is an example of an oral medication that can be irritating
to the GI tract and therefore often is administered in a buffered form to protect the stomach lining as it passes through.
Uptake of drugs by this route is
altered by activity of the gut and by the presence of food in the stomach; in
general, drug uptake is slower if the drug is taken with food.
2. Intravenous (IV) administration of drugs bypasses the GI tract and permits immediate activity of the drug as blood filled with the drug directly
enters the body organs and tissues.
Again, as the drug passes through the
liver in the general circulation, it will be chemically altered, increasing or
decreasing its activity.
3. Subcutaneous (SC) administration of drugs is infiltration of tissue below
the skin with the drug in question. The drug is absorbed in the SC tissue
and taken up by the bloodstream; this method is therefore not very efficient in animals that are dehydrated, have inflammation beneath the skin,
or have very little SC fat.
Drugs to be administered subsequently cannot
be irritating because the overlying skin will slough off.
4. Miscellaneous—Various other routes of drug administration have been
described and have their uses. Intraperitoneal (IP) administration is infusion of the drug into the abdominal cavity. It is slowly absorbed through
the peritoneum, the lining of the abdominal cavity. This route is most
commonly used in small laboratory animals.
Intraosseous (IO) administration is infusion of drugs or fluid into the marrow cavity of a long bone.
Because the marrow cavity has a good blood supply, drugs are readily
taken up by this route. This is the most commonly used route in neonatal
animals, in which IV access is restricted by size. Intracardiac (IC) administration, direct infusion of drugs into the heart, is used in emergency situations only.
B. ABSORPTION AND DISTRIBUTION
After administration, drugs generally are widely distributed throughout the
body. The selective effect of drugs in various tissues is due to the presence of receptors on the cells in those tissues.
These receptors, on the surface of the cells,
bind to the drug and either allow its absorption into the cells or set off a cascade
of events within the cell. You may get the same effect from two drugs acting in
very different ways; for example, an antibiotic decreases fever by killing the bacteria that are causing the infection, whereas aspirin decreases fever by acting at
the level of the brain and altering the animal’s temperature-control mechanism.
Absorption and distribution of drugs depend on the solubility of the drugs.
Those that are soluble in fat may be distributed more slowly in the body but
then persist for a much longer time as they are slowly broken down in fatty tissue.
Water-soluble drugs distribute readily into blood and extracellular and intracellular fluids (fluid between and within cells, respectively).
All body cells
have an outer fatty cell wall; movement of drugs within the cells themselves,
then, is faster for fat-soluble drugs than for water-soluble drugs. Many drugs
bind to proteins in the body. Bound drug usually is not active; higher doses of
drug must be administered to ensure that there is enough free (unbound) drug
to effect a change.
As already mentioned, many drugs undergo a chemical
change once they enter the body. The primary drug and the compounds
formed by chemical action (the metabolites) may or may not all be active. The
size of the drug compound itself (its molecular weight) also may alter its distribution; very large chemicals are less likely to diffuse readily into cells or in
and out of the bloodstream. Finally, the electrical charge of a drug molecule
may alter its ability to move within the body.
The electrical charge may vary
with the pH (i.e., acidity or alkalinity) of the fluid into which it moves, trapping the drug in some parts of the body and not permitting it into others.
C. EXCRETION
Excretion of drugs primarily occurs via the urine. The primary drug or its metabolites are passed into the urine through the bloodstream either free or bound to body proteins. Minor routes through which drugs are excreted from the body include feces, the lungs, milk, sweat, tears, and saliva.
D. PHARMACOTHERAPEUTICS
All these factors contribute to what dose and what frequency of administration
are required for a drug to achieve the desired effect. Drugs that are quickly metabolized must be administered more frequently to maintain concentrations of
drug in the tissues.
Drugs that are highly fat soluble and then slowly released
require less frequent administration to ensure continuing tissue concentrations. Drugs that are bound to protein to a large extent must be administered
at higher doses.
The goal is to maintain tissue concentrations of the drug at a level high
enough to ensure the desired effect but not at a high enough level to produce
side effects and to administer the drug frequently enough that the average
amount of drug present in the bloodstream is in this effective and safe range at
all times .
Many drugs have not been rigorously evaluated for use in dogs. The degrees
of absorption, metabolism, and excretion are not known for many common
drugs. The FDA is responsible for approving drugs for various species. The
manufacturer is required to show efficacy, tolerance, and safety.
Many commonly used drugs are not approved for use in dogs in the United States, but
veterinarians are legally permitted to use them if there is no approved alternative; a good example is aspirin, a commonly prescribed anti-inflammatory
drug that works well in dogs but has never undergone the rigorous approval
process. Other government organizations responsible for licensing of drugs in
the United States include the United States Department of Agriculture (USDA)
and the Drug Enforcement Agency (DEA).
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