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.


GENERAL PHARMACOLOGY OF DOGS

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).