Pharmacology

2 Pharmacology




FREQUENTLY ASKED QUESTIONS



1) Why is it that the veterinarian will not dispense drugs to me without seeing the animal first?

Veterinarians cannot dispense antibiotics or other drugs unless they have a client-patient-doctor relationship with you and that animal. We are required by the Food and Drug Administration (FDA) to ensure that we are not giving a medication to an animal that may be detrimental to that animal; that is a condition of our keeping our license. Also, veterinarians try to decrease the use of antibiotics overall so as to decrease the number of resistant “super” bacteria created, bacteria that no antibiotic can kill.


2) Why do I have to give the drug so many times a day and for so long after the animal appears to be cured?

The number of times a day a drug is given determines the concentration of that drug in the bloodstream. When the drug is given, concentrations in the bloodstream are high initially and gradually fall. The idea is to give the drug again as the concentration falls off, to keep the concentration in a range that will be effective at all times. Most drugs are given for a while after the problem is resolved to allow the body to resolve the problem completely. For example, the outward signs of infection (redness, swelling, discharge) may be cleared up by antibiotics well before the dog’s immune system has completely cleared all the infection from the body.


3) Are generic alternatives to expensive drugs okay to use?

All new drugs that are patented have a period during which their patent is protected and no other company can make that drug. After the patent period is over, others can make the drug but may not make it with exactly the same formulation. For many drugs the exact formulation does not matter and the generic forms are equally as effective as the brand names. I do know of cases, however, in which the brand-name drug did work better than the generic drug did, probably because of the binders and other products in the drug that helped it to be absorbed. If you have concerns about the cost of a medication, ask your veterinarian about the availability and effectiveness of generic equivalents.


4) Are some breeds more sensitive to anesthesia?

Only one breed, the greyhound, has been reported to be sensitive to one class of injectable anesthetics. No other reports are supported by the veterinary literature. Veterinarians do their best to ensure that an animal can tolerate anesthesia before administering any drug. Where I work, preanesthetic bloodwork and a complete physical examination always are performed and a heart monitor is always used during anesthesia.


5) Is it safe to give drugs, including heartworm preventative, to my pregnant bitch?

As a general rule, I try not to give a pregnant bitch anything she does not absolutely require. Where I live, mosquitoes and heartworms are a real problem in the summer months, so I recommend heartworm preventative for any bitch that is going to go outside. Bitches should be wormed for intestinal parasites late in pregnancy. For all other medications, a risk-benefit analysis must be made for each individual case.



I. GENERAL PHARMACOLOGY


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.



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 (Figure 2-1). 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.

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Figure 2-1 Biotransformation of aspirin.



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 (Figure 2-2). This graph demonstrates the necessity of administering medications at the dose and interval recommended by the manufacturer and your veterinarian; other doses or frequency intervals may not permit maintenance of therapeutic concentrations of drug in tissues.


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Figure 2-2 Changes in plasma concentration of a given drug over time.


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).



II. CLASSES OF DRUGS


Drugs are chemicals. A given drug has a number of names by which it may be called, including the following:


• The chemical name is a chemical description of the molecular structure of the drug (sodium 5-ethyl-5-[1-methylbutyl] barbiturate and sodium 5,5-diphenyl-2,4-imidazolidinedione).

• The generic name is the drug’s official name per the FDA (pentobarbital sodium and phenytoin)

• The proprietary name is the trade name, generated by the company of manufacture (BeuthanasiaD).

• The common name is the name most commonly used by the public (euthanasia solution).


A. ANTIBIOTICS


Antibiotics are compounds that kill living agents. Antimicrobials are specifically those compounds that destroy microorganisms. The term antiseptic generally is taken to mean an agent that will be used in the environment; the term antibiotic implies a drug that can be absorbed or ingested safely by animals or humans (Figure 2-3).


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Figure 2-3 Antibiotics.


Antibiotics are broken down by the body fairly quickly and often have poor absorption into infected tissue. It is important to treat with an appropriate dose for an appropriate length of time to ensure that adequate concentrations of antibiotic are attained within infected tissue and to maintain effective concentrations in tissue for 24 to 60 hours after regression of infection so as to decrease likelihood of recurrence of infection. With antibiotics more is not better; toxicity can develop if excessive concentrations of antibiotic are reached in the blood. Finally some antibiotics can affect fetal development and should not be administered to pregnant bitches (Table 2-1).



Table 2-1 Characteristics of Some Antibiotics

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on Pharmacology

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