module 17

Before we can look too far into the study of pharmacology, we must consider what a drug is. A drug is a substance that is used to treat, diagnose, cure, or relieve symptoms of a disease or abnormal condition. In America, the Food and Drug Administration (FDA) regulates all drugs to ensure that they are both effective and safe. The FDA determines whether a drug requires a prescription or if it is safe enough to be available over-the-counter (OTC) to the public. Dietary supplements are substances that promote general good health and include substances such as vitamins, minerals, and herbs. These are not regulated by the FDA.
In addition, the independent United States Pharmacopeia (U.S.P.) also reviews drugs as clinically useful and pure.
The complicated nature of drugs demands a wide field of study and research. Pharmacology’s (pharmac/o = drug + -logy = study of) broad medical specialty demands the study of medicinal chemistry (new drug synthesis and biological effects vs. chemical structure), pharmacodynamics (drug effects on the body), pharmacokinetics (drug disposition in the body over time), molecular pharmacology (subcellular drug interactions), chemotherapy (drugs that destroy harmful microorganisms and cells), and toxicology (harmful effects of drugs on the body). A pharmacologist is someone who studies drugs and their effects.

Marketed drugs are always assigned at least two, often three, different names. For example, every drug has a chemical name, which is simply its chemical formula. For legal and scientific purposes, it is also assigned a generic name. If the drug falls into competitive marketing, each manufacturer will distribute and sell the drug under its own trade name, or brand name, to differentiate it from competitors’ products.
Here we see an example of amoxicillin, a fairly common prescription antibiotic drug, with its three names.
In Europe, a pharmacist is called a chemist and takes the role of a doctor for minor disorders. Patients go directly to the “chemist’s shop,” describe their symptoms, and the chemist is authorized to diagnose and prescribe—and then dispense. By contrast, in the United States, only certain state-authorized medical personnel (usually a medical doctor, physician assistant, or nurse practitioner) can diagnose and prescribe. Pharmacists here are generally not allowed to diagnose or prescribe.
Let’s look at the pharmacist’s role in this country.
When a patient receives a prescription for a drug, a pharmacist is licensed to prepare and dispense that drug. The pharmacist is the most accessible health care professional to the public, so they regularly provide advice regarding disease and medications to anyone who asks. A pharmacist may also consult with and advise licensed practitioners about drug choices for specific cases. A pharmacist must have completed a 6- to 7-year Doctorate of Pharmacy (Pharm.D.) course of study as well as pass a licensing examination in his or her state.

Routes of administration—how a drug is introduced into the body—vary widely, depending on the chemical nature of the drug in question and the needs of the patient. Many drugs have more than one dose form so that they can be delivered in ways that are amenable to more than one situation or type of patient.
Enteral administration is any route that uses the gastrointestinal tract, including oral, sublingual and rectal routes of administration. Oral administration is the most convenient form of administration and refers simply to drugs given by mouth. However, the oral form is slower than most other forms and also requires that the drug be able to withstand the digestive system’s challenges. A much faster route is sublingual administration in which drugs are dissolved under the tongue rather than swallowed. This route of absorption bypasses the slower, more cumbersome digestive route and is valuable when time is crucial, as in the use of nitroglycerin for treatment of angina. Rectal administration involves the insertion of a suppository or solution into the rectum. This route is helpful when the patient is experiencing nausea and vomiting and cannot tolerate swallowing. Parenteral administration includes any route that avoids the digestive tract. Finally, transdermal patches and ointments are designed to control the release of drugs directly into the systemic circulation. Patches for the administration of pain-relieving drugs, birth control, and smoking cessation drugs are being prescribed regularly.
cavit/o
cavity

cutane/o
skin

derm/o
skin

enter/o
small intestines

lingu/o
tongue

muscul/o
muscle

or/o
mouth

rect/o
rectum

thec/o
sheath, meninges

topic/o
surface, location

ven/o
vein

-al
pertaining to

-ar
pertaining to

-ary
pertaining to

-ic
pertaining to

-ous
pertaining to

hypo-
below, deficient

intra-
within

par-
near, abnormal

sub-
under

trans-
across, through

Injections involve the administration of a drug from a tube syringe through a hollow needle placed directly into the body. There are six basic types of parenteral injections. The least invasive is the subcutaneous injection (Fig. A). In this injection, a hypodermic needle is inserted into the subcutaneous tissue under the skin, usually in the upper arm, thigh, or abdomen.
The second type of injection is the intradermal injection (Fig. B), which is made into the upper layers of the skin. This type of injection is used in skin testing for allergies.
The intramuscular (IM) injection (Fig. A) goes into muscle tissue and is a common site for vaccination injections. The intravenous (IV) injection (Fig. B) is given directly into the vein for an almost immediate effect and is used most commonly in the hospital setting.
Other types of parenteral injection are more complex. In an intrathecal injection, the drug is delivered into the space underlying the membranes, or
meninges, that surround the spinal cord and brain. An example of this technique is in the delivery of chemotherapy for the treatment of leukemia. An intracavitary injection is made into a body cavity, such as the peritoneal cavity or the pleural cavity.

Topical administration is the application of a spray, ointment, cream, lotion, or transdermal patch to deliver drugs through the skin.
Inhalation administration involves the patient inhaling a vapor or gas through the nose or mouth. The medication is absorbed through the thin walls of the air sacs in the lung, often through the use of an aerosol, which suspends drug particles in air. Thus, inhalation is a pulmonary route
Now that we’ve examined how drugs are named and the various ways they’re administered, let’s take a quick look at some additional abbreviations that describe how and when drugs are to be taken.
The number of times a day is indicated with b.i.d (bis in die, or two times per day), while t.i.d is Latin for ter in die, or three times per day, and q.i.d stands for quater in die or four times per day.
Some drugs are most effective if taken on an empty stomach, while others need to be taken with or after meals. The abbreviation a.c. (ante cibum or before food) is used for the first, while p.c. (post cibum) indicates after food.
The general time of day is referred to by qAM (every morning), qPM (every evening), and qhs (every bedtime).

a.c.
before meal

ad lib
as desired

b.i.d.
two times per day

NPO
nothing by mouth

p.c.
after meal

p.o.
by mouth

prn
as needed

q.i.d.
four times per day

qAM
every morning

qhs
every bedtime

qPM
every evening

t.i.d
three times per day

A drug goes through a number of processes to generate its action(s) within the body. It starts with absorption, which is the process of passing into the bloodstream. Once in the bloodstream, the drug heads toward its target, or receptor, by moving across cell membranes as it needs to in a process called distribution. This receptor may be intracellular or may be on the cell’s surface.

After absorption, a drug’s metabolism refers to the changes the drug undergoes within the body. Excretion is the drug’s elimination from the body. Sometime between absorption and excretion, the drug’s therapeutic effects can take place.
If two or more drugs are administered that produce the same outcome, the therapeutic effects can be additive—a combination of the effects of two or more drugs taken together—or they can result in synergism, or potentiation. This means that the drugs given in combination cause an effect that is even greater than the sum of the individual effects if each were given alone.
cras/o
mixture

erg/o
work

iatr/o
treatment

idi/o
unknown, unique

toxic/o
poison

-ic
pertaining to

-ism
condition

-phylaxis
protection

-y
process of

ana-
apart, away from

contra-
against, opposite

syn-
together

There are a wide range of negative effects possible from a drug—many of them much more serious than a stomachache. These reactions are called side effects or adverse reactions. For instance, we know that Sophie has come to depend heavily on antacids to give her some relief. With some drugs, the body gets so used to a drug that greater amounts are required to achieve the same effect; this is called drug tolerance. Although tolerance can be a feature of addiction, it is not the same thing. Addiction is more severe, occurring as a physical and psychological dependence that shows clear negative effects when the drug is withdrawn.

There are other possible negative effects from drugs as well. Drug toxicity, the poisonous or dangerous effects of some drugs, can fall into several categories. Idiosyncrasy, for example, can be mild, hardly toxic at all, or severely toxic. In itself, idiosyncrasy is simply an unexpected effect of a drug. This occurs rarely in very specific patients but may be life-threatening. For instance, people allergic to penicillin may go into anaphylaxis, an acute hypersensitivity, which is often a life-threatening condition. When a patient has a serious unwanted reaction to a drug, often an antidote must be given. This is a drug that counteracts the unwanted effect of another drug.

Instead, more predictable are the iatrogenic effects, which are produced by treatment itself or as a result of errors or individual sensitivity. Side effects are predictable toxic effects that are considered tolerable—the advantages of drug use often outweighing the disadvantages. Finally, contraindications are features that make using the drug unwise where the risks outweigh the benefits. Factors that can be contraindications include the patient’s condition or other, more crucial drugs already in the patient’s treatment regimen, perhaps for another condition.

combining form for dynam/o is power
Mrs. Sandano took her prescription for Tamoxifen to the drugstore to be prepared and dispensed by the ________.

pharmacist

The nausea, vomiting, and alopecia that routinely accompany cancer chemotherapy are considered:

iatrogenic effects

Missy’s anaphylactic reaction to penicillin means future use of the drug is dangerous and ill-advised. The severe allergic reaction that prevents future use of the drug for Missy is called:

an idiosyncrasy

Analgesics are drugs that relieve pain and can range from mild to potent. Among the most potent are the narcotics (narc/o = numbness, stupor, or sleep) or opioids, which are used to relieve only the most severe pain; morphine is an example. Derived from opium, opioids induce a near unconsciousness that inhibits mental and physical activity. Because they can be habit-forming and induce tolerance with use, they are limited in their applications.

None of these, however, describe the pills Sophie has been taking for her swollen ankle. Milder, non-narcotic analgesics—non-steroidal anti-inflammatory drugs (NSAIDs)—reduce fever, pain, and inflammation without exposing the patient to steroid hormones, such as cortisone. NSAIDs inhibit the prostaglandins that sensitize our peripheral pain receptors.

alges/o
pain

bacteri/o
bacteria

cid/o
to kill

bi/o
life, living

emet/o
vomiting

esthet/o
sensation, feeling

narc/o
numbness, stupor, sleep

oste/o
bone

por/o
porous, space

sept/o
infection

vir/o
virus

-al
pertaining to

-ar
pertaining to

-ary
pertaining to

-cidal
pertaining to killing

-coagulant
clotting

-emetic
pertaining to vomiting

-osis
abnormal condition

-ous
pertaining to

-static
pertaining to controlling

-tic
pertaining to

an-
without

anti-
against

non-
not

Anesthetics reduce or eliminate our sensitivity to all kinds of sensation. They can inhibit nerve conduction in a single region, as when using a local anesthetic such as novocaine. Or, using a general anesthetic, particularly for surgical procedures, can depress the activity of the central nervous system and produce a loss of consciousnes
Antibiotics fight disease-producing organisms that cause infection and can take two forms—bacteriostatic antibiotics inhibit bacteria, fungi, or parasites; and bactericidal antibiotics actually kill rather than inhibit them. In addition, antiviral drugs do the same against viruses, such as the herpes virus and HIV.

More caution is taken now with the use of antibiotics than when they were first used in the mid-1940s. Considered wonder drugs, these remarkable agents were used with increasing frequency to treat more and more disorders and with excellent success. Indiscriminate use, however, revealed that the pathogenic organisms we were targeting could become resistant to that agent

Anticoagulant and antiplatelet drugs affect blood clotting, or coagulation, in slightly different ways. Anticoagulants like heparin or warfarin prevent clotting in conditions such as thrombosis and embolism or in blood used in transfusions. Others, like tissue-type plasminogen activator (tPA), can dissolve clots in the coronary arteries after a myocardial infarction, thus reopening the pathway for blood flow.

Antiplatelet drugs, like aspirin, have a slightly different effect, reducing the tendency of platelets to stick together. This can be helpful in coronary artery disease

The purpose of an anticonvulsant is to depress or prevent abnormal spontaneous brain activity, thus reducing or preventing convulsions without affecting normal brain function. This can take some dosage and treatment adjustments but has drastically improved the quality of life for patients with epilepsy and certain kinds of brain tumors.

Anticonvulsants have proved so effective in some cases of epilepsy that patients who were not allowed to drive, in case they should have a seizure, are now able to drive safely. In most states, there is a time limit—typically six months to a year—during which an individual who has experienced a seizure must remain seizure-free before he or she is allowed to resume driving.

Antidiabetics, drugs used to treat diabetes mellitus, vary significantly depending on the type of diabetes. Patients with type 1 diabetes are insulin-dependent. In other words, they must receive daily injections of human insulin (as opposed to the animal-derived insulins of just a few years ago) because their own body’s insulin hormone is either not being produced or is ineffective. However, patients with the milder type 2 diabetes, which is not insulin-dependent, may receive oral antidiabetic drugs, such as the sulfonylureas, which lower glucose levels by stimulating insulin production; the biguanides, which increase the body’s sensitivity to insulin and reduce liver production of glucose; the alpha-glucosidase inhibitors, which temporarily block enzymes that digest sugars; the thiazolidinediones, which enhance glucose uptake; and the meglitinides, which stimulate the beta cells in the pancreas to produce insulin. As type 2 diabetes disease progresses, insulin may be required. These can be in the form of a basal (long acting), an NPH (medium acting) or regular, a short acting insulin
The body’s release of histamine causes many allergic reactions. These reactions can range from common hay fever to a dangerous state of anaphylactic shock. Antihistamines can relieve the symptoms of anaphylaxis, and some are also used to prevent motion sickness since they have strong antiemetic properties. By contrast, an emetic is invaluable in inducing vomiting, in the case of certain ingested poisons.

Antiosteoporosis drugs help prevent abnormal loss of bone density and increase calcium deposition in bone. These include calcium, vitamin D, and estrogen. The bisphosphonates prevent bone loss, while the hormone-like drugs—that is, the SERMs (selective estrogen receptor modulators)—actually increase bone formation.

Dr. Teller is able to determine that although Sophie had been experiencing some frustration and sadness as she adjusted to her new environment, these are reasonable reactions. Had this been a true clinical depression, however, Dr. Teller may have prescribed an antidepressant.

Antidepressants, such as amitryptyline, relieve depression in a variety of ways: by elevating mood, increasing activity and alertness, and improving appetite and sleep patterns. Their sites of actions can also vary. For instance, the tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) increase available neurotransmitters by blocking their reuptake from synapses between nerve cells. Others, like the monoamine oxidase inhibitors (MAOIs), help neurotransmitters to work longer by blocking their natural inhibitor, the enzyme monoamine oxidase.

Because Sophie has mentioned that she has been treated for hypertension, Dr. Teller pays close attention to her blood pressure now. The state of Sophie’s blood pressure will guide him in his choice of treatment. Hypertensive agents vary and are quite specific in their applications. Let’s begin by looking at the overall category of cardiovascular drugs.

Cardiovascular drugs are as varied in effect and purpose as the variety of cardiovascular disorders. However, these drugs do have one thing in common: They act on the heart or blood vessels to treat hypertension, angina, heart attack, congestive heart failure, and arrhythmias.

One of the first steps in preventing or controlling several cardiovascular disorders is the administration of aspirin to prevent blood vessel clots. Emergency sublingual nitroglycerin dilates coronary blood vessels, slows the heart rate, and puts more force into the heart’s contractions. Digoxin can control arrhythmias by slowing the heart rate and is used to treat congestive heart failure by helping the heart to pump more forcefully.

It is common to use angiotensin-converting enzyme inhibitors (ACE inhibitors) to improve the heart’s performance and reduce its workload as well as keep the blood vessels dilated to lower blood pressure. These work by preventing angiotensin I from converting to the powerful vasoconstrictor angiotensin II. This contributes to the treatment of patients with hypertension (like Sophie), congestive heart failure, and a history of a heart attack.

For those patients who do not tolerate ACE inhibitors, the angiotensin II receptor antagonists lower blood pressure by preventing angiotensin from acting on receptors in blood vessels. Note, then, that the word antagonist, which you will encounter in many discussions of drugs, refers to an agent or substance that slows or prevents another agent’s effects.

In the past, Sophie says, she has taken beta-blockers for her hypertension, combining this with her strong interest in physical activity and a healthful diet.

But what exactly are beta-blockers?

Useful in the treatment of angina, hypertension, arrhythmia, and following heart attack, beta-blockers act as vasodilators. They work by blocking the action of epinephrine at receptor sites in the heart and blood vessels to reduce blood pressure as well as decreasing muscle tone in blood vessels and increasing the output of the heart. They also work to decrease the number of contractions of the heart, decreasing the heart rate – thus improving the output and work load of the heart.

Calcium is necessary for blood vessel contraction. By inhibiting its entry into the heart muscles and blood vessels, calcium channel blockers, or antagonists, dilate the blood vessels, lowering blood pressure. This makes them particularly useful in treating angina and arrhythmias.
Antiarrhythmics, another type of heart drug, can reverse abnormal heart rhythms by slowing the response of heart muscle to nervous stimulation or by slowing the rate at which nervous system impulses are carried through the heart.

By now, most consumers are aware that high cholesterol levels in the blood, or hypercholesterolemia, are a contributor to heart disease. Part of Sophie’s normal health regimen—ever since being diagnosed with hypertension—has been to watch her blood cholesterol through healthy eating.

But exercise and good diet are not always enough. Cholesterol-lowering drugs reduce circulating levels of bad cholesterol. There are a variety of agents with different mechanisms available that can affect the blood levels of either good or bad cholesterol and also triglycerides. Statins, or HMG-CoA reductase inhibitors, are the most commonly prescribed agents in this class.

Finally, diuretics are used to reduce blood volume by stimulating the kidney to remove water and salt through urine, as shown in the illustration.

The chief respiratory drugs, the bronchodilators, are used to treat respiratory disorders, such as emphysema, asthma, and infections like pneumonia and bronchitis. These drugs, often administered either intranasally or by oral inhalation, open the air passages or bronchial tubes. Leukotriene modifiers prevent asthma attacks by blocking the bronchoconstrictor leukotriene from binding to respiratory tissue receptors.

Endocrine drugs are intended to mimic the actions of specific naturally occurring (or endogenous) hormones. For instance, androgens are hormones that are normally produced by the testes and adrenal glands. They are used for male hormone replacement therapy; in women, they are helpful in treating endometriosis and breast cancer. The female hormones, or estrogens, are normally produced by the ovaries. They can be used in replacement therapy to ease the symptoms of menopause and to prevent osteoporosis associated with postmenopause.

Both categories of drugs have antagonists—these are drugs that have the opposite effect or that offset the effects of these hormones when they occur naturally. For instance, one antiandrogen drug is flutamide. It is useful in the treatment of prostate cancer. Estrogens, too, have an opposite effect. The drug tamoxifen is an anti-estrogen drug used to prevent the recurrence of breast cancer and to treat metastatic breast cancer. Aromatase inhibitors also reduce the amount of estrogen (estradiol) in the blood.

Earlier, in our discussion of antiosteoporosis drugs, we discussed SERMs, or selective estrogen receptor modulators. These drugs bind to estrogen receptors in bones. A SERM has estrogen-like effects specifically on bone and blood lipids to reduce blood cholesterol and the risk of osteoporosis, but it does not have estrogen’s effects on uterine and breast tissues.

Progestins are endocrine drugs used as part of hormone replacement therapies and as oral contraceptives. They are also used to reduce abnormal uterine bleeding and hormonal imbalances. In its natural state, the hormone progestin affects the lining of the uterus during pregnancy.

Thyroid hormones can be administered therapeutically when the patient’s thyroid gland produces an insufficient quantity (a condition known as hypothyroidism). In patients with hyperthyroidism or thyroid cancer, antithyroid agents are used to reduce the production of thyroid hormones.

The adrenal corticosteroids—mineralocorticoids or glucocorticoids—have a wide range of uses. They are used in the treatment of inflammation; arthritis; gastrointestinal, skin, respiratory, and blood disorders; and cancer

Dr. Teller wants a complete list of medications Sophie has tried for her stomach disorder because there are many different drugs on the market to relieve gastrointestinal disorders. Although a few are curative, most just relieve symptoms. For instance, epigastric discomfort and the symptoms of peptic ulcer and esophagitis are usually treated with antacids to neutralize the stomach’s hydrochloric acid.

If Sophie’s symptoms included diarrhea, she might be prescribed an antidiarrheal drug to decrease the rapid movement of the walls of the colon.

By contrast, a cathartic agent is used to either relieve constipation or to promote defecation for diagnostic or treatment procedures. Cathartics can act in one of several ways: to increase intestinal salts, which encourages fluid to fill the intestines; or to increase fecal bulk, which prompts movement in the intestinal wall, called peristalsis. A third way in which cathartics can act is to lubricate the intestinal tract and soften stools. Cathartics are either laxatives, which are mild, or purgatives, which are strong.

Antiemetics reduce nausea and vomiting. Sometimes symptoms of nausea and vomiting are caused by inner ear disturbances, such as vertigo, dizziness, motion sickness, or labyrinthitis, which is an inflammation of the inner ear (see illustration of the inner ear). In some instances nausea and vomiting can be a side effect of another drug, such as a chemotherapeutic agent.

Antibodies (immunoglobulin G [IgG]) to H. pylori can be measured in serum, plasma, or whole blood. If this is not definitive, Dr. Teller will conduct an upper GI endoscopy.

Test results show that Sophie does indeed have peptic ulcer disease (PUD). In her case, an anti-ulcer drug (like Prevacid) will promote healing by blocking secretion of histamine, which stimulates secretion of gastric acid from the lining of the stomach. Dr. Teller also prescribes two antibiotics to be taken in conjunction with the anti-ulcer drug.

Sophie is back for a follow-up visit and is excited to tell Dr. Teller that the pain from the peptic ulcer has disappeared. While that is certainly good news, that the new life changes Sophie has been going through (including a new marriage) are still a lot for her to deal with. Now, she is battling insomnia.

For patients with insomnia and other sleep disorders, sedatives and hypnotics can depress the central nervous system to help promote drowsiness and sleep. Some drugs can play the role of both sedatives and hypnotics. Many of these drugs have a risk of dependency, so they are not always the optimal treatment of insomnia.

Mild tranquilizers, like the benzodiazepines, control minor anxiety symptoms. For instance, after traumatic events, patients may receive mild tranquilizers in association with grief therapy. The major tranquilizers, like the phenothiazines, control more severe behavior disturbances and disorders.
In cases of shock and collapse, patients need quick intervention to speed up vital processes in the heart and respiratory system and to increase alertness as well. These patients are commonly administered drugs called stimulants. In non-emergency uses, these same drugs can be used to inhibit hyperactive behaviors, particularly in children. Amphetamines, a type of stimulant, are used to prevent narcolepsy, suppress appetite, and also to calm hyperkinetic children

a.c.
before meal

ACE inhibitor
angiotensin-converting enzyme inhibitor

ad lib
as desired

b.i.d.
two times per day

FDA
Food and Drug Administration

IgG
immunoglobulin G

IM
intramuscular

IV
intravenous

MAOI
monoamine oxidase inhibitors

NPO
nothing by mouth

NSAIDs
nonsteroidal anti-inflammatory drugs

p.c.
after meal

p.o.
by mouth

prn
as needed

q.i.d.
four times per day

qAM
every morning

qhs
every bedtime

qPM
every evening

SERM
selective estrogen receptor modulator

SSRI
serotonin selective reuptake inhibitor

t.i.d
three times per day

TCAs
tricyclic antidepressants

tPA
tissue-type plasminogen activator

tranquilizer

anxiety

Lasix is prescribed for Mr. Garrison to lower his blood pressure. Since it reduces blood volume by stimulating the kidney to remove water and salt (excreted in the urine), it is categorized as a(n):
diuretic