Module 1: Basic Principles of Pharmacology

Question 1

In ancient societies, medicine men acted as both physicians and priests. For this reason, therapy was heavily influenced by both religion and magic. In most parts of the world, plants were found which contained intoxicating substances. These intoxicating substances were used by medicine men and their followers in order to alter their states of consciousness and facilitate communication with their gods. In Mexico, the Peyote cactus was widely used to achieve a mystical state. What did the peyote cactus contain and what was it used for?

Answer 1

The Peyote cactus contains the potent substance known as mescaline, which causes hallucinations, a feeling of well-being, and distorts perception. It has been reported that some colourful Mexican-Indian paintings and intricate embroidery patterns were inspired by hallucinatory visions produced by consumption of the Peyote cactus.

Question 2

Who was this qoute by: “All substances are poisons.

There is none which is not a poison.

The right dose differentiates a poison and a remedy.”?

Answer 2

by a 16th century Swiss physician named Paracelsus

Question 3

How was the calabar bean used in West and Central Africa ? What purpose does it serve now?

Answer 3

Ordeal trials were held in West and Central Africa and Madagascar. The purpose of ordeal trials was to identify sorcerers.To achieve this end, members of the tribe were grouped in a circle around a traditional healer who gave each person a poison. Those who vomited from the poison were saved, those who did not, died and were proclaimed sorcerers. Some of today’s valuable drugs are derived from some of these crude poisons. A case in point is the drug physostigmine (used in the treatment of glaucoma), which is derived from the calabar bean.

Question 4

How was the Curare plant used in the Amazon and what purpose does it serve now?

Answer 4

ndigenous people of the Amazon dipped their arrows in a poison known as curare. This poison, upon entering the animal, acted upon the voluntary muscles of the animal causing paralysis and death.
Normally, nerves which effect skeletal muscle release acetylcholine from nerve endings. The acetylcholine combines with receptors in skeletal muscle causing the muscle to contract. Curare interacts with the receptors in the muscle normally reserved for acetylcholine. By doing so, it prevents acetylcholine from combining with the receptor, and therefore prevents muscle contraction. Eventually, this poison curare, was used by anesthetists during surgery. By giving a small dose of curare to the patient, muscle relaxation was achieved, thereby greatly facilitating the surgeon’s work.

Question 5

How was the ergot fungus used in Russia in the past and what terrible epidemics arose form this? (there are 4)

Answer 5

ergot grows on the heads of rye during wet seasons, due to the fact that it was ground together with rye it found its way into bread. this resulted in epidemics whig totalled to 20 000 deaths.
the effects are:
a. burning in the limbs: a;so referred to as the holy fire of Saint Anthony’s.
b.constriction of blood vessels: fingers and toes became deprived of blood supply which led to them turning black in some extreme cases they fell off.
c. mental frenzy, hallucinations, and convulsions: some of the compounds resemble LSD
D. abortion: Ergot caused violent contractions of the uterus. As early as the 16th century, some midwives recognized the fact that small amounts of ergot could be useful in hastening labour. In 1808, Dr. John Stearns of New York State introduced ergot into modern medicine. He called it Pulvis Parturiens, which means the powder to be used in childbirth. He stated that this powder would expedite lingering labour, but warned that it had to be used with the greatest care. Other physicians of this era did not use it with the care which Dr. Stearns had recommended. For this reason, many deaths occurred to women in childbirth. Cynical doctors who had obtained bad results labelled it the Pulvis ad mortem.

Question 6

How is the ergot fungus used today? (two active principles)

Answer 6

In the modern era, two active principles have been isolated from ergot:

i. Ergotamine: This substance is useful in the treatment of migraines. One theory suggests that migraines are caused by pulsation of the arterial blood vessels that carry blood to the head. Ergotamine constricts these blood vessels, reducing the amplitude of the pulsation.
ii. Ergonovine: This substance is no longer used to hasten birth, as there is too great a risk that the force of uterine contractions may be too strong and the mother may be injured by too rapid delivery of the child. It is, however, still used in the practice of obstetrics. After the baby has been delivered and the placenta has separated from the wall of the uterus, there can be a large loss of blood. Ergonovine causes the uterus to contract forcibly and arrests the bleeding. Thus, the main value of ergonovine is to arrest uterine bleeding after childbirth.

Question 7

What was the earliest recorded drug experiments in China in the year 2700 B.C?

Answer 7

the emperor Shan Nung classified all drugs by taste

Question 8

The drug Ma Hung was classified as a ________? what was isolated from this drug and how was it sussed in early Chinese medicine?

Answer 8

it was classified as a medium drug and used in treating coughs, influenza and fevers,
ephedrine was isolated from Ma huang and it is used to treat asthma, and a derivative of ephedrine is used as a decongestant.

Question 9

true or false

The Chinese believed that herbs and animal material s as therapeutics were completely useless.

Answer 9

false
it was widely practiced an example would be shaving of the horn of he antelope is more effective than aspirin when reducing a fever.

Question 10

Egyptian’s used breast milk to_____?

Answer 10

heal sick children. the milk would be filled in a container that looked like a mother holding a child the container dates to about 1400BC.

Question 11

Ancient Egyptian history was recorded on documents called ?
What did this document contain?
Some of the drugs recommended for use were?

Answer 11

Papyri dates back to 1550 BC.
it had a lot of true observations on drugs particularly on purgatives which are drugs used to cause bowel movements.
some of the drugs recommended for movement were castor oil, figs and senna.

Question 12

Theophrastus was the first to dicuss opium. what was isolated from Opium in 1803 Germany? what benefits were found when tested on themselves?

Answer 12

morphine was isolated from opium, it has pain relieving capabilities. opium has 10 percent morphine, it was named after the god of dreams Morpheus. it can relieve pain of grew intensity. it remains the gold standard because its the best analgesics (psin relieving drug) , in comparison to aspirin and acetaminophen (Tylenol).

Question 13

What other toxin can be extracted from opium?

Answer 13

opium also contaisn 0.5 percent Codeine and it is used as a pain relief and is a constituent of Tylenol 1, an over the counter drug in Canada.

Question 14

Spain, persia, and Mesopotamia

During the 10th and 11th century, the plant _____ was introduced for _________.

Answer 14

colchicum and gout

Question 15

What century began the movement of synthetic drugs?

Answer 15

the 19th century

Question 16

Name three plants used to treat heart diseases?How was it used? What are the benefits?

Answer 16

Digitalis purpurea also referred to as foxglove.
you dried it, powdered it then boldd the powder, the boiled powder was given to the patients. In certain forms of heart disease, the heart muscle becomes weak and cannot expel the blood with force. As a result, the flow of blood through small blood vessels is decreased. When this medication is given to patients with this type of heart disease, there is a marked improvement in performance of the heart muscle. While the powdered leaf of digitalis was used in therapeutics for many years, modern physicians now use the purified major active component, digoxin (Lanoxin), to treat patients. Digoxin is also used to treat certain types of disordered rhythms of the heart, known as arrhythmias.
Nitroglycerin: its the explosive material used in dynamite and it can be used in treating angina pectoris ( latin for choking in the chest). amyl nitrite was used, though it was short lived and we needed something stronger so we got nitroglycerin. it opens blood vessels in the heart and elsewhere in the body and increases the supply of oxygen to the heart. still remains the main treatment for agina pectoris.

quinine: its a constituent of the bark Cinchona tree. when quinine was isolated and used to treat malaria.
A Dutch sea captain, when taking quinine, noticed that the drug improved his disordered heart rhythm and he reported this finding to an Amsterdam cardiologist. This report led to the introduction of quinidine into therapeutics, which is a close relative of quinine, for treatment of certain heart arrhythmias.

Question 17

Name three drugs that act on the brain, there use and benefits.

Answer 17

Reserpine and Chlorpromazine:
two drugs led to a great change in the treatment of mental patients who were excitable and sometimes uncontrollable. Extracts of the rauwolfia plant had long been used in Indian medicine to reduce tension and anxiety and to lower blood pressure. However, outside India at this time, little attention was paid to these rauwolfia extracts. It was not until the 1950’s that a Swiss pharmaceutical company isolated the chemical reserpine from the rauwolfia plant and studied its action in both animals and patients. When reserpine was given to monkeys or dogs who were fierce and aggressive, the animals became placid.

Today, chlorpromazine and newer related drugs are preferred to reserpine for the management of mentally ill patients, as determining the correct effective dose of reserpine is difficult. Chlorpromazine was obtained by synthetic procedures, and is a valuable drug, converting the anxious, tense, and hostile person into someone who is placid and tranquil.

The introduction of reserpine and chlorpromazine had a large social benefit, as the number of mentally ill patients requiring constant care decreased, with many former unmanageable mentally ill patients being able to return both to their families and to productive work.
Lysergic Acid Diethylamide (LSD): Albert Hofmann, who worked for a Swiss pharmaceutical firm, was involved in trying to synthesize improved pharmaceutical products based on components of ergot (a poisonous fungus that grows on rye). In 1943 he synthesized a chemical, LSD, which was similar in chemical structure to ergotamine and ergonovine. Dr. Hofmann wrote the following report on April 22, 1943 during the time he was working with LSD:

“Last Friday, April 16, 1943, I was forced to stop my work in the laboratory in the middle of the afternoon and to go home, as I was seized by a peculiar restlessness associated with a sensation of mild dizziness. On arriving home, I lay down and sank into a kind of drunkenness which was not unpleasant and which was characterized by extreme activity of imagination.”

Hofmann suspected that these effects were due to minute amounts of LSD which must have accidentally found its way into his body. To test this idea, several days later he ingested what he thought was a small amount of LSD (0.25 mg). This time he reported that the symptoms were much stronger than the first time. In subsequent studies, it was shown that the dose of LSD he had selected was five times greater than the average effective dose. This discovery supported the idea that certain mental illnesses might be due to the production of potent substances in the brain that could produce psychic disturbance.
Anesthetics : nitrous oxide, and ether have similar properties in that pain isn’t felt. it was widely used in dentistry for pulling teeth and in surgeries.

Question 18

name and describe 4 antimicrobials that target infectious diseases. and who discovered them.

Answer 18

Paul Ehrlich: he cured syphilis by designing complexes of arsenic and organic molecules

gerhard Domagk: introduced sulfa drugs. they were used for the treatment of bacterial disease.
Alexander fleming: discovered the first antibiotic penicillin. its major use was in the therapy of gram-positve bacterial disease.
Selman Waksman: discovered streptomycin. turning point in the treatment of tuberculosis and gram negative bacterial diseases.

Question 19

name the stages in drug development.

Answer 19

1. identify a new drug molecule . example: a target for a new potential drug could be a receptor that when activated, causes an increase in blood pressure, in the first step its isolated and the biological and chemical characteristics are studied. then after these are understood you start developing a drug to interact with the receptor.
   The general approach to obtaining a molecule that binds to the receptor is to synthesize a lot of the receptor protein and to test the ability of a large number of chemicals to bind to the receptor. Once a compound that binds well to the receptor is identified, it will be studied to determine the pharmacological effects of the chemical at the molecular, cellular, organ, and whole animal level. For instance, in the example of developing a new drug to lower blood pressure, the effect of the drug on blood pressure would be studied. If the drug showed promise in these initial studies it would enter more detailed studies for safety and efficacy. (theres a table on 1.2 , take a look at it).

Question 20

what are preclinical studies?

what are the two main categories?

Answer 20

they are conducted prior to testing new drug in humans.
the two main categories are pharmacological and toxicological studies. they generally progress from molecular and cellular studies, to tissue and whole animal studies.

Question 21

what is the purpose of pharmacological studies?

Answer 21

the detailed mechanism of action of the new drug. for example if the drug lowers high blood pressure they would try and determine how this drug does so.

Question 22

what is the purpose of toxicological studies?

Answer 22

its to determine the safety and tolerability of the new drug. these studies are conducted to asses the affect of the new drug on organ systems other than the targeted organ. these studies can take up pro 6 years to complete.

Question 23

Why are clinal trials important?

one it passes the preclinical stage of development what happens?

Answer 23

Since differences between humans and animals exist, clinical trials are the only studies that will tell us if a drug is truly safe and effective in humans for the intended purposes. As such, well conducted clinical trials are the basis for the clinical use of drugs.
he pharmaceutical company or other group developing the drug will apply to the appropriate drug regulatory body (e.g. Health Canada) for permission to proceed to clinical trials. All clinical trials must be registered with a central agency to which the public has access.

Question 24

what led o better regulations of drugs?

Answer 24

in 1938 a sulfonamide antibacterial drug dissolved in solvent was introduced into therapeutics in the U.S.A. it was toxic and resulted in 100 deaths. now they have to undergo a procedure that prove that toxicity levels are adequate. this was to show safety
while in 1962 a sleeping tablet , thalidomide was introduced, then it was shown that it was prescribed during pregnancy, it produced fetal malformations. so they has more regulations for both safety and efficiency, more animal testing was done on several species.

Question 25

what are the requirements if a drug is to be tested on humans in a clinical trial?

Answer 25

The manufacturer is required to submit proof of both the safety and the efficacy of the drug in several animal species to the government regulatory agency in the particular country concerned. In Canada this is the Health Protection Branch, and in the U.S.A. it is the Food and Drug Administration.
The detailed methodology of the proposed clinical trial in humans is required.
The pharmaceutical manufacturer’s detailed submission is carefully evaluated by qualified scientists in the regulatory agency. If the regulatory agency is satisfied, permission will be given for highly qualified investigators, usually clinical pharmacologists, to initiate careful investigation of the drug in humans. Particular care is required, since animal studies will not always predict drug behaviour in humans, no matter how carefully the studies are conducted.

Question 26

name and describe the four phases of a clinical trial.

Answer 26

phase 1: The study is conducted in a limited number of healthy volunteers. The absorption, distribution, elimination and adverse effects of the new drug are carefully studied. Usually one or two doses of the new drug are administered and the tolerability of the drug is determined. Whether the drug is effective is not assessed in this phase.
phase 2: The objective of this phase is to determine whether the drug is effective in treating the condition for which it is recommended for, in a limited number of people. As such, the drug is given to patients with the disease for which the drug is designed to treat, and the effect is studied. Careful attention is paid to the safety of the drug. Phase 2 studies are often called ‘proof of concept’ studies.
phase3: The drug is now tested in a larger number of people, usually approximately one thousand or more. The safety and efficacy of the drug is carefully studied. Phase 3 trials are also called ‘controlled trials’ or ‘efficacy trials’. Phase 3 trials are discussed in more detail below.
phase 4: Risks that are delayed or less frequent than 1 in 1,000 administrations may be missed in the Phase 3 trial. Thus, surveillance of the effects of drugs are required after the drug is released for general use. This phase is therefore referred to as post-marketing surveillance.

Question 27

describe phase 3 clinical trial in more detail.

Answer 27

they are often called controlled randomized clinical trials and important step when licensing and marketing a drug.
so this trial takes longer than phase two and has a larger population being tested on in different places to ensure the required diversity of patients.
it is the most expensive phase can cost from 1 to 50 million dollars. they need to make sure that very location is following the steps exactly so that data is accurate when analyzed.

Question 28

what are the fundamental elements of a clinical trial? there are 10 !!!!

Answer 28

target population- the people being tested on have to be carefully designed for ex: these people should actually have a disease or an illness tuts the drug can target.
inclusion and exclusion criteria- The patient population has to be carefully defined in order to try to eliminate all variables other than the drug under study. For instance, patients with multiple diseases that could influence the results are excluded. Another consideration in inclusion and exclusion criteria is the stage of the disease on which the new drug is to be tested. Most diseases have different levels of severity (e.g. the different stages of cancer) and the patient with a mild form of the disease may see greater benefit from a drug than the patient with a severe form of the disease. Therefore, the severity of disease also has to be defined.
Ethical considerations and consent- so the people need to know exactly whats happening it can’t be written in scientific language, all the risks have to be outlined with you is conducting the study with the ri contact inf. it also has to be run through Ethics review board to protect the rights of the participants.
comparator- you have a control or a placebo with the trial drug. so the control is usually a gold standard which is the best drug to treat the disease , if not you use the placebo.
randomization- its to remove any type of bias. so grouping diff people by ethnicity.
blinding- this is also to prevent scientists and patients form being bias. o the scientists nor the patients will know which drug was used. only after looking at the feedbcks (wether its positive or neg) will they know which drug it is).
what is measured: The result of the treatments should be measured in an objective and reliable manner, if possible. Guidelines are set to ensure that the results are measured in a reliable manner. For example, measuring blood pressure would be done at the same time of day, by the same person, using the same technique, ensuring consistency from day to day.
compliance- this is to see how often the patients are taking the drug. they return the rest of the drugs that they haven’t used and are given a new set of drugs. this is to see how much the patient took.
Quality of Life Measure: Most clinical trials will measure the impact of the drug or treatment on the quality of life of the participants. Although the hope is that all drugs will improve quality of life, this is not always the case. Some drugs may be effective in treating the disease, but may not improve quality of life. This should be considered when determining the usefulness of a drug.
nalysis of the Results: The experimental drug results obtained in a clinical trial must be compared to the control drug results using statistics. In some clinical trials the difference between the experimental drug and the control drug may be as small as 10% and only proper use of statistics can determine whether this difference is real or happened by chance.

Question 29

describe the placebo response

Answer 29

its a fake drug that makes you believe that its working when it doesn’t do anything.

Question 30

The purpose of advertising is to persuade someone to buy a product. In the case of drugs, the purpose of advertising is to convince the physician to prescribe a certain drug, or a certain company’s product if there is a choice of drugs to treat the same condition. name 6 advertising techniques used to advertise drugs.

Answer 30

catch audience attention- it needs to be eye catching :This ad features bright colours, and a picture of a happy and healthy newly retired couple on the beach. The colourful and happy picture catches your attention, drawing you in to read about the advertised drug.
2.use of celebrities or authorities to endorse products
3.fear-This technique is pretty straight forward. The tactic is to illicit fear in the person, and then provide a drug that will help abate that fear.
4.offerign easy solutions to problems- his technique focuses on how easy it is to treat the specific disease or ailment with the advertised drug
before after techniques- This technique is very simple, yet very effective. Often the ad will have a person in an undesirable circumstance, then the ad will have a subsequent picture of the same person after taking the advertised drug who is now in a desirable circumstance.
discredit drugs produced by other manufacturers and praise your own: to make the drug look better than the other drugs- think of the bounty commercials.

Question 31

what is a drug ?

Answer 31

In general terms, a drug can be defined as any substance received by a biological system that is not received for nutritive purposes, and which influences the biological function of the organism. This broad definition means that chemicals, biological agents, and herbal products are all considered drugs.

Question 32

define a receptor.

Answer 32

A receptor can be any functional macromolecular component of an organism, such as regulatory proteins, transporters, enzymes, or structural proteins.

Question 33

how do drugs work with receptors? (think of a key analogy)

Answer 33

Most drugs influence biological systems by interacting with and binding to receptors, resulting in an increase or decrease in the activity of the receptor. Receptors in the body are normally bound to and activated by endogenous ligands, which are substances ordinarily found in the body, such as hormones and neurotransmitters. Drugs modify the interaction between endogenous ligands and their receptors, and can either increase or decrease the activity of the receptors. drugs that bind and stimulate response are agonist while drugs that bind but block are referred to as antagonist.
just remember that it can be detrimental or beneficial the same receptor can be located in a different area than targeted and cause adverse effects.

Question 34

what are some examples of drugs that do not bind to receptors but by chemical reactions to physical-chemical forces?

Answer 34

commonly used antacids neutralize stomach acid through a simple acid-base neutralization reaction. Another example is cholestyramine (a drug used to lower cholesterol in the blood) that works by chemically binding to bile acids in the gastrointestinal tract, preventing their reabsorption and hence increasing the elimination of bile salts that are used to make cholesterol.

Question 35

dose relationships are very important. an example in the text: comparison of marijuana and alcohol were done. there was more alcohol consumers than marijuana which made the test inaccurate. what are 4 questions that should be asked when conducting experiments such as these?

Answer 35

How much alcohol compared to how much marijuana?
Used how often?
By what people?
Under what circumstances?

Question 36

define the dose response relationship

Answer 36

The dose response relationship is a fundamental concept in pharmacology. Activating just one receptor will not result in the desired response in our bodies. To achieve the desired effect, many receptors need to be activated at once. Therefore, at low doses of drug, very little response is observed. But, as the dose or concentration of drug increases, more and more receptors are activated, until the desired response is seen. In other words, there is a threshold, where a certain number of receptors need to be activated before an effect will be seen. Once this threshold is reached, a small increase in dose results in a large increase in response. This increase in response is not indefinite, however, as our bodies have a maximal effect. Once this maximal effect is reached, continuing to increase the amount of drug will have no further increase in the response.

Question 37

define a dose response curve

Answer 37

its how much drug you need to a specific effect this is illustrated in a graph. he relationship is a straight line, at least where small changes in dose result in large changes in response. The linear portion of the curve allows for the accurate determination of drug effectiveness. For instance, 50% of the maximal response means the dose of drug that will produce half of the maximal effect. This is called the ED50.

Question 38

describe the efficacy of a drug

Answer 38

The maximum pharmacological response that can be produced by a specific drug in that biological system.

Question 39

describe the potency of a drug

Answer 39

he dose or concentration of a drug that is required to produce a response of a certain magnitude, usually 50% of the maximal response for that drug.

Question 40

what is the difference b/w efficacy and potency?

Answer 40

Efficacy is different from potency in that the amount of drug needed does not matter, what matters is the maximum effect that the drug can produce. For example, morphine has greater efficacy than aspirin in the relief of pain. This is because aspirin is only effective in relieving mild to moderate pain, while morphine is able to relieve pain of nearly all intensities.

Clinically, efficacy is more important than potency. This is because the maximal effectiveness of a drug (efficacy) is generally what determines which drug is chosen to treat a specific condition. Potency does not matter as much clinically, as the dose can be adjusted to achieve the desired response.

Question 41

define a therapeutic range

Answer 41

pretty much staying above minimum to get a response and below max so that its not toxic.
ill not cause the desired effect in all people. Every human is a bit different, so with the recommended dose, some people may not see the desired effects, and some people may see toxic effects. A wide difference in responses to a drug exists within a population, which is why drug doses sometimes need to be adjusted based on the individual’s response.

Question 42

why does the usual dose accomplish little in most people?

Answer 42

As mentioned, the so-called ‘usual dose’ of some of our most effective drugs will accomplish little in some persons, cause serious toxicity in others, and be fully satisfactory in some. Let us consider why this is so. When a drug is administered to a patient, it must first be absorbed into the blood stream, then carried by the blood to its site of action where it will exert its effect. A good relationship exists between the concentration of a drug in the blood and the intensity of its pharmacological or therapeutic effect. However, for some drugs there is a very poor relationship between the dose of a drug administered and its concentration in the blood. When the same dose of a drug is given to different individuals, the concentration of the drug in the blood can vary by a factor of as much as 10 between different people.

Question 43

what are the 5 stages that drugs undergo after administration?

Answer 43

Drugs undergo five stages or events after administration: Absorption from the site of administration; distribution to the site of action of the drug; target interaction (i.e. combination with a receptor or other target); biotransformation; and excretion from the body (covered in detail in lesson 1.4). Theoretically, any influence at any stage of these processes can contribute to the variability in the observed response among patients. What are these factors?

Question 44

Name 5 factors that can affect the body after drug administration.

Answer 44

Genetic factors: It is known that responses to many drugs are influenced by the genetics of the patient. There is genetic variability in the receptors to which the drug binds, and genetic variability in the manner in which the body handles and eliminates drugs. For example, the activity of the enzymes involved in the biotransformation of drugs can vary many fold in an individual. (Biotransformation means the conversion of a drug into a different compound in order to eliminate it, and is discussed in detail in lesson 1.4). Some individuals are considered slow biotransformers, and others fast biotransformers. For example, the activity of the enzyme that converts the analgesic codeine into morphine varies from person to person.
Environmental factors: Exposure to certain chemicals can increase the enzymes in the liver responsible for the biotransformation of drugs, therefore these persons eliminate the drug more rapidly than the unexposed portion of the population. For example, chronic alcohol use increases the amount of one of the enzymes involved in drug biotransformation.
Other disease states: The presence of another disease state will alter the manner in which drugs are handled by the body. Patients with liver disease will metabolize drugs at a slower rate than patients with normal liver function. In liver disease the drug metabolizing enzymes are usually reduced in activity and drugs are eliminated more slowly. Cardiovascular and kidney disease also alters the manner in which the body handles drug.
Altered physiological state: A number of changes in physiological state can influence drug response. The two most common are described below:
a. Age of the patient: A newborn is more susceptible to some drugs than a young adult. The drug metabolizing enzymes in a newborn are poorly developed, which results in a slower rate of drug biotransformation than that which occurs in young adults. The overall result is that the active drug stays in a newborn longer. The elderly are also more susceptible to drug action than young adults, especially to drugs acting on the central nervous system. As we age, we lose some of the reserve, or redundancy, in neural function and drugs have a greater effect than expected based on the response in the young adult. Liver and kidney function also decreases with age, which reduces the rate at which the elderly eliminate some drugs.

b. Pregnancy: The body undergoes a number of changes during pregnancy that influences drug response. There is an increase in blood volume, cardiac output, and rate of renal excretion. It must be kept in mind that when treating a pregnant woman with drugs, two patients are receiving the drug, both the mother and the baby.

Presence of other drugs. Drug-drug interactions can also cause variability in response to drugs. Drug-drug interactions are discussed in detail in lesson 1.5.

Question 45

what is the purpose of monitoring drug concentration in blood? use phenytoin (Dilantin) as an example

Answer 45

In cases where the drug has a low therapeutic index, or where a change in blood concentration can be of major significance, blood concentrations are monitored. Drug concentrations should also be periodically monitored when drugs are given for long periods of time; for example, the use of phenytoin (Dilantin) for the prevention of epileptic attacks. The purpose of monitoring blood concentrations of a drug is to ensure that the drug concentrations are within the therapeutic range. Recall that if the drug concentration is above the therapeutic range, toxic effects to the drug will occur, whereas if the drug concentration is below the therapeutic range, the patient will not be getting the full benefit of the drug.

Question 46

However, when it comes to the naming of drugs, care is required to avoid confusion. Every potential drug has a formal chemical name. However, this name is generally a complex one and not satisfactory for general use. If a drug undergoing development shows promise, and a manufacturer wishes to place it on the market, then a special name is selected by a nomenclature committee sponsored by the American Medical Association, the Pharmaceutical Association, and the U.S. Pharmacopeial Convention. This name is referred to as the generic name of the drug. The manufacturer will also apply for a patent with a brand name for the drug, which will give the company exclusive rights to market the drug for 20 years. The 20 year life of a patent begins when the patent is filed, usually during the preclinical development phase. As the time it takes to develop a new drug is years, the effective patent life of a drug is in the range of 10 to 12 years. After a patent on a drug expires, other manufacturers can make what we call generic drugs, which are copies of the original brand name drug.

The generic drug will contain the identical active ingredient as the brand name drug, in the same amount and usually in the same dosage form. Randomized Phase 3 clinical trials are not normally conducted to show the efficacy of a generic drug. A comparative bioavailability study is conducted, which compares the blood levels after administration of both the brand name drug and the generic drug to healthy volunteers under controlled conditions. The assumption, based on our knowledge that drug levels predict response, is that if the blood levels are the same, the response will be the same. Two drug products, generic and brand name, which contain the same active ingredient(s) and give similar blood levels are said to be bioequivalent. This process has ensured that all generics are as effective as the original brand name drug.

The Ontario government now publishes a Drug Benefit Formulary/Comparative Drug Index. This book is prepared by a medical committee and lists only drug products which it believes to be of good quality. The quality of the drugs is determined by inspection of drug factories, by analysis, and by data made available by the Manufacturer, to Health Canada. A recent edition of the Drug Benefit Formulary lists a well-known drug by its generic name, Diazepam, followed by three preparations of this drug under different brand names from different manufacturers.

Valium Hoffman LaRoche Ltd.

Apo-Diazepam Apotex Inc.

Diastat Valeant Canada Ltd.

When these three products are listed in the Formulary, they are regarded by experts as being therapeutically interchangeable. Thus, the drug with the generic name, diazepam, has a variety of brand names. The large number of brand names for a single drug is very confusing. It would be clearer if companies would name the drug by the generic name and add the company name after the generic name.

Historically, it had been shown that drug products made by different companies could result in markedly different blood levels (i.e. not bioequivalent), which can be of considerable therapeutic importance. When drugs are manufactured, additives are used together with the drug in order to ensure appropriate disintegration and dissolution of a drug. Today, strict regulations are in place that ensure that drugs made by different manufacturers result in the same blood levels of drug after administration.

Answer 46

:)

Question 47

define therapeutic jungle.

Answer 47

although there is only one name for drugs it can have many different brand names.
also because when there is a successful ne drug, other companies will change it slightly and sell it themselves, a commerce technique to survive.
a third prob is determining which drug is better , the new or the old. there are so many drugs that are advertised in a bias way that its hard to determine which is right. using letter on drugs and therapeutics is the best solution.

Question 48

define pharmacokinetics. What are the four phases?

Answer 48

its the movement of the drug throughout the body.
the four processes are:
1. absorption: movement of a drug from the stite of administration into the blood.
2. distribution-movemt of the drug from the blood to the site of action and other tissues.
3.botransformation- its when the drug gets converted into a different compost , to a more water soluble compound- referred to as metabolism
the last 4. excretion- removing the drug from the body.

Question 49

there is always a good relationship between the concentration of the dry but why ismt there a good relationship with the dose of the drug with the concentration in the blood?

Answer 49

during the process of absorption not all the drug gets in the blood, bioavailabity differs between drugs.

Question 50

define bioavailability.

Answer 50

the fraction of an administrated drug that reaches circulation in an active form. this depends on he routes. if its directly placed in blood then its there 100 percent any other route can vary 5 to 100 percent.

Question 51

drugs can enter either enteral, topical or parenteral routes. describe these routes

Answer 51

enteral routes. so these are drugs that are given directly into the gastrointestinal tract. drugs given anywhere form the mouth to the anus.
the three would be :
Oral: The oral route of administration includes drugs taken by mouth and those administered via a nasogastric tube. Taking a drug by mouth is by far the most convenient and least expensive means of taking a drug. In addition, taking a drug orally is non-invasive and can be self-administered. As such, taking a drug orally is the most common route of drug administration, with over 90% of all drugs being taken by this route. Capsules and tablets are the most common dosage form administered orally, however, liquid forms of some drugs also exist, which are preferable for children or anyone who has difficulty swallowing a tablet or capsule. A newer form of oral dosage is the orally disintegrating tablet. These tablets disintegrate rapidly in the mouth and the drug is swallowed with the saliva or a small sip of water. Unfortunately, oral administration of a drug is not always possible. For instance, some drugs are inactivated by the digestive enzymes in the stomach and intestine, or are destroyed by the acid in the stomach, ruling out oral administration. In addition, with oral administration it is up to the patient to take the drug correctly and on time, which does not always happen.
All drugs orally ingested have to be absorbed from the stomach and intestinal tract into the blood. Absorption from the intestinal tract can be variable between patients due to differences in intestinal motility and disease. When a drug is absorbed into the blood from the gastrointestinal tract, it is first delivered to the liver, which contains enzymes that can decrease the amount of active drug left to enter the general circulation. This is called the first pass effect.
Since time is required for the drug to be absorbed from the gastrointestinal tract in sufficient amounts to give a pharmacological effect, the time for onset of the response following oral administration is 30 minutes to one hour or more. The bioavailability of drugs following oral administration ranges from 5% to 100%, depending on the drug.
Rectal: Rectal administration of drugs can be for systemic or local effect. The dosage form is usually a suppository that is inserted into the rectum and held in position for as long as possible, but at least 30 minutes, allowing time for absorption. The rectal route of administration can be used in patients who are nauseated or vomiting, or as a less invasive route for those who are comatose. The other advantage is that the digestive enzymes of the stomach and intestine are bypassed. Disadvantages of rectal administration are that not all drugs are available as suppositories, and absorption from the rectal mucosa is slow, incomplete, and variable, depending on the time the suppository is retained. Bioavailability ranges from 30% to 100%.
Sublingual and Buccal: For sublingual or buccal drug administration, the tablet or capsule is not swallowed, but placed under the tongue or in the cheek pouch respectively. The mucosa of the mouth has a rich blood supply and provides a good absorptive surface for many drugs, specifically drugs that are effective in small doses. Absorption from under the tongue is rapid, with some drugs acting within one to two minutes. Absorption from the cheek pouch is somewhat slower than that from under the tongue, but is still faster than absorption from oral administration. An advantage of sublingual and buccal administration of drugs is that the enzymes of the stomach, intestine, and liver are bypassed. However, not all drugs are adequately absorbed from this route. In addition, if the patient is not given proper instructions the drug may be swallowed, and then the drug behaves as if it was taken orally.
Topical Routes

Topical application of drugs refers to drugs applied to the skin, the membranes of the eye, ear, nose, urinary tract, and vagina. Drugs applied topically have local effects and sometimes systemic effects.

On the Skin: A large number of drugs can be applied to the skin to treat local skin conditions such as eczema, acne, and infections. Drugs from topical preparations are slowly released from the ointment, cream, or other dosage form and this route can be used for the treatment of mild to moderate severity skin diseases. Systemic therapy is usually used for severe disease, or where the disease involves a large area of the body (e.g. some cases of acne).
Did you know? Drugs applied to the skin for local effect can be absorbed and produce a systemic effect. For example, some topical steroids used to treat a skin condition can be absorbed and cause toxicities elsewhere in the body.
Through the Skin: A number of drugs can be applied to the skin for absorption into the general circulation and for a systemic effect. This is called transdermal drug delivery. Drugs that are lipid soluble can penetrate the skin in sufficient amounts to exert a systemic effect. The amount of drug that can be transferred across the skin is small, thus any drug administered by this route must be effective in small doses (high potency). The most common method of administering drugs through the skin is transdermal patches, a sophisticated adhesive bandage containing the drug. The patches deliver a known amount of drug per area (cm2) and the size of the patch is used to control the dose. Transdermal drug delivery systems are convenient, and the system can deliver a steady drug supply for several days, eliminating frequent oral dosing. It also bypasses the enzymes of the stomach, intestine, and liver. On the other hand, transdermal patches are more expensive, and can cause local irritation. Bioavailability ranges from 80% to 100%.
Intraocular: Instilling a drug in the eye is a common means to treat local inflammatory conditions, infections, glaucoma, and dryness. A disadvantage of this route is that the preparation must remain sterile throughout the use of the drug. Absorption to other parts of the body is usually minimal.
Intraotic: Drugs are administered into the ear to treat local inflammation and infections.
Intranasal: Drugs can be administered in the nose for both local and systemic effects, and is absorbed from the nasal mucosa. Drugs such as steroids, decongestants, and antibiotics are available as drops and sprays and are applied for local effect.
Inhalation: Drugs are administered through the lungs for both local and systemic effects. Gaseous anesthetics are administered by inhalation for a systemic effect, while steroids and other drugs for lung diseases are administered for local effect in the lungs. Drugs are rapidly absorbed from the lungs and indeed, a number of recreational drugs are administered by this route. To reduce the systemic effect and toxicity of drugs intended for local effect, the properties of these drugs have been designed so that they are removed rapidly from the body after systemic absorption. One advantage of administering drugs by inhalation for local effect is that the quantities of drugs administered by inhalation are small and often less than that required for a systemic effect, thus avoiding the toxicity associated with oral administration of the drug. A disadvantage is that the method requires proper use by the patient. Systemic bioavailability is 5% to 100%, depending on the drug.

parenteral routes
The parenteral administration of drugs is generally considered to be any route where the drug is injected directly into the body. The common parenteral routes are intramuscular (i.m.), subcutaneous (s.c.), and intravenous (i.v.). All parenteral routes bypass the destructive effects of acid in the stomach and the enzymes in the intestine and liver.

Did you know? The hypodermic syringe was invented in 1853 in order to inject morphine subcutaneously to relieve the pain of neuritis (inflammation of the nerve). It was introduced by a Scottish physician, Alexander Wood. An interesting account of the history of the hypodermic syringe is available in Scientific American, Volume 224, No. 96 (1971).

Intravenous: The intravenous route places the drug directly into the blood, removing the requirement for absorption. This route can be used for drugs that are poorly absorbed, providing that they can be made into a solution in water for injection. The onset of action with i.v. administration is 15 to 30 seconds, and the response continues for as long as the drug administration continues. The i.v. route allows for the administration of large volumes of solutions and the continuous infusion of drugs maintaining effective levels of the drug. However, i.v. administration carries the greatest risk of any of the routes of administration in terms of drug reactions since the response is immediate, intense, and irreversible. In addition, it is more costly than other routes, and the preparation must be sterile and free of fever producing substances (pyrogens). Bioavailability is 100%.
Intramuscular: The intramuscular route of administration injects the drug deep into a muscle. The volume of drug is limited to 5 to 10 ml in an adult. The onset of effect is 10 to 20 minutes, depending on the preparation. Bioavailability ranges from 75% to 100%.
Subcutaneous: For subcutaneous administration, the drug is injected into the deepest layer of the skin. The volume administered is usually limited to one ml. The absorption of drugs from the subcutaneous site is often slower than from the intramuscular sites, but not significantly. Onset of response is observed in 15 to 30 minutes. Drug preparations can be modified to control the timing of the release of the drug from s.c. injection sites. Bioavailability is 75% to 100%.

The four processes involved in pharmacokinetics will now be explained in detail. The factors that determine the pharmacological response to a drug after oral administration will be examined, but the same principles apply to drugs administered by all routes.

Question 52

name the three types of diffusion during absorption( when the drug has to diffuse through membranes).

Answer 52

1.diffusion through aqueous pores: