Module 1 Section 1 (Pharmacodynamics)

Question 1

What is pharmacology?

Answer 1

It’s the study of substances that affect or alter living systems through chemical processes. These living systems are usually (but not always) affected by increasing or decreasing the activity of normal regulatory processes within the living system.

Question 2

What is a drug?

Answer 2

It’s s any substance received by a biological system that is not received for nutritive purposes. According to this definition, chemicals, biologicals, and herbals are all considered drugs

Question 3

What is phamacodynamics?

Answer 3

It’s what a drug does to the body. In other words, the effects of a drug on the body, and the mechanism of action by which the drug causes these effects

Question 4

What is pharmacokinetics?

Answer 4

It’s how the body handles the drug. That is, the fate of the drug once it is in the body, including its absorption, distribution, metabolism, and excretion

Question 5

Why are drugs administered?

Answer 5

1) To achieve a beneficial effect on an individual. For example, taking a drug to dilate blood vessels to decrease blood pressure.
2) To exert a selectively toxic effect on an individual (i.e. selective toxicity). Common examples of selective toxicity are taking an antibiotic to kill a bacterial infection or taking a chemotherapeutic to target cancer cells

Question 6

How do drugs influence biological systems?

Answer 6

Drugs bind to receptors (regulatory proteins, enzymes, etc) which result in a response. Receptors are normally bound to and activated by endogenous ligands (such as hormones or neurotransmitters). Drugs modify the interaction between endogenous ligands and their receptors, and can either increase or decrease the activity of the receptors.

Question 7

Does it matter what receptor is activated by a drug?

Answer 7

. The location of these receptors determines where a drug will act and whether the response that results from the drug-receptor interaction is beneficial or detrimental.
Ex: morphine activating opioid receptors in brain and spinal cord = pain alleviated. Morphine activating opoid receptors on GI tract = constipation.

Question 8

What are the 4 common types of receptors?

Answer 8

1) Regulatory proteins
2) Transporters
3) Enzymes
4) Structural protein

Question 9

What are regulatory proteins? Give an example.

Answer 9

They are proteins that mediate the actions of endogenous chemical signals, such as neurotransmitters. Generally, regulatory proteins mediate transmembrane signalling, which can occur by four common signalling mechanisms.

Ex: decongestants activate alpha receptors in blood vessels causing constriction of blood vessels. Alpha receptors can also be activated by the endogenous ligand norepinephrineto perform the same function.

Question 10

What occurs once an endogenous ligand or drug binds to the receptor of a regulatory protein (aka signal transduction)?

Answer 10

With regulatory proteins, once an endogenous ligand or drug binds to and activates its receptor, the activated receptor triggers a series of biochemical events that result in the pharmacological effect. This process is often referred to as signal transduction

Question 11

What are the 4 common signaling mechanisms of regulatory proteins?

Answer 11

1) Ligand gated ion channels as receptors
2) G-protein coupled receptor
3) Intracellular receptors
4) Regulated Transmembrane Enzyme

Question 12

What are ligand gated ion channels as receptors? Where are the receptors located?

Answer 12

They are the regulatory proteins used to transport sodium, chloride, and other ions.

The channels span across the cell membrane, having a portion of the channel on the outside of the cell membrane and a portion protruding into the inside of the cell

Question 13

What occurs when an endogenous ligand or drug binds to the portion of the receptor outside the cell membrane of a ligand gated ion channel?

Answer 13

When an endogenous ligand or drug binds to the portion of the receptor outside the cell membrane, it causes a conformational change in the channel protein, opening it and allowing the flow of ions into the cell.

Question 14

Give an example of a ligand gated ion channel. How fast is this response?

Answer 14

Ex: a nicotinic receptor. The endogenous neurotransmitter ACh binds to nicotinic receptors in muscle, causing the channel to open and allowing Na ions to enter the muscle cell. The increased concentration of Na ions causes depolarization of the muscle cell membrane, and muscle contraction results.

This response occurs in milliseconds and since ACh is removed quickly, the response is of short duration.

Drugs can alter the response at these channels

Question 15

What are G-protein coupled receptors? Where are the receptors located?

Answer 15

They are the largest and most diverse group of membrane receptors in eukaryotes. Many drugs, hormones, neurotransmitters, and other signaling molecules can bind to and activate G-protein coupled receptors.

The G-protein coupled receptor spans the outside to the inside of the cell membrane.

Question 16

What occurs when a drug binds to the receptor on the outside of the cell membrane of G-protein coupled receptors? How fast is this response?

Answer 16

1) When a drug binds to the receptor on the outside of the cell membrane, it causes a change in the shape of the receptor protein, which activates the G-protein.
2) The activated G-protein then activates one of a number of common second messenger systems (e.g. cyclic adenosine monophosphate, calcium ions, and phosphoinositides). These second messengers activate an enzyme or an ion channel that results in an amplified effect.

This is a slower process than ligand activated ion channels due to the activation of the second messengers

Question 17

What are intracellular receptors?

Answer 17

Most of these receptors, called intracellular (or nuclear) receptors, are part of the elements required for gene expression and exist as inactive protein complexes.

Question 18

What can activate intracellular receptors? Give an example.

Answer 18

A number of lipid soluble drugs that gain access to the inside of cells can activate receptors inside the cell.

The drug binds to and (if an agonist) activates the receptor.Receptor binding increases gene expression and subsequent protein synthesis.

Ex: steroid hormones (e.g. cortisol) and thyroid hormones (e.g. Thyroxine).

Question 19

How long does the process for intraceullar receptors take?

Answer 19

The process carried out by intracellular receptors is relatively slow, taking from 30 minutes to several hours before a response is observed.

The effects of gene activation can also be of longer duration, as the effect continues as long as the enzyme or other proteins persist.

Question 20

What are regulated transmembrane enzymes? Where are the receptors located?

Answer 20

Another receptor signalling mechanism involves receptors that are on the outside of the cell but linked to an enzyme inside the cell.

Question 21

Give an example of regulated transmembrane enzymes.

Answer 21

Ex: insulin and many growth factors act on receptors that are on the outside of the cell but are linked to an enzyme inside the cell

Question 22

What occurs when a drug binds to the extracellular receptor of regulated transmembrane enzymes?

Answer 22

When the drug binds to the extracellular receptor, the change in the receptor-drug complex allows for the activation of an enzyme that in turn activates biochemical reactions to produce a biological effect.

Question 23

What are active regulated transmembrane enzymes called?

Answer 23

Protein kinase

Question 24

What do protein kinases do?

Answer 24

Protein kinases phosphorylate and activate a cascade of biochemical events, ranging from transport of ions and metabolites, to gene expression.

Question 25

Identify the signalling mechanism described in each of the below questions:

1) Regulatory proteins that transport ions across the cell membrane when an endogenous ligand or drug binds to the receptor.
2) Receptors that activate an enzyme inside the cell when an endogenous ligand or drug binds
3) Receptors that undergo a conformation change when an endogenous ligand or drug binds, activating a second messenger system.
4) Receptors that move into the nucleus when bound to an endogenous ligand or drug, increasing gene expression

Answer 25

1) Ligand gated ion channels
2) Regulated transmembrane enzymes
3) G-protein coupled receptor
4) Intracellular receptors

Question 26

What are transporters?

Answer 26

Transporters are proteins that transport endogenous substances across cell membranes.

Question 27

What occurs when a drug targets transporters? Give an example.

Answer 27

Drugs targeting transporters often inhibit the function of the transporter.

Ex: the selective serotonin reuptake inhibitors (SSRIs), which are drugs used in the treatment of depression, block the transporter responsible for removing the neurotransmitter serotonin from the synaptic cleft. This prolongs the availability of serotonin within the cleft, enhancing its effect.

Question 28

What are enzymes?

Answer 28

Enzymes are proteins that catalyze a biological reaction.

Question 29

What occurs when a drug targets enzymes? Give an example.

Answer 29

Often drugs targeting enzymes inhibit the catalytic function of the enzyme.

Ex: the cholesterol lowering drugs known as statins inhibit the enzyme HMG-CoA reductase, which is the enzyme responsible for synthesizing cholesterol

Question 30

What are structural proteins?

Answer 30

Structural proteins are proteins that contribute to the cell structure.

Question 31

What occurs when a drug targets structural proteins? Give an example.

Answer 31

Drugs can bind to structural proteins in a cell and disrupt their normal function.

Ex: some anticancer drugs work by binding to microtubules, thereby inhibiting spindle formation, which stops cell division.

Question 32

True or false: Some drugs interact non-specifically with the biological system and not through receptors.

Answer 32

True

Question 33

Give an example of drug actions not mediated by receptors.

Answer 33

Ex: commonly used antacids neutralize stomach acid through a simple acid-base neutralization reaction.

Ex: a number of drugs used in the chemotherapy of cancer do not bind to specific receptors, but kill cancer cells by chemically disrupting normal cell function (f anti-cancer drugs known as alkylating agents kill cancer cells by chemically reacting with the DNA in the cells, preventing the DNA from being able to function correctly, inhibiting cell division and therefore cancer growth).

Question 34

Drugs can be classified into five groups, based on how the drug interacts with its receptors. What are the 5 groups?

Answer 34

1) Agonist
2) Partial agonist
3) Allosteric activator
4) Competitive antagonist
5) Non-competitive antagonist

Question 35

What occurs when agonists bind to a receptor? Give an example.

Answer 35

Agonists bind to the receptor and activate it, causing the desired effect or response.

Agonists can be endogenous ligands, such as neurotransmitters, or drugs.

Ex: when an agonist binds to and activates beta 2 receptors in the lung, the bronchioles dilate

Question 36

What occurs when partial agonists bind to a receptor? Give an example.

Answer 36

Partial agonists bind to the receptor and activate it, but produce a weaker response than the agonist.

Ex: a partial agonist binding to beta 2 receptors would still dilate the bronchioles, but would not dilate them as much as the agonist would.

Question 37

True or false: Partial agonists never achieve the maximal biological response.

Answer 37

True

Question 38

What occurs when allosteric activators bind to a receptor? Give an example.

Answer 38

An allosteric activator binds to a different area of the receptor than the agonist, but makes it easier for the receptor to be activated. The result = an increase in the ability of an agonist to activate the receptor and therefore an overall increase in the effect or response when both the allosteric activator and agonist are present.

Ex: when an allosteric activator and an agonist are bound to beta 2 receptors in the lung, you will get more bronchiole dilation than the agonist would achieve regularly.

Question 39

What occurs when competitive antagonists (inhibitors) bind to a receptor? Give an example.

Answer 39

A competitive antagonist binds to the same spot on the receptor as the agonist, but does not produce a response.

Essentially, antagonists occupy the receptor site and do not allow agonists to bind and exert their effect.

Ex: when a competitive antagonist binds to beta 2 receptors in the lung, it blocks dilation of the bronchioles. If a small dose of a competitive antagonist is given with a normal dose of agonist, the competitive antagonist will compete with the agonist for the receptor and reduce the overall response to the agonist. Since the competitive antagonist binds to the same spot on the receptor as the agonist, you can overcome the inhibitory effects of the competitive antagonist by increasing the amount of agonist at the receptor site.

Question 40

What occurs when non-competitive antagonists bind to a receptor?

Answer 40

A non-competitive antagonist binds irreversibly, or nearly irreversibly, to a receptor but does not activate it.

They can bind to the same site as the agonist, or to an allosteric site, causing a conformational change that inhibits the ability of the agonist to bind to and activate the receptor.

In the presence of a small dose of a non-competitive antagonist, the agonist will produce a response that is less than the maximal response, as less receptors are available to be activated.

Question 41

True or false: The inhibition produced by a non-competitive antagonist cannot be overcome by increasing the amount of agonist at the receptor site. Therefore, a non-competitive antagonist blocks an effect more permanently than a competitive antagonist.

Answer 41

True

Question 42

Identify the drug-type for each of the described responses at the receptor:

1) Binds to a different area of the receptor than the agonist, but makes the receptor easier to activate.
2) Reversibly binds to the same receptor site as an agonist, but does not activate it.
3) Binds to the receptor and activates it, but produces a weak response.
4) Binds to and activates the receptor, producing a full response.
5) Irreversibly binds to and blocks the receptor.

Answer 42

1) allosteric activator
2) competitive antagonist
3) partial agonist
4) agonist
5) non-competitive antagonist

Question 43

Whay is the dose-response relationship?

Answer 43

Generally, the intensity of the pharmacological effects produced by a drug increases in proportion to the dose.

Question 44

True or false: gy. 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.

Answer 44

True

Question 45

True or false: an antagonist does not occupy all of the receptors except at high doses.

Answer 45

True

Question 46

What are spare receptors?

Answer 46

The receptors not occupied at any given dose of an agonist or antagonist.

Question 47

What is the dose-response curve?

Answer 47

A dose response curve is a graphical representation of how much drug you need in the body to see a specific effect.

Question 48

Explain the components of the dose-response curve.

Answer 48

1) The effect of the drug is on the y-axis and plotted on a linear scale. The maximal response the body can produce is set at 100%. Agonists can achieve the maximal response, however, partial agonists can never reach the maximal response – no matter the dose.
2) The dose of the drug is on the x-axis of the graph and is plotted on a logarithmic (log) scale. A logarithmic scale is a non-linear scale of measurement where each unit of increase or decrease represents a ten-fold change in the quantity being measured. It is commonly used when there is a large scale of quantities.
3) Increases in dose are not corresponding to increases in response. The receptor threshold has not yet been reached, that is, the minimum number of receptors that need to be activated to observe a measurable response has not yet occurred.
4) In this region of the curve, the receptor threshold has been reached and the dose of the drug is directly proportional to the response. Small changes in dose result in large changes in response. This linear portion of the curve allows for the accurate determination of drug effectiveness.
5) This is the ED50. The dose of drug that will result in 50% of the maximal effect. The ED50 can also be interpreted as the dose of drug that is effective in 50% of a population.
6) The maximal response has been reached, and further increases in dose no longer correspond to increases in therapeutic effect

Question 49

Which of the five classifications of drugs activate receptors:

a) Competitive antagonists and non-competitive antagonists
b) Agonists and competitive antagonists
c) Agonists and partial agonists
d) Allosteric activators, competitive antagonists, and non-competitive antagonists

Answer 49

c) Agonists and partial agonists

Question 50

Picture 3 dose-response curves in a graph. C is the highest, followed by A then by B. Predict what letter is associated with the following terms: agonists, partial agonists, and allosteric activators plus agonists

Answer 50

A = agonist 
B = partial agonists
C = allosteric activators plus agonists

Question 51

What is efficacy?

Answer 51

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

Question 52

What is potency?

Answer 52

The 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. Potency refers only to the amount of drug that must be given to obtain a particular response.

Lower dose of drug = more potent

Question 53

What do we mean when we say Drug A is more potent than Drug B?

Answer 53

When we say that Drug A is more potent than Drug B, it simply means that one needs to take less of Drug A (e.g. 10 mg) to achieve the same effect that is obtained from Drug B (e.g. 20 mg).

Question 54

What is the difference between efficacy and potency? Provide an example.

Answer 54

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.

Ex: morphine has greater efficacy than Tylenol in the relief of pain. This is because Tylenol is only effective in relieving mild to moderate pain, while morphine is able to relieve pain of nearly all intensities.

Efficacy deals with Y-axis (max effect). Potency deals with the X-axis (it usually looks at the 50% response to determine the dose).

Question 55

What is more important: efficacy or potency?

Answer 55

Clinically, efficacy is more important than potency. This is because the maximal effectiveness of a drug 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 56

True or false: potency and efficacy comparisons between drugs can only be done when the drugs act through the same receptor and on the same biological system.

Answer 56

True

Ex: you can compare potency and efficacy between two drugs that both act on beta 2 receptors in the lungs. You cannot directly compare two drugs if one acts on beta 2 receptors in the lungs and the other acts on dopamine receptors in the brain.

Question 57

Complete the sentences:

1) The dose-response curve of a drug with low potency is shifted ___ compared to the dose-response curve of a drug with high potency?
2) The dose-response curve of a drug with low efficacy is ___ compared to the dose response curve of a drug with high efficacy.

Answer 57

1) The dose-response curve of a drug with low potency is shifted right compared to the dose-response curve of a drug with high potency?
2) The dose-response curve of a drug with low efficacy is condensed compared to the dose response curve of a drug with high efficacy.

Question 58

What is the therapeutic range?

Answer 58

The aim of therapy is to give a dose that keeps the blood concentration of the drug above the minimum concentration that produces the desirable response, but below the concentration that produces a toxic response.

Question 59

What is the recommended dose of a drug?

Answer 59

The recommended dose of a drug is the amount of drug that will cause the desired effect in most people, but it will not cause the desired effect in all people.

A frequency distribution curve (bell curve) is what is used which is then transformed to log dose (the ED50 is observed).

Question 60

A new drug called Quickfix acts by binding to an area on beta 2 receptors, making it easier for Salbutamol (a beta 2 agonist) to activate the receptor. Quickfix is best described as:

a) A partial agonist
b) An allosteric activator
c) A non-competitive antagonist
d) A full agonist

Answer 60

b) An allosteric activator

Question 61

Your tooth is hurting, and you have been told that you can take either acetylsalicylic acid (Aspirin) or ibuprofen (Advil) for the pain. You read that the dose of Aspirin needed is 325 mg, while the dose of Advil needed in 200 mg. From this information, you can conclude that:

a) Advil has greater efficacy than Aspirin
b) Aspirin has greater efficacy than Advil
c) Advil is more potent than Aspirin
d) Aspirin is more potent than Advil

Answer 61

c) Advil is more potent than Aspirin