Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

BLOCK A > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is pharmacology?

A

The study of all compounds that interact with the body at all levels of organization. It includes the study of the therapeutic and adverse effects of these compounds.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the difference between natural and synthetic compounds?

A

Natural: Produced by living organisms or derived from natural sources (plants, animals, microorganisms)

Synthetic: Artificially created in a laboratory through chemical reactions.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the difference between endogenous and exogenous compounds?

A

Endogenous: Substances produced naturally within an organism or system.

Exogenous: Substances that originate outside of an organism or system and are introduced from an external source.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Are pharmacology and pharmacy synonymous?

A

No. Pharmacy is a professional field that trains and qualifies individuals to prepare and dispense drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the 5 drug uses?

A
  1. Therapeutics
  2. Diagnosis
  3. Prophylaxis or prevention
  4. Veterinary medicine
  5. Horticulture (insect/parasite control)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

We use drugs in therapeutics to…

A

treat specific conditions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe an example of drugs being used for diagnosis

A

Tuberculin purified protein derivative is used in a skin test to help diagnose TB infection.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Name examples of drugs used for prophylaxis/prevention

A

Anti-histamines (e.g. to prevent seasonal allergies) or birth control (prevent pregnancy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Many of the same drugs are used to treat both humans and …

A

animals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pesticides are …
What is the concern about pesticides?

A

Pesticides are drugs that are increasingly entering into human exposure (contaminated air, food, water).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Drugs have three names…

A
  1. Chemical name (long, complex, of interest to chemists)
  2. Generic (nonproprietary) name (recognized internationally, usually only one)
  3. Proprietary, brand or trade name (patented exclusive property of the drug manufacturer; multiple for one drug)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Give an example of a chemical, generic and proprietary name of a drug

A

Chemical: N-acetyl-para-aminophenol
Generic: Acetaminophen
Proprietary: Tylenol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pharmacokinetics

A

Studies the effect the organism has on the drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pharmacodynamics

A

Studies the effect the drug has on the organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the 4 stages of pharmacokinetics? (ADME)

A

A: Administration
D: Distribution (how the drug moves through the body)
M: Metabolism (how the body metabolizes the drug)
E: Excretion (how the body removes the drug, if at all)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the 3 features of drugs studied by pharmacodynamics?

A
  1. Drug effect
  2. Clinical efficacy
  3. Toxicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the difference between efficacy and potency of a drug?

A

Efficacy: Ability of the drug to produce the maximal desired response, regardless of the dose.
Potency: Amount of drug necessary to elicit a given response.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Potency is often expressed as an…

A

EC50, or half-maximal effective concentration (indicates how much of a drug is needed to inhibit a biological process by half).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Example of efficacious vs less efficacious drug

A

Opioid receptor agonists: morphine and codeine.
Desired response: Total pain relief
No dose of codeine can produce the same degree of pain relief as morphine, therefore morphine is a more efficacious drug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Which is considered more potent?
a) A drug that can relieve pain at a higher dose?
b) A drug that can relieve pain at a lower dose?

A

b) A drug that can relieve pain at a lower dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Is an efficacious drug necessarily potent?

A

No. An drug may be efficacious but not potent (can have a high maximum effect, but require a higher dose to achieve that effect than another drug). Conversely, a drug may be potent but not efficacious (can have significant effects at lower dose, but not necessarily the maximum possible effect).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

When choosing a drug, what is more important? Why?
a) efficacy
b) potency

A

a) efficacy
Efficacy is more important in determining whether a drug will be useful clinically, because if the drug does not produce the desired outcome, its potency is irrelevant.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

If two drugs have similar efficacies, which is often the most desirable?
a) the least potent drug
b) the most potent drug

A

b) the most potent drug
(you will have to take less of the drug to obtain the same effect)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Define the therapeutic index (TI)

A

It is the margin of safety and the ratio between the dose of drug producing undesirable effects and the dose of drug producing the desired therapeutic effect.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Therapeutic index formula

A

TI = TD50/EC50
*TD50 = median toxic dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Drugs with a large TI have a
a) large margin of safety
b) small margin of safety

A

a) large margin of safety

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Why do drugs with a small TI need to be monitored in the plasma?

A

Because even small increases of the plasma levels could move the indiviual into the toxic zone

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

If toxic effects of a drug can start to occur at a dose only slightly higher than that needed for therapeutic effect, it has a…
a) large TI
b) small TI

A

b) small TI (small margin of safety)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

When a drug has a large TI, we can monitor the … and adjust the dose as needed. When a drug has a small TI, we monitor … to readjust the dose as needed.

A

When a drug has a large TI, we can monitor the OUTCOME (e.g. sufficient decrease in blood pressure in a person suffering from hypertension).

When a drug has a large TI, or an effect that is difficult to monitor, we monitor PLASMA CONCENTRATIONS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the 4 possible outcomes from drug treatment, given to different individuals with the same diagnosis and the same treatment?

A
  1. Clinical benefit, no toxicity
  2. Clinical benefit, toxicity
  3. No clinical benefit, no toxicity
  4. No clinical benefit, toxicity
    (*4 is the least desirable outcome - if we’re going to tolerate some toxicity, it is only if there is an important clinical outcome)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

In what context is the outcome “clinical benefit, toxicity” often expected?

A

In oncology during cancer treatment. Cancer drugs often target rapidly dividing cells, which can include both cancerous cells and normal, healthy cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Do drugs always work?

A

No! A lot of drugs have high rates of poor responses (e.g. beta-agonists for asthma have a poor response rate of 40-75%)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Why do drugs not always work?

A

Due to inter-patient variability! There is a plethora of different factors that may influence the effect of a drug on a given individual (environment, exercise, nutrition, smoking, metabolism, etc.)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Name 4 important factors contributing to inter-patient variability in drug responses

A
  1. Age
  2. Pregnancy
  3. Menopause
  4. Altered hormone status
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

PK, PD and drug responses differ between infants, adults and older adults largely due to…

A

normal physiologic changes associated with these periods of life (explains why same diagnosis and same treatment may lead to different outcomes).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Age affecting drug response: How does total body water change with age

A

It decreases with age (highest for infants, lowest for older adults)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Age affecting drug response: How does the percentage of lipophilic drugs retained in fatty tissue change with age?

A

The percentage of lipophilic drugs retained in fatty tissue increases with age (highest in older adults).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Age affecting drug response: How does liver metabolism change with age?

A

Liver metabolism peaks during adulthood, and decreases back down in older adulthood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Age affecting drug response: How does renal clearance change with age?

A

Renal clearance peaks during adulthood, and decreases back down in older adulthood.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

With age, there is also an increase in … which may affect drug response.

A

comorbidities

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Name 3 examples of socioeconomic factors that can contribute to variability in drug responses

A
  1. Inadequate nutrition
  2. Polypharmacy (how many drugs you’re on)
  3. Non-compliance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Pharmacogenetics

A

Area of pharmacology concerned with how genetic differences among individuals may affect both the therapeutic and adverse effects of drugs. Explains why the same diagnosis and same treatment can lead to different outcomes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

In pharmacogenetics, what are the two relevant genomes we must consider? What does each help determine?

A
  1. The patient’s genome (germline): drug exposure and toxicity
  2. The tumour genome (somatic): prognosis and effectiveness of targeted therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Cancer pharmacogenetics represent the standard of care in several cancer types, including… (3)

A

Breast cancer, non-small cell lung cancer, melanoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Define cancer pharmacogenetics

A

Study of response to cancer drug treatment based on genetic biomarkers. It is a type of precision medicine.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Define compliance to treatment (in the context of pharmacology)

A

Patient’s adherence to the prescribed drug dosage regimen (extent to which a patient follows treatment instructions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Therapeutic success of a drug depends on the patient’s… to the prescribed dosage regimen.

A

compliance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Describe the 4 types of non-compliance leading to poorer outcomes

A
  1. The patient fails to obtain the medication
  2. The patient fails to take the medication as prescribed
  3. The patient prematurely discontinues the medication
  4. The patient (or another person) takes the medication inappropriately
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Most patients prefer … drugs to … drugs.
a) oral
b) injectable

A

Most patients prefer ORAL drugs to INJECTABLE drugs.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is a major reason for therapeutic failure, especially in the long-term treatment, in pharmacology?

A

Non-compliance with the prescribed dosing schedule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Which is more common?
a) missed doses
b) too many doses

A

a) missed doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Which do patients struggle with more?
a) remembering the number of drugs that they must take
b) remembering the number of doses of a drug per day/week that they must take

A

b) remembering the number of doses per day/week that they must take

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Name one strategy to improve compliance to a drug treatment

A

Reducing the number of required dosing occasions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Why do patients fail to take their medication? (6)

A
  1. Denial regarding sickness or drug efficacy
  2. Forgetfulness (and other factors)
  3. Stubbornness
  4. Embarrassment
  5. Route of exposure (it is easier to take oral drugs vs intravenous or intramuscular)
  6. Intolerable side effects or interactions with other drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

What are the 4 steps of the drug discovery process?

A
  1. Research and development
  2. Preclinical studies
  3. Clinical trials
  4. Review and approval
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Explain the term “basket trial” (definition, focus, purpose)

A
  • A basket trial tests one type of treatment across multiple cancer types.
  • Focus: Patients with different cancer types but who share a common molecular or genetic alteration
  • Purpose: To assess whether a specific treatment can be used across different cancer types that share the same genetic profile
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

What is the advantage of a basket trial?

A

The trial is not limited by the patients’ diagnosis, but by the presence of a specific drug target

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Explain the term “umbrella trial” (definition, focus, purpose)

A
  • An umbrella trial tests multiple treatments within a single type of cancer
  • Focus: Different subgroups within the same type of cancer classified by different molecular or genetic markers
  • Purpose: Determine the best therapy (drug) for different genetic mutations within a single cancer type
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Cytochrome P450s are a large family of … that play a crucial role in…

A

Cytochrome P450s are a large family of ENZYMES that play a crucial role in the METABOLISM OF DRUGS.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Cytochrome P450s are mainly found in the …

A

liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Family of enzymes responsible for 50% of the elimination of common clinical drugs

A

Cytochrome P450s (CYPs)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

CYP enzymes exhibit genetic polymorphisms. Why is this important?

A

This means individuals will have different versions (alleles) of these enzymes, which will affect how quickly or slowly they metabolize certain drugs. This can influence drug efficacy and risk of side effects.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Define a “prodrug”

A

A prodrug is an inactive or less active form of a drug that must be metabolized within the body to produce an active compound.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What are the two possible outcomes of a drug being metabolized by the body?

A
  1. The prodrug is converted to its active form
  2. A drug is converted to its inactive form
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Take SSRIs (antidepressants) as an example. SSRIs are active drugs that are inactivated by the enzymes CYP2D6. How may an ultra-rapid metabolizer process the drug and what is the solution?

A

An ultra-rapid metabolizer will metabolize the drug too quickly, so the SSRI will rapidly inactivate.
Solution: Increase dose (if TI allows) or switch to a different drug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Take SSRIs (antidepressants) as an example. SSRIs are active drugs that are inactivated by the enzymes CYP2D6. How may a slow metabolizer process the drug and what is the solution?

A

The drug will be metabolized slowly and circulate in the body in its active form for a longer time. This could potentially lead to toxicity.
Solution: Decrease dose.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Pharmacodynamics

A

Study of the effects of drugs on the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

Drugs are ligands for …

A

Receptors

69
Q

Receptors are at the top of signaling pathways. Name two of their main roles.

A
  1. Recognize a transmitter or hormone
  2. Trigger a cellular response
70
Q

Endogenous ligand (name two types)

A

Compound naturally produced by the body which binds and activates a receptor (neurotransmitter or hormone).

71
Q

Agonist

A

A compound that mimics actions of the endogenous ligand

72
Q

Antagonist

A

A compound that counters the actions of an agonist (blocks or opposes natural action or response of a receptor).

73
Q

When trying to bind to a receptor, what do drugs compete with to exert their effects on cells?

A

Endogenous ligands

74
Q

Other than neurotransmitter and hormone receptors, what are some other drug targets? (7)

A
  1. Transporters
  2. Enzymes
  3. Voltage-gated ion channels
  4. Structural proteins
  5. DNA
  6. RNA
  7. Bacterial and viral enzymes
75
Q

What is the most common type of receptor targeted by drugs?

A

G-protein coupled receptor (GPCR)

76
Q

Name 3 types of common compounds that target GPCRs

A

Antihistamines
Caffeine
Opiates

77
Q

What are the most common therapeutic actions of drugs acting on GPCRs? (2)

A

Antihypertensive, anti-allergic

78
Q

Not all drugs act on “receptors”. NSAIDS target enzymes called…

A

cyclo-oxygenases

79
Q

Not all drugs act on “receptors”. Local anaesthetics target…

A

Voltage-gated ion channels

80
Q

Not all drugs act on “receptors”. L-DOPA, a drug used in Parkinson’s disease treatment, acts on…

A

precursor synthesis

81
Q

Not all drugs act on “receptors”. Prozac (fluoxetine) targets…

A

5-HT transporter

82
Q

Receptor-mediated actions tend to be…(4)

A
  1. Of high potency/affinity
  2. Tissue-selective
  3. Chemically-specific
  4. Inhibited by specific antagonists (assuming drug is an agonist)
83
Q

What does it mean for a receptor-mediated action to be of high potency/affinity?

A

The receptor is activated at low drug concentrations (nanomolar to micromolar).

84
Q

The difference in the chemical structure of adrenaline and noradrenaline is one methyl group. However, they have very different receptor-binding preferences. This is an example of…

A

Chemical specificity

85
Q

Define the following:
[D], [R], [DR], k1, k2

A

k1: forward rate constant (rate at which drug binds receptor)
k2: reverse rate constant (rate at which drug-receptor complex dissociates)

86
Q

The dissociation constant (KD) reflects the …

A

binding affinity of a drug for its receptor

87
Q

Low KD implies…
a) low affinity
b) high affinity
Explain your answer

A

b) high affinity
(because you can get 50% occupancy of the receptor at a low concentration)

88
Q

KD is the concentration of drug at which…

A

50% of the receptors are occupied

89
Q

At equilibrium, KD is equal to…

A

KD = k2/k1 = ([D][R])/[DR]

90
Q

If there are no spare receptors, KD is equal to…

A

the EC50 (50% receptor occupancy produces half-maximal effect)

91
Q

Receptor occupancy - definition and formula

A

Receptor occupancy describes the proportion of occupied receptors.
p = [D]/([D]+KD)

92
Q

Receptor occupancy is independent of… and entirely dependent on…

A

Independent of: the concentration of free receptors
Dependent on: concentration of the drug and the drug’s dissociation constant

93
Q

What are the two assumptions we make when relating drug concentration to drug effect?

A
  1. There is a linear relationship between the number of occupied receptors and drug effect
  2. Only one agonist molecule at a time can bind one receptor.
94
Q

When relating drug concentration to drug effect, we make 2 simple assumptions. If these assumptions are true, then…
Effect = ? x ?

A

Effect = max effect x proportion occupied
Effect = max effect x ([D]/([D]+KD))

95
Q

Explain the concept of spare receptors

A

The maximal effect of an agonist can be achieved in a situation where less than 100% of the receptors are occupied.

96
Q

How do occupancy and effect curves compare in a situation with no spare receptors (KD = EC50)

A

Both curves are identical

97
Q

If 50% of the receptors are spare, how does the effect curve compare to the occupancy curve?

A

The maximum effect is achieved at only 50% occupancy. Therefore, the effect curve reaches a maximum 2x faster than the occupancy curve (it reaches a maximum BEFORE the occupancy curve). KD is NOT equal to EC50.

98
Q

What is the efficacy of a full agonist, partial agonist and antagonist?

A

Full agonist: high efficacy
Partial agonist: medium efficacy
Antagonist: zero efficacy
*make sure you review the graphs in your slides

99
Q

How does the binding affinity of a partial agonist compare to that of a full agonist?

A

A partial agonist will have the same binding affinity as a full agonist! However, it will have a decreased ability to produce the same degree of downstream effect.

100
Q

How do partial agonists impact full agonists? Explain.

A

Partial agonists antagonize full agonists, because they can bind to the same receptor with the same affinity, but produce a weaker response.

101
Q

When full and partial agonists compete for receptors, how is the overall response of the system affected?

A

The overall response of the system is reduced, as fewer receptors are available for the full agonist to elicit its maximum response.

102
Q
  1. In the absence of a full agonist, a partial agonist acts as an…
    a) agonist
    b) antagonist
  2. In the presence of a full agonist, a partial agonist acts as an
    a) agonist
    b) antagonist
A
  1. a) agonist (can still produce a response, though weaker than full agonist)
  2. b) antagonist (reduces the possible max response by competing for receptors with the full agonist)
103
Q

Buprenorphine is an example of a…

A

partial agonist for the mu-opioid receptor

104
Q

Name 3 key facts about buprenorphine (other than that it is a partial agonist)

A
  1. It is a safer analgesic than heroin (heroin = full agonist)
  2. It can blunt the heroin high
  3. It can trigger withdrawal
105
Q

Define constitutive receptor activity (aka basal activity)

A

Intrinsic activity of a receptor in the absence of a ligand.

106
Q

What is the efficacy of an inverse agonist?

A

Negative efficacy
* make sure to review the graph in your slides!

107
Q

Define the concept of inverse agonist. How does it differ from an antagonist?

A

Inverse agonist: Binds the same receptor as an agonist, but produces the opposite effect. It reduces the receptor’s activity below its basal level.

Antagonist: Binds to the receptor but does not produce an effect on its own. It simply blocks or prevents the action of an agonist!

108
Q

Explain how reverse agonists can be clinically useful?

A

Many diseases are characterized by genetic mutations that cause increased basal activity of receptors. Inverse agonists can then be used to reverse this excess activity.

109
Q

Surmountable antagonism reflects…

A

competitive reversible antagonism

110
Q

Describe surmountable antagonism and summarize its 3 key characteristics

A

Effects of an antagonist can be overcome by increasing the concentration of an agonist.

  1. Reversible binding (antagonist can dissociate allowing agonist to bind instead)
  2. Shift in dose-response curve to the right (the greater the antagonist concentration, the greater the agonist concentration needed to achieve the max effect)
  3. No change in max response (efficacy)
    *EC50 increase
111
Q

Insurmountable antagonism reflects either … or …

A

competitive irreversible antagonism or noncompetitive antagonism

112
Q

Describe competitive irreversible antagonism

A

Antagonist makes a permanent or near-permanent bond with the receptor - cannot be displaced by increasing the concentration of the agonist.
Efficacy is decreased because the maximum effect can no longer be achieved. EC50 will increase (a higher dose will be required to achieve the half maximal effect).

113
Q

Describe noncompetitive antagonism

A

The antagonist binds to a site on the receptor other than the active site (i.e. it binds an allosteric site). Since they are not competing for the same binding site, increasing agonist concentration will not influence antagonist binding. This results in decreased efficacy as [antagonist] is increased. EC50 will increase.

114
Q

Noncompetitive antagonism is an example of…

A

allosteric modulation (particle affecting receptor activity by binding to a site other than the ligand-binding site)

115
Q

Some allosteric modulators can increase the effects of an agonist. How is the efficacy impacted?

A

The allosteric modulators could increase the maximum effect exerted by an agonist, therefore increasing its efficacy.

116
Q

Toxicology

A

Science of adverse effects of substances on biological and ecological systems

117
Q

Toxicant

A

Any substance that is harmful to a living organism

118
Q

Difference between toxicant and toxin

A

Toxins: produced by biological organisms
Toxicants: synthetic, human-made txic chemicals

119
Q

What differentiates a poison from a remedy?

A

Dose (Paracelsus)

120
Q

Difference between pharmacology and toxicology

A

Pharmacology: studies drugs in order to produce desired effects
Toxicology: studies chemicals to identify whether they produce undesired effects, actions of poisons (non-therapeutic), effects of environmental chemicals on human health

121
Q

Natural substances do NOT necessarily mean safe substances! Name some examples

A

Star of Bethlehem Oak - blocks channels, can cause cardiac arrest
Belladona - dilates pupils
Poison Ivy - skin irritation
Yew - used to make taxol (anti-cancer drug)

Natural substances can be very toxic or make powerful drugs.

122
Q

Adverse effects of drugs may be… (2)

A
  1. Dose-related (extension of the desired or therapeutic effect)
  2. Surprise toxicity (unrelated to the therapeutic effect i.e. side effect)
123
Q

DDT is an organochlorine insecticide. Explain its mechanism of action.

A

DDT blocks sodium channels in the nervous system and disrupts the propagation of action potentials. It causes uncontrolled repetitive spontaneous discharges along the nerve.

124
Q

What were the advantages and disatvantages of DDT?

A

Advantages: great insecticide, killed millions of mosquitoes and reduced malaria rates significantly
Disadvantages: immense environmental impact + cancer

125
Q

DDT was banned in the US in 1972. Why is it still being used in Mexico?

A

Because a decrease in use of DDT is strongly correlated with an increase in cases of malaria

126
Q

Toxicology also looks at ADME. Define this acronym and explain how it differs from the pharmacological approach.

A

A: Administration
D: Distribution
M: Metabolism
E: Excretion

In toxicology, the difference is in administration, which is more limited than that of drugs (we cannot ethically inject a toxicant).

Administration is limited to:
- skin (dermal)
- inhalation
- ingestion

127
Q

What is the purpose of toxicity testing?

A

To characterize the toxicity profiles of chemicals (or biologicals).

128
Q

All drugs developed for human use are tested in 2 disciplines…

A
  1. Safety pharmacology
  2. Preclinical toxicology
129
Q

What are the different phases of “safety” pharmacology in drug development?

A
  1. Early drug discovery
  2. Nonclinical studies (to enable first-in-human testing - FIH)
  3. Clinical trials (3 phases)
  4. Launch of new drug

Toxicology is involved in ALL of these phases

130
Q

During drug development, close to 30,000 early drugs are narrowed down ton only one clinical drug product. What is one of the main reasons for elimination of potential drugs in this process?

A

Toxicology assessments show that the drugs have toxic, adverse effects.

131
Q

What is the ICH?

A

International Council for Harmonisation of technical requirements for pharmaceuticals for human use

132
Q

What is the role of the ICH?

A

Standardize and harmonize international scientific and technical guidelines for pharmaceutical DRUG development and registration.

This means DRUGS are highly regulated before being made accessible to humans.

133
Q

We are exposed to chemicals in… (3)

A
  1. The workplace
  2. Consumer products
  3. Our environment
134
Q

What is the most important risk factor for global deaths by pollution?

A

Air pollution causes the highest number of estimated global deaths

135
Q

There are 80 million synthetic substances, 140,00 of which are chemicals used in commerce. What percentage of these chemicals is tested?

A

Less than 10%

136
Q

What is the OECD?

A

Organisation for Economic Co-operation and Development

137
Q

What is the role of the OECD?

A

Organisation promoting policies for improving global health, safety and well-being, including policies for chemical testing. It is responsible for determining the safety levels for chemicals used in manufacture.

138
Q

Name examples of OECD guideline tests.

A
  • Skin sensitization
  • Dermal toxicity
  • Ocular toxicity
  • Inhalation toxicity
  • Oral toxicity
  • Neurotoxicity
  • Immunotoxicity
  • Cytotoxicity
  • Developmental toxicity
  • Reproductive toxicity
  • Genotoxicity
139
Q

The OECD uses a … strategy to test the effects of chemicals on health.

A

Tiered testing strategy

140
Q

Describe the tiered testing strategy

A

It is a stepwise approach for testing used to evaluate the safety and toxicity of chemicals.

Tier 1:
Tier 2:
Tier 3:
Tier 4:
Tier 5:

141
Q

Animal studies are often used for estimating human toxicity. However, there is a level of uncertainty when applying what we learn from animals to humans. Why is that?

A

Most toxicology studies are done on rats, which tend to be extremely similar to each other (similar weight, similar ages, similar health).
Humans are not so uniform (there are enormous fluctuations in height, weight, age, health status, obesity, etc.)

142
Q

What are some modifiers of toxicity that create uncertainty in a given individual’s response to a potential toxicant?

A
  • Exposure (route, site)
  • Genetic polymorphisms
  • Nutritional status (e.g. obesity)
  • Presence of other drugs or chemicals
143
Q

What is the CEPA?

A

Canadian Environmental Protection Act

144
Q

Based on the CEPA, substances are deemed to be toxic if they enter, or may enter, the environment in amounts that… (3)

A
  1. have an immediate or long-term effect on the environment or its biological diversity
  2. Endanger the environment upon which life depends
  3. Endanger human life or health
145
Q

To assess whether a chemical should be banned, we must determine the …, … and … of exposure that is experience or anticipated.

A

We must determine the type, level and duration.

146
Q

4 mechanisms for hazard identification

A
  • structure-activity analysis
  • in vitro tests
  • animal bioassays
  • epidemiology
147
Q

Formula for risk assessment

A

Risk = exposure * hazard

148
Q

Risk occurs when exposure concentrations exceed those at which…

A

toxic effects are observed

149
Q

What is an endocrine disrupting chemical (EDC)?

A

An EDC is an exogenous substance that alters functions of the endocrine system and consequently causes adverse health effects.
*EDCs are everywhere in our everyday environment!

150
Q

What are some of the reported health impacts of EDCs (6)?

A
  1. Obesity
  2. Female fertility
  3. Embryo development
  4. Thyroid
  5. Male fertility
  6. Brain functions
151
Q

In toxicology, we do not always see simple dose-response curves. Explain the difference between monotonic and non-monotonic dose-response relationships

A

Monotonic: Effect of a substance consistently increases (or decreases) with increasing dose (linear or sigmoidal relationship)

Non-monotonic: Effect of a substance does not follow a single, predictable pattern as dose increases (u-shaped, inverted u-shaped, multi-phasic).

152
Q

Exposure to EDCs may have long-lasting consequences, sometimes even … effects

A

transgenerational effects (if a chemical is toxic to germ cells)

153
Q

International laws do not contain specific provisions for EDCs. What else poses a problem for the coherent identification and risk management of EDCs?

A

Absence of an EDC hazard class in Classification Labelling and Packaging (CLP) Regulation and/or the Globally Harmonized System of Classification and Labelling of Chemicals.

154
Q

Why do we have poison centres?

A

In Canada, 1,500 people lose their lives and 8,000 are hospitalized due to unintentional poisoning from common substances in our homes

155
Q

More than 1/3 of the Poison Centre cases involve a …

A

child aged 5 or less

156
Q

What do you do when you see a poisoned patient?

A
  1. Maintain vital signs
  2. Identify the poison
  3. Decontaminate
  4. Enhance elimination of the poison
  5. Administer antidote (note that antidotes rarely exist for most poisons)
157
Q

Name 3 examples of poison antidotes

A
  • antivenom
  • chelating agents
  • receptor antagonists (Naloxone)
158
Q

In pharmacology, we design specific drugs to target a specific receptor to produce a specific effect. In contrast, in toxicology chemicals can act on … in … and can have …

A

In toxicology, chemicals can act on multiple receptors in multiple tissues and can have multiple effects (we do not control their effects by design).

159
Q

Most toxicants have…
a) irreversible interactions with target receptors
b) reversible interactions with target receptors

Explain why.

A

b) reversible interactions with target receptors

Because unlike drugs, they are not designed to be high-affinity binders.

160
Q

LOAEL

A

Lowest Observed Adverse Effect Level: lowest dose at which adverse effects are first observed

161
Q

NOAEL

A

No Observed Adverse Effect Level: highest dose at which no harmful effects are observed

162
Q

Threshold

A

Concentration at which any effects of a chemical are observed (usually not yet adverse effects)

163
Q

Why is there a threshold to observe any effects of a chemical?

A

Our bodies have the ability to neutralize “nasty” chemicals to some degree (e.g. cytochrome P450 enzymes in the liver). Thus up to a given THRESHOLD, you can administer a drug/chemical without producing an effect.

164
Q

During the drug development process, more expensive and lengthy tests (e.g. cancerogenicity) are carried out … in the drug development process.
a) sooner
b) later

A

b) later
(to avoid wasting effort and money testing drugs, most of which are eliminated upstream because of toxicity)

165
Q

Describe the tiered testing strategy

A

Aimed at making chemical testing quicker and more cost-effective.
Tier 1: In silico, computer-based analyses (comparing chemical structure to known compounds)
Tier 2: In vivo and in vitro screens
Tier 3: In vitro whole cell activity assessment
Tier 4: Fish and amphibian whole animal assessment
Tier 5: Mammalian whole animal assessment

We only move on to the next tier if we find that the chemical is not likely to be toxic.

166
Q

To account for the uncertainty of moving from animal tests to human conclusion, the NOAEL is decreased by a factor of… and then to account for human variability, it is decreased by another order of …

A

10

167
Q

How do we determine risk?

A

By determining the level of exposure to a chemical and determining the specific hazard (what chemical is posing the risk).

168
Q

Risk occurs when…

A

exposure concentrations exceed those at which toxic effects are observed.

BLOCK A (5 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions