Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

FPP > Fundamental Principles of Pharmacology > Flashcards

Fundamental Principles of Pharmacology Flashcards

1
Q

What is a drug?

A

A drug can be defined as; a chemical substance of known structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect.

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

drugs that are used theraputically have how many names? what are they?

A
  • chemical name –
    e.g. (RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid
  • common name – ibuprofen
  • Proprietary (trade) names – e.g. “Nurofen”;
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

by what 2 things are drugs grouped

A
  • Usually grouped according to therapeutic use e.g. analgesics, antihypertensives, antibiotics
  • Or sometimes by mechanism of action e.g. cyclooxygenase inhibitor, beta- blocker

IE Ibuprofen is a cyclooxygenase inhibitor that acts as an analgesic

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

what kind of molecules are drugs?

A

Drugs are exogenous molecules that mimic or block the actions of endogenous molecules

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

what are 4 target proteins for drugs

A
  • Receptors for neurotransmitters or hormones
  • Enzymes
  • Ion channels
  • Carrier or transporter molecules
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are ligands?

A

The small drug molecules that bind to large target proteins are called “ligands”

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

What do modern computer modelling techniques allow for?

A

Modern computer modelling techniques allow drugs to be designed in silico.

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

how well a drug fits into its binding site is governed by 2 things, what are they?

A

the size and flexibility of the drug (steric factors)

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

how well a drug bind to its target protein is determined by what?

A

the nature of the chemical bonds that form between the molecule and binding site

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

what type of bonds do most drugs form with their target proteins?

(reversible)

A

hydrophobic & hydrogen bonds plus weaker van der Waals interaction

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

what type of bonds do most drugs form with their target proteins?

(irreversible)

A

covalent interactions

this leads to the formation of a ligand-protein complex which will alter the activity of the protein in some way

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what are the two “S’s” essential in therapeutic drug use?

A

selectivity and specificity

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

what is one way we can achieve selectivity in drugs?

A

design drugs that bind with a high degree of specificity to their target protein.

Ideally they will bind ONLY to their target protein and no others

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

What is pharmacodynamics?

A

= what the drug does to the body

drugs actions at a molecular level on physiology of an organism

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

What is pharmacokinetics?

A

= what the body does to the drug

how its handles, how does it get to site of action, how. is it metabolised

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

What are PK/PD studies?

A

When drugs are being developed for therapeutic use, a true understanding of the drug’s effectiveness only comes when pharmacodynamics and pharmacokinetics are considered together, so-called PK/PD studies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the 4 critical elements of pharmacokinetics?

A

ADME;

  • Absorption
  • Distribution
  • Metabolism
  • Excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how long does the preclinical stage last?

A

5-10 years

only one or two drug candidates taken forward to human clinical trials

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

how long does a patent for a new drug last?

A

20 years

after which time anyone can copy the drug

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

what is Phase I of clinical trials known as?

A

Exploratory; first in human.

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

how is the chronic toxicity of the drug assessed in Phase I of clinical trials?

A

Chronic toxicity of the drug will have been assessed in at least 2 mammalian species (1 non rodent)

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

how long does phase I of the clinical trial last and what is its purpose?

A

6 months to a year

  • SAFETY (check for side effects)
  • TOLERABILITY (unpleasant symptoms e.g. headaches, nausea)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what do we look for in phase II of clinical trials?

A

Efficacy, proof of concept and safety

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

what is the primary purpose of Phase II of clinical trials?

A

to determine how clinically effective the drug is in patients

to confirm safety and tolerability

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Describe Phase IIa of clinical trials.
- *Exploratory* - 50-200 patients; lasts approximately 1 year - Dose and treatment regimen based on Phase 1 results - Usually placebo-controlled, randomised, double-blind
26
describe phase 11b
**Phase IIb** - *Confirmatory* - 200-500 patients; lasts approximately 2 years - Safety and efficacy compared to placebo or current treatment in randomised, double-blind design
27
what happens during phase III of clinical trials?
- Full scale evaluation of how EFFECTIVE and SAFE the treatment is compared to current standard treatment (or placebo)
28
how many patients is the drug tested in during phase III?
2000-10 000
29
how long does phase III last?
several years
30
what is the ultimate purpose of phase III of clinical trials?
Provides data to support registration; once completed can apply for registration for use in specified condition
31
what is the point of phase IV of clinical trials?
**post-market surveilance,** monitors consequences of increasing exposure in tens of thousands of patients Also **yield information on the drug’s efficacy** in sub-groups of the population (elderly, young) **ongoing**
32
the relationship between drug concentration (or dose) and the response produced by the drug. is called what?
concentration-response curves.
33
what concentration-response curve do you get when looking at 'drug concentration'
rectangular hyperbola
34
what concentration-response curve do you get when looking at 'log drug concentration'
symmetrical sigmoid
35
What is the Emax of the log concentration-response curve?
Emax is the maximum effect (response) that a drug can produce e.g. an increase in heart rate of 70 beats per minute
36
Where is the EC50 on the log concentration-response curve?
The EC50 is the concentration of a drug that produces 50% of the maximum response
37
what does the EC50 indicate?
indicates the position of the curve on the concentration axis, used to quantify the potency of a drug
38
What is a receptor
Receptors are protein macromolecules usually inserted across the lipid bilayer of the cell
39
what are 2 main functions of a receptor
- Recognition or detection of extracellular molecules - Transduction; having detected the presence of an extracellular molecule they then bring about changes in cell activity
40
Describe the binding of a drug to a receptor (and what it looks like graphically when receptors occupied (p) vs drug concentration [D]).
D+R ⇌ DR Binding is reversible (in most cases
41
Describe the binding of a drug to a receptor (and what it looks like graphically when p vs log[D]).
D + R ⇌ DR
42
What is KD in terms of affinity?
The affinity of a drug for its receptor is quantified as “the MOLAR concentration of drug required to occupy 50% of the receptors at equilibrium”
43
what does the symbol KD stand for?
This concentration of drug is given the symbol KD
44
whats the relationship of KD and a drugs affinity?
Drugs with HIGH affinity have a LOW KD
45
What is KD in terms of equilibrium?
KD is the equilibrium dissociation constant - k+1 and k-1 are rate constants that tell us something about the likelihood of the forward and backward reactions occurring - Rate of FORWARD reaction = k+1[D][R] - Rate of BACKWARD reaction = k-1[DR] - At equilibrium, backward rate = forward rate, so k-1[DR] = k+1[D][R] KD = k-1/ k+1 = [D][R]/ [DR]
46
What is KD a measure of?
The KD is a measure of how tightly the receptor holds on to the drug once they come together
47
What do agonists do which differs to other drugs?
- Many drugs bind to the receptor (i.e. have affinity), occupy it, and do little else - AGONISTS however bind and then activate the receptor i.e. the agonist has efficacy - After binding, agonists produce a change in the shape of the receptor - a conformational change - that will ultimately lead to a response in a cell or tissue - Activation of receptor (R) by an agonist (A) produces a biological response
48
What are agonists?
- So agonists bind to the receptor (have affinity) and activate it (have efficacy) - All naturally occurring neurotransmitters and hormones are agonists e.g. adrenaline, acetylcholine, insulin, dopamine + many more - Agonists can be either partial agonists or full agonists
49
whats the efficacy of full agonists and how effective it is at producing a biological response
Full agonists have **high efficacy** and as a result are **very effective** at activating receptors and producing a biological response
50
whats the efficacy of partial agonists and how effective it is at producing a biological response
Partial agonists have **low efficacy** and are therefore **less effective at activating receptors** and less able to produce a biological response
51
what kind of response do full agonists make
Full agonists often produce **maximal response** whilst activating only a fraction of the available receptors (p) i.e. there are lots of spare receptors
52
what kind of response do partial agonists make
Partial agonists often fail to produce a full response despite occupying all the available receptors
53
Why as an agonist is EC50 = KD not possible?
the overall response to an agonist is determined by both its affinity and its efficacy; receptor occupancy is determined only on affinity
54
What are antagonists?
They act to inhibit the effects of a neurotransmitter or another drug
55
What is the most common type of drugs used?
- Reversible competitive antagonists e.g. pancuronium, cetirizine, propranolol
56
What effect do reversible competitive antagonists produce on a log concentration vs response curve?
Reversible competitive antagonists produce a parallel shift to the right of the AGONIST log concentration vs response curve.
57
The extent of the shift in the position of the agonist curve produced by the antagonist can be measured using what
the “dose-ratio” i.e. the ratio of the concentration of agonist producing the same response in the presence and absence of the antagonist
58
What is the 'extent of the shift' a measure of?
The 'extent of the shift' is a measure of the affinity of the ANTAGONIST for the receptor
59
what is the affinity of an antagonist quantified by
pA2
60
what does a bigger pA2 mean?
bigger the pA2, higher the affinity of the antagonist for the receptor
61
how can you overcome the inhibitory effects of an antagonist?
increasing the concentration of the AGONIST

FPP (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions