Brainscape's Knowledge GenomeTM

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


See full index

Principles > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

What is the term used to describe what the drug does to the body?

A

Pharmacodynamics

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

What is the term used to describe what the body does to the drug?

A

Pharmacokinetics

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

Is the mechanism of action/ effects of a drug under pharmacokinetics or pharmacodynamics

A

Pharmacodynamics

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

What are the 2 principle factors that determines drug selectivity to distinguish between different molecular targets?

A
  1. Drug dose!!!

2. Administration route

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

When is drug selectivity absolute?

A

Rarely as targets can change with drug dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the mechanism of action of penicillin?

Why is it selective?

A

Inhibits PBP responsible for peptidoglycan cross-linking in bacteria to form cell wall
Eukaryotes have no cell wall/ peptidoglycan layer

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

Salbutamol is a selective B2-adrenoceptor agonist used for treatment of bronchospasm.
When the dose is not optimised, what could be an off-target effect?

A

It could lose selectivity and act on B1-adrenoceptors in the heart which increases heart rate and contraction force.

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

What is the ratio for an agonist to display high affinity?

A

Rate of agonist binding to low rate of agonist unbinding

Usually rate of binding is constant but dissociation rate changes (“stickiness of agonist”) (determinant)

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

What happens during the activation step of agonist binding?

A

REVERSIBLE conformation change that leads to TEMPORARY receptor activation

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

What does the term affinity mean?

A

Ability to bind or strength of association between ligand and receptor

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

What does the term efficacy mean?

A

Ability to evoke a cellular response

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

What is the ratio for an agonist to display high efficacy?

A

High rate of receptor activation to rate of receptor deactivation

**Rate of deactivation is constant while rate of activation changes (determinant)

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

Which 2 bonding forces contribute more to binding between ligand and receptor?

A

Ionic and H-bonds

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

What is the relationship between receptor occupancy/ effect (%; y-axis) vs agonist dose (x-axis)

A

Proportional, hyperbolic on linear graph

Proportional, sigmoidal if Log10 dose

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

What is effective concentration 50 (EC50)?

A

Dose of agonist to elicit half of maximum effect

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

Why is a semi-logarithmic plot (Log10 dose) more accurate to determine EC50?

A

Uses a broader range of dose

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

Which parameter indicates potency?

A

EC50

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

What is the difference between a full and partial agonist?

A

Full agonist reaches max (close to 100% receptor effect) while partial is lower than max

**Never 100% because a hyperbolic graph never becomes parallel to the x-axis

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

What is the term for the substance that blocks an agonist from activating a receptor?

A

Antagonist

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

How many steps does antagonist binding have?

A

1

Only a binding step as there is no resultant cellular response

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

Does an antagonist have affinity and efficacy?

A 
Have affinity (binding strength)
No efficacy (no receptor effect)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How many steps does agonist binding have?

A

2

Binding, activation

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

What are the 2 types of antagonism?

A

Reversible competitive

Non competitive

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

Where does reversible competitive antagonists bind to?

A

Same site as agonist (orthostatic) site, thus competitive site and binding is mutually exclusive

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

How can reversible competitive antagonists be overcome?

A

By increasing concentration of agonist

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

What are the 2 factors that influences reversible competitive antagonism?

A

Affinity of antagonist to receptor

Agonist concentration

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

What does reversible competitive antagonist do to the conc-response curve?

A

Parallel right shift without affecting max response (reduced potency and unchanged efficacy)
No gradient change

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

What does reversible competitive antagonist do to EC50 and max %effect?

A 
Lowers EC50 (needs higher dose for 50% response)
Unchanged max effect (just needs a higher dose)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

EC50 and %effect each corresponds to which axis on the graph?

A

EC50 - for the x-axis; relates to dose

% effect - for the y-axis

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

Where does non-competitive antagonist bind to?

A

Allosteric site therefore can occupy receptor reversibly and simultaneously to agonist (just that receptor will not be activated even if agonist is bound)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does non-competitive antagonist do to the conc-response curve?

A

Depressed slope and reduced max %effect without right shift

reduced efficacy and unchanged potency

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

What does non-competitive antagonist do to EC50 and %effect?

A

Reduces max response (depressed slope)

EC50 unchanged

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

What are the 4 factors to consider in pharmacokinetics?

A

Absorption
Distribution
Metabolism
Excretion

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

What are the 3 types of chemical signalling?

A

Autocrine (to itself)
Paracrine (close neighbours via ECF)
Endocrine (via lymphatics/ bloodstream to distant target)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Why must molecules be of high affinity to the receptor when signalling via endocrine?

A

Diluted in blood thus concentration is low thus high affinity needed to bind

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

What model is the receptor ligand selectivity known as?

A

Lock and key model

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

What are the 4 major types of receptors?

A
  1. Ion channels
  2. GPCR
  3. Kinase-linked receptors
  4. Nuclear receptors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What do signals cause the ion channels to undergo?

A

Changes reversibly between closed and open conformation (AKA Gating)
**Aquaporins always open

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

What happens when ion channels are in open/ conducting state?

A

Selected ions flow passively down electrochemical gradients

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

What can ion channels can be gated by? (3)

A

Ligand
Voltage (E.g. Action potential)
Physical stimuli (Heat/ Mechanical)

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

How fast do Ligand-gated ion channels (LGICs) or ionotropic receptors act? Where are they found?

A 
Rapid acting (millisecond) 
At plasma membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What are ionotropic receptors targeted by?

A

Hydrophilic signalling molecules (can’t cross membrane)

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

What kind of receptor does nicotinic ACh receptor fall under?

A

LGIC

*Found in neurons and skeletal muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

How many glycoprotein subunits a needed to form the LGIC?

A

5 for a psuedo-symmetrical central, ion conducting channel

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

How many agonists are needed for LGIC to work?

A

2 to bound simultaneously for rapid conformation change which eventually depolarises the membrane

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

What are the 3 reversible conformations of LGICs?

A
  1. Unoccupied and closed
  2. Occupied and closed (transient phase)
  3. Occupied and open
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

How fast do GPCRs/ Metabotropic receptors act? Where are they found?

A 
Slower acting (seconds)
At plasma membrane
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

What are GPCRs targeted by?

A

Hydrophobic signalling molecules

*Most drugs act via GPCR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Fast and slow action of neurotransmitters depend on?

A

Type of receptor

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

What are secondary messenger systems?

A

Receptor activation modulating activity of an effector

51
Q

How many components are there to GPCR signalling?

A

3.

Receptor, transducer, effector (can be enzyme or ion channel)

52
Q

Is GPCR in direct contact with the effector?

A

No, thus an intermediary proteins is needed (G-protein)

53
Q

What is the structure of a GPCR? (3)

A

Integral membrane protein (embedded)
Single polypeptide with extracellular NH2 and intracellular COOH termini
7 transmembrane a-helical spans with 3 extracellular and 3 intracellular loops

54
Q

What can enzyme effector and ion channel effector of GPCR each result in?

A

Enzyme: increase/ decrease rate of synthesis of 2nd messenger molecule
Ion channel: Changes to Membrane potential

55
Q

What is a G-protein?

A

Peripheral membrane protein at the interior side of membrane

3 polypeptide subunits (a,b,y)

56
Q

Which G-protein subunit contains the guanine-nucleotide binding site that holds GTP or GDP?

A

a

57
Q

Does b and y subunit in the G-protein separate?

A

No, they exist as dimers while a-subunit dissociates

58
Q

What happens when an agonist binds to GPCR? (6)

A 
GPCR and GDP-bound G-protein preferentially couple (via a-subunit)
Conformation change to a-subunit
GDP RELEASED and GTP binds
Activation
a-subunit dissociates 
Interacts with effector (s)
59
Q

Does GTP or GDP bound to the a-subunit of G-protein contribute to the active, signalling state?

A

GTP via guanine nucleotide exchange with GDP

60
Q

Can signalling still persist after agonist has dissociated from GPCR?

A

Yes because G-protein and receptor are separated

61
Q

How is signalling in GPCR turned off?

A

a-subunit is also a GTPase
GTP hydrolysed to GDP and Pi
Inactive GDP-bound a-subunit recombines with by-dimer

62
Q

Match for GPCR.
Activation vs Deactivation
GTP hydrolysis vs Guanine exchange

A

Activation - guanine exchange

Deactivation - GTP hydrolysis via a-subunit GTPase

63
Q

What are the 3 simultaneous indicators that show that there is no signal through the GPCR system?

A

Unoccupied GPCR
a-subunit bound to GDP
Effector not modulated

64
Q

What is an example of a Gs GPCR and what is it activated by?

A

B1-adrenoceptor, by noradrenaline.

65
Q

What happens during Gs GPCR activation? (After guanine-exchange) (5)

A 
Gs-GTP (a-subunit) dissociates 
STIMULATES adenylyl cyclase 
Converts ATP to cAMP and pyrophosphate
cAMP-dependent protein kinase A activity increases
Cellular effects

**Think Gs for stimulatory

66
Q

What is an example of a Gi GPCR and what is it activated by?

A

Muscarinic M2 ACh receptor, by ACh

67
Q

What happens during Gi GPCR activation? (After guanine-exchange) (5)

A 
Gi-GTP (a-subunit) dissociates
INHIBITS adenylyl cyclase
Decrease cAMP production
Decrease activity of cAMP-dependent protein kinase A
Cellular effects

**Think Gi for inhibitory

68
Q

What is an example of a Gq GPCR and what is it activated by?

A

a1-adrenoceptors, by noradrenaline

69
Q

What happens during Gq GPCR activation? (After guanine-exchange) (5)

A

Gq-GTP (a-subunit) dissociates
Activates Phospholipase C
Cleaves PIP2 to IP3 (soluble) and DAG

IP3 released and binds to specialized calcium channel in ER –> opens and releases calcium into cytoplasm

DAG remains bound –> acts with released calcium to activate Protein kinase C –> Cellular effects

70
Q

What amino acid residues are being phosphorylated in target proteins in Gs and Gq signalling?

A

Serine or Threonine

71
Q

Can the by-dimer act as a signalling unit too?

A

Yes

72
Q

How are the types of GPCRs named?

A

According to a-subunit type

73
Q

What are the modes of crossing cell membrane? (3)

A
  1. Simple/ passive diffusion
  2. Carrier-mediated
    a. Facilitated diffusion (shows saturation kinetics)
    b. Active transport (shows saturation kinetics)
  3. Endocytosis/ Pinocytosis (involves invagination and vesicles for larger drugs)
74
Q

At higher drug concentrations, for carrier-mediated transport, will the rate be first or zero order?

A

Zero order due to saturation of carrier (rate-limiting) thus transport becomes independent of drug concentration

75
Q

Do drugs exist in ionised or un-ionized form?

A

Both

76
Q

What is pKA?

A

The pH at which 50% of drug is ionised and 50% unionised

77
Q

Is the ionised or un-ionised form of drug more permeable to cross the membrane?

A

Un-ionised form

78
Q

What is the chemical reaction for weak acids?

A

AH (weak acid) –>/–< A- + H+

79
Q

What is the chemical reaction for weak bases?

A

BH+ –>/–< B(weak base) + H+

80
Q

How does pH influence trapping of drug across plasma membrane?

A

pH favoring unionised form will allow drug to diffuse and be absorbed (E.g. Acidic stomach for a weak acid drug)
As the pH changes (E.g. pH7.4 plasma), it will favour the ionised form of the drug, thus the drug will not be able to diffuse back into the GI tract

81
Q

Where do weak bases and weak acids preferentially accumulate/ trapped?

A

Weak bases - low pH environment (Better absorption at stomach)
Weak acids - high pH environment (Better absorption at intestine)

82
Q

Where do most oral absorption occur?

A

Small intestine due to larger surface area

83
Q

Do weak acids tend to ionise in high pH or low pH medium?

A

Ionises at high pH environment to donate H+

84
Q

What is the formula for Apparent volume of distribution (Vd)?

A

Vd = Dose/ [Drug]plasma

85
Q

A better distributed drug (e.g. lipophilic) drug will have a Vd more or less than total body water (41L)?

A

More

86
Q

What does low Vd signify?

A

Retained in vascular compartments

87
Q

What does high Vd signify?

A

Drug able to go to areas like adipose, muscle and non-vascular compartments

88
Q

For 2 drugs with the same potency (EC50), will the higher Vd drug require a higher or lower dose to reach the same [Drug]plasma as the lower Vd drug?

A

Higher dose.
Most of it would have diffused out of plasma to the non-vascular compartments thus more drug will be needed to increase plasma concentration

89
Q

What is the most abundant plasma protein?

A

Albumin

90
Q

What happens when drug is bound to albumin?

A

They are less available to diffuse out to non-vascular compartments to reach target organs

91
Q

What would be the Vd and [Drug]plasma if most of it is bound to albumin?

A

Low Vd

High [Drug]plasma

92
Q

What is the principle organ for drug metabolism?

A

Liver

93
Q

What is bio-availability and what reduces it?

A

Amount of drug available in systemic circulation

When drug is metabolized when administered through the PO route, it is less bioavailable

94
Q

How many phases of metabolism are there in the liver?

A

I and II

95
Q

Where are the microsomal enzymes for metabolising embedded in in the hepatocytes?

A

Smooth ER

96
Q

Are polar or non-polar molecules more readily metabolised?

A

Non-polar as they cross the membrane more easily

97
Q

What are the 3 processes involved in phase I metabolism?

A

Oxidation - by cytochrome P450 enzymes (Microsomal Haem proteins)
Reduction
Hydrolysis

98
Q

What are the products formed from Phase I metabolism like?

What can they result in?

A

More reactive/active/toxic metabolites which can cause cellular damage via binding covalently to membrane glycoproteins

99
Q

What is the pre-dominant process involved in Phase II metabolism?

A

Glucuronidation

100
Q

What are the products formed from Phase II metabolism like? (3)

A

More polar/ soluble by targeting the reactive group formed in Phase I with a polar molecule
Detoxifies
Readily excreted by kidneys

101
Q

What is 1 drug that directly enters Phase II metabolism to yield active metabolites?

A

Codeine

102
Q

What does high and low activity level of CYP450 enzyme result in?

A

High - lower drug plasma levels –> reduced desired effect

Low - higher drug plasma levels –> adverse effect

103
Q

What does drug interaction with P450 system result in?

A

Competitively induces P450 thus antagonistic effect to other drugs and reduces bioavailability

*Can also inhibit which increases bioavailability of drug

104
Q

What are the 2 enzymes involved in oxidation in the monoxygenase P450 system?

A

NADPH-P450 reductase

Cytochrome b5

105
Q

What is the principal organ for drug clearance?

A

Kidneys

Drugs that have undergone Phase II metabolism are not reabsorbed

106
Q

What is the yellow card scheme?

A

Reporting suspected side effects of medication

107
Q

What can happen when drug dose goes above EC50? (2)

A

Toxic effects from Phase I toxic metabolite accumulation or loss of selectivity/ off-target binding due to high dose

108
Q

How is drug clearance expressed?

A

Volume of blood removed of drug per unit time (L/hour or mL/min)

109
Q

What are the 3 routes contributing to total clearance?

A

Renal, hepatic, other routes

110
Q

What is the formula for drug clearance?

A

CL = Rate of drug elimination (mg/hour) / [Drug]plasma (mg/L)

111
Q

Does Vd affect CL?

A

No, they are independent of each other

112
Q

What is first-order kinetics?

A

Rate of drug elimination increases as [Drug]plasma increases

*Follows Michaelis-Menten kinetics

113
Q

What is zero-order kinetics?

A

Elimination mechanisms saturated and Vmax reached

Becomes independent of [Drug]plasma

114
Q

What is the desired [Drug]plasma for therapeutic effect known as?

A

Steady state

115
Q

What is the formula for Dosage rate?

A

[Drug]plasma Steady state x CL

116
Q

What is the ideal ratio for rate of administration to rate of elimination?

A

1:1

Steady state level

117
Q

What is the formula for T1/2?

A

(0.693 x Vd) / CL

118
Q

What to do if there is a high Vd value due to obesity or pathologic fluid?

A

Adjust regimen to avoid toxicity

119
Q

What to do if there is low Vd due to loss of muscle mass/ atrophy or aging?

A

Repeated dosing for therapeutic effect

120
Q

What are the 4 factors that may affect clearance rate?

A

Cytochrome P450 induction/inhibition

Cardiac, Hepatic and renal failure (slows circulation thus slows clearance rate)

121
Q

How many half lives are normally needed to reach steady state?

A

5

*Multiple doses - new baselines after each T1/2 till steady state

122
Q

How many half lives are normally required to wash the drug out (after stopping infusion)?

A

5

123
Q

What is the relationship of CL and Vd to T1/2?

A

Inverse: CL
Direct: Vd

124
Q

Do absorption and elimination occur simultaneously?

A

Yes

Principles (14 decks)

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