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BIOSCI 106 > Section 6: Signal Transduction > Flashcards

Section 6: Signal Transduction Flashcards

1
Q

What is signal transduction

A

Extracellular signals that eventually lead to a response inside the cell

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2
Q

Signal transduction - pathway

A 
Signal -->
Reception -->
Transduction -->
Amplification -->
Response(s)
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3
Q

Signal transduction: Pathway - signal

A

Initiates the pathway

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4
Q

Signal transduction: Pathway - reception

A

Where the signal is received

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5
Q

Signal transduction: Pathway - transduction

A

Inside the cell

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6
Q

Signal transduction: Pathway - amplification

A

For a small amount of signal, you’re able to create a large response in the cell

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7
Q

How do cells communicate

A

Via chemical signals, which rely on hormones

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8
Q

Hormones

A

Extracellular signals secreted by cells that then diffuse or circulate to specific target cells

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9
Q

Why is cell signalling important

A

Helps maintain homeostasis
Involved in multiple systems in body
Many medicines control cell signalling events via receptors

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10
Q

Origins of a signal: Endocrine signalling

A

Endocrine hormone is released from a gland and travels through the blood to act upon a distant target organ

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11
Q

Origins of a signal: Endocrine signalling - example

A

Insulin, glucagon

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12
Q

A hormone is an example of a(n)…

A

Extracellular signal

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13
Q

Origins of a signal: Paracrine signalling

A

Released from cells to act upon adjacent cells

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14
Q

Origins of a signal: Paracrine signalling - example

A

Release of ACh at neuromuscular junction

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15
Q

Origins of a signal: Autocrine signalling

A

Act upon the same cell type they are released from

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16
Q

Origins of a signal: Autocrine signalling - example

A

Growth factors

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17
Q

Origins of a signal: Signalling by PM-attached proteins

A

Cell-cell signalling may also occur

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18
Q

Origins of a signal: Signalling by PM-attached proteins - example

A

T-cell activation by proteins on surface of antigen-presenting cells in immune system

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19
Q

How do hormones and other extracellular signals initiate a chain of events

A

By activating receptors

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20
Q

Receptor

A

A molecule on the surface of within a cell that recognises/binds to specific molecules
Produces a specific effect

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21
Q

Lock and key analogy

A

Describes how each hormone has its own specific receptor
Only when the hormone/ligand engages with the correct receptor, can it activate the receptor and trigger intracellular signalling –> response

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22
Q

Receptor - conformational change

A

A receptor is a protein (flexible), so when a ligand binds it leads to a change in shape of inside of receptor –> allows substrates in receptor to bind to activated receptor

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23
Q

Receptor - gatekeeper

A

Receptor is a gate-keeper of cellular activity

Controls hormone activity at cell surface

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24
Q

Signalling can occur with/without the hormone passing through the membrane?

A

Without

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25
Q

Receptor: Hormone and affinities

A

Binding of hormone changes the chemical affinities of receptor –> changes shape

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26
Q

Lock and key mechanism: Drugs

A

Can create molecules that mimic endogenous hormones, e.g. asthma
Or, can design molecules that fit in receptor pocket but leads to no signal

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27
Q

Types of ligands: Agonists

A

Produce the maximal response for a given tissue

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28
Q

Types of ligands: Partial agonists

A

Produce a response which is below the max for that tissue

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29
Q

Types of ligands: Antagonists

A

Produce no visible response and block effects of agonists

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30
Q

Receptor types/classes

A

G-protein coupled receptor (GPCR)
Receptor tyrosine kinases (RTK)
Ligand-gated ion channels (LGIC)

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31
Q

Receptor types: GPCR

A

7 transmembrane domains
Ligand binding site on extracellular side
Ligand binds –> change in shape that allows a G-protein to bind on intracellular side
Signals via G-proteins and second messnegers

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32
Q

Receptor types: Receptor tyrosine kinases (RTK)

A

Enzyme-linked receptor

Signals by phosphorylation

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33
Q

Receptor types: Ligand-gated ion channels

A

Directly allows ions through

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34
Q

Transduction

A

Cascades of molecular interactions that relay signals from receptors to target molecules in cell

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35
Q

Signal transduction - why are there multistep pathways

A

Can greatly amplify signal

Provides more opportunities for coordination and regulation of response

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36
Q

Signal transduction - mechanisms

A

Second messengers

Phosphorylation

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37
Q

Signal transduction: Second messengers - when are they produced

A

Produced following receptor activation

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38
Q

Signal transduction: Second messengers - what are they

A

Chemical signals that are often not embedded in the membrane - can diffuse intracellularly to pass on message

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39
Q

Signal transduction: Second messengers - how they work

A

They change in conc in response to environmental signals, and this change in conc conveys info inside the cell
i.e. are dose-dependent

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40
Q

Signal transduction: Second messengers - first messenger

A

The hormone/ligand that activates the receptor

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41
Q

Common second messengers

A

cAMP, cGMP
IP3
Calcium
Diacylglycerol (DAG)

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42
Q

A second messenger can work on…

A

Multiple substrates

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43
Q

Signal transduction: Second messengers - types of responses

A
  1. Pathway leads to a single response
  2. Pathway branches –> 2 responses
  3. Cross-talk between 2 pathways (response can be controlled by diff pathway
  4. Diff receptor leads to diff response
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44
Q

Signal transduction: Phosphorylation and dephosphorylation act like…

A

A molecular switch - turns protein activity on/off or up/down as required

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45
Q

Signal transduction: Phosphorylation regulates…

A

Protein activity

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46
Q

Signal transduction: Phosphorylation - protein kinases

A

Transfer phosphates from ATP to protein (phosphorylation)

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47
Q

Signal transduction: Phosphorylation - relay molecules

A

Many relay molecules are protein kinases –> creates a phosphorylation cascade

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48
Q

Signal transduction: Phosphorylation - protein phosphatases

A

Rapidly remove phosphates from proteins - dephosphorylation

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49
Q

Signal transduction: Phosphorylation - amino acids commonly phosphorylated

A

Tyrosine
Serine
Threonine

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50
Q

Signal transduction: Does phosphorylation always turn things on

A

No, it can turn it off

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51
Q

Signal transduction: Phosphorylation - allows you to control your response…

A

Quite tightly

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52
Q

Amplification - what does it mean

A

Only a v small amount of initial hormone is needed, and few receptors need to be activated, to produce a response

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53
Q

Response

A

The changes in chemicals result in activation or inhibition of proteins

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54
Q

Termination of signal

A

After the cell has completed its response to a signal, the process must be terminated so the cell can respond to new signals

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55
Q

Failure of termination of signalling processes

A

Can have highly undesirable consequences

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56
Q

Receptors - function examples

A 
Vision
Taste
Smell
Neurotransmission
Cell growth
Development
Control of heart rate
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57
Q

Receptor types (classes)

A

GPCRs - work with help of a G protein
Receptor tyrosine kinases (RTKs) - attach phosphates to tyrosines to signal
Ligand-gated ion channel receptors - signal molecule binds as a ligand to the receptor –> opens receptor gate –> allows ions to pass

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58
Q

GPCR signalling - signal

A

Endocrine
Epinephrine

Binds to receptor

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59
Q

GPCR signalling - receptor

A

GPCR

Beta-adrenergic receptor

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60
Q

GPCR signalling - transduction

A

G-protein - αβγ, binds to –>
1° effector protein - adenylate cyclase, which makes –>
2nd messenger - cAMP, which activates –>
2° effector protein - protein kinase A, which causes –>
Phosphorylation - cascade

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61
Q

Effector proteins

A

Molecules (often enzymes) in a cell that respond to a stimulus and can be activated and further transduce a signal

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62
Q

Effector protein for G-proteins

A

Adenylate cyclase

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63
Q

Effector protein for cAMP

A

Protein kinase A

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64
Q

Where are GPCRs found

A

They exist in a range of organisms and express at the cell surface to respond to diverse extracellular signals

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65
Q

Structural features of a GPCR

A

7 transmembrane alpha helices
3 intracellular loops
3 extracellular loops
N-terminus on extracellular side, C-terminus on intracellular side

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66
Q

Receptor - ‘gatekeeper’

A

Controls hormone activity at cell surface

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67
Q

Conformational change of GPCR results in _____ affinity for G protein

A

Higher

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68
Q

GPCR - mutation on extracellular vs intracellular side of receptor

A

Extracellular - affects how it binds the ligand

Intracellular - affects how it binds a G-protein

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69
Q

Structure of a G-protein

A

Trimeric - 3 diff subunits (α, β, γ)

If α subunit binds GTP, it dissociates into 2 parts; the α subunit (acts on its own) and the βγ subunit (acts elsewhere)

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70
Q

What does G-protein stand for

A

Guanosine-binding protein

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71
Q

G-protein cycle

A
  1. Off position: GDP-bound - remains as a trimer and is inactive
  2. Ligand binds GPCR so receptor is attracted to G-protein –> conformational change –> G-α subunit releases GDP and binds GTP –> conformational change –> G-βγ dissociates
    G-α is now active (‘on’ position) so can act on effector enzymes downstream, e.g. adenylate cyclase
  3. G-α subunit hydrolyses GTP –> GDP, which reassociates with βγ –> off position
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72
Q

G-protein cycle - where can the system be shut off

A

At the point where G-α subunit is active because it has an intrinsic enzyme activity for GTPase

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73
Q

Types of G proteins

A

Gs
Gi
Gq

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74
Q

Types of G proteins: Gs

A

Stimulatory G protein

Activates adenylate cyclase by making it more catalytically active

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75
Q

Types of G proteins: Gi

A

Inhibitory G protein

Inactivates adenylate cyclase by making it less catalytically active

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76
Q

Types of G proteins: Gq

A

Activates a diff effector, phospholipase

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77
Q

Types of G proteins: Gs - steps

A

Binds ligand –> conformational change –> attracts Gαs stimulatory protein which is activated –> binds to adenylate cyclase

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78
Q

Types of G proteins: Gs - what does it result in

A

More ATP –> cAMP

More cAMP in cell

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79
Q

Types of G proteins: Gi - steps

A

Ligand binds –> conformational change –> attracts Gαi which binds to adenylate cyclase

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80
Q

Types of G proteins: Gi - what does it result in

A

Less ATP –> cAMP

Less cAMP in cell

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81
Q

Types of G proteins: Gs and Gi is an example of…

A

Cross talk (2 diff pathways that can affect each other

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82
Q

cAMP activates or inactivates….

A

Protein kinase A

83
Q

Adenylate cyclase is known as a(n)…

A

Effector protein

84
Q

cAMP is made by the enzyme…

A

Adenylate cyclase

85
Q

cAMP stands for..

A

Cyclic adenosine monophosphate

86
Q

Types of G proteins: Gq - steps

A

Ligand binds –> conformational change –> attracts Gq protein (now active) –> acts on phospholipase C (PLC), which converts PIP2 into DAG and IP3
DAG activates protein kinase C (PKC) but also need Ca2+ to activate PKC
IP3 causes release of Ca2+ from cell’s stores, so tgt they activate PKC

87
Q

5 sensory perceptions and what they rely on as receptors

A

Hearing and touch generally rely on ion channels

Vision, smell and taste generally rely on GPCR

88
Q

Neurons - normal RMP

A

About -70mV

89
Q

Depolarisation, repolarisation, hyperpolarisation

A 
Depolarisation = inside of cell becomes less -ve (influx of Na+)
Repolarisation = inside of cell goes back to normal (efflux of K+)
Hyperpolarisation = inside of cell becomes more -ve than RMP
90
Q

What is vision based on

A

Absorption of light by photoreceptor cells in the eye

91
Q

Vision: Types of photoreceptor cells

A

Rod and cone cells

92
Q

Photoreceptor: Rod cells

A

Responsible for vision in low light and peripheral vision

This is why at low light, you can see but things appear grey because rod cells encode vision but not colour

93
Q

Photoreceptor: Cone cells

A

Responsible for vision in bright light

Gives info about colour

94
Q

Vision - signal

A

Light (photon)

95
Q

Vision - receptor

A

GPCR (rhodopsin)

96
Q

What is the photoreceptor molecule in rod cells

A

Rhodopsin

97
Q

Rhodopsin - what is it made of

A

Consists of protein opsin, linked to 11-cis-retinal (prosthetic group)

98
Q

Opsin

A

A 7 transmembrane protein that determines wavelength of light absorption

99
Q

11-cis-retinal

A

A light-absorbing group (chromophore)

100
Q

What happens when light hits 11-cis-retinal

A

It causes it to isomerase from 11-cis-retinal to all-trans-retinal
Undergoes a 5-angstrom twist

101
Q

Vision: Where are cone receptors located

A

In cone cells

102
Q

What is colour vision mediated by

A

3 cone receptors

103
Q

Vision: Photoreceptor proteins (numbers)

A

In humans there are 3 distinct photoreceptor proteins with absorption maxima at 426 (blue), 530 (green) and 560 nm (red)
i.e. blue-opsin, green-opsin, red-opsin

104
Q

Mechanism of action: Rod vs cone cells

A

Cone cells work under same principle as rod cells, except cone cells’ opsins are diff –> absorb light at diff wavelengths

105
Q

Cone cells: Photoreceptor opsins - homology

A

Green and red photoreceptor opsins are 95% identical in amino acid sequences - theory is the green opsin mutated over time and became a red opsin
Blue and green photoreceptor opsins are 20% similar in amino acid sequence

106
Q

Vision: In the dark, what happens

A

Photoreceptor cells are depolarised with continual influx of Na+ and Ca2+ through cGMP-gated ion channels

107
Q

Vision - G-protein

A

Transducin

108
Q

Vision - primary effector

A

Phosphodiesterase

Cleaves cGMP into GMP

109
Q

Vision - second messenger

A

cGMP

110
Q

Vision: Photoreceptor - special neuron?

A

Constantly has leakage of +ve ions into cell, so RMP is more +ve (about -40mV)

111
Q

Vision: What happens when light hits rhodopsin (receptor)

A

Phosphodiesterase converts cGMP to GMP –> hyperpolarisation, which is sensed by next neuron

112
Q

How is vision pathway different from other neuron pathways

A

It works by hyperpolarisation

113
Q

Vision: Retinosa pigmentosa

A

A group of inherited diseases that affect photoreceptor (mainly rod) cells where they progressively deteriorate

114
Q

Vision: Retinosa pigmentosa - symptoms

A

Initially may just not see in low light
Overtime can lead to:
Tunnel vision (because rod cells are responsible for peripheral vision)
Blindness

115
Q

Vision: Retinosa pigmentosa - age

A

Can happen to people as young as 40 y/o

116
Q

Vision: Retinosa pigmentosa - what stage does something go wrong

A

Reception

117
Q

Vision: Colour blindness - how does it happen

A

Since red and green opsins sit on same chromosome v close tgt, during repro, 2 things could’ve gone wrong:

  • Recombination between genes –> individual won’t have protein to receive either green light, or red light
  • Recombination within genes –> individual has protein that can absorb neither green or red light
118
Q

Vision: Colour blindness - who is more likely to get it

A

Since it lies on X chromosome, males are more likely to get it

119
Q

Vision: Colour blindness - where in the pathway does it go wrong

A

Reception

120
Q

Vision: Colour blindness - what type of cell

A

Cone cells

121
Q

Why is taste perception important

A

Nutritious vs poisonous
Commercial value
Health intervention

122
Q

Taste: Where is the signal initiated

A

Papillae contain taste buds which are made up of taste cells, which contain taste receptors

123
Q

Taste: Papilla

A

Bumps on tongue

Creates trench around tongue to collect saliva

124
Q

Taste - signal

A

Food (tastant)

125
Q

Major taste sensations - receptors

A

GPCRs:
Sweetness
Umami
Bitterness

Ion channels:
Salty
Sour

126
Q

Major taste sensations - ligands

A 
Sweetness: sugars, sweeteners
Umami: amino acids
Bitterness: quinine and others
Salty: Na+
Sour: H+
127
Q

What is umami

A

Taste of savoury-ness

e.g. meat

128
Q

Taste: Taste receptors - families

A

T1 and T2 family

129
Q

Taste: Taste receptors (GPCRs) - subunits

A

Each family has subunits;
T1R: 1, 2, 3 = sweetness and umami
T2R: 1-65 = bitterness

130
Q

Taste: G-protein-coupled taste receptor subunits - structure

A

7 transmembrane domains

Extracellular N-terminus

131
Q

Taste: T1R

A

Each subunit has an additional venus fly-trap domain on extracellular side
Heterodimer required to be functional (i.e. requires 2 subunits)
Couples to / activates G protein

132
Q

Taste: T1R - heterodimers

A

T1R2 + T1R3 = sweet

T1R1 + T1R3 = umami

133
Q

Taste: T2R

A

Functions as monomer
Couples to / activates G protein
Have many of these to detect poisonous things

134
Q

Taste transduction pathway - tastant / ligand

A

Sweet, bitter, umami

135
Q

Taste transduction pathway - G protein

A

Gustducin

Activates phospholipase C, which cleaves PIP2 –> DAG and IP3 (second messengers)

136
Q

Taste transduction pathway - Ca2+

A

IP3 releases Ca2+ which activates V-gated ion channels

Na+ comes into cell (depolarisation) –> APs

137
Q

Taste disorders

A

Phantom taste sensation
Hypogeusia (lowered taste sensation) or ageusia (no taste)
Dygeusia (taste perceived isn’t what you ate)

138
Q

Blood glucose - always kept between…

A

4-8 mM of blood

139
Q

Hypoglycaemia

A

Too little glucose in blood

Can result in:
Coma or death
Brain damage

140
Q

Hyperglycaemia

A

Too much glucose in blood

Can result in:
Diabetes
Ulcers (since blood is thicker)
Nerve damage –> blindness

141
Q

Insulin

A

When too much glucose in blood, leads to uptake of glucose into muscle cells, and liver uses glucose to makes glycogen
Brings blood glucose back down

142
Q

Causes of low blood glucose

A

Fasting –> glucagon is released –> makes glucose and break down of glycogen stores –> brings glucose back up
Under stress –> release epinephrine –> more glucose

143
Q

Low blood glucose: Signal

A

Glucagon or epinephrine

144
Q

What is glucagon

A

A large peptide

145
Q

Glucagon and epinephrine: Receptor

A

GCGR (glucagon receptor)

AR (adrenoreceptor)

146
Q

Glucagon and epinephrine: Transduction

A

Activation of G-protein: Gαs
Primary effector: AC
2nd messenger: cAMP
PKA phosphorylates B kinase –> phosphorylates D into a –> converts glycogen into glucose

147
Q

Glucagon: Glycogen synthase

A

PKA is able to phosphorylate glycogen synthase –> inactivates it –> glycogen is not made
Avoids futile cycles

148
Q

What does glucagon result in

A

Increased gluconeogenesis
Increased glycogen breakdown
Decreased glycolysis

Increased blood glucose

149
Q

Where is glucagon recognised

A

By receptor cells on liver

150
Q

Gluconeogenesis

A

Making of glucose from non-carbohydrate molecules

151
Q

Glucagon - speed

A

Within 5 minutes, it causes glucose levels to rise, so works fairly quickly

152
Q

What does epinephrine result in

A

Increased glycogen breakdown (glycogenolysis)
Increased glycolysis

Increased blood glucose

153
Q

Where is epinephrine released from

A

Adrenal glands

154
Q

What is epinephrine recognised by

A

Liver cells

Also in muscle cells; increases glycogen breakdown and glycolysis

155
Q

Epinephrine: Liver vs muscle

A

Liver makes energy for body

Muscle makes energy for itself

156
Q

How is glycogen degradation turned off

A

Hormone that stimulates glycogen breakdown is removed - pancreas no longer secretes glucagon
At G protein, GTPase hydrolyses GTP –> GDP (inactive)
At 2nd messenger, cAMP –> AMP by phosphodiesterase
Protein phosphatases remove phosphate groups from phosphorylase –> inactivates enzymes

157
Q

High blood glucose: Signal

A

Insulin

158
Q

Insulin: Receptor

A

Insulin receptor

Not a GPCR, but a tyrosine kinase

159
Q

Insulin receptor - structure

A

V different to GPCRs
Dimer of two monomer - α and β subunits bound by disulphide bond
Tyrosine kinase - kinase is part of receptor

160
Q

Insulin: Transduction pathway

A

Insulin binds
Receptor monomers become close tgt from extracellular side
Drags intracellular domains close tgt –> kinase enzymes cross-phosphorylate
Active kinase phosphorylates downstream molecules –> cascade
GLUT4 transporters inserted into muscle cells

161
Q

What does insulin result in

A

Increased glucose uptake in muscles

Decreased blood glucose

162
Q

Insulin - target tissue

A

Muscle

163
Q

Insulin-glucagon regulation - complexities

A

Paracrine effects between β-islet cells can directly inhibit secretion of glucagon in α-islet cells

164
Q

Insulin deficiency

A

Type I diabetes

Defect in signal

165
Q

Insulin - drug

A

Used as a diabetes drug to mimic natural actions of this hormone at insulin receptor

166
Q

GPCR gene mutations / diseases

A

Defect in reception
Cone opsins - colour blindness
Rhodopsin - retinitis pigmentosa
MC4R - extreme obesity

167
Q

Cholera - what part of the pathway is affected

A

Transduction

168
Q

Cholera toxin

A

Stops Gα subunit from being able to hydrolyse GTP –> Gs always active –> increase AC –> increase cAMP –> increase PKA –> increase phosphorylation –> more extrusion of Cl- –> huge loss of water –> diarrhoea –> dehydration

169
Q

Affinity

A

A measure of how tightly a ligand binds to the receptor

Can generally be measured using dissociation constant Kd

170
Q

Kd

A

Ligand conc where receptor is 50% saturated with ligand

171
Q

Kd vs Ki

A

Ki = Kd if inhibitor

172
Q

Kd and affinity

A

Lower Kd = higher affinity

173
Q

What is the problem in asthma

A

Bronchoconstriction

174
Q

What signalling pathway might affect asthma

A

Epinephrine pathway

175
Q

Asthma: What kind of ligand-receptor action is desired

A

β-agonist –> relaxes airways (dilation)

176
Q

Asthma: What chemical structure is desired

A

β-agonist is structurally similar to epinephrine

177
Q

Asthma: How well does ligand/drug bind to receptor

A

β-agonist has low affinity, so need to keep taking it

178
Q

Asthma: How does β-agonist work

A

Activates G-protein –> activates AC –> cAMP –> PKA –> phosphorylated myosin light chain kinase –> muscle relaxation

179
Q

β-adrenoceptor agonists and asthma - function

A

Reverse bronchoconstriction associated with asthma

180
Q

Asthma: Salbutamol vs salmeterol

A

Salbutamol: low affinity - acute symptoms
Salmeterol: high affinity - long-acting

181
Q

Types of pain

A 
Pain receptor pain (receives signal/stimulus)
Neuropathic pain (nerves sensing pain regardless of presence of stimulus)
182
Q

Nociceptors

A

Senses pain

FNEs that respond to diff stimuli

183
Q

Nociceptors - process

A

Cells around cut release cytokines –> inflammation –> release prostaglandins which is received by nociceptor –> AP of neuron releases neurotransmitter, which relays signal to thalamus and is sensed as pain

184
Q

Pain: Interneurons

A

In spinal cord

Modulate what you feel

185
Q

Strategies to manage pain

A

Change initiator of pain

Change CNS modulation of pain

186
Q

Strategies to manage pain: Change initiator

A

Reduce inflammation –> reduce prostaglandin

e.g. paracetamol, NSAIDs, aspirin

187
Q

Strategies to manage pain: Change CNS modulation

A

All these drugs are opioids:

e.g. codeine, morphine, fentanyl, tramadol, oxycodone

188
Q

WHO’s pain relief ladder

A

First give non-opioid drugs, but for moderate pain onwards, start giving opioids because much more effective

189
Q

Opioids signal transduction pathway

A

Ligand + receptor: Endogenous opioids + m, k, d opioid receptors (GPCRs)
G-protein: Gαi/o
Effector: AC
2nd messenger: Decreased cAMP –> decreased Ca2+ influx and increased K+ efflux
Response: Less depolarisation

190
Q

What are opioids released by

A

Interneurons

191
Q

What do opioids bind to

A

GPCRs

192
Q

Pain relief - normal pathway

A
  1. AP arrives –> V-gated Ca2+ channels open –> Ca2+ influx
  2. Release of glutamate binds to LGIC –> post-sympathetic neuron depolarisation
  3. Neurons repolarise by K+ efflux
193
Q

Pain relief - opioid pathway

A
  1. Opioids bind to GPCR
  2. Goes through Gαi signal cascade
    - -> inhibits Ca2+ channel
    - -> no glutamate release into post-synaptic neron
  3. Increased K+ efflux –> harder for further depolarisation of neurons
194
Q

Drawbacks of opioid use - side effects

A

Since receptors also found in other areas:

  • bowel and anal sphincter
  • areas of brain responsible for respiration

Side effects include:

  • constipation
  • respiratory depression –> death
195
Q

Drawbacks of opioid use - tolerance

A

Receptor and effectors adapt (densensitised, down-regulated) and is no longer inhibited at same dose
Need higher and higher doses

196
Q

Drawbacks of opioid use - addiction

A

Apart form reducing pain, also causes release of dopamine that causes feeling of reward/pleasure

197
Q

What is the main factor that limits how much opioids you can take

A

Respiratory depression

198
Q

Opioid crisis

A

An exceptionally high mortality rate and harm linked to use/misuse of opioid drugs

199
Q

Key factors leading to opioid crisis

A

1990s: well-intentioned push for doctors to treat pain in patients
Mistaken info that addiction was rare
Increased prescriptions –> increased misuse –> increased overdose deaths

Move to shut down prescription drug misuse –> increased heroin use –> increased use of fentanyl and synthetic opioids –> more deaths due to high affinity and potency

200
Q

Opioid crisis: Solutions - antidotes

A

e.g. Naloxone
Competitive antagonist - itself doesn’t lead to pain relief, tolerance or addiction
Has higher affinity than opioids, so will preferentially bind to receptors –> reverse opioid overdose if administered in time

BUT this is not a solution to opioid crisis

201
Q

Opioid crisis: Solutions - change in policies

A

Use of prescription drug monitoring programs
Increase access to drug abuse treatment services
Enforce rules for drug makers

202
Q

Opioid crisis: Solutions - change doctors’ pain management practices

A

Opioids should be reserved as second or later line of pain management

203
Q

Opioid crisis: Solutions - develop better pain medication

A

Better alternatives with low side effects, tolerance and addiction risk should be investigated

204
Q

Opioid crisis: Solutions - develop better pain medication - strategies

A

Design opioid-like drugs that bind to receptor but doesn’t lead to adaptation of receptors or effectors
Design entirely novel drugs that use other mechanisms (non-opioid) that are efficient at reducing pain

BIOSCI 106 (6 decks)

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