Pharmacology Flashcards
1
Q
What was the first experiment that Langley designed?
A
- Application of pilocarpine and atropine on an isolated frog heart
- Application of pilocarpine and atropine on cat salivary glands
2
Q
What is the active ingredient of Jaborandi?
A
Pilocarpine
3
Q
What were the effects of pilocarpine in Langley’s experiment? (2)
A
- Slows heart rate
- Increases saliva secretion
4
Q
What were the effects of atropine in Langley’s experiment?
A
Blocks both actions of pilocarpine
5
Q
What did Langley conclude from his first experiment?
A
- There is some substance in the nerve endings or gland cells with which atropine and pilocarpine are capable of forming compounds
- Dependant on concentration and affinity
6
Q
What is affinity?
A
Tendency of a chemical/molecule to bind to a receptor
7
Q
What was the second experiment that Langley designed?
A
- Denervated skeletal muscle from chickens
- Applied nicotine and curare to observe whether they act on the nerve fibres or on the muscle itself
8
Q
What was the effect of nicotine in Langley’s experiment?
A
Causes muscle contraction (mimics the effect of stimulating the nerve)
9
Q
What was the effect of curare in Langley’s experiment? (2)
A
- Blocks the effect of electrical stimulation of the nerve (no contraction)
- Blocks the effect of nicotine (no contraction)
10
Q
What was the effect of nicotine in denervated muscle?
A
Caused muscle contraction
11
Q
What was the effect of applying curare with nicotine in denervated muscle?
A
No contraction (blocked the effect of nicotine)
12
Q
What did Langley conclude from his second experiment?
A
- The receptive substance for nicotine and curare is on the muscle itself
- The nerve must release a nicotine-like substance when stimulated
13
Q
What experiment did Ehrlich do?
A
- Staining white blood cells
- Different cell types were specific to different dyes
- Must have different receptors
14
Q
What are receptors? (2 definitions)
A
- Macromolecular proteins which serve as recognition sites for chemicals used in cell-cell communication e.g. neurotransmitters, hormones etc.
- Any protein of a cell that can bind a molecule/drug which then modulates some activity of the cell
15
Q
What is signal transduction?
A
Conversion of an extracellular signal to an intracellular signal
16
Q
What is a chemical mediator?
A
Extracellular signal molecules
17
Q
What is cell signalling?
A
Detection of an extracellular signal by a receptor which generates intracellular signals that alter cell behaviour
18
Q
What is endocrine signalling?
A
Chemical mediator is secreted into the bloodstream and distributed throughout the body so can act on various target cells
19
Q
What is paracrine signalling?
A
Chemical mediator acts locally so acts on neighbouring cells (doesn’t enter the bloodstream)
20
Q
What is autocrine signalling?
A
When paracrine signalling occurs between cells of the same type
21
Q
What is neuronal signalling?
A
- Faster and more specific than endocrine signalling
- Involves neurons and synapses
22
Q
What is contact-dependent signalling?
A
- The chemical mediator is not released into the extracellular space, anchored to the signalling cell
- Direct interaction is required for the target cell to recognise the membrane-bound chemical mediator
23
Q
Where is adrenaline secreted from?
A
Adrenal glands
24
Q
Where are the adrenal glands located?
A
On top of both kidneys
25
What are the receptors for adrenaline?
Adrenergic receptors
26
What kind of signalling does adrenaline do?
Endocrine
27
What happens during an extreme allergic reaction to a wasp sting?
- Mast cells in the skin release histamine
| - Histamine causes dramatic drop in blood pressure and closing of airways
28
What is epinephrine?
Adrenaline
29
What chemical is in epi pens?
Epinephrine (adrenaline)
30
What are the effects of adrenaline/epinephrine?
- Increases blood pressure
- Increases heart rate
- Increases metabolism
31
What kind of signalling does insulin do?
Endocrine
32
What kind of signalling does histamine do?
Paracrine
33
What kind of signalling does nitric oxide (NO) do?
Paracrine
34
How do over the counter allergy medicines work?
- Block histamine receptors
| - Anti-histamine (antagonist for histamine)
35
What is the effect of nitric oxide?
- Generated by endothelial cells
| - Causes smooth muscle relaxation and vasodilation
36
What is the function of Viagra?
- Prevents breakdown of nitric oxide
| - Prolongs the vasodilation of NO
37
What is the other name for eicosanoids?
Prostaglandins
38
What are eicosanoids?
Lipid mediators used in the immune system
39
What are endocannabinoids?
Lipid mediators synthesised in neurons
40
Which drugs interfere with eicosanoid signalling?
Over the counter pain medications e.g. paracetamol, aspirin
41
How do pain medications interfere with eicosanoid signalling?
Prevent their synthesis
42
How does cannabis work?
Mimics the effects of endocannabinoids
43
How might drugs acting on neurotransmission act?
- Interfere with neurotransmitter synthesis, storage or release
- Interfere with neurotransmitter receptors
44
Which drugs act on neurotransmitter receptors? (4)
- Nicotine
- Curare
- Pilocarpine
- Atropine
45
How does BoTox work?
Prevents vesicle fusion in neurotransmission
46
How do amphetamines work?
Interfere with the storage of neurotransmitter
47
What is an example of contact-dependent signalling?
- Delta-Notch signalling in development
| - T cell activation from an antigen-presenting cell
48
What are the 4 categories of cell-cell communication?
- Endocrine
- Paracrine
- Neuronal
- Contact-dependent
49
What is the effect of stimulating the vagus nerve on the heart?
Heart rate slows
50
What experiment did Loewi do?
- Stimulated vagus nerve, collect media surrounding heart
- Transfer media to a recipient heart
- Heart rate slows
51
What did Loewi call the first neurotransmitter?
Vagusstoff
52
What is Vagusstoff?
Acetylcholine
53
What does the vagus nerve release?
Acetylcholine
54
What experiment did Dale do?
- Proved that acetylcholine causes muscle contraction in the neuromuscular junction of leeches
55
Which receptors can acetylcholine act on? (2)
- Nicotinic
| - Muscarinic
56
How are nitric oxide and prostaglandins released from neurones? (lipid mediators)
- Synthesised on demand and leave via constitutive secretion
| - Rise in intracellular calcium activates the enzymes which produce them rather than cause their release
57
Which enzyme is involved in nitric oxide synthesis?
Nitric oxide synthase
58
Which enzyme is involved in prostaglandin synthesis?
Phospholipase A2 (PLA2)
59
What is synaptotagmin?
Calcium sensor protein on synaptic vesicles
60
Which neurotransmitter is released by cholinergic neurones?
Acetylcholine
61
Where is acetylcholinesterase found?
Anchored to the membrane of target cells
62
What does acetylcholinesterase do?
Breaks down acetylcholine into choline (pre-cursor) which is taken up again by the presynaptic neuron to be recylced
63
What are the 2 pathways of exocytosis?
- Constitutive
| - Regulated
64
What is the constitutive pathway of exocytosis?
Diffusion of molecules across the membrane
65
What is the regulated pathway of exocytosis?
Involves the storage of molecules in vesicles which fuse with the membrane in response to a signal
66
What is Fluoxetine used to treat?
- Depression
| - AKA Prozac
67
How does Fluoxetine work?
Inhibits the transporter responsible for reuptake of serotonin into presynaptic neurones
68
How does amphetamine work?
- Enters neurones via the noradrenaline transporter and enters synaptic vesicles instead of noradrenaline which causes NA to build up in the cytosol
- Causes increased NA secretion via the NA transporter to act on postsynaptic receptors
- NA reuptake is suppressed
69
Which neurotransmitter do amphetamines affect?
Noradrenaline
70
What side effects do opiates cause? (2)
- Constipation
| - Respiratory depression
71
What are opioids used for?
Pain relief
72
Which 4 classes of proteins are commonly targeted by drugs?
- Enzymes
- Transporters
- Ion channels
- Receptors
73
What are the 4 classes of receptors?
- Ligand-gated ion channels
- G-protein coupled receptors
- Kinase-linked receptors
- Nuclear receptors
74
What are ionotropic receptors?
Alternative name for ligand-gated ion channels
75
What are metabotropic receptors?
Alternative name for G-protein coupled receptors
76
What are the conserved features of ligand-gated ion channels? (3)
- Extracellular binding site
- Transmembrane domains
- Forms an aqueous pore selective for ions
77
What are the conserved features of G-protein coupled receptors? (3)
- 7 transmembrane domains
- Binding domain
- Intracellular G-protein binding domain
78
What are the conserved features of kinase-linked receptors? (3)
- Single transmembrane domain
- Extracellular binding site
- Intracellular catalytic domain
79
What are the conserved features of nuclear receptors?
- No transmembrane domain
- Found in the cytoplasm or nucleus
- DNA binding motif for regulating gene transcription
- Ligand must be able to cross plasma membrane
80
What is an agonist?
Ligands which produce a response when they bind to a receptor
81
What are examples of agonists? (4)
- Pilocarpine
- Nicotine
- Acetylcholine
- Morphine
82
What is an antagonist?
- Ligands which prevent/inhibit the action of an agonist
| - May bind to the receptor but do not cause a response
83
What are examples of antagonists? (2)
- Atropine
| - Curare
84
What would injection of atropine cause in a whole body system?
Increase in heart rate
85
How does atropine cause increase in heart rate?
Blocks the action of acetylcholine which slows the heart
86
What is the effect of antagonists on isolated tissues?
Nothing
87
Which receptor has the most rapid form of signal transduction?
Ligand-gated ion channels
88
What class of receptor are nicotinic ACh receptors?
Ligand-gated ion channels (ionotropic)
89
How long does signal transduction take with ligand-gated ion channels?
Milliseconds
90
How long does signal transduction take with G-protein coupled receptors?
Seconds
91
What class of receptor are muscarinic ACh receptors?
G-protein coupled receptors
92
How long does signal transduction take with kinase-linked receptors?
Hours (usually involves activation of transcription/protein synthesis)
93
What class of receptor are cytokine receptors?
Kinase-linked receptors
94
How long does signal transduction take with nuclear receptors?
Hours (involves transcription/protein synthesis)
95
What class of receptor are oestrogen receptors?
Nuclear receptors
96
Which receptors are involved in synaptic transmission?
Ligand-gated ion channels (fastest)
97
How many protein subunits do ligand-gated ion channels have?
3-5
98
How many transmembrane domains do each subunit of ionotropic receptors have?
2-4
99
What happens when an agonist binds to an ionotropic receptor?
Channel opens
100
What does nAChR mean?
Nicotinic Acetylcholine Receptor
101
What is curare an antagonist for?
Nicotinic ACh receptors (ionotropic)
102
What is GABA an agonist for?
Ionotropic receptors on inhibitory neurones
103
What is phenobarbitone?
- Mimics action of GABA
| - Used for euthanasia, inhibits CNS
104
What is picrotoxin an antagonist for?
GABAa receptors
105
What are GABAa receptors?
Ionotropic receptors for GABA
106
How many subunits do nicotinic ACh receptors have?
5
107
What disease results from malfunction of nicotinic receptors?
Myasthenia Gravis
108
What causes Myasthenia Gravis
Autoimmune attack of nicotinic ACh receptors on skeletal muscle
109
What are the symptoms of Myasthenia Gravis?
Muscle weakness
110
Which drug blocks the action of acetylcholinesterase?
Neostigmine
111
What does neostigmine do?
Blocks the action of acetylcholinesterase (therefore preventing breakdown of acetylcholine)
112
How is Myasthenia Gravis treated? (2)
- Anti-cholinesterase drugs
| - Immunosuppressants
113
How many subunits do G-proteins have?
3
114
What proteins can be effectors in G-protein coupled receptors? (2)
- Ion channels
| - Enzymes
115
How many types of G proteins exist?
Approx 20
116
What are the 3 subunits of G proteins?
- Alpha
- Beta
- Gamma
(Referred to as beta-gamma subunit because they stay together)
117
What is the structure of a G protein when it is inactive? (2)
- Alpha subunit has GDP bound
| - Alpha subunit has high affinity to beta-gamma subunit, forms complex
118
What happens when an agonist binds to a G-protein coupled receptor? (6)
- Causes a conformational change in the receptor which causes a conformational change in the G protein
- Alpha subunit dissociates from GDP and replaces it with GTP (G protein now active)
- G protein dissociates from the receptor
- Alpha subunit separates from beta-gamma subunit
- Separated subunits go on to regulate effectors
- Receptor can continue to activate G proteins as long as the agonist remains bound
119
How does a G protein become inactive?
Alpha subunit hydrolyses GTP to GDP and re-associates with the beta-gamma subunit
120
What are the 3 types of G proteins?
- Gs
- Gi
- Gq
121
What does Gi/Gs/Gq refer to?
Which alpha subunit is in the G protein (alpha i/s/q)
122
What does Gs do?
- S=stimulatory
- Stimulates adenylyl cyclase
- Causes increased production of cAMP (second messenger)
123
What does adenylyl cyclase do?
Converts ATP to cAMP
124
What does Gi do?
- I=inhibitory
- Inhibits adenylyl cyclase
- Causes decreased production of cAMP (second messenger)
125
What does Gq do?
- Activates Phospholipase C
- Increased production of IP3 and DAG (second messengers)
- IP3 causes increase of intracellular calcium
- DAG causes activation of Protein Kinase C
126
What is PLC?
Phospholipase C
127
What is DAG?
Diacylglycerol
128
What effectors do alpha subunits of G proteins regulate?
Enzymes
129
What effectors do beta-gamma subunits of G proteins regulate?
Ion channels
130
What are GIRKs?
Potassium channels
131
How do beta-gamma subunits affect GIRKs?
- Causes opening of GIRKs in neurones
- Leads to hyperpolarisation
- Prevents action potentials firing
132
Which receptors does morphine bind to?
Opioid receptors
133
Which G protein associates with opioid receptors?
Gi
134
How does morphine reduce pain?
- Binds to opioid receptor coupled to Gi protein
| - Beta-gamma subunit opens GIRKs which reduces calcium influx, therefore reducing pain transmission in the CNS
135
How do morphine/heroin cause addiction?
- Binds to opioid receptor coupled to Gi protein
- Alpha i subunit causes reduction of cAMP
- Leads to changes in gene transcription associated with addiction
136
Which enzyme breaks down cAMP?
cAMP phosphodiesterase
137
What is cAMP broken down into?
5'-AMP (no signalling activity)
138
What are 3 proteins which cAMP can regulate as a second messenger?
- Protein Kinase A (PKA)
- EPAC
- CREB
139
What is CREB?
Transcription factor
140
How does cAMP regulate PKA?
- Binds to regulatory subunits of PKA which causes them to dissociate
- Frees catalytic subunits to phosphorylate targets
141
How does IP3 cause increase of intracellular calcium?
- Binds to IP3 receptors (ion channels) on the endoplasmic reticulum
- Channels open and release calcium
142
What causes smooth muscle contraction?
- Agonists bind to receptors coupled to Gq proteins
- Increased PLC activity leads to increased intracellular Ca2+
- Ca2+ causes contraction
