BB CAL Flashcards
(89 cards)
1
Q
Sodium ion concentrations
A
Axoplasm = 15
Interstitial fluid = 150
2
Q
Potassium ion concentrations
A
Axoplasm = 150
Interstitial fluid = 5
3
Q
Chloride ion concentrations
A
Axoplasm = 9
Interstitial fluid = 125
4
Q
Anion concentrations
A
Axoplasm = high
Interstitial fluid = very low
5
Q
Resting membrane potential
A
-65mV
6
Q
Depolarised membrane potential
A
+40mV
7
Q
Equilibrium potential for sodium
A
+58mV
8
Q
Fast vs slow axonal transport
A
Fast = 400mm/day Slow = 2.5mm/day
9
Q
Typical synaptic delay
A
0.5ms
10
Q
Number of vesicles in a nerve terminal
A
10,000
11
Q
Number of NT molecules stored in each vesicle
A
3000
12
Q
How manyy vesicles fuse for each action potential?
A
1-10
13
Q
What is the effect of autoreceptors?
A
Depends if they are excitatory or inhibitory
Control how much NT is released in subsequent APs
14
Q
Examples of retrograde NTs
A
NO
Endocannabinoids
15
Q
In a GCPR, which subunit is GTP attached to?
A
Alpha
16
Q
What is the approximate threshold value/
A
-55mV
17
Q
Structure of a ligand gated ion channel
A
Hetero-oligomeric proteins
4-5 subunits
18
Q
Structure of a GCPR
A
Single polypeptide chain
Crosses the membrane 7 times
19
Q
What can cause depolarisation?
A
Influx of Na+
Influx of Ca2+
Closing of K+ channels
Efflux of Cl-
20
Q
What causes hyperpolarisation?
A
Opening of K+ channels
Influx of Cl-
21
Q
Which amino acid is tyrosine synthesised from?
A
Phenylalanine
22
Q
What is the first step of dopamine synthesis from tyrosine?
A
Tyrosine –> L-Dopa
By tyrosine hydroxylase
This is the rate limiting step
Requires THB as a cofactor
23
Q
What is the second step of dopamine synthesis from L-Dopa?
A
L-Dopa –> dopamine
By dopamine decarboxylase
Uses vitamin B6 as a cofactor
Also catalyses the final synthetic steps of 5-HT, histamine, tyramine and tryptamine synthesis
24
Q
What is the molecule responsible for dopamine transport into vesicles?
A
VMAT2
Vesicular monoamine transporter 2
Requires ATP
25
Which type of calcium channels open in response to terminal bouton depolarisation?
N type
26
What happens when dopamine binds to D2 autoreceptors?
Inhibits dopamine synthesis
27
Two fates of dopamine
- -> homovanilic acid by COMT then MAO
- this is the major pathway
- can be used to monitor dopamine turnover
--> 3,4-dihydrophenylacetic acid (DOPAC) by MAO and aldehyde dehydrogenase
28
D1 receptor family
D1 and D5
GCPRs
Postsynaptic
Activate adenylate cyclase
29
D2 receptor family
```
D2, D3 and D4
GCPRs
Mostly postsynaptic but some presynaptic
Inhibit adenylate cyclase
Activate K+ channels
Decreased Ca2+ conductance
```
30
Where are D1 and D5 channels found?
```
D1 = basal ganglia
D5 = hippocampus and hypothalamus
```
31
Where are D2, D3 and D4 channels found?
```
D2 = basal ganglia
D3 = limbic areas
D4 = frontal cortex, midbrain and medulla
```
32
What are the 3 dopamine pathways in the brain?
Nigrostriatal
- 75% of brains dopamine
- cell bodies in SNPC
- axons terminate in corpus striatum
- involved in motor control
- death leads to PD
Mesolimbic
- cell bodes in VTA of midbrain
- axons terminate in the NA and olfactory tubercle
- involved in Schizophrenia
Mesocortical
- cell bodies in the VTA of midbrain
- axons project to the frontal and cingulate cortices
- involved in memory, motivation, reward, addiction
33
Alpha methyl-p-tyrosine
Inhibits tyrosine hydroxylase
| Blocks dopamine synthesis
34
Reserpine and tetrabenazine
Inhibits VMAT2
Inhibits vesicular storage of dopamine
Used in Huntingdon's disease
35
Dopamine agonists
```
Pergolide
Quinpirole
Bromocriptine
Apomorphine
Used in PD
```
36
Dopamine receptor antagonists
Antipsychotics --> schizophrenia
Chlorprozamine, haloperidol, clozapine (D4 mainly)
Also have affinity for ACh , H1 and 5-HT2 receptors
37
Amantadine
Causes dopamine release
Blocks dopamine reuptake
Used in PD
38
Selegiline
MAOb inhibitor
+ rasagiline
Used in PD
39
Entacapone, tolcapone
COMT inhibitors
Used in pD
Used alongside L-Dopa
40
Antimuscarinics
Benzhexol, benztropine
Can be used in PD
Increase release and inhibit reuptake
41
How is 5-HT synthesised?
Tryptophan taken up into nerve terminal
Tryptophan --> 5-hydroxytyptophan 5-HTP b
- by tryptophan hydroxylase
- required tetrahydrobiopterin
- rate limiting step
5-HTP --> 5-HT
- by DOPA decarboxylase
42
What is needed for 5-HT storages
Vesicles
ATP
Na+
43
How is 5-HT inactivated?
Degraded by MAO initially
- -> 5-HIAA by aldehyde dehydrogenase (predominant) = oxidation
- -> 5-hydroxytryptophol by alcohol dehydrogenase = reduction
44
What type of receptors are 5-HT receptors?
All GCPRs
| Except 5-HT3 which are ligand gated ion channels
45
5-HT1
```
Negatively coupled to adenylate cyclase
Activate K+ channels
A = anxiety + pain
B = cranial blood vessels
F = uterus
```
46
5-HT2
Coupled to inositol phosphate
A = anxiety, depression, pain, vascular, tracheal and bronchial smooth muscle contraction
B = rat fundic strip contraction
C = spinal distribution --> CSF formation rate
47
5-HT3
Ligand gated ion channels
| Role in emesis
48
5-HT4
Positively coupled to adenylate cyclase
Relax oesophageal smooth muscle
Increase heart rate and force
49
5-HT6&7
Positively coupled to adenylate cyclase
| Low peripheral expression
50
Which receptors affect serotonin release?
Inhibitory 5-HT1a receptors
| Inhibition 5-HT1b/d autoreceptors
51
Buspirone, ipsapirone
5-HT1a partial agonists
Desensitise 5-HT1a receptors
Increase firing rate and 5-HT release
Used to treat anxiety
52
Sumatriptan
5-HT1b/d agonist
Used for migraine and cluster headache treatment
Induces cerebral blood vessel vasoconstriction and reduces release of neuropeptides
53
Ondansetron
5-HT3 antagonist
| Anti-emetic
54
LSD
Agonist of 5-HT1 receptors
55
Irreversible MAOIs
```
Phenelzine, isocarboxazid
Non-selective
Cheese reaction (with tyramine ingestion)
```
56
Moclobemide
Reversible MOAIs
More selective for MAOa
Much less severe risk effects and Cheese reaction
57
Drugs that do not give rise to dependence
Cannabinoids
| LSD
58
Psychological effects of withdrawal
```
Produced by all drugs of dependence
Due to effects on the limbic system
Mood changes
Anxiety
Agitation
Feeling unable to cope
```
59
Drugs that only produce psychological withdrawal
Cocaine
Amphetamine
Nicotine
Caffeine
60
Physical dependence
Clear cut syndrome of physical symptoms
| Relatively short lived --> 2 weeks
61
Opiate withdrawal
```
Diarrhoea
Nausea/vomiting
Abdominal discomfort
Convulsions
Sweating
```
62
Barbiturate withdrawal
```
Anxiety
Insomnia
Epileptic fits
Sweating
Tremors
Delirium, delusions and hallucinations
```
63
Benzodiazepines withdrawal
Convulsions
Panic attacks
Anxiety
64
Alcohol withdrawal
Convulsions
Sweating
Tremors
Anxiety
65
Which drugs develop tolerance but not dependence?
LSD
GYN
Anticholinesterases
66
What is acute tolerance?
Tachyphylaxis --> densitisation
Occurs when a receptor becomes desensitisied after the first dose
Occurs with nicotine
67
Types of chronic tolerance
```
Cellular = pharmacodynamic
Pharmacokinetic = metabolic
```
68
What is cellular tolerance?
Due to neuroadaptive changes that produce diminished responses to drugs
Follows chronic exposure
Major contributor to drug tolerance
69
What is pharmacokinetic tolerance?
Due to an increase in metabolism of a drug
Caused by induction of liver enzymes
Overcome by taking a larger dose
70
Psychomotor stimulants
Nicotine
Amphetamine
Cocaine
Caffeine
71
CNS depressants
Alcohol
Opiates
Barbiturates
Benzodiazepines
72
Nicotine tolerance
All 3 types
Acute - to HR changes
Cellular - to nausea, dizziness
PK - only to a small degree
73
Where does nicotine act?
NA and VTA --> dependence and reward
Hippocampus --> increased attention
Reticular formation --> increased alertness
74
BZ tolerance
Cellular type
| To antipsychotic effects more than anxiolytic effects
75
Where do BZs and barbiturates act?
Raphe nuclei --> increase 5-HT transmission
| Reticular formation --> sedation
76
Barbiturate tolerance
PK --> p450 enzyme induction
| Some cellular tolerance
77
Alcohol tolerance
Acute - in one session
Cellular = in regular drinking
PK = only in severe alcoholics --> p450
78
Opiate tolerance
Early = nausea and vomiting
Medium = euphoria, analgesia and respiratory depression
No tolerance = constipation, pupillary constriction
79
Opiate receptors
Mu --> euphoria, analgesia, resp depression, constipation
Kappa --> analgesia
Delta --> analgesia
80
Where do opiates act?
VTA and NA --> euphoria and dependence
PAG --> analgesia
Reticular formation --> sedation and respiratory depression
Area postrema = nausea and vomiting
81
Cocaine dependence
Psychological but not physical
82
Cocaine tolerance
Euphoria is lost
| Cardiovascular effects do not show tolerance easily
83
Cocaine MoA
Inhibition dopamine reuptake
84
Where does cocaine act?
NA --> euphoria and dependence
Hypothalamus --> increased temperature and decreased food consumption
Reticular formation --> increased alterness
85
Caffeine tolerance
Fast = unpleasant effects
| Little tolerance = psychostimulant effects
86
Caffeine MoA
Inhibits adenosine A1 receptors
| Inhibits PDE which inactivates cAMP
87
Amphetamine tolerance
Cellular type
| Means overdose is likely --> psychosis
88
Amphetamine MoA
Stimulate release of catecholamines (DA, NA, A)
Inhibit reuptake
Inhibit MAO
89
Where do amphetamines act?
NA --> euphoria and dependence
Hypothalamus --> increased temperature and decreased food consumption
Reticular formation --> increased alterness
