Pharmacology Flashcards
At rest, a neutron is positively or negatively charged?
Negative
There are two types of receptors, what are they?
- Ion chanels
2. G-Protein coupled
Ion channel and G-Protein coupled things are both examples of
Neuroreceptors
Of the two types of receptors we learned about, which work through ‘second messengers’?
G-Protein receptors
Neurotransmitters can fall into two categories based on their impact on the post-synaptic neutron. What are those categories?
Excitatory or inhibitory
Are excitatory neurotransmitters are typically found in long or short neutrons?
LONG
Are inhibitory neurotransmitters are typically found in long or short neutrons?
SHORT
Based on the slides, where in the brain does it seem that Serotonin comes from?
Raphe Nuclei
What is the Raphe Nuclei associated with?
Production of Serotonin
Based on the slides, where in the brain does it seem that Norepinephrine comes from?
Locus Coeruleus
What is the Locus Coeruleus associated with?
Production of Norepinephrine
Based on the slides, where does it seem that Dopamine comes from?
Substantial Nigra (SN)
and
Ventral Tegmental Area (VTA)
The Substantial Nigra (SN) and Ventral Tegmental Area (VTA) are associated with what?
Production of Dopamine
What are the seven stages of the neurotransmitter cycle?
- Synthesis
- Release from synaptic vesicles
- Binds to receptors
- Influence post-synaptic neuron
- Broken down (by enzymes)
- Reuptake of transmitter
- Formation and storage in synaptic vesicles
When a drug acts as an agonist, what is it doing to the relevant receptors?
Binding and activating like a natural compound…
What were the four ‘non-traditional’ neurotransmitters discussed in the slides?
- Peptides
- Nucleosides
- Lipids
- Gases
What are the two most common neurotransmitters in the CNS?
Glutamate and GABA, baby
Who is the main excitatory neurotransmitter?
GLUTAMATE
What is Glutamate made of?
Glutamic Acid, of course
Is Glutamate an amino acid?
Yup
Can Glutamate be synthesised in your toe?
Nope, it must be synthesised in the brain
It can’t pass the blood-brain barrier
Of the four major types of Glutamate receptors, which is the one Olivia wants us to worry about?
NMDA receptor
How many binding sites has your NMDA receptor?
At least 6
Is the NMDA receptor a G-Protein or Ion Channel variety?
Ion Channel
What are the two preconditions that the NDMA receptor needs in order to work?
Glycine molecule must be attached
Magnesium ion is NOT bound to the inside
Which everyday drug is an antagonist for the NDMA receptor?
Alcohol
Phencyclidine (PCP) and Ketamine are both antagonists for what type of receptor?
NDMA
Is psychosis associated with changes to brain structure?
Nope, meaning it is coming down to brain chemistry
What would happen if there were no inhibitory synapses in the brain?
Seizures, all the time
What is GABA produced from
Glutamic Acid
Wait, are you saying that Glutamate and GABA are made from the same stuff?
Yep - Glutamic acid in both cases…
Glutamate and GABA can be converted into each other
What are febrile seizures?
When a kid has a seizure associated with a fever (I think)
What is the base ingredient from which Dopamine is synthesised?
Tryrosine
What are cheese, avo and almonds high in?
Tryrosine
What is the synthesis pathway for Dopamine?
- Initial synthesis enzyme = Tryrosine Hydroxylase… makes DOPA
- Subsequent synthesis enzyme = Amino Acid decarboxylase… makes Dopamine
- Final synthesis and then breakdown enzyme = Dopamine β-hydroxylase… leads to Noradrenaline
What does Dopamine become after it is broken down?
Noradrenaline
What causes Parkinson’s
Death of dopamine cells in the Substantia Nigra (SN)
What disease is treated by upping the dopamine?
Parkinsons
Treatment of what disease can lead to impulsivity, hyper sexuality and gambling?
Parkinson (through upped dopamine)
What is the circumstance in which Dopamine (DA) neurons become particularly active?
Following an UNEXPECTED reward
What is the name given to the event/thingy that gives rise to a surge of Dopamine?
A Reward Prediction Error
If you’re expecting a reward and you don’t receive it, what happens to the level of excitation in your Dopamine (DA) neurons?
It gets suppressed
Which neurotransmitter is associated with coding goal reward and effort costs linked to cognitive effort?
Dopamine
Which neurotransmitter does cocaine primarily work on?
Dopamine
Changes to dopamine operation are associated with which elicit drugs? (2)
- Cocaine
2. Amphetamine
Which part of the dopamine life-cycle does cocaine interact with?
REUPTAKE…!
Blocks it, basically. Meaning you’re swimming in more dopamine
Which part of the dopamine life-cycle does amphetamine interact with?
REUPTAKE…!
Actually REVERSES it. Meaning you’re swimming in even more dopamine
What is special about addictive drugs in relation to the reward prediction error thing?
Addictive drugs are ALWAYS coded as unexpected
as in, even if you are habituated to the beep, you still get a burst of dopamine when you get the line of cocaine
What are the two changes that addictive drugs appear to produce in people?
- initiate WANTING
2. reduce COGNITIVE CONTROL (impaired function of prefrontal cortex)
Drugs containing what substance contribute to the synthesis of dopamine?
L-DOPA
Dopamine codes reward relative to what?
Expectations
What neurotransmitter appears to be particularly relevant to motivation and mental effort?
Dopamine
We talked about arousal and depression and reward… which one is dopamine associated with?
Reward
Which neurotransmitter do we associated with arousal, decisions and anxiety?
Noradrenaline
Which neurotransmitter do we associated with the four Fs?
Noradrenaline
What is the base ingredient from which Noradrenaline is synthesised?
Tryrosine
What is the synthesis pathway for Noradrenaline?
- Initial synthesis enzyme = Tryrosine Hydroxylase… makes DOPA
- Subsequent synthesis enzyme = Amino Acid decarboxylase… makes Dopamine
- Final synthesis and then breakdown enzyme = Dopamine β-hydroxylase… leads to Noradrenaline
The synthesis pathway for dopamine and noradrenaline is basically same same, T/F
TRUE
Dopamine gets broken down into noradrenaline
Noradrenaline has two breakdown pathways. What are their mechanisms and where do they lead…?
- An extra synthesis step converts it to old fashioned adrenaline
- an enzyme called MONOAMINE OXIDASE (MAO) converts it to an inactive metabolite
Low many neurones does the Locus Coeruleus have? HOW MANY?
~30,000
Which is small
What two types of transient event really get the Locus Ceruleus going?
One that is either noxious or extremely positive
Confusing…
What is the neurotransmitter that is associated with anxiety, stress and panic attacks?
Noradrenaline
How does noradrenaline relate to decision making
It consolidates decisions
Which neurotransmitter is associated with pupil size in the dark?
Noradrenaline
You can use pupil dilation to index the release of which neurotransmitter in the brain?
Noradrenaline
Mood disorders are associated with which neurotransmitter?
Serotonin
What is the secret code name for serotonin?
5-Hydroxytryptamine (5-HT)
What is 5-Hydroxytryptamine (5-HT) the secret code name for?
Serotonin
Is serotonin best considered a neurotransmitter or a neuromodulator?
NeuroMODULATOR
Serotonin receptors have lots of subtypes
Oh really
What is the synthesis pathway for Serotonin?
- Synthesised from TRYPTOPHAN by an enzyme
2. Broken down by the enzyme Monoamine Oxidase (MAO)
What is serotonin made from?
Tryptophan
What is Tryptophan the building block of?
Serotonin
What are the three theories that purport to explain why SSRIs take so long to reduce an effect?
- Altered gene expression (new gene info»_space; new enzyme balance»_space; changes neuron activity»_space; new neurotransmitter synthesis/storage OR changed neutron structure (synaptic
remodelling) - Shuts off pathologically elevated STRESS RESPONSE, allowing adaptive neural stuff to happen
- Increased neurogenesis, improve strength of mood related brain circuits
What is the powerful class of antidepressant that causes death by cheese?
Monoamine Oxidase Inhibitors (MAOIs)
Although the four non-traditional neurotransmitters don’t fit the strict definition of ‘neurotransmitter’ they still do three neurotransmittery things. What are they?
- They are present in the presynaptic terminals
- They get released from presynaptic terminal after the neuron fires
- There are receptors for them on the postsynaptic neurons
What are peptides made out of?
Two or more amino acids
Both peptides and proteins are made from amino acids, so how are they different?
I’m not really sure, but proteins are much bigger apparently.
Peptides in the brain are typically created through larger compounds being broken down (as opposed to being specially synthesised themselves)
Okay
Tell me some interesting things about peptides
- Most serve as modulators
- Many (known to be hormones) also act as neurotransmitters
- these ones often co-release with other neurotransmitters
Endogenous opioids are an example of what?
Peptide neurotransmitters
If you wanted to rapidly prevent an overdose of heroin, what would you administer?
Naloxone
What is Buprenorphine?
An agonist that is used to treat heroin dependence
What is the most common synthesis pathway for lipids?
NOBODY KNOWS
What is the name of the best known lipid neurotransmitters?
Endocannabinoids
What are Endocannabinoids?
A class of lipid neurotransmitter
What do Endocannabinoids do, actually?
Modulate the mf modulators
What types of patients are the first to receive medicinal cannabis in Victoria?
Kids with severe intractable epilepsy
What are nucleosides?
A subunit of Nucleic Acids… which are the heredity controlling components of all living cells (such as RNA and DNA)
What chemical process gives rise to nucleosides?
Usually, from chemical/enzymatic breakdown of nucleic acids
What role do nucleosides have around neurotransmission?
Modulate the mf modulators!
Give me an example of a nucleoside
Adenosine!
Wtf is adenosine?
A nucleoside that acts as an INHIBITORY neurotransmitter
Where does adenosine come from?
From the breakdown of adenosine triphosphate (ATP).
ATP is the primary energy source for cell transport and many enzymes
How does adenosine operate?
The longer you are awake, the more it builds up, promoting sleep
Name an adenosine receptor antagonist?
Caffeine!
Which two gases are used as neurotransmitters?
- Nitric oxide (NO)
2. Carbon monoxide
How is Nitric Oxide (NO) produced in the brain?
From the amino acid Arginine…
made in a very small subpopulation of 1-2% of neurons in the cortex
Although the exact function of Nitric Oxide is unclear, what are two things we believe it is involved in?
- Learning and memory (impacts synaptic plasticity)
2. dilating blood vessels in regions of the brain that become metabolically active
Where is Nitric Oxide synthesised and stored
NITRIC OIXIDE IS NOT SYNTHESISED AND STORED
If it doesn’t get synthesised like a normal neurotransmitter, how does nitric oxide get just so?
It is produced throughout the cell including dendrites and defuses out of the cell as soon as it is produced.
Tell me all about the receptors for Nitric Oxide?
NITRIC OXIDE DOES NOT HAVE RECEPTORS
It just floats into the next cell
How long does Nitric Oxide last?
Not long, honey… only a few seconds
On what types of neurons would you find cannabinoid receptors?
Well actually, cannabinoid receptors are found near the synapses of MOST neurons that release neurotransmitters
