1a Pharmacology and Neurotransmitters Flashcards
What is the definition of pharmacology?
The study of how chemical agents can influence the function of living systems
What are the four most common drug targets?
Receptors, Enzymes, Transport Proteins and Ion channels
What must a successful drug show?
high levels of specificity for a particular target - this is to prevent the drug binding to different things and causing undesired effects
What is an adverse affect?
A side effect which has negative health consequences
What can cause side effects?
When the drug results in off-target effect, or the drug acts on different targets on the same tissue
What is the “safest drug”
Where there is the largest difference between the dose required to induce the desired effect and the dose required to induce side/adverse effects
Why is selectivity more important for drugs than endogenous products of the body?
Endogenous products are produced specifically where they act, where as drugs have to travel in the blood stream to reach their target - more chance of the drug binding to the wrong thing and causing adverse effects
What is the size range of the synaptic cleft?
20-100nm
What type of transmission if an action potential?
Electrical transmission
What type of transmission is synaptic transmission?
Chemical transmission
What ion is essential for NT release?
Ca2+ - bind to vesicles which allows them to fuse with pre-synaptic membrane and release NT via exocytosis into synaptic cleft
What are some amino acid NT’s?
Glutamate, GABA and glycine
What are some amine neurotransmitters?
Noradrenaline, adrenaline and dopamine
Describe the stages of NT release?
- Action potential arrives at pre-synaptic bouton
- AP results in the opening of Ca2+ ion channels
- This results in a large influx of Ca2+ ions into the neurone
- The Ca2+ ions bind to the NT vesicles and cause the vesicles to fuse with the pre-synaptic membrane
- This releases the NT into the synaptic cleft via exocytosis
- The NT then makes contact with the receptor allowing for the depolarisation of the other neurone due to Na+ influx
- The NT is then enzymatically degraded or taken back up into the pre-synaptic bouton
How are dendrites specially adapted to their function?
They have many spines to increase the surface area for information reception
What is an example of a neurotoxin?
Botulinum toxin
Explain how botulinum toxin acts as a neurotoxin?
the botulinum toxin cleaves the SNARE proteins on the presynaptic membrane which would normally allow the NT vesicle to fuse
Therefore, the vesicle cannot fuse, and NT cannot be released
What are SNARE proteins?
They are specific proteins found on the pre-synaptic membrane which help the NT vesicle to fuse so the NT can then be released via exocytosis
What does botulinum cause?
Flaccid paralysis due to complete muscle relaxation
Give a use of botulinum toxin in plastic surgery
Botox - causes smoothing of brow as muscle becomes flaccid
What is alpha latrotoxin?
Stimulates transmitter release to depletion - this means that eventually there will no ACh, leading to muscle paralysis
What is the effect of Zn2+ dependant endopeptidases?
They inhibit transmitter release
What is an example of a Zn2+ dependant endopeptidases?
Tetanus toxin C tetani
How does tetanus toxin C tetani work?
Blocks GABA release
Since GABA is an inhibitory NT, blocking it results in paralysis due to violent musclar spasms as the muscles are continually contracted
What is the speed of the response when using ion channel-linked receptors?
Fast response
What are some examples of ion channel linked receptors?
nAChR, GluR, GABAR and GlyR
What is an example of an inhibitory neurotransmitter?
GABA
What is meant by an inhibitory neurotransmitter?
A NT which makes the post-synaptic membrane less likely to propagate an action potential
How does GABA work as in inhibitory neurotransmitter?
It allows an influx of Cl- ions, which makes the membrane potential more negative = hyperpolarised so less likely to reach the threshold for an action potential to fire
What are the two types of Glutamate receptors?
NMDA receptors
AMPA receptors
Which ions are NMDA receptors permeable to?
Na+ and Ca+
Which ions are AMPA receptors permeable to?
Na+
Where are AMPA receptors found?
In the majority of fast excitatory synapses
What speed of response do G-Protein-Coupled Receptors mediate?
Slow
What are some examples of G Coupled Protein receptors?
Muscarinic ACh receptors, dopamine receptors, noradrenaline receptors, seratonin receptors
What happens to glutamate in glial cells?
It is enzymatically modified by glutamine synthetase into glutamine in glial cells
What happens to neurones firing patterns during a seizure?
they begin firing in an abnormal, excessive and synchronised manner
Following excessive depolarisation during a seizure, what facilitates the hyperpolarisation?
GABA receptors or K+ channels
Which neurotransmitter is present in excess in the synpase during a seizure?
Glutamate
Draw an gluatmate and glutamine curve
Large peak of glutatmate followed by large glutamine peak - this is because the excess glutamate is metabolised into glutamine
Which drugs facilitate GABA transmission?
Anti-epileptic
Anxiolytic
Sedative
Muscle relaxants
What word is used to describe the shape of the GABA receptor?
Pentameric
What is the drug target for diazepam?
The GABA receptor
How does Diazepam work?
Binds to the GABA receptor and increases the effectiveness of GABA activation, therefore more CL- ion uptake which hyperpolarises the post-synaptic membrane, meaning an action potential is less likely to fire, therefore decrease seizure symtpoms
What is a febrile seizure?
A convulsions when a child has a fever over 38*
How does Lamotrigine work as an ant-epileptic medication?
Acts on voltage gated sodium channel, so less depolarisation in the neurone, and less glutamate transmission
How does pregabalin work?
Blocks Ca2+ ion channels meaning less Ca2+ influx which is needed to bind to NT vesicles so they can fuse with the membrane and be released - less glutamate transmission
How does levetiracetam work?
Interferes with vesicle fusion which reduces the exocytosis of glutamate which decreases the excitory activation of the post-synaptic neurone
Why should sodium valpoate not be used on females with child bearing potential?
It is teratogenic - this means it can impact the development of the foetus
