NS Pharmacology Flashcards
Pharmacology and Neurotransmitters
Pharmacology defination?
Chemical substance that interacts with a specific target within a biological system to produce a physiological effect
How drugs produce effects?
What is the target for the drug?
Where is the effect produced?
What is the response produced after interaction with this target
Why do side effects happen?
Dependent on dose of drug
Can be due to effect on other targets in the body or the same target ( in the same or different tissue e.g. dopamine receptors in gut can cause constipation from pramipexole - structurally similar to dopamine - agonist) - can happen as dose increases, enough receptors will increase to see side effect
What makes a drug safe?
Having a large difference between dose required for required effect and dose required for side effects
Atorvastatin drug target class
Enzyme HMG coA
Amlodipine drug target class
Ion channel
Salbutamol drug target class
Receptor Beta 2 in lung = bronchodilation
Citalopram drug target class
Transport protein
Why might selectivity be more important for drugs than endogenous compounds e.g. dopamine, noradrenaline
Neurotransmitters are released from nerves specifically to the corresponding nerve receptors so this overcomes issue of similar shaped neurotransmitters.
Drugs, however go into bloodstream and so can cause effects to multiple receptors if the drug looks alike. (lock and key)
As dose increases…
Selectivity decreases
What are the small membranous protrusions from a neuron’s dendrite ?
Protein molecules called spine = increase SA to increase information coming in
What are the two important amino acid neurotransmitters?
Glutamate - excititory transmitter
y-aminobutryric acid - (GABA) - inhibitory transmitter
Amines as neurotransmitters?
Noradenraline and Dopamine
What Neuropeptides can act as Neurotransmitters?
Opioid peptides
Activation of synapse:
Action potential reaches ‘x’ and causes ‘y’. This activated voltage sensitive ‘z’ channels. ‘z’ floods into terminal and activates exocytotic release of NT into cleft. Fusion and release is aided by ‘a’ on the vesicles, presynaptic
x = axon terminal
y = depolarisation
z = calcium ions
‘a’ = vesicular proteins (e.g. synapsin, SNAP 25 - SNARE proteins)
How much Calcium increase is required for synaptic transmission?
200 microMolars from around 1 microMolar
- has the highest concentration gradients
How many molecules of NT in each vesicle
4000-10,000 loaded into vesicles before release = idea of NT release of Quanta
Alpha Latrotoxin and muscular paralysis
from black widow spider, stimulates transmitter release to depletion. targets for the vesicular proteins to do so
Zn2+ dependent endopeptidases?
Inhibit transmitter release
e.g. Tetanus toxin inhibits glycine and GABA - spasms and pralysis
Botulinum toxin causing flaccid paralysis?
From clostridium botulinum
Due to muscle relaxation, can cause respiratory arrest in fatal doses or lethal food poisoning. Botux uses this method.
Bi-chain molecule, one part binding to nerve terminal, 2nd chain penetrates nerve terminal and cleaves peptide bonds on vesicular proteins. no more exocytosis.
What are ion channel linked receptors in synapses?
Fast responses in msecs, mediate all fast excitatory and inhibitory transmission
e.g. in CNS glutamate, GABA
in NMJ Acetylcholine at nicotine receptors
What NT receptor mediates slow responses?
G-protein-coupled receptors. secs/mins
CNS and PNS : ACh at muscarinic receptors, dopamine, noradrenaline, serotonin, neuropeptides, 5HT, endorphins
Why are G-protein coupled receptors named as such?
When the agonist reaches the receptor the receptor will couple with g-protein, which will couple with the effector e.g. enzymes or channels
Do the NT go through ion-linked channels and what are subunits?
No,
E.g. Glu binds and causes Na+ influx = depolarisation
GABA binds and causes Cl- influx and Gly causes Cl- influx = hyperpolarisation
Multiple subunit combinations lead to distinct functions
Explain EPSP vs IPSP?
Excitatory postsynaptic potential (depolarisation) from e.g. glutamate
Inhibitory postsynaptic potential (hyperpolarisation) e.g. GABA
What are the two main types of Glutamate receptors?
AMPA Receptors : fast excitatory responses, rapid onset and offset and desensitisation
NMDA Receptors : Permeable to Na+ but also Ca2+
slow component of excitatory transmission. Serve as coincidence detectors
What role to Glial cells play in an excitatory Glu synapse?
After transmission Glu needs to be taken up by the presynaptic axon and loaded back into vesicles.
It can also be taken up into Glial cells by excitatory amino acid transporters EAATs
Glutamine synthetase creates it into glutamine
What measures electrical activity in the brain?
EEG
Electroencephalography
Epileptic Seizures
Abnormal cell firing leads to seizures associated with excess glutamate in synapse increasing brain activity as well as physical seizures.
Recurrent activity
How is GABA synthesized?
Decarboxylation of glutamate by glutamic acid decarboxylase - GAD
GABA in Glial cells?
GABA transporters take in GABA and modified by GABA-transaminase to succinic semialdehyde = succinate which goes into TCA
Why is GABA receptor units considered?
Pentameric organisation
Different drugs can bind to different subunits and can facilitate transmission of GABA E.g. Antiepileptic Anxiolytic Sedative Muscle relaxant
