Drugs affecting synaptic transmission Flashcards
What is the requirement for centrally acting drugs?
Must cross the blood brain barrier.
Must be lipid soluble - unionised - at blood pH.
What are the types of drugs that work centrally?
Psychiatric - depression, schizophrenia, anxiety.
Neurological - Parkinson’s disease, epilepsy.
General anaesthetics.
Analgesics
What are the critical process of synaptic transmission?
Biosynthesis
Action potential propagation
Neurotransmitter release
Receptor coupling
Post synaptic effect
Signal termination - re-uptake/enzyme degradation.
What is biosynthesis?
Neurotransmitters are made in the synapse - biosynthesis.
Dedicated enzymes in presynaptic terminal for making neurotransmitter.
What is action potential propagation?
Begins at axon hillock.
Nodes of Ranvier help, as VGNaC in between.
Causes action potential to fire at nodes.
What is neurotransmitter release?
VGCaC expressed on membrane on presynaptic terminal, allows Ca2+ influx which triggers exocytosis.
Exocytosis is fusing of vesicles to the membrane and releases neurotransmitter into synapse.
What is receptor coupling?
Neurotransmitter is an agonist, stimulates receptor on postsynaptic membrane, allows movement of ions through channel into postsynaptic membrane.
What is the postsynaptic effect?
Change in excitability of presynaptic neurone, due to ion movement, can cause an action potential.
What is signal termination by re-uptake?
Depends on neurone and neurotransmitter.
Specific sites on presynaptic membrane bring neurotransmitter back into the presynaptic terminal.
This reduces the concentration in the synapse, and terminates the signal.
After uptake, neurotransmitter can be metabolised by enzymes.
What is signal termination by enzymatic breakdown?
Depends on neurotransmitter and neurone.
After release, enzymes in synapse hydrolyse the neurotransmitter.
Acetylcholine uses enzymatic breakdown by acetylcholinesterase.
What drugs effect transmitter biosynthesis?
L-Dopa, a dopamine precursor, when given it increases dopamine production in neurones which are dying due to Parkinson’s disease.
An effective treatment for Parkinson’s disease - offsets symptoms of tremor and movement difficulty.
What drugs affect the action potential propagation?
VGNaC channel blockers.
Decreases high frequency firing associated with epilepsy.
Use dependent block - the inactivated state is selectively blocked.
Treatment for epilepsy as an anticonvulsant, using phenytoin and carbamazepine.
What drugs affect neurotransmitter release?
VGCaC channel blockers, which reduce neurotransmitter release.
Anticonvulsant activity for epilepsy, by phenytoin, and ethosuximide - for absence epilepsy.
What antagonists are used to affect the receptors?
D-2 receptor antagonists
ACh muscarinic antagonist, by benztropine for Parkinson’s.
5-HT3 antagonists, antiemetic by ondansetron.
What are D-2 receptor antagonists?
Antipsychotic (neuroleptic) drugs by haloperidol.
Antiemetic (antinausea) by metoclopramide, chlorpromazine.
What are agonists used to affect receptors?
D-1 receptor selective agonist, for Parkinson’s, by bromocriptine.
Opioid (u receptor) agonists, for analgesic effect, by morphine.
5-HT1A agonists, anxiolytic (anti-anxiety) by buspirone.
What are allosteric modulators that affect receptors?
Positive modulator of GABA A receptors:
Benzodiazepine e.g. diazepam
Barbiturates e.g. phenobarbitone
Enhance inhibitory transmission.
What are the uses of GABA A positive allosteric modulators?
Sedative, hypnotic, anxiolytic
Anticonvulsant
Anaesthetic
What drugs are used for re-uptake inhibition?
Tricyclic antidepressants e.g. amitriptyline, which are unselective between noradrenaline and 5-HT re-uptake.
Selective serotonin re-uptake inhibitors e.g. fluoxetine.
GABA uptake blocker, anticonvulsant, by tiagabine.
Dopamine uptake inhibitor, anti-Parkinson’s, by nomifensine.
What drugs are uses to inhibit degradative enzymes?
Monoamine oxidase (MAO) inhibitors as antidepressant, by phenelzine.
Selective MAO-B inhibitor, antiparkinsonian, by selegiline.
GABA transaminase inhibitor, anticonvulsant, by vigabatrin.
What is auto receptor-mediated feedback inhibition?
Mianserin, hasA2 antagonist properties.
Antidepressant.
Stops the neurotransmitter acting on its presynaptic terminal to decrease further neurotransmitter release.
What types of drugs are used for depression?
Re-uptake inhibition
Degradative enzyme inhibition
Auto receptor antagonism
What treatments are used for Parkinson’s disease?
Targets Dopamine deficit:
Replacement therapy by L-dopa precursor.
Direct agonism
Re-uptake inhibition
Degradative enzyme inhibition
Muscarinic receptor antagonist
What are the treatments for epilepsy?
Targets the excitatory/inhibitory imbalance:
Na+ and Ca2+ channel blocker to reduce overactivity.
GABA A receptor positive allosteric modulation.
GABA re-uptake inhibition
GABA degradative enzyme inhibition.
These enhance inhibition.
What are the treatments for Alzheimer’s disease?
It degenerative, loss of ACh:
Precursor replaces ACh.
Agonists
Degradative enzyme inhibition
AChE inhibitors, by donepezil, rivastigmine, galantamine.
