Autonomic Pharmacology Flashcards
Mention the key neurotransmitters of the NS.
Mention the steps in chemical neural transmission that may act as sites for drug action.
- AP Conduction
- Neurotransmitter Synthesis
- Neurotransmitter Storage
- Neurotransmitter Release
- Neurotransmitter Inactivation (Uptake)
- Neurotransmitter Inactivation
- Receptor Activation
Example of Drug for AP Conduction.
Na+ Channel Blockers: inhibit AP conduction
Example of drugs that affect Neurotransmitter Synthesis.
L-DOPA + Carbidopa
L-DOPA, which is a dopamine precursor, works on both the CNS and PNS. Carbidopa, a DOPA decarboxylase inhibitor, prevents dopamine synthesis. It is used in conjunction with L-DOPA as it only affects the CNS, preventing any adverse effect of L-DOPA in the CNS.
Example of a drug that affect Neurotransmitter storage.
Pseudoephedrine, an indirectly acting sympathomimetic, displaces the NA in the synaptic vesicles. Displaced NA then “leaks” through the membrane into the junction. It then activates receptor.
Used for nasal decongestant.
Example of drug that affects neurotransmitter release.
Botulinum Toxin A: inhibits exocytotic release of ACh from choligernic neuron.
The toxin is specific to choligernic neurons - the light chain of the toxin cleaves the SNARE proteins - not allowing fusion of teh membranes.
Describe the process of neurotransmitter release.
- Priming: Synaptobrevin forms SNARE complex with Syntaxin and SNAP-25
- Ca2+ enters nerve terminal and binds to synaptotagmin on vesicle membrane
- Ca2+ bound synaptotagmin interacts with SNARE complex, driving membrane fusion and exocytosis of neurotransmitter
Example of drug that affects neurotransmitter inactivation (uptake)
Cocaine: blocks NA transporter (NET) => inhibit NA reuptake into sympathetic nerve terminals. Cocaine blocks the high-affintiy neuronal uptake, hence cocaine is taken up extraneuronally.
Example of drug that affects neurotransmitter inactivation (degradation).
Neostigmine: Acetylcholinesterase (AChE) Inhibitor - preventing ACh degradation
Usage: Myasthenia Gravis, where antibodies binds and block nAChR => weak muscle signal
AChE Inhibitor allows ACh to remain longer in the synapse and activate the nAChR.
Describe the types and features of adrenoreceptors.
Adrenoreceptors are examples of a GPCR. It is responsible for post-ganglionic sympathetic responses (except for sweat glands). Some of the receptor subtypes are:
Describe the features of muscarinic receptors (mAChRs) and its subtypes.
It is considered as a GPCR. Two of its subtypes are of the following:
Describe the features and subtypes of nAChRs.
They are considered as ligand-gated ion channels (ionotropic).
N1 is usually found in NMJ, while N2 is neuronal. Functional isoforms are present either as homopentamers or heteropentamers. These differences in subunit composition may lead to differences in ligand specificity, cation permeability, and physiological function.
Recall the Signalling Pathways in the SNS and ANS.
Mention some agonists and antagonists drug acting on alpha-adrenoreceptors.
Mention agonists and anatagonists drugs acting on beta-adrenoreceptors.
Mention agonists and antagonists acting choligernic receptors.
