BIOM20002 Lecture 14: 6. Lecture 14 - Autonomic pharmacology
22 Aug 2018
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Lecture 14 - Autonomic pharmacology
Steps in chemical transmission
1. Different neurotransmitters
2. Sites of drug action
3. Different types of receptors
Different neurotransmitters
Sites of drug action
1. Inhibit action potential conduction
- Sodium channel blockers can inhibit the conduction of action potential on the
axon by blocking the voltage-gated sodium channels
- Preferably inhibit neurons that are repetitively firing (firing excessively)
- Prevent abnormal recharge of neurons
- Anti-epileptics
2. Neurotransmitter synthesis
- L-DOPA is a dopamine precursor and when given to patient he or she can get
alleviation in symptoms associated with dopamine deficiency
- Carbidopa is a DOPA-decarboxylase inhibitor which prevents the synthesis of
dopamine
- Carbidopa does not go across the blood-brain barrier, so it’s restricted to
peripheral neuron, so that less dopamine will be formed in peripheral system
while more L-DOPA can be converted where dopamine is needed
3. Neurotransmitter storage
- Pseudoephedrine – indirectly acting sympathomimetic
- Sympathomimetic – to describe something mimics the response shown by
sympathetic system; indirectly acting – the drug itself does not activate the
receptors that mediate the sympathetic nervous system; it gains access to the
nerves’ terminals and displays the NA in synaptic vesicles. Displayed NA leaks
into junction and activates receptors to a series of responses in the tissue
- To treat nasal decongestant
- Constriction of blood vessels
4. Neurotransmitter release
- Botulinum toxin A – inhibits exocytotic release of ACh from cholinergic neurons
- Used in dystonia and cosmetics
- Steps of how it blocks ACh release
o Heavy chain of botulinum toxin selectively and irreversibly binds to
receptors on nerve terminals containing ACh
o Botulinum toxin is endocytosed
o Light chain detaches from heavy chain, enters cytosol and cleaves SNARE
proteins
o SNARE complex does not form
o Vesicles and plasma membranes do not fuse. Thus neurotransmitter
release is inhibited
- Paralysis of muscle fibres
- Restricted administration – the most lethal drug known
o Small injection in localized areas
o Causes muscle paralysis in the particular effective areas
5. Neurotransmitter inactivation
- Cocaine blocks neuronal uptake transporter – inhibits NA reuptake into
sympathetic nerve terminals
- Ach is predominately inactivated by degredation and NA is predominately
inactivated by neuronal reuptake
- Neostigmine prevents Ach degradation
by an
- Normal pathway of Ach degradation
o Arrival of a single nerve impulse releases a package of Ach
o Some Ach binds and activates nAchRs to elicit an end-plate potential
(local depolarization by influx of Na+ that initiates AP in muscle fibre to a
skeletal muscle contraction)
o Once Ach disassociates from the nAchRs, it can then be rapidly
hydrolysed by acetylcholinesterase
o End of tissue response
- Myasthenia Gravis
- acetylcholinesterase inhibitor
Document Summary
Steps in chemical transmission: different neurotransmitters, sites of drug action, different types of receptors. Sodium channel blockers can inhibit the conduction of action potential on the axon by blocking the voltage-gated sodium channels. Preferably inhibit neurons that are repetitively firing (firing excessively) L-dopa is a dopamine precursor and when given to patient he or she can get alleviation in symptoms associated with dopamine deficiency. Carbidopa is a dopa-decarboxylase inhibitor which prevents the synthesis of dopamine. Carbidopa does not go across the blood-brain barrier, so it"s restricted to peripheral neuron, so that less dopamine will be formed in peripheral system while more l-dopa can be converted where dopamine is needed: neurotransmitter storage. Displayed na leaks into junction and activates receptors to a series of responses in the tissue. Constriction of blood vessels: neurotransmitter release. Botulinum toxin a inhibits exocytotic release of ach from cholinergic neurons.
