Lecture 30 - ANS Drugs Flashcards
- Describe the major physiological roles of the ANS. - Describe the major neurotransmitters and receptors involved in transmission within the ANS and somatic NS. - Describe the key sites at the synapse for possible drug modulation - Relate this specifically to the ANS and somatic NS. - Give examples of drugs at these sites and describe their pharmacological actions and any clinical uses they might have.
What are the two most import neurotransmitters in PNS?
Noradranaline/norepinephrine (NA) and Acetyl Choline (ACh)
Pre-ganglionic cells of the sympathetic devision of the PNS release what neurotransmitter?
ACh
Pre-ganglionic cells of the parasympathetic devision of the PNS release what neurotransmitter?
ACh
Post-ganglionic cells of the sympathetic devision of the PNS release what neurotransmitter on to? What are the exceptions?
NA to most organs except ACh at sweat and adrenal glands.
Post-ganglionic cells of the parasympathetic devision of the PNS release what neurotransmitter onto their target organ?
ACh
Somatic motor neurons release what neurotransmitter onto their target tissue?
ACh
What type of channel is the nicotinic acetyl choline receptor (nAChR)?
Ligand-gated ion channel, often Na+ channels.
What type of receptor is the muscarinic acetyl choline receptor (mAChR)?
G-protein coupled receptor (GPCR/7-TM receptor)
What type of receptor are adrenoceptors? What are the two broad subtypes?
G-protein coupled receptor (GPCR/7-TM receptor), alpha and beta
How were the two type of ACh receptors named? What were they named after?
The discovery of selective agonists led to the naming of these receptors. Named after nicotine from tobacco (Nicotiana tabacum) and muscarine (from Amanita muscaria) respectively.
Other than selective agonists, how else can receptors be named?
Naming based on selective antagonists that block the release of endogenous agonists.
Give an example of an antagonist of the nAChR and an antagonist of the mAChR.
Muscarinic antagonist - atropine from Atropa belladonna/the deadly nightshade. (Note: atropine is not the only toxin present in the deadly nightshade - Hyoscine is also present)
Nicotinic antagonist - d-tubocurarine (dTC) from the Curare plant
What effect is produced upon injection of a small dose only ACh into a cat? Why is this effect observed?
Small and medium doses of ACh produce a transient fall in blood pressure due to arteriolar vasodilatation and slowing of the heart
A cat is injected with atropine and then a large dose of ACh? What effects are observed? Explain.
A large dose of ACh given after atropine produces nicotinic effects: an initial rise in blood pressure due to a stimulation of sympathetic ganglia and consequent vasoconstriction (and increased force of heart contraction), and a secondary rise resulting from secretion of adrenaline. Muscarinic effects of ACh are abolished by atropine
What are the cardiovascular effects of introducing the following compounds into circulation? Which are synthetic? Which adrenoceptors do they interact with?
Adrenaline
Phenylephrine
Isoprenaline
Adrenaline – vasoconstriction and increased heart rate (alpha and beta receptors), not synthetic
Phenylephrine – vasoconstriction but not increased heart rate (alpha receptors), synthetic
Isoprenaline – produces opposite effects: reduced heart rate and lower blood pressure (beta receptors), synthetic
How has the human genome project affected pharmacology?
It has revealed the diversity in the population, specifically in the amount of polymorphisms in receptors of pharmacological agents - a field called pharmacogenetics.
Why is patient specific medicine often more effective for an individual? What tool can potentially be used to increase the specificity of a treatment?
Can tailor a treatment to the biochemical and physiological needs of the patient. Genetic analysis can greatly improve the specificity of a drug treatment.
How does knowledge about the sympathetic and parasympathetic divisions of the PNS increase specificity of a drug?
If we know how specific organs are innervated and what receptors they have on them then we can make a drug that targets a specific set of organs.
Describe the basic factors involved in normal release of neurotransmitter from a pre-synaptic neuron and synaptic transmission.
- Reception of a signal (action potential)
- Synthesis of neurotransmitter – there must be an efficient and fast way of synthesizing the NTs from commonly existing precursors.
- Neurotransmitters (NT) are stored in synaptic vesicles that control the quantile amount of NT released when a signal is received.
- Vesicles have to fuse with the presynaptic membrane
- To produce their effects, NTs must be acting on their receptors.
- Mechanisms in place to terminate the action of the NTs, eg enzymatic degradation in the synaptic cleft
Is the only way we can modulate the PNS via directly affect the PNS?
No - the PNS is and can be modulated by the CNS
What is the general physiological role of the PNS? What are its divisions?
Main role of the PNS is to connect the CNS to the periphery.
Sympathetic, parasympathetic, and enteric divisions
What are the general roles of the sympathetic nervous system?
Generally encompasses the flight/fight, ie quick, responses of organs. For example, increased heart rate, vasoconstriction, pupil dilation, brachiodilation, activation of sweat glands.
What are the general roles of the parasympathetic nervous system?
Generally encompasses slower physiological mechanisms compared to the sympathetic NS. SLUDD - salivation, lacrimation, urination, digestion, defecation.
What is the relationship between sympathetic and parasympathetic divisions of the PNS? Do organs always receive innervation from both?
They generally act in opposition to each other - not antagonistically but more complementarily. Eg, sympathetic dilates pupils and parasympathetic constricts pupils. Organs do NOT necessarily receive innervation from both, eg blood vessels are only innervated by the sympathetic NS.
