Autonomic nervous system pharmacology Flashcards
Of what components does the central nervous system consist of?
brain and spinal cord
The peripheral nervous system can be subdivided between autonomic and somatic, describe the differences
sympathetic is arousing and parasympathetic is calming
What is the difference between the somatic and the autonomic nervous system?
The autonomic nervous system is repsonsible for actions inside of the body (what happens when you eat a sandwich), the somatic nervous system is active when you feel pain
The flight or fight reaction is dependent on adrenaline, true or not true
no not true, the initial reaction is not dependent on adrenaline
What happens when cortisol is released?
Breakdown of muscle proteins and increase in glucose levels. These muscle breakdowns are rectified by the parasympathetic nervous system
What does functional antagonism mean?
It is an interaction between the para and sympathetic nervous system on one organ. The different approaches to a neuron between the para and the sympathetic nervous system
Where does the pre and post ganglionic neuron come from in the sympathetic nervous system?
The preganglionic neuron comes from the cns in the lateral horn and the post lies in the pns
Where does the pre and post ganglionic neuron come from in the parasympathetic nervous system?
The pre ganglionic neuron comes from the higher part in the brainstem, medulla oblongata or the sacral spinal cord and the postganglionic neuron travel in the pns.
What is the difference in length of the neurons in the para and sympathetic nervous system?
In the para: the preganglionic neuron is very long and the post short
in the sympa: the pre is short and the post is long
The autonomic nervous system can be subdivided into
the para and sympathetic nervous system
Where are enzymes made?
These are made in the cell body and thus take a long time to replace
Acetylcholine has which receptor?
nicotinic receptor
Name what happens with the adrenal medulla
There is a preganglionic neuron, but no post. It goes directly from the cns to the adrenal medulla that will release epinephrine and norepinephrine into the bloodvessel
Describe the other exception of sweat glands
The preganglionic neuron goes to the acetylcholine receptor which is the same situation for the parasympathetic nervous system.
What does heterotropic interaction mean?
This means that the sympathetic nervous sytem tries to downtune the effect of the parasympathetic nervous system on the tissue and the other way around.
What does a homotropic interaction mean?
There is an inhibitory effect on the presynaptic terminal in the form of autoreceptors. These give the presynaptic terminal that it has to stop release neurotransmitters
What does co-transmission mean?
a single neuron releases multiple neurotransmitters to communicate with its target cells. This allows for a more nuanced and complex signaling system in the nervous system. The different neurotransmitters released may have distinct effects on the receiving cells, contributing to the diversity of neuronal communication.
How are neurotransmitters broken down? (3)
- reuptake by the presynaptic neuron
- an enzyme that breaks it down
- uptake by other cells
How is acetylcholine broken down as a neurotransmitter?
Acetylcholine is broken down by an enzyme called acetylcholineasterase
In which cells does reuptake by other cells take place when talking about the ending of neurotransmission?
astrocytes are involved by taking up the neurotransmitter
How is acetylcholine formed?
acetyl-coenzyme A and choline will form ACh and this is done by choline acetyltransferase
By which drug can the formation of vesicles of acetylcholine in the presynaptic neuron be blocked?
vesamicol
Name the pre and postsynaptic receptors of ACh
- muscarinic receptors
- nicotinic receptors (of the skeletal muscle)
How is ACh broken down?
This is done by acetylcholinesterase and this is broken down into choline and acetate.
Where is ACh produced and as a neurotransmitter used by?
-postganglionic parasympathetic neurons
-some postganglionic sympathetic neurons such as sweat glands and the adrenal medulla
- preganglionic (para)sympathetic neurons
- motor neurons innervating straited muscle tissue
-cholinergic neurons CNS
Name the 5 types of muscarinic receptor types and where you can find them
1,4,5: cns
2: heart
3: smooth muscle cells
Name the 2 types of the nicotinic receptor
- the skeletal muscle version: receptor m
- the cns: receptor n
Explain how nicotinic receptors work
When there is an activation of the receptor, the channel opens and there is an influx of sodium (Na). this is an ionotropic receptor.
Explain how muscarinic receptors work
Muscarinic receptors are G-protein coupled receptors and these are metabotropic. When you activate the receptor, a second messenger cascade will follow.
Which receptor is faster and why? nocotinic or muscarinic
Nicotinic receptors are faster as these are ionobotropic and not metabotropic and only need to open the gates
name the 4 classes of drugs that have a direct effect on ACh receptors (agonist or antagonist)
- parasympathicomimetics (agonist)
- parasympathicolytics (antagonist)
- Ganglion-blockers (antagonist)
- neuromuscular inhibitors (antagonist or agonist)
What does the parasympathicolytics do to ACh?
These are an antagonist and counteract/reduce the effects of activation of the parasympathetic nerves
What do ganglionic-blockers do?
They are antagonist and block all neurotransmission on the level of the ganglia
What do neuromuscular inhibitors do to ACh?
They bind the nicotinic receptor on skeletal muscle and thereby influencing control of these muscles.
What is the definition of parasymathicomimetics?
A group of drugs that selectively bind to ACh receptors as agonists and therefore elicit the same effects as activation of the parasympathetic system which means activation of the sweat glands (sympathetic nog steeds) and parasympathetic system
What is the difference between an agonist and an antagonist
An agonist activates or enhances a biological response, while an antagonist blocks or inhibits a biological response.
GIve examples of parasympathicomimetics (2 direct and 1 indirect)
direct:
1. carbachol
2. muscarine
indirect:
1. AChE inhibitors
What is the difference between the para and the sympathetic nervous system?
The parasympathetic nervous system promotes a “rest and digest” response, while the sympathetic nervous system triggers a “fight or flight” response
What are effects of parasympathicomimetics?
- lower heart rate and cardiac output
- contraction of smooth muscle cells (increased intestinal track movement, bladder contraction and bronchial contriction)
- increase lactation, saliva production and bronchial secretion (and sweat production)
- effect on the eye reduces ciliary tension (close range vision)
- increased excitation in the brain (m1 receptor): tremor, increased locomotor function and cognition
What happens to the bloodpressure when nicotine, ACh and muscarine
nicotine: sympathetic nervous system so increase in bloodpressure
ACh and muscarine: decrease in blood pressure, mimics the effect of the para
What causes the initial drop in bloodpressure when nicotine is inhected?
the vagal ganglia in the heart
What is the definition of parasympathicolytics?
Group of drugs that selectively and competittively antagonize the effects of ACh that are due to deactivatio of ACh receptors
Name examples of the parasympathicolytics (antagonist) anticholinergic drugs
atropine
scopolamine
methylatropine
butylscopolamine
What are the effects of parasympathicolytics (antagonists) anticholinergic drugs
- reduced saliva production
- relaxation of bronchial smooth muscle
- reduced intestinal motility
- pupil dilation and blurred vision
- cns: anxiety, agitation and disorientation
so imitate the sympathetic nervous system as it blocks ACh.
Ach is more associated with the para/ sympathetic nervous system
parasympathetic nervous system
Cholinergic neurotransmission is always EPSP, what does this mean?
Due to the fact that it reacts on the para and sympa nervous system, there is always excitation present
Name 3 examples of ganglionic blockers
- hexamethonium
- pentolinium
- trimetaphan
How are ganglionic blockers used in the clinic?
As an anti-hypertensive drug, but has numerous side effects.
What do reversible inhibitors do?
They are false substrates and compete with ACh
Name an example of an irreversible AChE inhibitor in real life
Sarin, enters the body trough breathing and skin contact, and will lead to an inhibition in neurotransmission in ACh.
insecticides
Name the symptoms of the use of Sarin
- runny nose
- watery eyes
- eye pain
- coughing
- lose consciousness
- death
What are the effects of AChE (breakdown of ACh) inhibitors:
- increase parasympathetic tonus
- paralyse skeletal muscle tissue
Name examples of clinical applications of reversible AChE blockers
-glaucoma
- myasthenia gravis
- antagonise non-depolarising neuromuscular blockers
What happens when there is a direct agonist on ACh on the muscles
There is no repolarisation, meaning there is a muscle block as the muscle cannot reset.
Name a drug in which a direct agonist works on neurotransmission
suxamethonium as a muscle relaxant in surgeries
AChE is ………
the stuff that breaks down acetylcholine
What are the effects of antagonists on neuromuscular transmission?
you get a non-depolarising neuromuscular inhibitor, so no neurotransmission
Name an example of an antagonist of neuromuscular transmission
toxic arrows made from lianas, alpha-tubocurarine
What would be an antidote for an antagonist of neuromuscular transmission
an AChE inhibitor, which results in an increase of ACh in the synaptic cleft
How is adrenaline made?
It starts with tyrosine,(tyrosine hydroxylase will make) DOPA, Dopamine, Noradrelanine, (PNMT) Adrenaline
Where is adrenaline found?
In the kidneys, in the adrenal medulla
Adrenaline is made from noradrenaline by
PNMT
noradrenaline and norepinephrine is the same
okay
by what enzymes is noradrenaline broken down?
- monoamine-oxidase (mao)
- catechol-o-methyltransferase (comt)
How is parkinsons disease treated
With inhibitors of mao and comt, so that there is no breakdown of noradrenaline. Parkinsons is a loss of dopamine which is a step before noradrenaline
What are adrenoreceptors?
They are G-protein- coupled receptors that respond to signals from adrenaline or noradrenaline.
What happens when adrenoreceptors are activated?
they mimic the activation of the sympathetic nervous system
What is an autoreceptor?
It is a receptor on the presynaptic cleft for the information for a feedback loop. alpha2 is an autoreceptor
What do direct acting sympathicomimetics do
activation of adrenoreceptors
What do direct acting sympathicolytics do?
Inhibition of adrenoreceptors
How does a false substrate for noradrenaline work?
alphamethyldopamine instead of dopamine so that alphamethyl noradrenaline is created and this has a lower efficacy
What does efficacy mean?
Efficacy refers to the ability of a drug or treatment to produce the desired therapeutic effect or response in a specific biological system.
What does reserpine do?
Reserpine prevents storage of noradrenaline in granules and lowers the release of na into the synaptic cleft. mao will metabolize na
What is an antagonist of reserpine
A mao inhibitor as it inhibits the conversion of noradrenaline in metabolites
Name inhibitors of the re-uptake of noradrenaline
cocaine, imipramine and amphetamines, so more in the synaptic cleft
Name an example of mao inhibitors
antidepressents
What is the cheese effect?
When there is a combination of mao inhibitors and food rich in amines, you can have severe sympathetic effects resulting in hypertensive crisis (sweating, tremors, dizziness)
amphetamine crosses the bbb and stimulates both na and da transmitter release
okay, it is an inhibitor in the reuptake of na
name an example of the a1, a2 adrenoreceptor antagonist and b1, b2 agonist adrenoreceptor
a1,2: vasodilation/ reduces blood pressure
b1: heart
b2: bronchia
Name examples of the beta blockers (beta adrenoreceptor antagonist)
propranol for cardiovascular diseases to decrease a higher heart rate
What is the difference between gaba a and gaba b receptors?
gaba a is ionotropic and gaba b is metabotropic
Name 3 excitatory neurotransmitters in the cns
- glutamate
- norepinephrine
- dopamine
Name 3 inhibitory neurotransmitters in the cns
- GABA
- serotonin
- dopamine
What does Gaba a do?
It surppresses CNS excitation:
- fear inhibition
- muscle relaxant
- induces sleep
What do bezo’s do?
They maken the GABA receptor more succesible
Dopamine is important for what disease
Parkinsons disease
activation of noradrenaline results in
results in restlessness, motor untrest and alertness
Serotonin is responsible for… (4)
sleep, sexual activity, pain transmission and night and day rhythm
Histamine receptors can be divided into H1, H2, H3, describe the differences
H1: smooth muscle contraction
h2: vasodilatation
H3: reduction of histamine release and secretion
What does vasopressin do? neuropeptide
memory and attention
What does oxytocin do? neuropeptides
social behavior, pleasure
What is the difference between neurotransmitters and neuropeptides?
neurotransmitters are produced locally in the pre synapse and neuropeptides are made in the cell body of the neuron (it will take a longer time to fill up)
