Autonomic Nervous System Pharmacology
Short introduction Of Nervous System:
The nervous system is divided into two;
A) Central Nervous System
B) Peripheral Nervous System
Central Nervous system composed of brain and spinal cord.While The peripheral nervous system includes neurons located outside the brain and spinal cord.i.e any nerves that enter or leave the CNS.
The Peripheral nervous system is subdivided into Two;A)Efferent B)Afferent
A)Efferent:The Efferent neurons carry signals away from brain and spinal cord to the peripheral tissues.
B)Afferent:The afferent neurons bring information from periphery to the CNS.These neurons provide sensory input to modulate the function of the efferent division through the reflex arc or neural pathways that mediate reflex action.
The efferent division further divided into;
In this Chapter we will Discuss about Autonomic Nervous system in detail.
Autonomic Nervous System Pharmacology
ANS is further classified into three
●Sympathetic and parasympathetic NS are working against each other.
●Under stress sympathetic Nervous system activate while in Relax position your parasympathetic nervous system activates.e.g When You are lying on your bed.
I will take advantage of Dr.Najeeb Very Famous Example.
Scenario Example : A Person walking on the road suddenly a very big dog appears behind him in a very hostile Manner.The sympathetic nervous system Will Activate & his body will prepare for fight or flight.Here his body will prepare for flight because the dog is big and dangerous but if the dog is too small your body will prepare for fight and the dog sympathetic nervous system will activate and the dog will run away.
Taking the first example we will see the sympathetic N.S of The Person.
Question: How the sympathetic N.S Will be activated?
1)Sympathetic preganglionic fibers release acetylcholine as a neurotransmitter at neuro effector organs.Means All the neurons Coming out of CNS are cholinergic.
2)Sympathetic Postganglionic fiber release Norepinephrine as a neurotransmitter.
3)The acetylcholine release in the 2 example will act on adrenal medulla and adrenal medulla will then release Epinephrine.The epinephrine released by adrenal medulla to the general circulation will act on all the receptors in the body.
Q)How adrenergic Receptor Work?
This is very important because a lot of drugs act on this area
The main neurotransmitter here is Norepinephrine This N.E is synthesized in the nerve ending.Basically, Amino acids come from absorption of food from GIT into the General circulation.This amino acid converted into tyrosine in the blood and then taken up intracellularly into nerve ending where tyrosine converts into Dopa with the help of Tyrosine Hydroxylase enzyme.The Dopa then converted into Dopamine by an enzyme which is called Dopa decarboxylase enzyme.The Dopamine then Stored in the vesicles if not stored the dopamine is destroyed in the cytosol by MAO(Monoamine oxidase) enzyme so that’s why they are stored in the vesicles.In the vesicle, the dopamine converts into Norepinephrine if the neuron is adrenergic but if the neuron is dopaminergic the dopamine inside the vesicle will and store and will release as such.Here the neuron is adrenergic so the Norepinephrine will release in the nerve ending.
》Now the Ca+ Channels will open intracellular Calcium Level will increase.
There is a protein on the wall of vesicles which is called synaptobrevin
And the other protein on the membrane of the neuron i.e Syntaxin.
Whenever sympathetic nervous system release Norepinephrine some of the N.E work on presynaptic membrane (alpha 2 AR)and causes inhibition of the cyclic AMP and Increase outflux of potassium (k+) from the nerve ending which control the release of N.E
Q)What Happens to N.E after Using?
》There is a special reuptake mechanism and unlike cholinergic system in which the acetylcholine is destroyed by acetylcholinesterase enzyme.But in this case, the N.E is reuptake to the cell.After Reuptake there is a 50 % chance for N.E to take back by vesicle or destroyed by MAO Enzyme.
》Small Amount of N.E is methylated by an enzyme COMPT Which cause methylation some very small amount of NE comes into General circulation.
Q)How Drugs Act On This Whole System?/ Autonomic Nervous System Pharmacology
Following are some of the drugs which work on this system and show their effects.
Sympatholytic Drugs/adrenergic antagonist:
These drugs work on the above system and reduce the release of Norepinephrine.
The mechanism of action of methyl tyrosine is same like that of tyrosine.This drug enters into the system just like tyrosine and will work/bind on methyl hydroxylase enzyme.The enzyme will not work properly and eventually less dopamine will produce so fewer N.E will produce Less N.E means adrenergic activity decreases so this drug is sympatholytic, or adrenergic antagonist.
This Drug Work On dopamine transporter on the vesicle and Don’t let dopamine to enter into the vesicle and we know that dopamine outside the vesicle will be destroyed by MAO enzyme.There will no or less N.vesicle.So after action potential, the Nerve ending will not release N.E because of empty vesicle.This drug is called resperine.
3)Bretylium & Guanadrel:
These drugs Don’t allow the vesicle to fuse with the membrane of neuron and don’t let the vesicle to expel N.E.So Less N.E release from the neve terminal.
4)Alpha Methyl Dopa:
This drug is taken up by the transport mechanism i same like tyrosine.It is going to fool the dopa. Dopa work/bind on this Drug (Alpha methyldopa) instead of dopa decarboxylase enzyme.The drug continuously fooling this system up to the end and in the end no N.E release but instead the nerve terminal release alpha methyl N.E. so When action potential generated alpha methyl norepinephrine will release into the synaptic cleft.
Note: These drugs decrease the activity of norepinephrine but by binding direct into the normal Mechanism.These drugs don’t work on receptor.
Drugs That Block the receptor:
These drugs are also called adrenergic receptor blockers/antagonist:
These drugs also decrease the effect of N.E but by blocking the receptor on which N.E act.
Sources: Lippincott Illustrated Reviews Pharmacology
Doctor Najeeb Lectures.
We Will Discuss Sympathomimetic Drugs In The Upcoming Posts.Keep Sharing Our Contents.