Pharmacology script #5

Autonomic Nervous System

Done by : Hashim Ghazo Mais Malol

The nervous system in our body is composed of two parts: 1 the central nervous system : the brain and the spinal cord . 2 the peripheral nervous system : it's the system that composed of : The autonomic nervous system : function involuntarily to regulate the everyday needs & requirements of the body without the conscious participation of the mind . it regulates the body function like : heart rate , breathing , urination , digestion . all of these are involuntary function . and it's two subtype : 1. sympathetic ( adrenergic system , because it release adrenalin or epinephrine ) SNS. 2. parasympathetic PSNS (cholinergic system , because it release acetylcholine ) . The somatic nervous system : its the system that innervate the skeletal muscle and it's responsible to induce muscle contraction { the neurotransmitter for it is acetylcholine and act on nicotinic receptor } . and these receptor can be stimulus by nicotine .

The SNS stimulates at the fear situation ( fight or flight ) The PSNS stimulates at rest situation like ( when we set in the middle hall ) The neuron is the functional unit of the nervous system , and inside it we have vesicles that contain a chemical substances called neurotransmitters . these neurotransmitters make connection between two neurons or between neuron and effected organ . When calcium secreted , it induce the vesicles to fuse with the pre-synaptic membrane , by this fusion a process called exocytoces this will release the neurotransmitters into the synapse . in which each transmitters will act on certain receptor , as u remember in the last lecture of doctor 5lel , the drug receptor interaction like key and the lock , there's a specific affinity , selectivity and specificity between the drug or the neurotranmitters and the receptor that will bind to it .

As u know the acetylcholine which is neurotransmitters in PSNS it act only on muscarinic receptor , it's not responsible to bind to adrenergic receptor . As u know the adrenergic receptor two types : Alpha and it has two subtype Beta and it has three subtype Again the PSNS acts on muscarinic receptor .

Now back to the ANS : We have two type of neurons : 1. pre-ganglionic : means before ganglia . 2. post-ganglionic : means after ganglia .

In PSNS :: pre-ganglionic release acetylcholine to ganglia that has connection of nerves cell bodies , so the acetylcholine will act on nicotinic receptor and by this stimulation , post-ganglionic neuron release acetylcholine again to act on muscarinic receptor .

In SNS : it's the same like PSNS in pre-ganglionic neuron by releasing acetylcholine and act on nicotinic receptor in ganglia , but in post-ganglionic will release norepinephrine and act on adrenergic receptors . **** so the difference between sympathetic and parasympathetic is the neurotransmitters that release in post-ganglionic neuron . The adrenal medulla is innervated by sympathetic system too , The adrenal gland contains two parts : 1. adrenal cortex , and it secrets : corticosteroids mineralosteroids androgen 2. adrenal medulla that secretes epinephrine ( adrenalin ) .

So : all pre-ganglionic neurons release acetylcholine and act on nicotinic receptors . In post-ganglionic : parasympathetic release acetylcholine which act on muscarinic Sympathetic release norepinephrine which act on adrenergic In medulla innervation release epinephrine act on adrenergic 90% of epinephrine releases from adrenal medulla .

Receptors type : Cholinergic Receptors : Two types, determined by: o Location o Action once stimulated The two types : 1. Nicotinic Receptors Located in the ganglia of both the PSNS and SNS and somatic nervous system . Affects the skeletal muscle Named nicotinic because can be stimulated by nicotine 2.Muscarinic Receptors Located mainly postsynaptically: Smooth muscle Cardiac muscle Glands of parasympathetic fibers Effector organs of cholinergic sympathetic fibers 1.

Q : Is the statement above right or wrong , cz we say sympathetic and cholinergic !!!! {{ Can SNS release acetylcholine !!! }} The answer : now most of our body is dual innervation , sympathetic and parasympathetic will act in opposed each other , for example : o Sympathetic responsible to increase heart rate , the parasympathetic responsible to decrease the heart rate . o Sympathetic responsible to dilute eye pupil , the parasympathetic responsible to contract the eye pupil . Named muscarinic because can be stimulated by the alkaloid muscarine We say that most of our body is dual innervated , but of course there's exception like : o Adrenal medulla just innervated by Sympathetic . o Thermo-regulatory sweat gland innervated by Sympathetic , but something strange that is sometimes releases acetylcholine and act on muscarinic receptor . ({ in sweat gland : Sympathetic innervation but cholinergic receptors }) . o The blood vessels innervated by Sympathetic . theres no parasympathetic nerves , but it has un-innervated cholinergic receptors , so if we give a patient acetylcholine or drug contain acetylcholine , this will induce vasodilation . So the action of cholinergic receptor will lead to release nitrite oxide { endothelial vasodilator } and cause dilation to blood vessels . 2. adrenergic receptor : it stimulated by catecholamine like norepinephrine , epinephrine and dopamine . * Adrenoceptors are classified as or receptors.

The differences between sympathetic & parasympathetic nervous system : Sympathetic Anatomy The preganglionic neurons come from thoracic & lumbar regions of spinal cord paraSympathetic The preganglionic neurons arises from cranial nerves (III. VII, IX, X)& sacral regions Oculomotor , facial , Glossopharyngeal and vagus Maintain essential body functions

Function

Adjusting response to stressful situations

Neurotransmitter receptors

Epinephrine (E) Norepinephrine (NE) Adrenergic receptors receptors

Acetylcholine (Ach) Muscarinic receptors (cholinergic)

Action on the effector organ

On the pic below .

Some notes : Heart : when increase heart rate we call it tachycardia . When decrease heart rate we call it bradycardia . Parasympathetic innervate SA node reduce heart rate and conduction of impulse between SA node and AV node .

Blood vessels : in skeletal muscle sympathetic effect is dilution . In skin and membranes sympathetic effect is constriction . Q : if u have a patient with bronchial asthma , and he has bronco constructive attack , shortness of breath . how can I treat him , wt drug type must give him ? The answer : sympathetic agonist or parasympathetic antagonist which lead to bronco dilation . Q : if I have patient with bradycardia less than 50 pulse / min , wt drug must be administrated to patient ? The answer : sympathetic agonist or parasympathetic antagonist . Rennin : enzyme secreted from glomerulus apparatus and responsible to convert angiotensinogen to angiotensin 1 . The urinary retention caused by SNS because sphincter keep close . Atonic bladder : loss of bladder effect , and can be treated by sympathetic agonist . And this the summary of ANS on effectors organs : Body Tissue/Organ Eye Lungs Heart Blood vessels GI Bladder Uterus Salivary gland Sympathetic Response Dilates pupils Dilates bronchioles Increases heart rate Parasympathetic Response Constricts pupils Constricts bronchioles and increase secretions Decreases heart rate

Constricts(skin) Dilates Dilates(skeletal muscles) Relaxes smooth muscles Increases peristalsis of GIT Relaxes bladder muscle Relaxes uterine muscles Decreases salivation Increases salivation Constricts bladder

Role of the Parasympathetic Division : Concerned with keeping body energy use low Involves the D activities digestion, defecation, and diuresis Its activity is illustrated in a person who relaxes after a meal Blood pressure, heart rate, and respiratory rates are low Gastrointestinal tract activity is high

 the pupils is constricted Role of the Sympathetic Division : The sympathetic division is the fight-or-flight system Involves E activities exercise, excitement, emergency, and embarrassment Promotes adjustments during exercise blood flow to organs is reduced, flow to muscles is increased Its activity is illustrated by a person who is threatened Heart rate increases, and breathing is rapid and deep the pupils dilate How do drugs influence the ANS? Mimic {{ means the same effect }} or block the effects of the two primary neurotransmitters, Acetylcholine and Norepinephrine/Epinephrine Drugs that mimic neurotransmitters are referred to as receptor agonists These drugs activate receptors

Drugs that block neurotransmitters are referred to as receptor antagonists These drugs block the endogenous neurotransmitters from activating receptors Classification of drugs affecting the ANS Parasympathetic nervous system

Mimic acetylcholine = cholinergic = muscarinic agonists = parasympathomimetic Block acetylcholine = anticholinergic = muscarinic antagonist = parasympatholytic Sympathetic nervous system

Mimic norepinephrine = adrenergic = adrenergic agonist = sympathomimetic Block norepinephrine = antiadrenergic = adrenergic antagonist = sympatholytic Note : The names of the drugs are written in the official name ( generic name ) Parasympathetic system : Acetyl choline synthesis :

Choline + acetyl CO-A by the action of choline acetyl transfers will give Ach

Ach is not used therapeutically because of :

1Rapid degradation of Ach : Ach has a brief duration of action t1/2 is very short because it is rapidly distort by an enzyme called cholinesterase that will convert Ach to the reactive metabolites choline and acetate 2Multiple effect of action : In all your muscarinic and Nicotonic receptors in your body , except quaternary amine which has a positive charge that doesn't penetrate the lipid membrane and at the same time it has a very short duration of time . So we can use other drugs that mimic Ach which is mainly equipped by 2 main process : 1Direct drugs that mimic the effect of Ach ( produce the same action as Ach )( stimulation of the receptors ) 2Indirect drugs by inhibiting the enzyme Acetylcholinesterase By inhibiting this enzyme we can elevate the concentration of Ach , Ach half life and Ach duration sooo Ach can stimulate cholenergic receptors. For example war gases or incase of agricultures and using of insictiside ( chemicals that kills insicts ) they are indirect acting cholenirgic agonist acting in this mechanisim .

The major groups of cholinoceptor-activating drugs

Both Direct and Indirect acting drugs are Agonist

o Direct acting cholinergic agonists: That directly stimulate the receptors 1. Bethanechol is a drug that can directly bind to muscarinic receptors in which by it's binding : Increase intestinal motility On the eye ( meiosis ) construction of the pupil On the bladder stimulates urination by the contraction of the muscle and relaxation of the sphinctor Direct agonist produce an action similar to that of parasympathatic nervous system . - Uses ( indication ): Stimulates atonic bladder, particularly in non obstructive urinary retention ( post operative urinary retention ) which is treated by inhancing yrination ( contraction of muscle and relaxation of the sphinctor ) . Indications Contra indication

Some adverse effects observed with cholinergic agonists

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Diarrhea assotiated with clumbes Nausea Diaphoresis (swetting) Miosis Urinary Urgency

2. Pilocarpine : adrug that is mainly applied topically to the eye . it's anatural Alkaloids induction miosis that inhance the drainage . We have an eye disease called Glaucoma Commone seen in elderly people espicially diabetic where there is an elevation of intraoccular prussure of the eye . but if the elevation of intraoccular pressure is not corrected it may lead to blindness . In the eye we have what is called aqueous humor that is responsible to control the intraoccular prussure . Controling the intraoccular prussure is done by either: 1-drugs inhibit the secretion of aqueous humor 2-drugs which inhance drainage ( muscarinic agonist) direct or indirect by induction of miosis and inhance the opening of what is called trabeculae meshwake (at the angles of the eye )

Indirect-acting agonists:
The Anticholinesterases is presented at the sites where Ach is released : 1Gangilia of Autonomic N.S 2The ends of Parasympathatic nerve fibers 3At the level of necotinic receptors in somatic N.S ( at the Neuromascular Junction ) Parasympathatic drugs

Reversible ( action may last For hours 2-8 )

Irreversible ( action last for days or weeks )

- For drug memorization the drugs in the same class have the same suffix for example Neostigmine, Physotigmine and Rivastigmi * Reversible Anticholinesterases

Examples: 1. Neostigmine Is adrug which affect Ach degradation at NMJ more than at the level of parasympathatic nerve endings Uses: Treatment of disorders in NMJ of voluntary muscles

(myasthenia gravis)

is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability. It is an autoimmune disorder, in which weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors throughout neuromuscular junctions. Myasthenia is treated medically with acetylcholinesterase inhibitors or immunosuppressants. In females more than males .

Paralytic ileus ( less intistinal motility ) Bladder atony

Q : How to increase Ach level at NMJ ? A: By using indirect acting cholenergic agonist 2. Physotigmine It is like neostigmine but most affect CNS ( nothing requried in this drug ) 3.Rivastigmine It is indirect acting reversible agonist Used in patients with Alzheimer's disease for the loss of cognitive function due to loss of cholinergic neuorons in CNS ( Neuoro degenerative diorder ).

Alzheimer's disease is the most common form of dementia a serious loss of

global cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging.