ANS Pharmacology

ANS:
 The nervous system is made up of CNS (Central Nervous System) & PNS
(Peripheral nervous System). The CNS is made up of brain and spinal cord.
And the PNS is made up of SNS & ANS.

 Autonomic nervous system (ANS) is mostly innervates visceral organs of the

body.
 Two neurons are present in the ANS pathway. One is called as preganglionic
neuron and other is called as post ganglionic neuron. The junction beween
two neurons is called as ganglion or synapse.
o Preganglionic neurons: Its cell body is present in the brain or spinal
cord and its axon is elongated from inside to outside of CNS. The axon
is myelinated. Actually, the cell body is present in the lateral horn of
gray matter in thoracolumbar division (sympathetic). And cell body of
cranio-sacral division is presence in the cranial nerves.
o Postganglionic neurons: It is the second neuron present after the
ganglia. Its cell body and dendrites are located in the autonomic
ganglion. It is unmyelinated.

 Autonomic nervous system (ANS) is mostly innervates visceral organs of the

body.
 Two neurons are present in the ANS pathway. One is called as preganglionic
neuron and other is called as post ganglionic neuron. The junction beween
two neurons is called as ganglion or synapse.
o Preganglionic neurons: Its cell body is present in the brain or spinal
cord and its axon is elongated from inside to outside of CNS. The axon
is myelinated. Actually, the cell body is present in the lateral horn of
gray matter in thoracolumbar division (sympathetic). And cell body of
cranio-sacral division is presence in the cranial nerves.
o Postganglionic neurons: It is the second neuron present after the
ganglia. Its cell body and dendrites are located in the autonomic
ganglion. It is unmyelinated.
o Ganglia: it is the junction between the preganglionic neuron and
postganglionic neuron. By positioning of ganglia in to the body, they
are sympathetic trunk, prevertebral and terminal ganglia.

SYMPATHETIC TRUNK GANGLIA: It is also known as

paravertebral ganglia because located parallel on the either
side of spinal cord. Mostly, the postganglionic neurons from
sympathetic trunk innervate the organs above the diaphragm
like heart, lungs, salivary glands, special senses etc.

PREVERTEBRAL GANGLIA: They are collateral ganglia located

outside the line of paravertebral ganglia. The postganglionic
neurons from vertebral ganglia innervate the organ below the
 diaphragm like stomach, intestine, pancreas, kidney,
reproductive organs etc. It is also sympathetic type of ganglia.

TERMINAL GANGLIA: The axons and cell bodies synapse in to

terminal ganglia are from the parasympathetic division. It is
also called as intramural ganglia. It is presence near the
walls of visceral organs. It innervates most of the visceral.

Adrenergic and Cholinergic Receptors

ANS receptors:
Adrenergic receptors:

In the ANS, adrenergic neurons release NA which binds with

adrenergic receptors and propogate the nerve impulses.
The two main types of adrenergic receptors are α-receptors & β-
receptors. These receptors further subclassified as α- α1, α2 and β- β1,
β2, β3.
α1 & β1 mostly produces excitation & α2 & β2 mostly produces inhibition.

Location:

α1: It is presence at the post junctional on effector organs like radial and sphincter
muscles of iris (eye), heart, some BV (blood vessels), bronchial glands (lungs), liver, gut,
skin, sex organs etc.

α2: It is presence on the prejunctional at the nerve ending. On the brain, pancreatic β
cells, fat cells, gut muscles, veins etc.

β1: They are located at heart, salivary glands, juxtaglomerular apparatus of kidney,
posterior pituitary.

β2: Lungs, BV, uterus, liver, eye, gut, urinary bladder, spleen, skeletal muscle, certain
veins etc.

β3: Brown adipose tissue, where there function is to generate the heat by thermogenesis.
Mostly presence in to the children.
Cholinergic receptors:

In ANS, cholinergic neurons release Ach a neurotransmitter. All

sympathetic and parasympathetic neurons are cholinergic and also all
parasympathetic postganglionic neurons are cholinergic.
Nicotinic receptors are presence on the dendrites or the cell bodies of
postganglionic neurons of both sympathetic & parasympathetic
neurons.
Muscarinic receptors are present on the all visceral organs. The
muscarine, obtain from mushroom, mimics the action of Ach on these
receptors.

There are two types of cholinergic receptors: muscarinic and nicotinic.

• Nicotinic receptors

o The nicotine is never observed in to normal (nonsmoker)

person still the receptors known as nicotinic, this is because this type
of receptors are known as nicotinic, because these types of receptors
stimulated by nicotine which mimics the action of Ach but having more
affinity than Ach.
o They are ligand gated ion channel having pentameric
structure. Activation of this causes opening of ion channel which
causes influx of cation & leads to depolarization and generate action
potential (AP).
o Depending on the location they are classified as NM & NN.
+ NM: They are presence on the neuromuscular junction
mainly on the skeletal muscles. They cause depolarization at the
muscle end plate which leads to contraction of muscle. They are
pentameric having 2α, β, δ and γ or ε subunits and agonist by nicotine
and PTMA and antagonist by tubocurarine.
+ NN: These are present on autonomic ganglia, adrenal
mdulla and CNS. At autonomic ganglia it causes depolarization of
postsynaptic neurons and propogate impulses through it. In the
adrenal medulla releases adr & NA by same mechanism. And at the
CNS causes excitation & inhibition depending up on the neuronal
chemical. Nicotine and di methyl phenyl piprizinium are agonist and
hexamethonium is antagonist to them.

• Muscarinic receotors

o The substance known as muscarine from mushroom (amatina

muscaria) is activating these type of receptors, so named as
muscarinic receptors. They are G-protein coupled receptors (GPCRs).
When Ach binds with them, they activated by Gi , containing 7-helical
segments of amino acids where the amino end of chain is extracellular
and carboxyl end of chain is intracellular & inhibit action of AC.
o By molecular cloning they are subdivided in to M1, M2, M3,
M4, and M5.
- M1 : It is presence on the autonomic ganglia, on the
gastric gland and at the certain part of the brain like hippocampus
from limbic system and at the corpous straitum. It has role in gastric
secretion. And histamine release. It acts through Gq protein and
activates phospholipase C (PLc) which generate DAG & IP3 as 2
messenger. Some time they also activate PL-A2.
- M2: they are act through Gi protein hich inhibits all the
functional activities. Located on the heart (SA node, AV node, atria,
ventricle), on the cholinergic nerve ending and visceral smooth
muscle. They inhibit AC resulting in hyperpolarisation of the neurons
and decrease activity of SA node & conduction through AV node leads
to bradycardia.
- M3: it is located on the visceral smooth muscle, iris,
ciliary muscle and exocrine glands. They are also GPCRs acts by Gq
protein. Their activity is dominated in smooth muscle the\an M2.
- M4: not abundant in body. They transmit
neurotransmitter in certain areas of brain and acts through Gi protein.
- M5: it acts by Gq protein. Derifinacin is selective
antagonist & related to dopamine release.

Cholinergic drugs
Ach is a neurotransmitter presence in CNS, ANS & SNS.
• Synthesis of Ach begins from the pyruvate which is obtained
from the mitochondria. Pyruvate is converted in to acetyl CoA,
which is further reacted with the choline which is, enters in to
the cytoplasm of axon with active transport along with the
sodium ion.
• This acetyl CoA & choline reacted to form Ach in the presence of
the enzyme, choline-acetyl transferase. Ach is chemically
trimethylamine-ethylacetate. It stored in to the synaptic
vesicles and in the presence of Ca+2 the merge of the vesicle
with the axoplasmic membrane occur which causes release of
Ach by exocytosis.
 • After release of Ach from the end bulb it acts up on the target
receptors like nicotinic & muscarinic. Ach is metabolized by AchE
enzyme presence near by the synapse.
•

ACTION OF Ach ON THE BODY:-

CVS:
The heart containing M2 type of receptors which decrease the rate of conduction in the
specialized tissue of SA node, AV node and decrease force of contraction .

Many ant arrhythmic are act through the cholinergic vagul stimulation
still the Ach is not given systematically (The drug given by I.V. in small
doses causes decrease in BP due to vasodilatation and large doses are
required to elicit bradycardia.) But large doses of Ach after
administration of atropine block the receptor of the Ach and free Ach
direct stimulates release of catecholamine .
Ach hyperpolarizes SA node and decreases the depolarization of nodal
cells. So, rate of impulse generation is decreases and lead to
bradycardia.

Ach decreases conduction velocity of impulse transfer at AV node and

increase RP force of contraction of atria and ventricle decreases.
The BV like salivary gland, some part of skin contain cholinergic nerve
ending still the most of the BV of the body are dilated, this is because
Ach inhibit the effect of the catecholamine release and also due to
release of endothelium derived relaxing factor (EDRF) NO. NO is
responsible for BV dilation.

SMOOTH MUSCLE:
It contracts the smooth muscle through the action of M3 receptor.
It increases the peristaltic movement in gut and urethra and relaxes
the sphincter of the gut and evacuation of bowel is carried out through
it.
In the asthmatic patient, it causes more lethal condition by constrict
the bronchioles smooth muscle.
Contraction of circular muscle of iris and ciliary muscle ANS decrease
intra-ocular pressure.
SKELETAL MUSCLE:
It effect on the skeletal muscle is depends on the rout of
administration.
The intravenous injection of the Ach have no effect in the body, this is
due to presence of Ach E in to the plasma which null the presence of
Ach in the body and also by hydrolysis. But in high dose can cause
twitching and fasciculation.
The effect on skeletal muscle is due to Nm type of receptor.
CNS:
Ach can not penetrate BBB itself and exert the effect on the brain and
s.cord. They stimulate the brain and followed by depresses it, if there
is any damage to BBB. Some cholinergic drug can penetrate the BBB
like arecoline.
It stimulate the autonomic neurons in both sympathetic and
parasympathetic nervous system.

Some cholinergic drugs like,

Methacholine, carbachol, bethanechol, arecoline, pilocarpine etc. are used.

Methacholine, carbachol, bethanechol are synthetic cholinomimetics where as arecoline, pilocarpine,

muscarine are obtained from the natural sources; alkaloids.

Methacholine :

(CH3)3-N+-CH2-CH(CH3)-O-CO-CH3

Many cholinomimetics were discovered out of which few have pharmacological action.

In Ach, one -CH3 group is added, which resist hydrolysis of methacholine by chE. Thus, its action is
prolonged than Ach. It has the effect on the muscarinic receptor. By intra-venous infusion of it produce
hypotension & bradycardia.

Carbachol & Bethachol:

(CH3)3N+-CH2-CH2-O-CO-NH2 -carbachol

They are carbomyl esters which are completely resistant to hydrolysis. Carbachol have effect on nicotinic
receptors and bethachol have action through muscarinic receptors.

(CH3)3N+-CH2-CH(CH3)-CO-NH2 -bethachol

They are only responsible for decrease in BP at low dose which affect GIT and urinary tract.

Pilocarpine:
It is obtained from the plants of pilocarpus genus. It is diaphoretic drug and also produces salivation. It also
has effect on the pupil. So it is used in the open angle glaucoma. It is used to decrease intraocular pressure.
It is also used in xerostomia.

Arecoline:

It is obtained from the seeds of betel nut. It acts at nicotinic receptors and it is euphoretic drug.

Differences between effect of Acetyl

choline, adrenaline, Atropine
 Adrenaline Acetyl choline Atropine
Heart: Heart: Heart:

β1 receptors M2 receptors M2- blockade—block in vagal

effect.
↑ HR, ↑ force of ↓ Force of contraction.
contraction, ↑ CO (SA Tachycardia.
node) SA node- hyperpolarization
(bradycardia) I.m/s.c- initial bradycardia—
↑ BP-followed by ↓ due to M1-R-autoreceptor.
feed back regulation. Av node- ↑ RP, ↑ PR interval
Av node- ↓ RP, ↓ PR interval
Av node-↑ conduction Delayed conduction.
velocity. ↑ Conduction velocity.

Reflex bradycardia-
carotid sinus compression.
Blood vessels: Blood vessels: Blood vessels:

α- more affinity-short Very less BV innervated with Tachycardia and VMC- ↑ BP.
time-vasoconstirction-↑ cholinergic transmission
BP (salivary gland, some part of Due to feed back regulation- ↓
skin) BP.
β- less affinity-prolong
time-vasodilation- ↓ BP EDRF- NO- vasodilation- ↓
BP.
Bipolar response

Reversal of it: Dale’s

vasomotor reversal.
CNS: CNS: CNS:

α2 – autoreceptors Fewer drugs penetrate- BBB. High dose- medulla

(stimulation)-vagal, vasomotor,
Not cross- BBB. If directly given-stimulation- VMC.
followed by- depression.
Not powerful CNS Depression- vestibular
stimulant excitation-antimotion sickness.

Restlessness, As a anti-parkinsonian drug

apprehension, headache
and tremor. Effect- irritation,restlessness,
hallucination, delirium,
amnesia.

-respiration dep-coma.
Glands: Glands: Glands:

Insulin secretion ↓ - β ↑ secretion of sweat & saliva - ↓ secretion by blocade of Ach

cells- α2 receptors ↑ Ca+2 receptors

Glucagons secretion ↑- α Dryness mouth-↓ secretion.

cells- β receptors.
↓ gastric secretion (Anti-ulcer)
Saliva- scanty mucus
secretion ↑ Temp- ↓ sweat

Sweat-↓

Lacrimal secretion-↓
Smooth muscles: Smooth muscles: Smooth muscles:

Bronchial mus- Bronchoconstriction- lethal in Relaxes-bronchodilation-

bronchodilation by- β2 - asthma. histamine, eicosanoids…
iinhibition of mast cell
secretion & α- effect on
mucosa.
Gut- ↑ peristalsis- relaxes Gut- ↓ motility.
Gut-relaxes-↓ motility- sphincter in gut.
sphincter contracts.
contraction
Urinary bladder- detrusor Relaxation of ureter and
muscle-relax ( β) & bladder.
trigone- contract ( α)-
hesitation in urination.
Eye: Eye: Eye:

Mydriasis (not given from Contraction-circular muscle Mydriasis-relaxation of iris

conjuctiva)
Contraction-ciliary muscle- ↓ And cyclopegia- relaxation or
↓ intra-ocular pressure i.o.p paralysis of ciliary muscle-
paralysis accommodation of
lens- ↑ FL
Anti-cholinergic drugs:

Muscarinic receptor antagonists (MRAs)

• The drug or substances bind to muscarinic receptors and

produce no intrinsic activity or inhibit binding of agonist called as
muscarinic receptor antagonists.For example: atropine,
scopolamine, tropicamide etc.
• They produce similar activity but some have specificity of action
on the selective tissue or organ like pirenzepine inhibits gastric
acid secretion due to its selectivity towards M1 receptors.
• They are broadly classified in to: Naturally occurring alkaloids,
Semi-synthetics and Synthetics

? Naturally occurring alkaloids: these types of alkaloids are

obtained from the plants and they are naturally occurring.
Atropine is obtained from Atropa Belladona (solanaceae) and
hyosciene is principally obtained from hyoscyamus niger
(solanaceae).

? Semi-synthetics have small changes in their chemical

structure than parent compounds. Ex- atropine mononitrite.
Homatropine produced by reaction between tropin & mandelic
acid.

? Synthetics: by lot of researches and development, these

types of drugs are discovered. They have similar action like
atropine but more selective to receptors. Ex- ipratropium,
tiotropium, tropicamide etc. most of the synthetic derivatives
like ipratropium(quaternary compounds) cannot cross BBB.

Effect of Adrenaline

Heart:
It is act on β1 receptors of heart. It increases slope of slow diastolic depolarization of SA
node. It activates SA node & latent pacemakers in AV node and purkinje fibre.

It causes arrhythmias at high dose that raise BP markedly. Raised BP reflex depresses SA
node. Anaesthetics sensitize the heart to arrhythmic action of adrenaline.

Due to Adr force of contraction increases leads to development of tension. So relaxation

period is also increases which shorten systole than diastole. So oxygen consumption
capacity and cardiac output is also increases.

Conduction velocity is also increases so partial AV-block overcomes. Refractory period

of all cells decreases.

Raised BP reflexes bradycardia due to stimulation of vagus by carotid sinus compression.

Blood Vessels:

Main effects of adrenaline exerted on smaller arterioles and precapillary sphincters

although veins and large arteries also respond to the drug. It constricts vessels of skin &
mucus (mucous) membrane.

It dilates BV of skeletal muscles. Thus net results of this is, decrease in the peripheral
resistance.

Adr can’t give in the hypotensive state. As it is raise systolic BP by its cardiac action but
it decreases diastolic action by its peripheral action.

BV contain both α1 & β2 receptors. Adr have more affinity to α1 for short period of time
which causes vasoconstriction and increase in BP. After action on α1, it acts on β2
receptors for long period of time causing vasodilation and decrease in BP. This type of
response is called as biphasic response.

If a α-blocker (ergotoxin) is given, it leads to decrease in BP. Called as DALE’S

vasomotor reversal.

In cerebral arteries doesn’t have marked effect due to autoregulatory mechanism which
limit the increase in cerebral blood flow.

High concentration of Adr leads to pulmonary edema. This is because of elevated

pulmonary capillary filtration pressure.

Blood Pressure:

It depends upon dose, route of administration & on the amine. NA increase systolic,
diastolic and mean BP. It doesn’t have β2 action so no vasodilation and peripheral
resistance increase consistently due to α action.
Isoprenaline increases in systolic but decreases in diastolic BP. The mean BP generally
falls.

Mean BP = diastolic BP + 1/3 (systolic – diastolic BP)

In normal individual BP is 120/80 mmHg, mean BP: 93.33

CO = HR . SV

CO = mean BP/ R => Mean BP = CO . R

If Adr is given rapidly by i.v route, it increases BP proportional to dose. It causes

increase in systolic pressure is greater than diastolic pressure, so pulse pressure
(difference between systolic & diastolic pressure) is also increases. This occurs due to α
receptor response predominant and vasoconstriction occurs also at skeletal muscle.
(Increase in BP by 3 mechanism: myocardial stimulation, increase HR and
vasoconstriction in most of the body.)

When Adr is given by slow i.v infusion or s.c route, it causes increase in systolic pressure
due to cardiac contractile force and increase in CO but decrease in diastolic pressure due
to β2 receptors of skeletal muscle causing vasodilation. So Mean BP is decreased.

Respiration:

Adr and isoprenaline are powerful bronchodilator not NA.

This effect is more marked in asthma (bronchoconstriction). Adr given by aerosol

additionally decongests bronchial mucosa by α action and inhibition of mast cell
secretion by β2 action. The mast cell secretion, autocoids causes bronchoconstriction and
Adr antagonized to this substances. (Bronchial asthma produced due to vagal stimulation,
choline-esters, histamine or Ag-Ab interaction, bradykinin, leucotrienes or prostaglandin
F2α which are antagonized by Adr)

Rapid i.v infusion of Adr causes transient inhibition of respiratory center causes apnoea
for some time. More dose causes pulmonary edema.

GIT:

Adr relaxes smooth muscles of the gut and reduces its motility (Due to α and β receptors).

Stomach relaxed and contraction of pyloric and ileocecal sphincter but it depends upon
pre-existing tone of muscle. (If tone is high, it causes relaxation and if tone is low, it
causes contraction.)

Uterus:
It can contract and relax depends upon phase of sexual cycle, state of gestation and dose.

Nonpregnant: Human-contraction Rat- relaxation

Pregnant : Human- relaxation Rat- relaxation

Bladder:

Adr relaxes detrusor muscle (β receptors) and contracts trigone and sphincter (α-agonist
activity). This cause hesitation in urination and may contribute to retention of urine in
bladder.

Eye:

Mydriasis is readily seen during sympathetic stimulation but not when epinephrine is
instilled in to conjuctival sac of normal eyes, (poorly cross the cornea.)

It decreases intra-ocular pressure, the mechanism of this is not known but due to decrease
production of aqueous humor due to vasoconstriction.

Other smooth muscle:

Pilomotar muscles of hair contracts by adrenaline leads to erection of hair.

Contraction of splenic capsule causes release of erythrocytes in to the peripheral

circulation.

Metabolic effect:

It causes hyperglycemia, hyperlactacidemia and lipolysis.

In liver & muscle, glycogen phosphorylase is activated which causing glycogenolysis

while glycogen synthetase is inhibited. Both lead to hyperglycemia and
hyperlactacidemia. Also gluconeogenesis is increased.

K+ is first released from liver which leads to hyperkalaemia followed by prolonged

hypokalaemia due to K+ uptake in muscle and liver itself.

In adipose tissue triglyceride lipase increases plasma free fatty acids. So, it causes
increase oxygen consumption and heat production (thermogenesis), mainly by brown
adipose tissue tissues by β3 receptors.

In pancreatic islet,

β2 receptors on α cell=> increase glucagons secretion.

α2 receptors decrease cAMP=> decrease insulin release; which also leads to
hyperglycemia.

CNS:

Adraniline can not enter in CNS due to poor permeability through BBB.

I.V or S.C route leads to excitant, vomiting, headache, apprehension, restlessness.

Anti-Adrenergic Drugs

Anti-adrenergic agents are those which act on adrenergic receptors

and block their activity. It reduces sympathetic out flow and
antagonised them.

α blockers:

These are agents which antagonised α receptors and decreases

sympathetic activity.
Non equilibrium type, Phenoxybenzamine.

Equilibrium type,

Non selective: ergotamine, ergotoxine, tolazoline, chlorpromazine.

Selective:

α1 selective: prazosin, doxazocin.

α2 selective: yohimbine.

β Blockers:

These are the agents which block the β-receptors present in the body.

β-receptor antagonists are classified as, Nonselective and Selective.

Non selective (β1 & β2):

Membrane stabilizing activity without intrinsic sympathomimetic activity: Propranolol,
Timolol, Sotalol.

Membrane stabilizing activity with intrinsic sympathomimetic activity: Pindolol.

With additional α blocking activity: Labetalol, Carvedilol.

Selective:

β1 selective: Atenolol, Metoprolol, Acebutolol, Esmolol.

β2 selective: Butoxamine.

β blockers

Propranolol (prototype):

Pharmacological Action:

Heart:

It has blocking effect on β-receptors which cause decrease in the activities of

catecholamines which have +ve inotopic and +ve chronotropic effects, β blockers
decrease heart rate and decrease force of contractility.

In normal functioning heart, it is not so effective but when sympathetic system is

activated, during emotions or exercise, β receptor antagonists turn off the sympathetic out
flow by blocking effect.

Heart contains β1 receptors chiefly but some of β3 receptors have been found in normal
myocardial tissues in human and other species. They are Gi protein coupled receptors.

It reduces RP of myocardial fibers and decreases automaticity.

Propranolol decreases diastolic depolarization and delayed Av conduction. Thus, it

reduces heart rate, decreases myocardial contractility and decrease AV conduction and
also decreases cardiac output.
During exercise, there is increase in heart rate, myocardial contractility and hence
increase in cardiac output. In presence of β blockade, there is decrease in HR and
contractility but CO is less affected. As there is increase in stroke volume during exercise
due to demand of tissues which cannot be altered. In elders, there is noted that decrease in
sympathetic activity and they are unaffected during exercise by β blockade markedly.
Cardiac work and oxygen consumption are reduced as the product of HR and aortic
pressure reduces. But in angina patients, it has no effect as the activity of β blocker is
restricted to subendocardial region. So over all there is improve of oxygen
supply/demand and exercise tolerance is increased.

Also in case of CHF patients dilation of ventricles occurs & CHF may be precipitated.

Blood Vessels:

Propranolol blocks β receptors and gradually cause rise in BP by rereversal of Dale’s

vasomotor reversal.

It causes vasoconstriction and increase TPR (total peripheral resistant), initially. But due
to fall in CO (initiated by sympathetic activity block) and increase TPR, the tissues are
not getting the sufficient blood supply and keep more blood with it, it cause adaption by
vasodilation and periodically fall in BP, both systolic and diastolic BP fall.

There are some evidence that it also reduce secretion of renin from juxtaglomerulas
apparatus by β1 blockade. But it is not directly affecting the rennin secretion but if the
concentration of renin is more in plasma, it reduces its level by β blockade. Pindolol have
no effect on plasma renin level.

β blockers also produces peripheral vasodilation by increasing production of nitric oxide,

blockade of Ca+2 entry, increase influx of K+ and anti-oxidant activity.

Respiration:

Bronchial smooth muscles contain β2 receptors which are blocked by propranolol and
other β2 blockers and leads to contraction of bronchial smooth muscle and constriction of
bronchioles.

It is contra-indicative in asthmatic patient because it causes airway resistance.

CNS:

It has very less effect on CNS like behavioral changes, forgetfulness, increase dreaming
and nightmares with high doses. It decreases anxiety which occurs due to stressful
stimulation.

Metabolism:

It decrease lipolysis and reduces free fatty acid level in plasma. Thus, it increases
HDL/LDL ratio. It also inhibits glycogenolysis in heart, skeletal muscle, etc. In patients
with hyperglycemia when propranolol treated with insulin, coma or death occurs. This is
because, insulin induces hypoglycemia and propranolol reduces glycogenolysis. So, free
glucose is not available for basic metabolism.
Propranolol therapy may reduce carbohydrate tolerance by deceasing insulin release.

Eye:

It blocks adrenaline effect on ciliary muscles and causes contraction of ciliary muscles
and decreases secretion of aqueous humor by constricting capillaries of ciliary muscles.
Ultimately it decreases intra-ocular pressure and is useful in glaucoma.

Skeletal Muscle:

It reduces tremor which are provoked by adrenaline.

Uterus:

It causes relaxation of uterus.