ANS Pharma.

Physiology and pharmacology
of
Autonomic Nervous System
Prepared by Mesay. M 05/11/2022 1

Objectives
 At the end of this session students will able
to:-
 Explain physiology of ANS
 Explain pharmacokinetics and
pharmacodynamics of drugs that act on ANS

 Describe indication, contraindication, dosage
and clinical effects of each drugs

Terms
 Synapse – junction between 2 neurons that
communicates the message from the presynaptic
neuron to the postsynaptic neuron
 Ganglion (pl. ganglia) – a cluster of neuronal cell
bodies in the PNS

 Preganglionic neuron – cell body lies within the
CNS
- its axon, the preganglionic fiber synapses with the 2nd
motor neuron, the ganglionic neuron, in a peripheral
autonomic ganglion
 Postganglionic fiber (axon) of the ganglionic
neuron extends to the visceral organs
Cont…
 Agonist- is a substance that interacts with
the receptor to evoke a biologic response.
 Antagonist- is a substance that interacts with
the evocation of a response at a receptor site

by an agonist.
 Receptors-are therefore target sites that lead
to a response by the the effector cell when

activated by an agonist. And protein
macromolecules and are located in the
plasma membrane.

Introduction
 The word AUTONOMIC drived From two Greek
words:
Autos means self
Nomos means law = Self governing
 Therefore, Autonomic nervous system means
self governing system.
 It is also called
Visceral nervous system,
Involuntary nervous system, or
Animalic nervous system.

Autonomic nervous system(ANS)
 Chiefly concerned with the regulation and
maintenance of the internal environment.
 Play a key role in the maintenance of the
homeostasis
 It innervates cells of visceral system includes
the cardiovascular system, digestive system,

respiratory system, endocrine system.
 ANS also divides in to three
1. Sympathetic nervous system &
2. Parasympathetic nervous system
3. Enteric nervous system

ANS…..
 The autonomic nervous system encompass
12 paired cranial nerves which originate from
brain 31 pairs of spinal nerves originating
from spinal cord.

CRANIAL NERVES
 The 12 pairs of cranial nerves are nerves
originated or attached to the brain.
 Each cranial nerve has both a number,
designated by a roman number, & a name.

 The number designates a nerve’s distribution or
function.
 Cranial nerve can be classified as:
Sensory nerves: CI, CII, & CVIII
Motor nerves: CIII, CIV, CVI, CXI & CXII
Mixed nerves: CV, CVII, CIX & CX

Spinal nerves
 The 31 pairs spinal nerves
Cervical nerve 8 pairs = C1 through C8
Thoracic nerve 12 pairs = T1 through
T12
Lumbar nerve 5 pairs = L1 through L5
Sacral nerve 5 pairs = S1 through S5
Coccygeal 1 pair of spinal nerve
 There are two bundles of axons called
ROOTS connect the spinal nerve to a
segments of the spinal cord
◦ Dorsal (posterior) root : carry sensory
fibers
◦ Ventral (anterior) root: carry motor
fibers
 Therefore all spinal nerves are mixed
nerves
General Functions, properties and Organizations of
ANS
 Controls most visceral functions such as
Heart and lungs in thorax
Gastrointestinal, genital, urinary system in the abdomen
 Controls other functions such as
Blood chemistry, Respiration, Circulation & Digestion
Body temperature (SNS increases heat production in cold
weather)
Immune response
 Along with endocrines, ANS maintains the
homeostasis of the body.

ANS
 Rapidity and intensity of changing effectors
functions
◦ With in 3-5 seconds it doubles the heart rate
◦ With in 10-15 sec it doubles the ABP
 ANS is controlled by centers located in the
◦ Spinal cord
◦ Brain stem
◦ Hypothalamus
◦ Portions of cerebral cortex specially in Limbic cortex

ANS
 Most visceral organs receive dual innervation
supplied by both sympathetic and parasympathetic
This Dual innervation with SNS and PSNS has opposite
effects on most organs of the body
this results in dynamic antagonisms that precisely
control visceral activity
Both divisions do not normally innervate an organ
equally
 Even if most organs of the body have dual
innervation with both branches, few organs like
Adrenal medulla, errector pili muscle, sweat
glands, & most blood vessels receive only
sympathetic innervation
ANS
 The effects of dual innervations are either:
A. Antagonistic effects
◦ oppose each other
 heart rate decreases (parasympathetic) and
increases (sympathetic)
◦ exerted through dual innervation of same effector
◦ exerted because each division innervates different cells
 pupillary dilator muscle (sympathetic) dilates
pupil constrictor pupillae (parasympathetic)
constricts pupil

ANS
 The effects of dual innervations are either:
B. Cooperative effects
◦ Seen when 2 divisions act on different effectors to
produce a unified effect
 parasympathetics increase salivary serous cell
secretion
 sympathetics increase salivary mucous cell
secretion
◦ ANS cooperation is best seen in control of the
external genitalia
 Parasympathetic fibers cause vasodilation and are
responsible for erection of the penis and clitoris
 Sympathetic fibers cause ejaculation of semen in
males and reflex peristalsis in females
Branches of ANS
 Autonomic nervous system has three branches
1. Sympathetic Nervous System: emerges from all
thoracic segment and upper two lumbar segments.
 Therefore, it is called Thoracolumbar
outflow
2. Para Sympathetic Nervous System: arises from four
crania nerves (III, VII, IX & X) and lateral horn cells of
1st to 4th sacral nerves.
 Therefore, it is also called Craniosacral
outflow
3. Enteric nervous system

SYMPATHETIC
NERVOUS
SYSTEM

Sympathetic
(Thoracolumbar) Division
 Originates in the
thoracic and lumbar
spinal cord.
 Preganglionic cell bodies
in lateral horns of spinal
cord T1-L2:
thoracolumbar

General properties of the SNS
 Mediates the body's response to activity, stress,
danger or environmental challenge.
 Preganglionic fibers are short, postganglionic
are long.
 Sympathetic neurons branch extensively.
◦ One cell may innervate many target cells, leading to
more generalized sympathetic responses in the body.

General properties of the SNS
 Primary target tissues are:
Cardiovascular system
Lungs
Smooth muscle in all organs
Some glands (sweat, salivary, and digestive) &
Metabolic tissue (fat cells, liver).
 The overall pattern of sympathetic activation is
typified by the fight or flight or fright reaction
to danger.
 Involved in expending energy

Responses to Exercise
(Fight or Flight Fright Response)
 Increased heart rate and force of contraction
 Blood vessel dilation in skeletal and cardiac
muscles
 Dilation of air passageways
 Energy sources availability increased
◦ Glycogen to glucose
◦ Fat cells break down triglycerides
 Muscles generate heat, body temperature
increases
 Sweat gland activity increases
 Decrease in nonessential organ activities

PA R A S Y M PAT H E T I C
N E RV O U S
SYSTEM
22 05/11/2022
Prepared by Mesay. M
Parasympathetic
(Craniosacral) Division
 Responsible for
"housekeeping" functions
of the body, many of them
are vital for life.
 Involves the D activities
Digestion
Defecation and
Diuresis
 Involved in conservation or
restoration of energy
"rest and digest"

Parasympathetic Division
 Most PSN fibers do not travel within spinal
nerves.
 Little branching of the neurons is found
One neuron innervates just a few target cells.
This gives specific, fine control for regulation.
No massive discharges or not activated as a whole.
 Stimulation of separate parasympathetic nerves.
 Primary targets include: heart (atria), GI
system, excretory organs, exocrine glands, eye
& genitalia.
 Does not innervate structures in the body wall
(muscle & skin) & most blood vessels.

Parasympathetic Effects
 In general, PNS important for resting
conditions: SLUDD:
Salivation
Lacrimation
Urination
Digestion &
Defecation
 Release ACh as NT.
 Relaxing effects:
◦ Decreases HR.
◦ Dilates visceral blood vessels.
◦ Increases digestive activity.
25 05/11/2022
Enteric nervous system
 This is an extensive web-like structure that is
capable of functioning independently of the
reminder of the nervous system.
 It contains over 100 million neurons of over
15 morphologies, greater than the sum of all

other peripheral ganglia and is chiefly
responsible for the regulation of digestive
process.

Neurotransmitters of ANS
 ANS utilizes chemicals for transmission of
information known as Neurotransmitters (NTs )
 Neurotransmitters: are small chemicals
(molecules) that transmit the nerve impulses

across a synaptic cleft.
 Neurotransmitters released from the nerve
terminals into the synaptic cleft.

 And then they cross the cleft by diffusion &
activate / inhibit the post synaptic cells by

binding to receptors.

Neurotransmitters
 Autonomic nerves release neurotransmitters
that may be stimulatory or inhibitory.
 Neurotransmitters can be single amino acids,
short chains of amino acids, or derivatives of

protein.
 They take nerve impulses across synapses.
 Common Autonomic Neurotransmitters
Acetylcholine
Norepinephrine
Epinephrine
Dopamine

neurotransmitters
 The preganglionic neurons that secrete
acetylcholine are called cholinergic
All preganglionic neurons of the SNS & PSNS are
cholinergic.
The PSNS postganglionic fibers are also cholinergic
Exception, PSNS neurons that secrete nitric
oxide
Some SNS postganglionic neurons in sweat glands and
blood vessels in skin are cholinergic.
 The neurons that secrete norepinephrine
(noradrenalin) are called adrenergic .
Most sympathetic postganglionic neurons are
adrenergic.

COMMON CHEMICAL TRANSMISSION AT AUTONOMIC
JUNCTIONS
Acetylcholine (Cholinergic Neurons)

◦ All preganglionic neurons
◦ Parasympathetic postganglionic neurons
◦ Sympathetic postganglionic neurons to sweat
glands & blood vessels in skin

Norepinephrine (Noradrenergic neurons)
◦ By all the remaining post ganglionic
sympathetic neurons
◦ Primarily an alpha receptor stimulant
Epinephrine (Adrenergic neurons)
◦ By Adrenal medulla (essentially sympathetic
ganglion)
◦ Stimulate alpha and beta receptors equally
Dopamine
◦ By Adrenal medulla

ANS neurotransmitter receptors
 Autonomic neurotransmitters produce actions
by binding to protein receptors in the
membranes of effector cells.
 Receptor binding alters the membrane.
 Acetylcholine can combine with two types of
cholinergic receptors
A. Muscarinic receptors and
B. Nicotinic receptors.
 Norepinephrine (noradrenaline) can combine
with two types of adrenergic receptors
A. Alpha receptors and
B. Beta receptors.

Cholinergic Receptors
 Muscarinic receptors
 Its name comes from muscarine, a toxin from a
fungus that can activate muscarinic receptors.
 The muscarinic receptors are located in the
membranes of effector cells at the ends of :

All postganglionic parasympathetic nerve fibers and
The cholinergic sympathetic fibers.

Cont…
 The muscarinic receptors can be further
classified into five subtypes(M1-M5).
 Responses from these receptors are excitatory and
occur relatively slowly.

Cholinergic Receptors
 Nicotinic receptors
 Its name comes from nicotine, a toxin of
tobacco that can activate nicotinic receptors.
 Nicotinic receptors are found :
In the synapses b/n the pre & post ganglionic neurons
of the PSNS and SNS pathways.
At neuromuscular junctions of skeletal muscles
The hormone-producing cells of the adrenal medulla
 They produce rapid, excitatory responses.
 The effect of ACh binding to nicotinic receptors
is always stimulatory

Adrenergic Receptors
 The two types of adrenergic receptors are
alpha and beta.
 Each type has two or three subclasses
(1, 2, 1, 2 , 3)
 Exciting them elicits different responses in the
effector organs.
 Effects of NE binding to:
◦  receptors is generally stimulatory
◦  receptors is generally inhibitory
 A notable exception – NE binding to 
receptors of the heart is stimulatory

Alpha-1 receptors:
 α1-Receptors are primarily present at postsynaptic sites
in vascular smooth muscle, but are also present in
bronchi, bladder, intestine, uterus, iris, liver and heart.
 They mediate a wide variety of autonomic effects,
including
 vasoconstriction in most blood vessels
 bronchoconstriction contraction of the bladder and
uterus
 relaxation of intestinal muscle
 mydriasis
 glycogenolysis
 cardiac inotropic effects

Alpha-2 receptors
 α 2-receptors are present in platelets, in
pancreatic - cells, in vascular smooth muscle and
at sympathetic nerve endings.
 They mediate a number of physiological effects,
including :
 inhibition of noradrenaline release from
sympathetic postganglionic neurons.

 platelet aggregation
 inhibition of insulin release
 vasoconstriction (in some vascular smooth
muscle beds)

Beta-1 receptor
 β1-Adrenoceptors have been identified at postsynaptic
sites in the heart, at adrenergic nerve terminals, in the
juxtaglomerular cells in the kidney and in salivary
glands. At these sites, activation of β1-receptors:
 increases the rate and force of cardiac contraction
 facilitates the release of noradrenaline
 increases the secretion of renin from juxtaglomerular
cells
 increases amylase secretion in salivary glands.
 At most β1-receptors, noradrenaline is equipotent
with adrenaline (although both are less potent than

isoprenaline).

Beta-2 receptor
 They are widely present in vascular,
bronchial, vesical and uterine smooth muscle,
and at presynaptic sites on adrenergic
neurons. In some tissues (lymphocytes, liver,
skeletal muscle) they are not associated with
a sympathetic nerve supply.
 Despite this commonality, β -stimulation
2
relaxes smooth muscle, resulting in
bronchodilation, vasodilation, and relaxation
of the uterus (tocolysis), bladder, and gut.

Beta-2……
Activation of β 2-receptors produces
 vasodilatation
 bronchodilatation
 vesical smooth muscle relaxation
 uterine relaxation( tocolysis) post ponmnt of
preterm labor
 increased noradrenaline release from sympathetic
nerves
 glycogenolysis
 increased insulin secretion
 muscle tremor and hypokalaemia

Beta-3 receptor
 β3 Receptors are found in the gallbladder and
in brain adipose tissue.
 They mediate atypical metabolic responses,
including:
 thermogenesis (in skeletal muscle and
adipose tissue)
 lipolysis (in adipose tissue)
 glucose uptake (by skeletal muscle)

Dopaminergic receptors
Dopamine is the immediate metabolic

precursor of noradrenaline and small
concentrations are released from sympathetic
nerve terminals.
 Although its peripheral role is limited, it is an
important central neurotransmitter, and five

different types of dopamine receptor have
been identified in the CNS.

Dopaminergic receptors…..
 D1-D5 receptors found in CNS mediate:

 decreases the secretion of prolactin
 produces emesis (via receptors in the CTZ
and NTS
 influences the local release of acetylcholine
and endorphins

Cont…
 D1- and D2-receptors have also been identified at
peripheral sites, where they may have a limited
functional role.
 D1-receptors are present in the renal and
mesenteric blood vessels, and their activation

causes vasodilatation and increased Na+ excretion
 In autonomic ganglia dopaminergic stimulations
acts on ganglionic D1-receptors, producing

hyperpolarization and decreasing the release of
noradrenaline from sympathetic neurons.

AUTONOMIC NERVOUS SYSTEM
47 05/11/2022
Adrenergic agonists
 Adrenergic agonists can be categorized as

direct or indirect.
 Direct agonists bind to the receptor, whereas
indirect agonists increase endogenous

neurotransmitter activity.
 Mechanisms of indirect action include
increased release or decreased reuptake of

norepinephrine.

Cont…
 The differentiation between direct and
indirect mechanisms of action is particularly
important in patients who have abnormal
endogenous norepinephrine stores, as may
occur with use of some antihypertensive
medications or monoamine oxidase
inhibitors.

Alpha-1 agonist
 Phenylephrine: predominantly direct α1-
agonist activity (high doses may stimulate α
2- and β-receptors).
 The primary effect of phenylephrine is
peripheral vasoconstriction with a
concomitant rise in systemic vascular
resistance and arterial blood pressure.
 Reflex bradycardia can reduce cardiac output.

Alpha-1 agonist…..
 Coronary blood flow increases because any
direct vasoconstrictive effect of
phenylephrine on the coronary arteries is
overridden by vasodilation induced by the
release of metabolic factors(NO).
 Dose: Small intravenous boluses of 50–100
µg (0.5–1 µg/kg) of phenylephrine rapidly

reverse reductions in blood pressure caused
by peripheral vasodilation (eg, spinal
anesthesia).

 A continuous infusion (100µ g/mL at a rate of 0.25–
1µ g/kg/min) will maintain arterial blood pressure
but at the expense of renal blood flow.
 It is also used as a mydriatic agent or a
decongestant, and is sometimes incorporated into
local anaesthetic solutions for topical use in ENT
surgery (lidocaine with phenylephrine solution).
 Tachyphylaxis occurs with phenylephrine infusions
requiring upward titration of the infusion.
Phenylephrine must be diluted from a 1% solution
(10 mg/1-mL ampule), usually to a 100 µg/mL
solution.

 Ergometrine which has powerful uterotonic
activity, and is used in obstetrics to control
postpartum bleeding is also drug with high
affinity for α1 receptors.

Metaraminol
 Metaraminol is a vasopressor drug with
direct and indirect sympathomimetic effects.
It directly stimulates α 1-adrenergic
receptors, and also releases noradrenaline
from synaptic vesicles in postganglionic
sympathetic nerves.

 Metaraminol (15–100 mg, intravenously) is
sometimes used in the treatment of
challenging hypotension during anaesthesia,
particularly after subarachnoid or extradural
blockade or when ganglion-blocking drugs
have been employed.
 It has a longer duration of action than
ephedrine,and excessive vasopressor

responses may cause a prolonged rise in
blood pressure.

Alpha-2 agonist
 Clonidine is an α2-agonist that is now commonly

used for its antihypertensive action.
 More recently, clonidine and other α -agonists
2
have been found to have sedative properties.
Investigational studies have examined the
anesthetic effects of
 oral (3–5µ g/kg),
 intramuscular (2 µ g/kg),
 intravenous (1–3 µ g/kg),
 intrathecal (75–150 g), and
 epidural (1–2 g/kg) clonidine administration.

α2 agonist….
 In general, clonidine appears to decrease
anesthetic and analgesic requirements (decreases
MAC) and to provide sedation and anexiolysis.
 Other possible benefits include decreased
postoperative shivering,
 inhibition of opioid-induced muscle rigidity,
 attenuation of opioid withdrawal symptoms,
 the treatment of some chronic pain syndromes.
 Side effects include bradycardia, hypotension,
sedation, respiratory depression, and dry mouth.

α2 agonist….
 Methyldopa is a centrally acting antihypertensive
agent. It is metabolized to a-methylnorepinephrine
in the brain, and this compound is thought to
activate central α2 receptors and lower blood
pressure in a manner similar to that of clonidine.
 A fall in peripheral vascular resistance is
responsible for a drop in arterial blood pressure
(peak effect within 4 h). Renal blood flow is
maintained or increased. The usual initial dose of
methyldopa is 250 mg twice daily, and there is little
additional effect with doses above 2 g per day.

α2 agonist….
 Dexmedetomidine is highly selective for the
α2-receptors.
 Its half-life of 2.3 hours and distribution
half-life of less than 5 minutes make its

clinical effect quite short.
 It has sedative, analgesic, and sympatholytic
effects that blunt many of the cardiovascular

responses seen during the perioperative
period.

α2 agonist….
 When used intraoperatively, it reduces
intravenous and volatile anesthetic
requirements; when used postoperatively, it
reduces concurrent analgesic and sedative
requirements.
 Rapid administration may elevate blood
pressure, but hypotension and bradycardia may

occur during ongoing therapy.
 The usual dosing is an infusion of 0.3 to 0.7
mg/kg/hour either with or without a 1 mg/kg

loading dose given over10 minutes.

Beta agonist
 Epinephrine: Direct stimulation of β1-
receptors by epinephrine raises cardiac
output and myocardial oxygen demand by
increasing contractility and heart rate.
 Clinical uses
◦ Cardiac arrest
◦ Anaphylaxis
◦ Low cardiac output states
◦ Upper airway obstruction
◦ Combination with local anesthetics

Epinephrine Cont’d
 Side effects
• Increase in myocardial oxygen consumption
 Post-resuscitation hypertension
 tachycardia
 headache
 nausea
 vasoconstriction severe enough to decrease
peripheral blood flow

Epinephrine
Implications
 Effects of Epinephrine are depressed in
acidosis.
 Extravasation may cause local ischemia and
tissue necrosis.
◦ assure patent IV
◦ preferably a central line
 Monitor patient status q. 1 - 5 min

Ephedrine
 Ephedrine: Ephedrine has α-, β1- and β2-
effects on adrenergic receptors due to its direct
and indirect sympathomimetic activity.
 The cardiovascular effects of ephedrine are
similar to those of epinephrine: increase in

blood pressure, heart rate, contractility, and
cardiac output. Likewise, ephedrine is also a
bronchodilator. The indirect agonist properties
of ephedrine may be due to central stimulation,
peripheral postsynaptic norepinephrine release,
or inhibition of norepinephrine reuptake.

Cont…
 Ephedrine is commonly used as a vasopressor
during anesthesia. As such, its administration
should be viewed as a temporizing measure while
the cause of hypotension is determined and
remedied.
 Unlike direct-acting α1-agonists, ephedrine does
not decrease uterine blood flow. This makes it the
preferred vasopressor for most obstetric uses.
 The usual dose is 2.5 to 25 mg given
intravenously or 25 to 50 mg administered
intramuscularly.

Norepinephrine
 Norepinephrine, the primary adrenergic
neurotransmitter, binds to α-and β-receptors.
 It is used primarily for its α 1-adrenergic
effects that increase systemic vascular
resistance.
 Like all the endogenous catecholamines, the
half-life of norepinephrine is short
(2.5minutes), so it is usually given as a
continuous infusion at rates of 3 mg/min or
more and titrated to the desired effect.

Cont…
 The increase in systemic resistance can lead
to reflex bradycardia. Prolonged infusion of
norepinephrine can also cause ischemia in
the fingers because of the marked peripheral
vasoconstriction.

ISOPROTERENOL

 Isoproterenol is of interest because it is a
pure β-agonist. β1-Effects increase heart rate,
contractility, and cardiac output. β2-
Stimulation decreases peripheral vascular
resistance and diastolic blood pressure.
 Myocardial oxygen demand increases while
oxygen supply falls, making isoproterenol or

any pure -agonist a poor inotropic choice in
most situations.

Isoprenaline
 Isoprenaline is a synthetic catecholamine with
powerful effects on β1- and β2-adrenoceptors.
After infusion of isoprenaline, both heart rate and
cardiac output are increased, and arrhythmias are
not uncommon. Peripheral resistance falls, and
coronary perfusion may be reduced due to
tachycardia and a reduction in diastolic pressure.
 At one time, isoprenaline infusions were used in the
management of cardiovascular shock, various
bradyarrhythmias and bronchospasm. Its use is now
obsolete and it is only available on special order.

Dopamine
 Dopamine: The clinical effects of dopamine (DA),
a nonselective direct and indirect adrenergic
agonist, vary markedly with the dose.
 Small doses (≤2 µg/kg/min) of dopamine have
minimal adrenergic effects but activate

dopaminergic(D1) receptors. Stimulation of these
noradrenergic receptors vasodilates the renal
vasculature and promotes diuresis.
 At moderate doses (2–10 µg/kg/min), β -
1
stimulation increases myocardial contractility,
heart rate, and cardiac output.

Dopamine clinical Use
 hypotension with poor peripheral perfusion
to maintain renal function.
 shock which fails to respond to volume
loading
 is not a drug of choice in treating
hypovolemic shock
 Routes of Administration--IV drip It is
administered as a continuous infusion (400

mg in 1000 mL D5W; 400µg/mL) at a rate of
1–20 µg/kg/min.

Dobutamine
 Dobutamine has predominantly β1-
adrenergic effects. Dobutamine is a synthetic
catecholamine that resembles dopamine. It
directly increases cardiac contractility and
output by activating β1-adrenoceptors, and
produces moderate vasodilatation by its
effects on β2-receptors.
 Dobutamine has little or no effect on α -
adrenoceptors.

Dobutamine….
 Unlike dopamine, endogenous
norepinephrine is not released nor does it act
at dopaminergic receptors. Dobutamine is
particularly useful in patients with congestive
heart failure (CHF) or myocardial infarction
complicated by low cardiac output.
 Dose smaller than 20 mg/kg/min usually
does not produce tachycardia.

Dopexamine
 Dopexamine hydrochloride (an analogue of dopamine) is
a potent β2-adrenoceptor agonist and also acts on
peripheral dopaminergic receptors (both D1 and D2).
 In contrast to dopamine, it has no α- and β1-agonist
activity, although it inhibits the neuronal uptake of
noradrenaline
 Dopexamine has positive inotropic effects, due to its
effects on cardiac β2-adrenoceptors and the inhibition of
released noradrenaline
 In addition, it produces vasodilatation by its effects on
peripheral β2-receptors. It is normally infused at rates of
0.5–6.0 g kg−1 min−1, and sometimes induces
tachycardia or tachyarrhythmias.

Digoxin
 Although they are not classified as autonomic

drugs, digoxin and related cardiac glycosides
have inotropic effects, and increase the force
of myocardial contraction as well as reducing
atrioventricular conduction.
 Their inotropic action is dependent on the
inhibition of membrane Na+/K+ ATPase in

myocardial cells

Selective β2-adrenoceptor agonists
 Selective 2-adrenoceptor agonists are used in the

treatment of bronchospasm. They have relatively
specific effects on β2-adrenoceptors in bronchial
smooth muscle, but little or no direct effect on the
heart. Tachycardia and palpitations occasionally
occur (particularly after systemic administration),
and probably reflect direct effects on cardiac 2-
receptors, rather than a reflex response to
vasodilatation.
 These effects may be enhanced in cardiac failure,
when there is a relative preponderance of β2-
adrenoceptors.

Cont…
 All β2-adrenoceptor agonists, including
adrenaline and isoprenaline, may cause
hypokalaemia, due to stimulation of
membrane bound Na+/K+ ATPase and
increased K+ uptake by skeletal muscle.

Salbutamol
 Salbutamol can be given orally, by injection,
by inhalation or as a nebulized solution.
Salbutamol may be given as a bolus dose
(250 μg, intravenously) or by continuous
infusion (3–20μg min−1) in the treatment of
severe bronchospasm.
 Alternatively, salbutamol may be
administered in severe asthmatic states as a

respirator solution through a suitably driven
nebulizer.

 β2-Adrenoceptor agonists relax uterine
smooth muscle, and some of them,
particularly ritodrine, salbutamol and
terbutaline, are given by continuous infusion
to inhibit premature labour between 24 and
33 weeks gestation.
 These drugs cause tremor and nervous
tension, although it is not clear whether these

are central or peripheral side effects.).

Cont…
 Beta 2-Agonists are used to treat reactive airway
disease. With large doses the β2-receptor
selectivity can be lost, and severe side effects
related to β1-adrenergic stimulation are
possible.
 Commonly used agents include metaproterenol
(Alupent, Metaprel), terbutalline (Brethine,
Bricanyl), and albuterol (Proventil, Ventolin).
 Beta 2-Agonists are also used to interrupt
premature labor. Ritodrine (Yutopar) has been
marketed for this purpose.

Muscle relaxants(NMJB)
NMJ Physiology
The neuromuscular junction =The region of
approximation between a motor neuron and a muscle
cell which consists of:
1.a motor nerve ending with mitochondria and
acetylcholine vesicles (prejunctional)
2.a synaptic cleft of 20-30nm in width containing
extracellular fluid .
3. A highly folded skeletal muscle membrane
(postjunctional)
4. Nicotinic cholinergic receptors located on a
specialized portion of the muscle membrane, the
motor end-plate

CONT…
• Junction between motor nerve end-plate
and muscle fibre= the synapse between
motor neuron and muscle fiber
• Allows action potential in neuron to
activate muscle fibre
• A neurone may supply one or many muscle
fibres

Cont…
Action potential
Ca2+
1
Presynaptic
Synaptic terminal
vesicle
Voltage-gated
Ca2+ channel Synaptic cleft
2
Acetylcholine Postsynaptic
membrane
Na+
Acetylcholine bound
to receptor site opens
ligand-gated Na+ 44
channel

Neuromuscular blockers/muscle
relaxant
 DEFN:- are drugs act at NMJ to produce skeletal
muscle paralysis
 Skeletal muscle relaxation or paralysis can also be
achieved by higher dose of VAA or regional
anesthesia.
 They have neither anaesthetic nor analgesic
properties

Roles of NMB in surgery
NMB’s are co-administrated with anasthetics
in the induction phase to induce muscle
paralysis
 facilitate the surgery, especially intra-
abdominal and intra-thoracic surgeries
 facilitate endotracheal intubation.
 BUT bcz NMB paralyze muscles required for

breathing, mechanical ventilation should be
available to maintain adequate respiration.

Classification of Muscle Relaxants
Muscle Relaxants are classified as:
I)Peripherally acting
A. Neuromuscular blocking agents:-
1) Depolarizing muscle relaxants.
2) Non-depolarizing muscle relaxants
B.) Directly acting: Dantrolene, Quinine
II)Centrally acting
o Diazepam, Baclofen, Tizanidine,

Depolarizing Neuromuscular Blockers
 Mechanism of Action:
◦ Depolarizing Drugs:
 Phase I Block (depolarizing):
succinycholine reacts with nicotinic
receptors to opens the channel and
cause depolarization of the motor end
plate which will spread to adjacent
membranes, causing contractions of
muscle motor units

Cont…
 Phase II Block( desensitizing): with continued
exposure, depolarization decreases and
postjunctional membrane becomes
repolarized but do not respond to ACh and
can not be depolarized again b/c it is
desensitized.
 Sux is the only depolarizing muscle relaxant with fast
onset and it has short duration.

 Dose 1-2mg/Kg

NONDEPOLARIZINGNEUROMUSCULAR
BLOCKERS/NDNMB
Mechanism of Action
 They are capable of competing with ACh for receptor
sites, and will block ACh from causing an action
potential.
 NDP muscle relaxants are incapable of inducing a
conformational change in the Ach receptor, as their
large structures to not resemble ACh
 NDP are competitive antagonists to ACh.
 NDP prevent depolarization.
 NDP do not cause fasciculations
 Nondepolarizing Agents =ACh Receptor Antagonists =
Competitive Block,

Common Dosing Regimens For
Muscle Relaxants

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ANS Pharma.

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Physiology and pharmacology

Prepared by Mesay. M 05/11/2022 1

pharmacodynamics of drugs that act on ANS

and clinical effects of each drugs

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bodies in the PNS

the evocation of a response at a receptor site

to a response by the the effector cell when

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the cardiovascular system, digestive system,

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designated by a roman number, & a name.

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(muscle & skin) & most blood vessels.

15 morphologies, greater than the sum of all

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(molecules) that transmit the nerve impulses

terminals into the synaptic cleft.

activate / inhibit the post synaptic cells by

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short chains of amino acids, or derivatives of

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Acetylcholine (Cholinergic Neurons)

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membranes of effector cells at the ends of :

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sympathetic postganglionic neurons.

 inhibition of insulin release

 vasoconstriction (in some vascular smooth

Prepared by Mesay. M 05/11/2022 39

with adrenaline (although both are less potent than

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 vesical smooth muscle relaxation

 uterine relaxation( tocolysis) post ponmnt of

 increased insulin secretion

 muscle tremor and hypokalaemia

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Dopamine is the immediate metabolic

important central neurotransmitter, and five

Prepared by Mesay. M 05/11/2022 44

 D1-D5 receptors found in CNS mediate:

Prepared by Mesay. M 05/11/2022 45