In addition to cardiac muscle, there are 2 further types of muscle in the body.

The first type involved in ‘voluntary’ movement is termed striated muscle. Such muscles are
used for skeletal movement such as walking, talking and writing. The respiratory muscles
(intercostals and diaphragm) also fall into this category.

Each muscle cell is supplied by a single motor nerve

Striated muscle

All motor nerves to striated muscles are part of the somatic (voluntary) nervous system and are
excitatory.

The second type of muscle is the smooth muscle. This type of ‘involuntary’ muscle is found in
the digestive tract, air passages, bladder, uterus, blood vessels and controlling the pupil of the
eye. The muscle cells here are also supplied by nerves. When nerve impulses pass along these
nerves, the fibre (cells) either contract or relax.

In many parts of the body, the smooth muscle is in a state of partial contraction and there are
then 2 directions in which its length can be changed-the fibres may be made to shorten further or
they may be made to lengthen.

In order to bring about these two changes, the smooth muscle has a double nerve supply. One
nerve is excitatory and brings about contraction, the other nerve is inhibitory and brings about
relaxation of the muscle.

+
-
+
-

Smooth muscle
The part of the nervous system that supplies the smooth muscle is termed the Autonomic
Nervous System. The Autonomic nervous system is subdivided into

a. The sympathetic nervous system

b. The parasympathetic nervous system

When a smooth muscle cell has a double nerve supply, one nerve will come from the
sympathetic nervous system and the other from the Parasympathetic nervous system. In some
parts of the body, the sympathetic is the excitatory and in others it is the inhibitory nerve.

The Autonomic Nervous System (ANS) also supplies

a. The heart
b. Secreting glands such as sweat glands and digestive glands

The sympathetic nervous system is a 2 neuron system i.e. the nerve fibre (neurone) which leaves
the spinal cord is not the same one that arrives at the smooth muscle.

The first nerve fibre stops in a sympathetic ganglion.

The second nerve fibre starts from the ganglion and runs to the end.

SPINAL CORD

Preganglionic fibre

Synapse Ganglion

Postganglionic fibre
Acetylcholine

Noradrenaline

Smooth muscle cell

In the ganglion the preganglionic fibre comes into contact with the post ganglionic fibre forming
a synapse. Here, impulse are transmitted from the preganglionic across the synapse by the release
of acetylcholine (Ach) when the nerve impulse reach the end of the postganglionic nerve fibre,
they bring about the release of another chemical transmitter, i.e. Noradrenaline. This bridges the
small gap between the end of the nerve and the muscle fibre. This Noradrenaline acts on the
smooth muscle and bring about either a contraction or relaxation depending on whether it is an
excitatory or inhibitory. Thus, the sympathetic nerves are described as Noradrenergic or
adrenergic.

The Noradrenaline is rapidly removed after release so that the muscle is able to respond to future
nerve impulses.

The adrenal medulla endocrine glands release noradrenaline and its derivative adrenaline as
hormones when nerve impulse pass along the preganglionic sympathetic fibres leading to the

gland. These two chemical are referred to collectively as catecholamines.

When they are released by the adrenal medulla they arrive through the blood stream of the local
sympathetic nerve and increase the effect of the local sympathetic nerve activity. Thus they are
said to be sympathomimetic.

FUNCTIONS OF THE SYMPATHETIC NERVOUS SYSTEM

The sympathetic nervous system is active in states of emotional excitement and stress that is
states associated with “fight, fright or flight” reaction.

Increased sympathetic activity causes the heart to speed up and the force of contraction of the
ventricles to increase. This leads to an increase in blood pressure. The pupils of the eye dilate.
The air passages increase in diameter.

Sweating occurs and contraction of the arrector pili muscles causes the ‘hair to stand on end’ and
goose pimples form.
Movement of the digestive tract will be reduced. There is a stimulation of breathing as a result of
the action of higher centres on the respiratory centre (Respiratory muscles are straited muscle
and not under control of the ANS but the muscle in the bronchi and bronchioles are smooth
muscle and hence relaxed by the sympathetic nervous system and hence the dilation of air
passages.

THE PARASYMPATHETIC NERVOUS SYSTEM

It is also a 2 neurone system but in most cases, the postganglionic fibre is very short and the
ganglion and this fibre often lie in the organ supplied.

When a nerve impulse reaches its termination, it brings about the release of the chemical
transmitter acetylcholine. Hence, these nerves are said to be cholinergic.

The acetylcholine released may bring about either contraction or relaxation of the muscle. Unlike
the sympathetic nervous system and the adrenal medulla, there is no endocrine gland that also
increases the activity of the paraysympathetic nervous system by also releasing acetylcholine as
a hormone.

Both activities of Acetylcholine (contraction of relaxation) are blocked by the drugs atropine and
hyoscine and hence these drugs are referred to as anticholinergic. Other examples are
Propantheline. Like Noradrenaline, Acetylcholine is rapidly removed after its release but by an
enzyme called Cholinesterase

BRAIN OR SPINAL CORD

Preganglionic fibre

acetylcholine

Postganglionic fibre
 Acetylcholine

FUNCTIONS OF THE PARASYMPATHETIC NERVOUS SYSTEM

In most parts of the body, the action of the parasympathetic nervous system is opposite that of
the sympathetic.

 It slows the heart.

 Lowers the blood pressure
 Constricts the pupils
 Constricts the air passages
 Speeds up the digestion of food and plays an important part in defecation and micturation

The parasympathetic nervous system stimulates the production of saliva, gastric juice, pancreatic
juice and increases the motility of the digestive tract at the same time relaxing the sphincters.
The activity of the parasympathetic unlike the sympathetic may be restricted to certain organs or
parts of the body at any given time.

Muscarinic and Nicotinic Actions of Acetylcholine: The action of acetylcholine at the

postganglionic parasympathetic termination is termed the MUSCARINIC ACTION of
Acetylcholine. This action is blocked by atropine. (the muscainic action is also given by
muscarine an extract from a mushroom called Amanita Muscaria).

The action of acetylcholine at both the sympathetic and parasympathetic ganglia is termed the
Nicotinic action since it is also given by nicotine from tobacco. This action is not blocked by
atropine but by ganglion blocking agents such as Pentolinium.

The action of acetylcholine at Neuromuscular junctions of the voluntary nervous system is also
considered to be nicotinic and is blocked by neuromuscular blocking agents e.g. Pancuronium,
Suxamethonium

This neuromuscular blocking agents are anticholinergic and a drug that reverses its effect will be
described as cholinergic.
COMBINED ACTION OF THE SYMPATHETIC AND PARASYMPATHETIC NERVOUS
SYSTEM

Since the smooth muscle has a double nerve supply, there are 2 ways in which the activity can be
modified. Thus, a muscle can be made to contract by increasing the activity of the excitatory
nerve or inhibiting the action of the inhibitory nerve.

EXAMPLES

1. The size of the pupil of the eye depends on the balance between the sympathetic nervous
system which dilates it and the activity of the parasympathetic which constriction it.
If it is desired to clinically dilate the pupil for an inspection of the eye, then either the
sympathetic nervous system activity should be increased on the parasympathetic activity
should be reduced. The latter is usually used and Homatropine drops (a derivative of
atropine) is applied to the eye.
2. Bronchospasm: The air passage contain smooth muscle. Sympathetic NS brings about
dilatation of the bronchi (bronchodilation) while the parasympathetic NS brings about
bronchoconstriction.
If the parasympathetic nervous system is reactive or the bronchi are constricted such as
occurs during antigen-antibody reacton with release of histamine (in asthma) an injection
of adrenaline will bring about an increase in sympathetic activity and bring relief.
Isoprenaline is a derivative of noradrenaline that is active on the bronchial beta cells
causing relaxation.
Salbutamol has a more specific β2 agonist. Care should be taken because excessive
dosage can cause excessive stimulation of sympathetic nervous system which will affect
the heart and can even lead to arrhythmias.
3. Premedication: A patient who is unconscious or aneasthetized can no longer swallow.
As a result any saliva produced may be inhaled into the longs. To prevent such an
occurrence during anaesthesia, the parasympathetic supply to the salivary glands which
bring about salivation is blocked by giving a premedication containing atropine or
hyoscine.
 Organ Supplied Sympathetic Activities Parasympathetic activity
Pupil of eye Dilates Constricts
Air passages, bronchi and Dilates Constricts
bronchioles
Salivary - Salivary secretion and
dilatation of blood vessels
Heart Speeds up increases force of Slows
ventricular contraction
Digestive tract Reduced motility Increases motility
Sphincter of digestive tract Constricts Relaxes
Rectum Allows filling Empties, relaxes internal anal
sphincter
Blood vessels Vasoconstriction (except salivary gland and
external genitalia vasodilation
Bladder Allows filling Empties
Relaxes internal sphincter
Sweat Sweat Nil

 Cholinergic

 Cholinesterase
 Anticholinergic – Atropine, Glycopyrronium, Hyoscine
 Anticholinestrase – Neostigmine, Edrophonium, Pyridostigmine
 Competitive neuromuscular blockers – Vercuronium, Pancuronium, Atracurium

Side effects are chiefly due to excessive cholinergic stimulation and mostly include increased
salivation, nausea and vomiting, abdominal cramps and diarrhea. Overdosage may lead to a
“cholinergic crisis” characterized by both muscarinic and nicotinic effects. These include
excessive sweating, lacrimation, increased peristalsis, involuntary defecation and urination or
desire to urinate, bradycardia, hypotension, muscle cramps, weakness and paralysis, hypotension,
muscle cramps, weakness and paralysis, tight chest, wheezing, increased bronchial secretion
combined with bronchoconstriction.

Death may result from respiratory failure or cardiac arrest.

Another example of an acetylcholinesterase inhibitor is edrophonium chloride and
pyridostigmine.

ANTICOLINERGIC OR ANTIMUSCARINIC DRUGS (PARASYMPATHOLYTICS

The two terms are used synonymously. These drugs antagonize the effects of acetylcholine and
other parasympathomimetic drugs on all the structures that are controlled by the parasympathetic
nervous system. Muscles innervated by postganglionic parasympathetic nerves:

Smooth muscle

Cardiac muscle

And certain glands (salivary, mucous gastric, lacrimal and sweat)

Some are also found in the CNS

(Muscarinic receptors differ from nicotinic receptors in autonomic ganglia and on skeletal
muscle, which are stimulated by Acetylcholine but are not blocked by atropine).

Blockade of muscarinic receptors is competitive which means that it can be overcome by making
more agonist available. This can be done for example by administering a parasympathomimetic
drug e.g. Bethanechol, carbachol, pilocarpine or by giving an acetylcholinesterase inhibitor e.g.
Neostigmine (anticholinesterase)

Atropine sulphate is the prototype of this group of drugs. Another example is glycopyrronium
bromide. Other examples – cyclopentolate, tropicamide, propantheline bromide.
ABSOPRTION, DISTRIBUTION, METABOLISM AND EXCRETION

Atropine is readily absorbed from the GIT and all parenteral sites. Atropine and other
antimuscarinics are applied topically primarily to the eye and are absorbed well to cause
systemic effects.

Atropine is distributed throughout the body. It crosses the blood brain barrier and enters the CNS
easily. It crosses the placental barrier and enters breast milk.

Most of the atropine in the bloodstream is metabolized in the liver. Hence, intensity and duration
of antimuscarinic effects are increased when liver function is impaired. Peak effects of atropine
occur 1-2 hours after oral administration. Most or its effects last 4-6 hours but some ocular
effects last up to a week. It is excreted in urine as unchanged drug and metabolites.

USES

Atropine is used for a variety of purposes including;

 In anaesthesia – as a premedicant
 To treat bradycardia
 As antispasmodic in GI disorders
 To treat or prevent bronchospasm
 In treatment of poisoining with mushrooms that contain muscarine
 As a mydriatic and cycloplegic in ophthalmology

FOR EYE DISORDERS

Atropine dilates the pupil to produce mydriasis. It also blocks the ability of the eye lens to
chance shape to focus on nearby objects (accommodation). Paralysis of accommodation is called
cycloplegia. Mydriasis opens the pupil for a full view of internal eye structures and cycloplegia
prevents the lens from changing shape and aids the examiner in measuring refraction, to help
prescribe proper corrective lens.
Glaucoma is a major contraindication to antimuscarinic drugs and must be ruled out before
giving any antimuscarinic.

USE FOR THE CARDIOVASCULAR SYSTEM

A number of chronic cardiac diseases and many drugs can cause bradycardia – i.e. an
excessively slow heart rate. Sympathomimetic drugs can be administered but often parenteral
atropine (0.4-0.5mg preferably by iv) is used Antimuscainics are not often used for long term
management of bradycardia.

For the nurse: Measure vital signs especially heart rate, peripheral pulse and BP in all patients
before giving any antimuscarine drug parenterally.

FOR GIT DISORDERS

Antimuscarinics have been used to inhibit gastric acid secretion in peptic ulcer disease (more
effective drugs are now available). Also to inhibit excessive motility or spasm of the gut e.g.
propantheline bromide, dicyclomine.

For the nurse: Monitor drug therapy to help detect constipation. Also, antimuscarinics for GI
disorders may affect other body system to monitor especially elderly. Oral dosage forms should
be taken 20-30min before meals to avoid reduction in absorption caused by food.

USE FOR URINARY TRACT DISORDERS

Some drugs with antimuscarinic activity are used to treat neurogenic bladder disease where an
increased sensitivity of bladder to parasympathetic influence causes urinary frequency or
incontinence e.g. is oxybutynin antimuscarinics can also be used to manage bladder spasm or
incontinence due to other causes such as enuresis in children.

USE IN ANAESTHESIA AND SURGERY

Antimuscarinics have several important uses in the setting of surgery and anaestehsia. Injectable
atropine or related drugs e.g. glycopyrrolate or scopolamine are used as premedication before
general anaesthesia.
They help to reduce airway secretions during surgery but their major role is to prevent the
intense reflex slowing of the heart that occurs during induction of anaesthesia and intubation o
the airway.

They can also be given during surgery to manage bradycardia.

Antimuscarinis may also be used in motion sickness, common colds and seasonal allergies,
parkinsonism etc.

DOSES

In anaesthetisa for premed 300-600mg may be given SC or IM 30-60mins before anaesthesia.

Alternatively, 300-600mg may be given IV immediately before induction of anaesthesia.

Suitable paediatric premedication doses of Atropine SO4 and 100mg Sc for children up to 3kg.

200mg S for children up to 7-9kg

300mg SC for children up to 12-16kg

400mg SC for children up to 20-27kg

500mg SC for children up to 32kg

And 600mg SC for children up to 41kg

In bradycardia atropine is given in doses of 0.5-1.0mg iv repeated every 3-5 minutes to a total
dose of 0.04mg/kg body weight. If an IV line cannot be established, atropine can be given by
endotracheal tube.

Atropine is used to produce mydriasis and cycloplegia for ophthalmic examination.

For adults instill one drop into eye twice daily -2 days before examination.

In children, instill 1-2 drops (0.5% solution only) twice daily for 1-3 days before examination
and 1 hour before examination.
Dilation of pupil occurs in half an hour following one local application and lasts for a week or
more. However, other antimuscarinics may be preferred because they have a more rapid onset
and shorter duration of action than atropine such as cyclopentolate, homatropine or tropicamide.

Atropine is available as a 0.5% or 1% solution or ointment.

PREPRATIONS

1. Eye drops
2. Eye ointment
3. Injection
4. Tablets
5. As solution in combination with other drugs

SIDE EFFECTS

At therapeutic doses, adverse effects include dryness of the mouth with difficulty in swallowing
thirst, reduced bronchial secretions, dilatation of the pupils, difficulty in micturation, reduction in
tone and motility of the GIT leading to constipation et. In overdose, other symptoms such as
hyperthermia, hypertension, increased respiratory rate, nausea and vomiting may occur.

INTERACTIONS

Effects of atropine and other antimuscarinics may be enhanced by co-administration with drugs
with antimuscarinic properties such as some antihistamines, tricylic antidepressants.

The reduction in gastric motility caused by antimuscarinics may affect absorption of other drugs.

ANTICHOLINESTERASE OR ACETYLCHOLINESTERASE INHIBITOR

Sometimes, it is necessary to increase the activity of a body system that is regulated by the
parasympathetic nervous system. For e.g. it may be necessary to constrict the pupil of the eye,
slow the heart or stimulate the urinary bladder to empty. There are several ways to do this. One
approach may be the inhibit sympathetic nervous system activity. Another approach is to
administer a drug that inhibits the activity of acetylcholinesterase, the enzyme that metabolically
inactivates acetylcholine. Another way is to administer a parasympathometic drug.

There are limitations or disadvantages of all these approaches

Parasmpathominietic drugs stimulate only the muscarinic receptors so they are not suitable when
the goal is to stimulate skeletal muscle, which involves nicotinic receptors. Also, acetylcholine is
metabolized quickly so it’s not suitable when long lasting effects are needed. Large amounts of
acetylcholine will have to be administered fast enough and for long periods to overcome this.
This is impractical!

However, the acetylcholinesterase inhibitors have longer duration of action and can cause
prolonged and increased activity of acetylcholine

NEOSTIGMINE

The anticholinesterase actions of neonstigmine are reversible.

Neostigmine and most of the other Acetylcholinesterase inhibitors are poorly absorbed from the
GIT following oral administration. Most of their molecules are ionized due to local pH which
limits their diffusion out of the gut into the bloodstream.

Onset of action is about 1 hour when given orally but about 5 minutes when given IV. Effects
last about 2-4 hours. Neostigmine does not cross the blood brain barrier. Most of the absorbed
dose is metabolically inactivated in the liver and blood plasma. The metabolized and
unmetabolized drug are excreted in the urine.

SKELETAL MUSCLE EFFECTS

It increases the action of Acetylcholine released from motor nerves that supply skeletal muscle.
Skeletal muscle activity increases through stimulation of nicotinic receptors on the muscle cells.
This is clinically useful in myasthenia gravis, characterized by skeletal muscle weakness.

AUTONOMIC NERVOUS SYSTEM EFFECTS

In present of neostigmine there is inhibited breakdown of acetylcholine released by
postganglionic parasympathetic nerves. Major effects include;

 Constriction of pupil of eye (miosis)

 Decreased heart rate
 Increased tone and motility of the GI tract
 Stimulation of the urinary bladder and relaxation of the sphincter
 Increased activity of sweat and lacrimal glands
 Bronchoconstriction and increased muscus secretion in the respiratory tract

Neostigmine is used in the treatment of myasthenia gravis. It is used in anaesthesia to reverse the
neuromuscular blockade produced by competitive neuromuscular blockade produced by
competitive neuromuscular blockers.

Neostigmine bromide has been administered as eye drops to lower intraocular pressure in the
treatment of glaucoma.

Neostigmine is given as the bromide and as the methylsulphate.

Neostigmine is given by mouth and topically as the eye drop.

The methylsulphase is administered by IM, IV, SC

Manufacturer state that 0.5mg neostigmine methyl SO4 y IV is approximately equivalent to 1-

1.5mg of neostigmine methyl sulphate given by IM or SC or 15mg neostigmine bromide by
mouth

In the treatment of myasthenia gravis, neostigmine is given by mouth as the bromide in a total
daily dose usually between 75-300mg daily in divided doses. Max dose that most patients can
tolerate is 180mg usual total daily dose in children is 15-90mg by mouth.

To reverse neuromuscular blockade produced by competitive neuromuscular blockers, usual

adult dose used in the UK are 50-70ug/kg body weight given by IV injection over a period of
60sec.
Additionally, patient should be well ventilated until complete recovery or normal respiration is
assured.

To counteract any muscarinic effects 0.6-12mg of atropine sulphate is administered by IV

injection with or before the dose of neostigmine. If bradycardia is present, atropine Sulphate
should be administered several minutes before neostigmine.

Side effects are chiefly due to excessive cholinergic stimulation and mostly include increased
salivation, nausea and vomiting, abdominal cramps and diarrhea overdosage may lead to a
“cholinergic crisis” characterized by both muscarinic and nicotinic effects. These include
excessive sweating, lacrimation, increased peristalsis, involuntary defecation and urination or
desire to urinate, bradycardia, hypotension, muscle cramps, weakness and paralysis, tight chest,
wheezing, increased bronchial secretion combined with bronchoconstriction. Death may result
from respiratory failure or cardiac arrest.

Another example of an acetylcholinesterase inhibitor is edrophonium chloride and

pyridostigmine.

DIAGAM
Effects of acetylcholine form postganglionic parasympathetic nerves are mediated by muscarinic
receptors. Effects of acetylcholine from skeletal somatic nerves are mediated by nicotinic
receptors and effects of noradealine and adrenaline from the sympathetic nervous system are
mediated by ∝1 + β1 + β2 receptors.

Sympathetic preganglionic nerves originate from the thoracolumbar division of the spinal cord

Parasympathetic preganglionic nerves originate from the cranio- sacral region of the spinal cord.

Although all effector organs innervated by the parasympathetic nervous system have muscarinic
receptors, the kind of response (stimulation of inhibition) depends on the particular effector cell
(organ)

For example;

Activation of parasympathetic nerves to the heart causes an inhibitory response i.e. a reduction in
heart rate but activation of parasympathetic nerves to the smooth muscle of airways causes an
excitatory response i.e. muscle contraction (bronchoconstriction)

Some drugs interact directly with muscarinic receptors

= parasmpathomimetic drugs

Others do not interact directly but inhibit the normal metabolic inactivation of the
neurotransmitter.

= acetylcholinesterase inhibitor

Other drugs also block the ability of acetylcholine and parasympathominetic drugs to bind to and
activate the muscarinic receptors
= anticholinergic, antimuscarinic or parasympathetics

Drugs that block acetylcholine from binding to its nicotinic receptors particularly those on
skeletal muscle i.e. neuromuscular blocking drugs

e.g. vercuronium, suxamethonium, tubocurarine

NERVOUS SYSTEM

TWO PRINCIPAL DIVISIONS

CNS Peripheral Nervous System

Brain and Spinal cord Automatic nervous Somatic nervous

system system

controls smooth muscle controls skeletal muscle

cardiac muscle (voluntary movements)

secretary glands

parasympathetic sympathetic

these maintain homeostasis and control

involuntary actions
 periphery afferent nervous CNS efferent nerves periphery
monitors
interprets
& processes incoming information and
Transmits signals which modify body activity

Sympathetic Nervous System Parasymathetic Nervous System

Also referred to as thoracolumbar division of also referred to as craniosacral
Autonomic nervous system division of the autonomic nervous
System

SPINAL CORD BRAIN OR SPINAL CORD

T1 – L2

Acetylcholine Nicotinic receptors

Nicotinic Acetylcholine
receptors

Adrenergic Noradrenaline Acetylcholine

Receptors

∝1 β 1 β 2
Muscarinic receptors

Somatic Nervous System

Effects of acetylcholine from postganglionic parasympathetic
nerves are mediated by muscarinic receptors. Effects of
acetylcholine from somatic nerves are mediated by nicotinic
receptors and effects of noradrenaline and adrenaline from the

Acetylcholine sympathetic nervous system are mediated by ∝1 β 1& β 2

Sympathetic preganglionic nerves originate from the thoracolumbar division of the spinal cord.

Parasympathetic preganglionic nerves originate from the craniosacral region of the spinal cord.

Noradrenaline affects ∝1 & β 1 receptors. Adrenaline affects ∝1 β 1& β 2 receptors

∝2 receptors are found on postganglionic sympathetic nerve ending. These receptors provide a
negative feedback to inhibit noradranaline release from the nerve.

β 1 adrenagic receptors are found mainly in heart whereas ∝1 and β 2 are found on many
sympathetic target organs.

Because of the different locations of these receptors, different drugs can be used to stimulate or
block them and the response they mediate.

SYMPATHOMIMETIC drugs mimic some or all of the effects produced by Noradrenaline and
Adrenaline on stimulation of the sympathetic nervous system.

Other synonyms are adrenergic agonists, adrenergic drugs or sympathetic amines.

Adrenaline, Noradrenaline and several other sympathominetic are classified as catecholamines

because of their chemical structure. They may stimulate ∝ -adrenergic receptors, β-receptors or
both.

Sympathominetic drugs act in one of three ways:

A. DIRECT ACTING SYMPATHOMIMETICS cause their effects by interacting directly

with receptors on the effectors. The response depends on the agonist’s specificity (∝
and/or β) and the receptor types found on effect cell.
 They range from being totally non selective (they stimulate all ∝ and all β receptor. The
least selective is adrenaline (epinephrine)
B. INDIRECT ACTING SYMPATHOMIMETICS work only by entering the nerve and
releasing noradrenaline which then stimulates the receptors. Unlike the other group, these
do not even have weak actions on adrenergic receptors e.g. amphetamines.
C. MIXED ACTING SYMPATHOMIMETICS act directly on target all receptors and also
at the same time release noradrenaline from adrenergic nerves which also act on the
effectors. Depending on the particular drug the responses may be similar to those caused
by adrenaline and noradrenaline.
e.g. Ephedrine (not a catecholamine) 2 related mixed acting symapathomimetics are
Mephentermine and metararminol 2 others found in OTC preparations are phenyl
propanolamine and pseudoephedrine.

Selectivity of Direct Sympathominetics

1. Non selective (∝ and β) Agonists

e.g. Adrenaline (Epinephrine)
∝1 & β1 Agonist
e.g. Noradrenaline
2. Selective and agonist
Found in various OTC preparations
e.g. phenylephrine for colds, allergy or ophthalmic
other related drugs Methoxaine decongestant production
naphazolne
oxymetezoline
tetrahydrozoline
xylometazoline
3. Non selective beta Agonist (β 1and β 2)
e.g. Isoprenaline (Isoproterenol)
4. Selective β 2 Agonists
e.g. Salbutamol (Albuterol)
terbutaline

Selective β 1 Agonists
Dopamine

Dobutamine

INOTROPES

An agent that increases or decreases the force or energy of muscular contractions of the heart
muscle. Positive inotropes increase the force of muscle contraction.

Negative Inotropes decrease the force of muscle contraction.

E.g. of Positive Inotropic Agents

 Calcium
 Cardiac glycosides
e.g. Digoxin
 Catecholamines
e.g. Dopamine
Dobutamine
Adrenaline
Isoprenaline
Noradrenaline
 Phosphodiesterase inhibitors
e.g. Enoximone
milrinone

e.g. of Negative Inotropic Agents

β – blockers

Diltiazan

Verapamil
Responses of Major Effector Organs Sympathomimetic Drugs (∝ or β Agonist)

Organ Receptor Type Response

Eye
Iris, dilator muscle ∝ Contracted causing mydraisis
Respiratory system
Bronchial smooth β2 Decreased (relaxation)
Muscle tone
Mucus secretion ∝ Decreased (thickened)
Heart
Force of contraction β1 Increased
Rate β1 Increased
Automaticity β1 Increased
Impulse conduction β1 Increased
Arterioles and ∝ Constriction
Large veins β2 Dilation
Metabolic Effects
Fat cells β1 Increased hipolysis
Skeletal muscle β2 Glycogen breakdown
Liver
Pancreas β2 Increased insulin release
Gastrointestinal Tract
Motility ∝1 β 2 Decreased
Sphincters ∝ Contracted
Overall effect Decreased tone, motility
Urinary bladder
Detrusor β2 Relaxation

GENERAL ANAESTHETIC DRUGS

General anaesthetics depress the CNS and cause a loss of consciousness associated with an
inability to perceive pain.

An ideal anaesthetic would produce amenesia with unconsciousness, analgesia and muscle
relaxation suitable for all surgical procedures and would be metabolically inert and rapidly
eliminated.
No single anaesthetic fulfills all these requirements in safe concentrations and so a number of
drugs are often used to achieve the required conditions whiles minimizing the risk of toxicity.

General Anaesthetics are administered either by inhalation or intravenously

IV anaesthetic agents include

The barbiturates e.g. thiopentone

Phenol e.g. propofol

Carboxylated Imidazole e.g. Etomidate

Phencyclidine e.g. Ketamine

Inhalation anaesthetics include Halothane, Enflurane, Isoflurane, Nitrous oxide, anaesthetic

ether

The activity of any anaesthetic is dependent on its ability to its ability to reach the brain. With
the injectable anaesthetics, their activity is dependent on their ability to cross the blood brain
barrier and recovery from their effects is determined by their redistribution and excretion.

Conventional General Anaesthesia may be divided into a number of stages including:

premedication