Parasympatholytic drugs

Parasympatholytic drugs
Prepared by- Shagufta Farooqui
Department of Pharmacology
Nanded Pharmacy College, Nanded

Introduction
Drugs that block or inhibit the action of acetyl choline(Ach) in the
parasympathomimetic nervous system.
Also called cholinegic blocking agent or parasympatholytics
Often referred to as anticholinergics or antimuscarinics

Atropine is obtained from Atropa belladonna, and Datura stramonium.
Scopolamine is found in the shrub Hyoscyamus niger and Scopolia
carniolica.
Atropine consists of equal parts of d-and l-hyoscyamine, but the
anitimuscarinic activity is almost wholly due to the l-isomer.
The active ingredient in scopolamine is l-hyoscine. Atropine
(hyoscyamine) is composed of tropic acid (active) and tropine (tropanol-
inactive).

Atropine Pharmacological action
At low doses atropine produces slowing of heart rate
High doses accelerate heart beat.
Atropine like drugs antagonize the fall in B.P caused by choline esters
The most prominent effect of atropine is
tachycardia. It is due to blockade of M2 receptors
on the SA node through which vagal tone
decreases HR

Atropine blocks waterly salivary secretions
induced by parasympathetic stimulation.
The drug which decrease the salivary secretion is
termed as anhidrotic (Anhidrosis is the
inability to sweat normally. When you don't
sweat (perspire), your body can't cool itself,
which can lead to overheating and sometimes to
heatstroke a potentially fatal condition.
Anhidrosis — sometimes called hypohidrosis.
It causes dry mouth (Xerostomia) a
characteristic state of anxiety and sudden fear.
Salivary Secretions:

Atropine does not affect normal peristaltic
movement. It relieves on hyper motility.
Atropine can reduce the volume and total
acidity of gastric secretion.
Atropine blocks the secretions increased by
parasympathomimetic drugs
GIT:

Atropine produces an antispasmodic action
on biliary tract.
Biliary secretion

Urinary bladder: (Urinary tract). Atropine
of reduces the tone of urinary bladder and
tends to produce urinary retention.
Atropine has relaxant action on ureter and
urinary bladder; urinary retention can occur in
older males with prostatic hypertrophy.
However, this relaxant action can be beneficial
for increasing bladder capacity and
controlling detrusor hyperreflexia in
neurogenic bladder/enuresis.

Bronchi:
Atropine relaxes smooth muscles of bronchi.
It reduces the secretions so it is not
recommended in the treatment of bronchial
asthma.
They dry up secretion in the respiratory tract,
may lead to its inspissation and plugging of
bronchioles resulting in alveolar collapse and
predisposition to infection.
The mucociliary clearance is also impaired.

Orally administered atropinic drugs are
bronchodilators, but less effective than
adrenergic drugs; not clinically used.
Inhaled ipratropium bromide has been
found to be specially effective in asthmatic
bronchitis and COPD, though less so in
bronchial asthma.

Eye: Atropine produces mydriasis by
blocking the cholinergic supply.
Atropine causes increase in focal length of
the lens.
Individual can see the objects at long
distance, cannot constrict the pupil for
seeing near objects or in response to bright
light.
Individual suffers from photophobia.
The process is known as, "Paralysis of
accommodation of the eye or cycloplegia.
Atropine on local instillation produces
both mydriasis and cycloplegia.
Atropine cause increase in ocular tension.

Topical instillation of atropine causes mydriasis, abolition of light reflex
and cycloplegia lasting 7–10 days.
This results in photophobia and blurring of near vision.
The ciliary muscles recover somewhat earlier than sphincter pupillae.
The intraocular tension tends to rise, especially in narrow angle
glaucoma.

Body temperature: Rise in body temperature occurs at higher doses.
The rise in temperature occurs inspite of the coetaneous vasodilatation
produced by the drug.
It is due to both inhibition of sweating as well as stimulation of
temperature regulating centre in the hypothalamus. Children are highly
susceptible to atropine fever.
This effect of atropine may be due to its anhidrotic action. In case of
atropine poisoning the body temperature may rise to 104 to 105 degree F

CNS: Atropine has an overall CNS stimulant action. However, these effects are
not appreciable at low doses which produce only peripheral effects because of
restricted entry into the brain.
Hyoscine produces central effects (depressant) even at low doses.
• Atropine stimulates many medullary centres—vagal, respiratory, vasomotor.
• It depresses vestibular excitation and has antimotion sickness property.
• By blocking the relative cholinergic over activity in basal ganglia, it suppresses
tremor and rigidity of parkinsonism.

Pharmacokinatics: Atropine i.e. belladonna alkaloids are well absorbed orally
and parenteral administration. Atropine crosses the placental barrier and also is
secreted in breast milk. It is partially metabolized in the liver and partly excreted
unchanged by kidneys.
Interaction:
Absorption of most drugs is slowed because atropine delays gastric emptying.
This results in slower absorption and greater peripheral degradation of levodopa—
less of it reaches the brain.
This does not occur when a peripheral decarboxylase inhibitor is combined.
Antacids interfere with absorption of anticholinergics.
Antihistaminics, tricyclic antidepressants, phenothiazines, disopyramide,
pethidine have anticholinergic property—additive side effects occur with atropinic
drugs

Contraindications: Atropine generally is contraindicated in patients with
glaucoma, pyloric stenosis or prostatic hypertrophy, except in doses
ordinarily used for preanesthetic medication.
Atropine Sulfate Injection, should be used with caution in all individuals over
40 years of age.

As antisecretory
As antispasmodic
2.Motion sickness
To antagonise
muscarinic effects
of
drugs and poisons
As mydriatic and
cycloplegic
Peptic ulcer
Pulmonary
embolism
For central action
1. Parkinsonism
Uses

Toxic effects of Atropine
1) Due to toxicity, there is difficulty in speech, swallowing and dry
mouth
2) The skin becomes dry and there is an increase in the body
temperature,
3) There is mydriasis and paralysis of accommodation (cycloplegia),
4) There is urinary urgency and difficulty in micturition.
5) The excitement, restlessness and there is motor incordination

SCOPOLAMINE:
It is also known as Hyoscine. It is a belladonna alkaloid, is anticholinergic agent.
Mechanism of action: It acts: i) as a competitive inhibitor at postganglionic
muscarinic receptor sites of the parasympathetic nervous system and is it act on
smooth muscles that respond to acetylcholine but lack cholinergic innervation.
It binds to muscarinic receptors This prevents acetylcholine from binding to and
activating the receptors which would re in contraction of the smooth muscle. The
inhibition of contraction reduces spasms and their related pain during abdominal
cramping.

Pharmacological Action:
It possesses the same pharmacologic properties as atropine, but in some cases
to differing degrees.
The vagolytic action of scopolamine is less than that of atropine, as is its effect
in producing mydriasis.
In addition, whereas atropine produces a stimulation of the CNS, scopolamine
depresses the cerebral cortex.
Scopolamine possesses a more intense drying effect than atropine.

Side effect: It has possible side effects are excitement, restlessness,
disorientation, and delirium during the postoperative recovery period.
This does not occur with atropine or glycopyrrolate.
Emergence delirium, as it is known, is more likely to be observed in the very
young or older adult patient.

Pharmacokinetics: It is well absorbed by transdermal patch. The oral
bioavailability is 27% and 0.25% ophthalmic solution is rapidly absorbed after
ocular administration. The distribution is not well characterized, but may be
reversibly bound to plasma proteins and known to cross the placenta and
blood-brain barrier. Time to peak concentration after transdermal
administration is 24 hours. It is extensively metabolized and conjugated. The
renal excretion is less than 10 %, and less than 5% is unchanged.

Uses:It is a medication used to treat motion sickness and postoperative nausea
and It is also sometimes used before surgery to decrease saliva. It is used
antimuscarinic, anticholinergic agent.
It is used to treat pain and discomfort caused by abdominal cramps,
vomiting.menstrual cramps, or other spasmodic activity in the digestive system. It
is also effective at preventing bladder spasms

ATROPINE SUBSTITUTES
Many semisynthetic derivatives of belladonna alkaloids and a large number
of synthetic compounds have been introduced with the aim of producing
more selective action on certain functions.
Most of these differ only marginally from the natural alkaloids, but some
recent ones appear promising.
Quaternary compounds
These have certain common features—
• Incomplete oral absorption.
• Poor penetration in brain and eye; central and ocular effects are not seen after
parenteral/ oral administration.
• Elimination is generally slower; majority are longer acting than atropine.
• Have higher nicotinic blocking property. Some ganglionic blockade may occur
at clinical doses
→ postural hypotension, impotence are additional side effects.
• At high doses some degree of neuromuscular blockade may also occur.

Ipratropium bromide:
40–80 μg by inhalation; it acts selectively on bronchial muscle without altering
volume or consistency of respiratory secretions.
Another desirable feature is that in contrast to atropine, it does not depress
mucociliary clearance by bronchial epithelium.
It has a gradual onset and late peak (at 40–60 min) of
bronchodilator effect in comparison to inhaled sympathomimetics.
Thus, it is more suitable for regular prophylactic use rather than for rapid
symptomatic relief during an attack. Action lasts 4–6 hours.
It acts on receptors located mainly in the larger central airways (contrast
sympathomimetics whose primary site of action is peripheral bronchioles

Tiotropium bromide:
A newer congener of ipratropium bromide which binds very tightly to
bronchial M1/M3 muscarinic receptors producing
long lasting bronchodilatation.
Binding to M2 receptors is less tight confering relative M1/M3 selectivity (less
likely to enhance ACh release from vagal nerve endings in lungs due to M2
receptor blockade).
Like ipratropium, it is not absorbed from respiratory and g.i. mucosa and has
exhibited high bronchial selectivity of action.

Propantheline
15–30 mg oral; it was a popular anticholinergic drug used for peptic ulcer and
gastritis.
It has some ganglion blocking activity as well and is claimed to reduce gastric
secretion at doses which produce only mild side effects.
Gastric emptying is delayed and action lasts for 6–8 hours. Use has declined due
to availability of H2 blockers and proton pump inhibitors.

Vasicoselective drugs
1. Oxybutynin This newer antimuscarinic has high affinity for receptors in
urinary bladder and salivary glands alongwith additional smooth muscle
relaxant and local anaesthetic properties.
It is relatively selective for M1/M3 subtypes with less action on the M2 subtype.
Because of vasicoselective action, it is used for detrusor instability resulting in
urinary frequency and urgeincontinence.
Beneficial effects have been demonstrated in post-prostatectomy vasical spasm,
neurogenic bladder, spina bifida and nocturnal enuresis. Anticholinergic side
effects are common after oral dosing, but intravasical instillation increases bladder
capacity with few side effects. Oxybutynin is metabolized by CYP3A4; its dose
should be reduced in patients being treated with
inhibitors of this isoenzyme

Parasympatholytic drugs

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