Parasympathetic (PNS)

✔The parasympathetic nervous system carries on many of the day-to-day

functions:-

(a) Flow of saliva, lacrimation&sweeting.

(b) Peristalsis

(c) Constriction of pupils

(d) Accommodation for near vision

✓Exclusively neurotransmitter. uses Acetyl choline (Ach) as a

✓ Parasympathetic actions do not require quick response, they are a slower

set of reactions.

✓Acetylcholine is a neurotransmitter at all autonomic ganglia. It is released

by preganglionic nerve endings and stimulates nicotinic receptors on

postganglionic neurons.

✓Acetylcholine is also the neurotransmitter at all parasympathetic nerve

endings. After release, ACh stimulates muscarinic receptors on the

innervated tissue.

✔Within the nerve, ACh is stored in synaptic vesicles, which are released in

response to depolarisation of the nerve terminal and an increased influx of

Ca++
✓Rapid hydrolysis of ACh at the synaptic cleft by

acetylcholinesterase(AChE)=TrueCHE inactivates the ACH

NICOTINIC MANIFESTATIONS

1. •Stimulation of neuromuscular junction and skeletal muscle

contraction.

2. •Antidiuersis due to stimulation of hypothalamus and release of

antidiuertic hormone.

3. •Hypertension and tachycardia due to stimulation of release of

adrenaline.

MUSCARINIC MANIFESTATIONS

1. •Bronchospasm and dyspnea.

2. • Nausea and vomiting.

3. •Diarrhea and colic.

4. •Urination and salivation.

5. • Sweating and lacrimation.

6. •Hypotension and bradycardia.

PARASYMPATHOMIMETICS
Definition: These are drugs which produce manifestation like

parasympathetic stimulation.

Classification:
A) Direct parasympathomimetics:

Which directly stimulate muscarininc or nicotinic parasympathetic receptors

or both and these drugs include:

1) Choline esters e.g. Acetylcholine, Methacholine, Carbachol,

and Bethanechol( Urecholine).

2) Natural alkaloids e.g. Pilocarpine and muscarine.

B) Indirect parasympathomimetics:

1) Reversible anticholine esterases e.g. Neostigmine and Physostigmine.

2) Irreversible anticholine esterases e.g. Organic phosphorus drugs.

1- Acetylcholine
It is physiological transmitter of parasympathetic nervous system which

stimulates both nicotinic and muscarininc receptors.

Formation : 1) Acetic acid + Co A produce active acetate (acetyl CoA).

2) Active acetate + Choline in presence of choline

acetyltransferase enzyme produce Acetylcholine and Co A.

Storage :-

In Cholinergic nerve endings.

Release:

Acetylcholine is released at the following sites:

1) All preganglionic nerve fibers.

2) All autonomic ganglia.

3) All postganglionic parasympathetic nerve endings.

4) All motorend plates (skeletal muscles).

Pharmacological actions:
1) It has muscarinc and nicotinic actions.
2) It has very short duration of action because it is rapidly hydrolysed by

pseudo and true cholinoesterases.

3) It is not effective orally.

4) It has multi pharmacological actions:-

•On the eye: miosis by stimulating constrictor papillae muscle, decrease

intraocular pressure and vasodilatation.

•On salivary glands: large watery false secretions.

•On respiratory system: bronchospasm, increase secretions and congestion.

•On CVS: bradycardia and hypotension.

•On GIT: increase intestinal motility and secretions leading to defecation.

•On urinary bladder: urination or micturation.

•On Skeletal muscles: it produces contraction.

Indications:-
Practically Ach is not used in medicine because it has very short duration of

action and effective orally also it has multiequipotent pharmacological

actions but clinically we prefer other parasympathomimetics because they

are effective orally and locally and also they are more selective with less

side effects.
Parasympathomimetics are used in the following cases:

1) Glaucoma: we use pilocarpine and physostigmine (eserine).

2) Xerostomia: we use neostigmine and carbachol.

3) Paralytic ileus:we use neostigmine and Carbachol

4) Myasthenia gravis: we use neostigmine and its substitutes

N.B.
•Pilocarpine is more selective on the eye

•Physostigmine is more selective on the eye

•Neostigmine is more selective on skeletal muscles

Adverse effects of parasympathomimetics

These adverse effects are due to muscarininc manifestations which are :

1 - Hypotention and brady cardia due to cardiovascular depression

2 - Bronchospasm and dyspnea

3 - Nausea and vomiting

4- Diarrhia.

5- Urination and lacrimation

6- Sweating and salivation

Organic phosphorus compounds

These drugs are used as insecticides. They are not used in medicine.

e.g. parathion, malathion, D.F.P.and echothiophate.

We study these drugs in medicine because of their toxicity

Mode of toxicity by organophosphorus drugs:

1. Accidental between children and farmer

2. Suicidal attempts

3. As war gas

Manifestations of toxicity:
1- Hypotension

2- Severe constriction of pupil (pin point pupil)

3- Nausea and vomiting

4- Diarrhea and colics

5- Bronchospasm and dyspnea

6- Lacrimation and salivation

7- Lastly convulsions may develop.

Treatment of organophosphorus (insecticides poisoning):
1- Gastric lavage, prevent further exposure.

2- Skin wash if it is contaminated.

3- Atropine sulphate 1mg intravenous every 15 min till full pupillary dilated

(full atropinization).

4- Choline esterase reactivators (oximes) e.g. pyridine-2- aldoxime

methochloride (PAM), DAM.

5- Artificial respiration and oxygen inhalation.

Contraindications of parasympathomimetics
• Peptic ulcer.

•Heart block.

•Parkinsonism.

•Bronchial asthma.

•Angina pectoris.

•Hyperthyrodisum.

Parasympatholytics (anticholinergic drugs)

✔These are drugs that block muscarininc receptors only they

have no effect on nicotinic receptor.

✔They are also called cholinoreceptor blockers or anticholinergics.

✓ Antimuscarinic agents are competitive antagonists of ACh and other

muscarinic agonists.

Classification:
1)Atropine sulphate.

2)Scopolamine (Hyoscine).
3)Atropine substitutes.

Atropine
Sources: Plants ....Datura stramamonium, Atropa belladonna and

Hyoscyamus niger.

Mechanism of action: It competes with Acetyl choline for its muscarininc

receptors it forms An umbrella over the receptor.

Pharmacological actions:

1) On EYE: -Passive mydriasis due to paralysis of constrictor pupillae muscle.

-Increase intraocular pressure due to angle of eye closure and decreased

acqueous humor drainage.

-Cycloplegia or loss of accomdation reflex for near objects due to ciliary

muscle paralysis.

-Photophobia due to loss of light reflex due to paralysis of constrictor

pupillae muscle.

-Xerophthalmia (eye dryness) due to lacrimal gland paralysis.

N.B: The duration of action of atropine on eye is prolonged up to 7-10 days

and it is difficult to be reversed.

2-on Secretions: It decreases all exocrine secretions e.g. sweat, salivary,

bronchial, lacrimal and GIT seretions.

3) On Smooth muscles: It leads to relaxation because it block muscarininc

receptors in smooth muscles and also because it is direct smooth muscle

relaxant.

4) On Respiratory system: It stimulates respiratory center

.lt relaxes bronchial smooth muscles.

It decreases respiratory secretions.

5) On GIT: It relaxes smooth muscles of intestine. It decreases gastric

secretions. Prevent vomiting. Relax smooth muscles of gall bladder.

6) On Urinary bladder: It relax bladder wall It close uretheral sphincter

leading to urinary retention.

N.B:

Atropine should be avoided in old male patients for fear of Glaucoma in eye,

and urine retention as old males have enlarged prostate and susceptible for

urine retention.

Therapeutic uses (indications):

1) Pre anesthetic medication.

2) All types of colic: renal, biliary, intestinal, and uterine colics.

3) Antidote of all Parasympathomimetics poisoning e.g. insecticides

poisoning.

4) Motion sickness and vomiting.

5) Examination of the eye.

Adverse effects and toxicity:

Dry mouth, palpitation, tachycardia, atropine flush, fever and CNS

stimulation.

Treatment: Neostigmine methyl sulphate 1-3 mg IM.

Atropine substitutes
I-ANTISECRETORY/ANTISPASMODIC=•Hyoscine butyl bromide.

Il-Antiasthmatic Ipratropium •Ipratroium

III-Antiparkinsonism• Benztropine.
Drugs with atropine like action:-

•Antipsychotics.

•Antihistaminic.

•Tricyclic antidepressant.

Scopolamine (hyoscine)
✓Similar to atropine except in that hyoscine is central depressant while

atropine is central stimulant. Also atropine is more powerful in diminishing

secretions while hyoscine is more powerful as smooth muscle relaxant.

✓ Scopolamine has a more prominent action on the iris, ciliary body, and

exocrine secretory glands (salivary, bronchial & sweat)

✓ Scopolamine crosses the placenta

✓ Its duration of action is shorter

Anti-nicotinic drugs
•These are also called Ganglion blockers & neuro-muscularBlocker.

•Clinically used drugs

-----Trimethaphan.....G. Blocker.

-----Tubocurarine (Curare).

......Succinylcholine.

•These are used in anesthesia to facilitate intubation and to provide skeletal

muscle relaxation during surgery or mechanical ventilation.