Drugs acting on Autonomic Nervous System (ANS)

what is Autonomic Nervous System (ANS)

The part of the nervous system that is not in our own control is called the autonomic nervous system.

what Autonomic Nervous System (ANS) regulates

 Contraction and relaxation of smooth muscle

 Exocrine and some endocrine secretions

 Rate and force of contraction of the heart

 Certain metabolic processes (e.g. glucose utilisation)

N.B: The ANS functions for the most part at the subconscious level. We are not aware, for example, that our pupils are dilating or that our arteries are constricting

Division of ANS

1. Sympathetic system

2. Parasympathetic system

explain Sympathetic system in ANS

the larger of the two parts of the autonomic system and widely distributed throughout the body. The preganglionic fibres of the sympathetic system secrets acetylcholine, whereas the postganglionic fibres secrets nor-epinephrine with a few exception (acetylcholine at sweat gland, piloerector muscle etc.).

explain Parasympathetic system in ANS

Preganglionic and the postganglionic fibres of the parasympathetic system release acetylcholine

Drugs acting on ANS (Classification)

1. Drugs that act on cholinergic transmission

2. Adrenergic drugs

Drugs that act on cholinergic transmission can be devided into?

1. Cholinergic drugs

2. Anticholinergic drugs:

other classification of cholinergic drugs and its example

a. Direct acting:

1. Choline ester: Carbachol, Bethanechol Acetylcholine.

2. Alkaloids: Pilocarpine, muscarine.

b. Indirect acting (Anticholinesterase): Physostigmine, Neostigmine, Pyridostigmine, Edrophonium,

Organophosphorus compound

other classification of anticholinergic drugs and its example

a. Natural: Atropine (7-10 days), Hyoscine (3-7 days)

b. Synthetic /Atropine substitutes with clinical uses:

1. Atropine like mydriatics

   Homatropine (1-3 days), Cyclopentolate (1 day), Tropicamide (6 hours). Tropicamide is preferable.

2. b. Antispasmodic

   Hyoscine-n-butyl bromide, Propantheline, Dicyclomine

3. Antiparkinsoniun drugs

   Benztropine, Benzhexol, Procyclidine

4. Bronchodilator

   Ipratropium bromide, Oxytropium bromide

5. Ulcer healing agents

   Pirenzepine

other classification of adrenergic drugs and its example

a. Catecholamines (Having catechol nucleus & amino group in

their aliphatic side chain): Adrenaline, Noradrenaline, Dopamine, Isoprenaline

b. Non-catecholamines: Amphetamine, Tyramine, Ephedrine.

Pharmacological effect of cholinergic drugs

1. Eye: Miosis (due to contraction of ciliary muscle), Accommodation for near vision, decrease Intraocular pressure

2. Exocrine glands : increase secretion of salivary, lachrymal, bronchial and sweat glands

3. Heart: decrease heart rate (bradycardia) , decrease Force of contraction A-V block (Cardiac arrest)

4. Lung: Bronchoconstriction, increase bronchial secretion

5. Blood vessels: Dilatation (By Releasing EDRF, No), decrease BP

6. GIT, Bladder & ureters, Neuromuscular junction, CNS

type of Cholinesterase enzyme

I. True cholinesterase or acetylcholinesterase

II. Pseudocholinesterase

explain True cholinesterase or acetylcholinesterase

In the region of cholinergic nerve ending and in erythrocyte (RBC), there is an enzyme that destroys or metabolize acetylcholine is called true cholinesterase or acetylcholinesterase.

explain Pseudocholinesterase

In various tissue, especially blood plasma, there is other esterase enzyme which is not specific for acetylcholine but which also destroys or metabolize other ester (eg. Suxamethonium) is called Pseudocholinesterase. Hereditary absence of this enzyme may lead to suxamethonium apnoea.

The types and distribution of cholinergic receptors

1. Muscarinic receptors - M1 (Brain, nerve), M2 (Heart, nerve, smooth muscle), M3 (Endothelium of blood vessels, glands and smooth muscles)

2. Nicotinic receptors - NN (Autonomic ganglia, adrenal medulla), NM (Neuromuscular junction

Mechanism of action of Cholinergic drugs

 Direct acting cholinergic drug directly bind to and activate muscarinic or nicotinic receptors to induce response.

 The indirect acting cholinergic drugs increase the endogenous acetylcholine concentration in synaptic cleft by inhibiting acetylcholinesterase.

Clinical uses of cholinergic drugs

1. To lower intraocular pressure in chronic simple glaucoma (Pilocarpine).

2. To stimulate the bladder and bowel after surgery (Carbachol, Bethanechol).

3. Atropine poisoning (Physostigmine)

4. Reversal of neuromuscular paralysis induced by neuromuscular blocking drugs (Neostigmine).

5. For myasthenia gravis, both to diagnose (edrophonium) and to treat (neostigmine, pyridostigmine).

Organophosphorus compound (OPC) or irreversible acetylcholinesterase example

 Diiso propyl fluro phosphate (DPFP)

 Tetra ethyl pyro phosphate (TEPP)

 Parathion

 Malathion

Uses of OPC

They are used in agriculture as insectisides.

Clinical uses of Atropine like mydriatics

 Used in opthalmology for fundoscopic examination of retina

 Used in intraocular lens operation and cataract surgery.

 Used to prevent in synechia in uveitis and iritis.

Clinical uses of Antispasmodic

 GIT colic

 Ureteric colic

 Billiary colic

 Infantile pyloric stenosis.

Clinical use of Antiparkinsoniun drugs

Used in case of drug induced Parkinsonism by Chlorpromazine or Metoclopramide.

Clinical uses Bronchodilator

 Used in bronchial asthma.

 Chronic obstructive pulmonary disease (COPD)

Clinical uses Ulcer healing agents

Peptic ulcer

Mechanism of action of Atropine

Atropine competitively block the muscarinic receptor and inhibit or antagonize the action of acetylcholine

Pharmacological effects of Atropine

1. Exocrine gland: All secretion except milk are diminished. e.g : gastric acid secretion, Bronchial secretion, Salivary secretion

2. Eye: Mydriasis (Dilatation of pupil), Cycloplegia (Paralysis of ciliary muscle, Intraocular pressure, Loss of light reflex.

3. CVS: increased heart rate (tachycardia)

4. Smooth muscle: Relaxation of smooth muscle. e.g: Respiratory tract Relaxation of bronchial smooth muscle

5. CNS: Effective against both tremor & rigidity of Parkinsonism, Prevents or abates motion sickness.

6. Skin: It counteract the action of acetylcholine, Hot & dry skin, Sweating may be suppressed. So, increase body temperature (Atropine fever)

In toxic doses of Atropine to CNS

Excitement, agitation, hallucination

Clinical uses of Atropine

a. Treatment of organophosphorus poisoning.

b. As antispasmodic (GIT colic, genitourinary colic, billiary colic).

c. Preanesthetic medication

d. As anti-parkinsonism

e. As anti-motion sickness

Adverse effects of Atropine

 Dry mouth

 Blurring of vision.

 Constipation

 Urinary retention

 Hot dry skin

 Hyperthermia (Atropine fever)

 Mydriasis

 Arrhythmia

Pharmacological effect of adrenergic agonist

1. Cardiovascular system: increase heart rate and force of contraction

2. Blood vessels: Vasoconstriction (α receptor), Vasodilatation (β2 receptor)

3. Lung: Bronchodilatation (β2 receptor)

4. Eye: Dilatation of pupil (Mydriasis), Increase outflow of aqueous humor (α agonist), decrease production of aqueous humor (β agonist)

5. GIT: Relaxation of GIT smooth muscle.

6. Metabolic: increase lipolysis (β), increase glycogenolysis in liver (β2)

Adrenergic receptor distribution

1. α adrenoceptor (α1, α2):

   α1 (Most vascular smooth muscle,Prostate ), α2 (Adrenergic & cholinergic nerve terminals).

2. β adrenoceptor (β1, β2, β3):

   β1 (Heart), β2 (Bronchial smooth muscle, skeletal muscle blood vessels, human liver), β3 (Fat cell).

3. Dopamine receptors (D1, D2):

   D1 (Smooth muscle of renal blood vessels), D2 (Nerve ending)

Adrenergic Agonist

I. Adrenergic β agonist: Adrenaline, Noradrenaline, Dopamine, Isoprenaline, Ephedrine, Salbutamol

II. Adrenergic α agonist: Oxymetazoline, Xylometazoline, Phenylephrine

Clinical indication of adrenergic agonist

1. Cardiac arrest: Adrenaline

2. Cardiogenic shock: Dopamine

3. Treatment of asthma: Salbutamol

4. To prolong local anesthetic action by vasoconstriction: Adrenaline

5. To control local bleeding (epistaxis): Adrenaline pack

6. As nasal decongestant in rhinitis & common cold: Oxymetazoline

Role of Dopamine in Cardiogenic shock

1. Elevation of blood pressure

   Dopamine acts on β1 receptor on heart, Increase force of contraction & heart rate, Increase cardiac output (CO), Elevation of blood pressure (BP)

2. Increase perfusion of vital organs (kidney, brain, heart)

   Dopamine by acting on D1 & D2 receptor, increase renal & splanchnic blood flow cause Hyper-perfusion of vital organs

Why Adrenaline is used with local anesthetics

Adrenaline causes vasoconstriction, so it causes delayed absorption of local anesthetics due to blockage of blood flow to the injection site leading to prolongation of action of local anesthetics.

Action of Adrenaline on Blood pressure

Adrenalin acts on α1 receptor on blood vessels and causes Vasoconstriction leading to increase BP

Treatment of Adrenaline over dose

1. β effect: Cardiac dysrrhythmia: blocked by Propranolol (β blocker).

2. α effect: Severe hypertension: blocked by Phentolamine (α blocker).

3. Labetalol (both α & β blocker): would be an alternative.

Nasal decongestants: (Adrenergic α agonist)

 Oxymetazoline

 Xylometazoline

 Phenylephrine

How Nasal decongestants act?

In nasal congestion, there is vasodilatation and oedema. Nasal decongestants cause vasoconstriction and also anti-secretory. So, effective in rhinitis, common cold etc

Indication of adrenaline

1. Anaphylactic shock

2. Status asthmaticus

3. With local anesthetic to prolong action.

4. Cardiac resuscitation

5. Hypoglycemic shock

Contraindication of adrenaline

1. Hypertension

2. Ischemic heart disease

3. Diabetes mellitus

4. Cardiac arrhythmia

5. Hyperthyroidism