Autonomic Nervous

System
Cholinergic Drugs
 Parasympathetic Nervous System
Works to save energy, aids in digestion, and supports
restorative, resting body functions- Rest & Digest.
Decrease in heart rate
Increased gastro intestinal tract tone and peristalsis
Urinary sphincter relaxation
Vasodilation – decrease in blood pressure
Cholinergic Receptors
 Cholinergic Drugs
Often called parasympathomimetic drugs, because their action
mimics the action of the PSNS.
Also called as cholinomimetic.
Stimulate parasympathetic nervous system in same manner as
acetylcholine
Cholinergic agonists are two types : 1.Direct
acting
2.Indirect acting
 Direct acting cholinergic agonist

They act by binding directly to cholinoceptors.

Direct acting cholinergics are lipid insoluble.
Do not readily enter the CNS so effects are peripheral.
Resistant to metabolism by acetylcholinesterase.
Effects are longer acting than with acetylcholine.
Acetylcholine
Methacholine Muscarine

Carbachol Pilocarpine

Bethanechol Arecoline
Drug Effects of Cholinergic Agents

Cardiovascular effects
Decreased heart rate( Bradycardia)
Vasodilation (NO mediated)
Stimulate intestine and bladder
Increased gastric secretions
Increased gastrointestinal motility
Increased urinary frequency
Drug Effects of Cholinergic Agents
Stimulate pupil
Constriction (miosis), Spasm of accomodation
Reduced intraocular pressure (increased
outflow)
Respiratory effects
Bronchial constriction, narrowed airways
Increased salivation and sweating
Drug Effects of Cholinergic Agents
“MSLUBDD”
Many Smart Ladies Ultimately Bring Disaster
for
Dudes!
Miosis
Salivation
Lacrimatio
n
Urination
Bronchoconstriction
Defaecation
 Acetylcholine
One of the main neurotransmitters of the ANS is acetylcholine
Acetylcholine is released at preganglionic fibers of both the
sympathetic and parasympathetic nervous system
Also released from postganglionic sympathetic neurons that innervate
the sweat glands and from motor neurons that innervate the skeletal
muscles
It is a quaternary ammonium compound so cannot penetrate the
membrane.
Does not have any therapeutic importance, because rapid
inactivation by acetylcholinesterases.
It has both Muscarinic & Nicotinic actions .
 Bethanechol
Not hydrolyzed by acetylcholinesterases.
Actions:
Directly stimulates M receptors causing increased intestinal
motility & tone.
It stimulates detrusor muscle of the bladder while trigone &
sphincters are relaxed causing expulsion of urine.
Therapeutic Uses:
Paralytic ileus
Urinary retentions
Helpful for postsurgical atony of the bladder and GI
tract
 Pilocarpine
An alkaloid, lipid soluble & is stable to hydrolysis by
cholinsterases.
Actions:
When applied locally to cornea produces rapid miosis & contraction
of ciliary muscle produces spasm of accommodation.
Therapeutic Use :
In Glaucoma it opens trabecular meshwork around schlemm’s
canal
causes drainage of aqueous humor
IOP immediately decreases.
 Indirect acting Cholinergic agonists
They act through inhibition of Acetyl cholinesterase enzyme,
so increase Acetylcholine level in the synapse.
Accumulation of acetylcholine then occurs which enhances
the activation of the nicotinic and muscarinic receptors.
Anticholinesterase drugs are either reversible or
irreversible inhibitors of acetylcholinesterase.
Reversible: Irreversible:
Neostigmine Organophosphates
Physostigmine Dyflos,
Echothiopate
Pyridostigmine Parathion,
Malathion
Edrophonium Tabun, Sarin,
Soman
Tacrine Carbamates
Donepezil Carbaryl,
Propoxur(baygon)
 Physostigmine -
-only anticholinesterase capable of crossing the blood brain
barrier.
-Is more lipid soluble.
-Used as an antidote for overdosage of anticholinergics such as:
atropine, antihistamines, TCA, phenothiazines.
-May also be used in treatment of glaucoma.
Pyridostigmine -
is the maintenance drug of choice for patients with
Myasthenia gravis.
Neostigmine –
prototype anticholinesterase agent.
Used for long-term treatment of myasthenia gravis and as an
antidote for tubocurarine and other non- depolarizing agents
in surgery.
Donepezil -
Used in the treatment of mild to moderate
Alzheimer’s disease.
Helps to increase or maintain memory and learning
capabilities.
 Uses of Indirect Cholinergic agonists

Glaucoma – Pilocarpine, Physostigmine

Edrophonium to test Myasthenia gravis, Neostigmine
and pyridostigmine in treatment of M.gravis.
Postoperative paralytic ileus - Neostigmine
Postoperative decurarization –
Neostigmine(reverses muscle paralysis)
Cobra bite – edrophonium (prevent respiratory paralysis.
atropine poisoning – Physostigmine (antogonizes both
central and peripheral effects).
Alzheimer’s Disease – Donepezil, galantamine,
tacrine, rivastigmine.
TCA, Phenothiazines overdose -Physostigmine.
 Cholinergic Agents: Side Effects
Side effects are a result of overstimulation of the
PSNS.
Cardiovascular:
Bradycardia, hypotension, conduction abnormalities (AV
block and cardiac arrest)
CNS:
Headache, dizziness, convulsions
Gastrointestinal:
Abdominal cramps, increased secretions, nausea,
vomiting
 Cholinergic Agents: Side Effects

Respiratory:
–Increased bronchial secretions, bronchospasms
Other:
–Lacrimation, sweating, salivation, loss of binocular
accommodation, miosis
 Acute toxic effects of irreversible
cholinesterase inhibitors (OP poisoning )
These agents are lipid soluble
Can enter the body by the eye,skin, respiratory system and
GI tract.
organophosphate insecticides (malathion, parathion) or nerve
gases (sarin, tabun, soman)
These agents cause excessive cholinergic
stimulation (muscarinic) and neuromuscular blockade
 Treatment of OP poisoning
Emergency treatment includes:
Decontamination of clothing
Flushing poison from skin and eyes
Activated charcoal and lavage for GI ingestion
Atropine to counteract the muscarinic effects (2mg IV
every 10 min till pupil dilates, max 50-100mg)
To relieve the neuromuscular blockade by nicotinic
effects, give pralidoxime, a cholinesterase reactivator.
Pralidoxime causes the anticholinesterase poison to
release the enzyme acetylcholinesterase.
Give Pralidoxime as soon as possible as if too much time
passes, the poison bond becomes too strong (aging) for the
pralidoxime to work.
Other oximes- obidoxime, diacetylmonoxime
Anticholinergic Drugs
 Drugs that block or inhibit the actions of acetylcholine
(ACh) in the parasympathetic nervous system (PSNS).
Also called cholinergic blocking agents or
parasympatholytics.
Often referred to as anticholinergics or
antimuscarinics
 Mechanism of Action
Competitive antagonists
Compete with acetylcholine
Block acetylcholine at the muscarinic receptors in
the PSNS
Reversible blockade of acetylcholine at muscarinic
receptors by competitive binding
Once these drugs bind to receptors, they inhibit nerve
transmission at these receptors.
 Atropine

Prototype antimuscarinic drug - derived from Atropa

belladonna (deadly nightshade) and Datura stramonium
(thorn apple)
History:
plant extracts were used as cosmetic eye drops
hence the name belladonna or "beautiful lady" in Italian
 Actions
Cardiovascular effects-
Decreased cardiovascular response to vagal stimulation
resulting in tachycardia
Mainly, tachycardia due to antagonism of the vagal affect.

Vascular
no (direct) effect
except, dilate cutaneous vessels (red as a beet)
block hypotensive effect of muscarinic agonists
 Actions
CNS –
At normal doses atropine stimulates medullary centers,
However, at higher doses produce excitement, agitation,
hallucinations and coma.
Depresses vestibular excitation and has anti motion
sickness properties
Supresses tremor and rigidity of parkinsonism by
blocking cholinergic overactivity in basal ganglia.
 Actions
Ey
e:
Dilated pupils (mydriasis)
Blocks muscarenic innervations on the circular muscles
(Mydriasis) and relaxes cilairy muscles (Cycloplegia)
worsens glaucoma
Gastrointestinal:
Relax smooth muscles of GI tract
Decrease intestinal and gastric secretions
Decrease motility and peristalsis
antispasmodic effect
↑ Sphincter contraction
 Actions
Respiratory system -
Decreases bronchial secretion (used as preanesthetic
Medication,COPD)
Dilated bronchial airways (used for treatment of Asthma)
Genitourinary -
Relaxes detrusor muscle
Increased constriction of internal sphincter
Result: urinary retention
Relaxation of smooth muscles of ureters.
Therefore, they are contraindicated for prostate hypertrophy
patients.
Glandular –
↓ Salivary secretion (Dry mouth)
↓ gastric Acid (used for Peptic Ulcer )
↓ Sweating → Dry skin
↓ Bronchial Secretion (used for COPD)
 Therapeutic Uses

Central Nervous System Disorders-

Parkinson’s disease – Benztropine,
Trihexyphenidyl
Those who cannot take Levodopa
Helpful in decreasing salivation, spasticity and tremors
Motion Sickness (Scopolamine)
Drug-induced extrapyramidal reactions(due to
antipsychotics)
 Therapeutic Uses
CVS –
Atropine is used to increase heart rate in symptomatic
bradycardias.
Sinus node dysfunction
Symptomatic second-degree heart block
Sinus or nodal bradycardia (due to myocardial infarction)
 Therapeutic Uses
Respiratory system-
Decreased secretions from nose, mouth, pharynx, bronchi
Relaxed smooth muscles in bronchi and bronchioles
Decreased airway resistance
Bronchodilation
Respiratory agents are used to treat:
Exercise-induced bronchospasms
Chronic bronchitis
Asthma
Chronic obstructive pulmonary disease
Ipratropium as inhalation (or Tiotropium)
 Therapeutic Uses
Gastrointestinal:
Blockade of PSNS results in:
Decreased secretions
Relaxation of smooth muscle
Decreased GI motility and peristalsis
Gastrointestinal agents are used to treat:
Peptic Ulcer: Pirenzepine
As antispasmodic :Butylscopolamine
Irritable bowel disease: Propantheline
GI hypersecretory states
 Therapeutic Uses

Urologic disorders-
Antispasmodic effects seen in overactive bladder and
in urinary incontinence- Oxybutynin
Detrusor hyper-reflexia
Enuresis
-Increase bladder capacity
-Decrease bladder pressure
 Therapeutic Uses

Opthalmological Disorders-
Homatropine, tropicamide
Accurate measurement of refractive error in
uncooperative patients (e.g, children)
Examination of retina (Mydriasis)
 Side Effects of anticholinergics
Body System Side/Adverse Effects
Cardiovascular Increased heart rate,
dysrhythmias
CNS excitation, restlessness,
irritability, disorientation,
hallucinations,delirium
CNS
 Side Effects of anticholinergics
Body Side/Adverse Effects
System
Dilated pupils, decreased visual
Eye accommodation, increased intraocular
pressure
Decreased salivation, decreased gastric
secretions, decreased motility

Gastrointestinal
 Side Effects of anticholinergics

Body System Side/Adverse

Effects
Genitourinary
Urinary retention

Glandular Decreased
sweating

Respiratory Decreased bronchial

secretions
 Toxicity of Anticholinergics
Anticholinergic overdose syndrome (Belladona poisoning-
consumption of seeds or berries of belladona or dhatura
plant) is characterized by:
- Hyperthermia, delirium, dry mouth, tacycardia, ileus, urinary
retention. Seizures, coma and respiratory arrest may occur.
Treatment –
- Gastric lavage with tannic acid, cold sponging or ice bags,
Physostigmine s.c. or i.v., diazepam to control convulsions.
 Contraindications
Glaucoma
Prostatic hypertrophy
Urinary tract obstruction
Gastrointestinal tract
obstruction
Infectious diarrhea
Reflux esophagitis
Tachyarrhythmias
Angina
Hyperthyroidism
Pregnancy
 Individual Drugs

Atropine - prototype. Antidote in OP Poisoning.

Ipratropium - Useful in rhinorrhea. Also excellent
bronchodilator.
Scopolamine - depresses CNS and causes amnesia,
drowsiness, euphoria, relaxation and sleep. Also good for
motion sickness. Given parenterally, orally and
transdermally.
Benztropine - temporary use in Parkinson’s disease. Useful
for dystonic reactions caused by antipsychotics.
 Individual Drugs
Trihexyphenidyl - also used for treating EPS by some
antipsychotics. Contraindicated in glaucoma.
Flavoxate - relieves dysuria, urgency, frequency, and
pain with GU infections
Oxybutynin - has direct antispasmodic effects on smooth
muscle and anticholinergic effects. Decreases frequency of
voiding.
ADRENERGIC DRUGS
Adrenergic Drugs/Sympathomimetics
These are the drugs that mimic the response of sympathetic or
adrenergic system.
Three major endogenous catecholamines are:
Adrenaline (Adr, Epinephrine)
Noradrenaline (NA, Norepinephrine)
Dopamine
Adrenergic Receptors

α β

α α β1 β2 β3
1 2
Synthesis:
Tyrosine
Tyrosine hydroxylase
Dopa
Amino acid decarboxylase
Dopamine
Dopamine β-Hydroxylase
Noradrenali
ne
Phenylethanolamine N-methyl transferase

Adrenaline
Adrenergic drugs acts through adrenergic receptors.
Adrenergic Receptors/Adenoreceptors are of 2 types: alpha
(α) & beta (β).
Alpha receptors (α)
Beta receptors (β)
Adrenergic drugs/Sympathomimetics
Clinical classification of Adrenergic drugs
 Pharmacological Actions:

Epinephrine (adrenaline) is a potent stimulant of both α and β adrenergic receptors.

Particularly prominent are the actions on the heart and on vascular and other smooth
muscle.
Norepinephrine (Noradrenaline) and epinephrine both are direct agonists on effector
cells, and their actions differ mainly in the ratio of their effectiveness in stimulating α and
β2 receptors.
They are approximately equipotent in stimulating β1 receptors.
Norepinephrine is a potent αagonist and has relatively little action on β2 receptors.
Adverse effects:
Adr-sc/i.m: restlessness, palpitation,
anxiety, tremor, pallor
Adr-i.v. high dose: cerebral
haemorrhage, arrhythmias
Contraindications:
Hypertensive, Hyperthyroidism, Angina
Pectoris
Patient receiving β-blocker.
During anesthesia by Halothane
 Dopamine is the immediate metabolic precursor of norepinephrine and
epinephrine.
Dopamine is a substrate for both MAO and COMT and thus is ineffective when
administered orally.
It doesn’t cross BBB.
In moderate dose (0.2-1mg) it increases BP & urine flow.
Mechanism of action:
Dopamine can activate α- and β-adrenergic receptors.
It acts on-

Dopaminergic receptors (D1-D5) present on peripheral

mesenteric and renal vascular beds. dopamine
Binding of
produces vasodilation.
Indication:
Given as i.v. infusion to patients with cardiogenic & septic shock.
Severe Congestive Heart Failure
Dose regulated by monitoring BP & urine formation.
At high concentrations, dopamine activates vascular α1 receptors,
leading to more general vasoconstriction.
Adverse Effects:
Nausea, vomiting, tachycardia, anginal pain, arrhythmias, headache,
hypertension, and peripheral vasoconstriction may be encountered during
dopamine infusion.
Contraindication:
Hypovolemic shock, depression (patients receiving MAO inhibitors or
tricyclic antidepressants)
 Dobutamine

Mechanism of Action:
Dobutamine is a derivative of dopamine that directly acts on adrenergic
receptors(β1).
Indications:
Dobutamine is used to increase cardiac output in acute congestive heart
failure as well as for inotropic support after cardiac surgery.
It increases cardiac output and does not significantly elevate oxygen
demands of the myocardium, a major advantage over other
sympathomimetic drugs.
It is used in pump failure (Myocardial Infarction, Cardiac surgery, CHF)
Contraindication:
Atrial fibrillation
May cause tolerance
Ephedrine
Mixed action adrenergic drugs
Orally effective & long acting than Adr
Crosses BBB so stimulation
Used in mild chronic bronchial asthma & hypotension during spinal
anaesthesia
Amphetamine
Synthetic compound similar to ephedrine but have more CNS action
Improves alertness, attention, concentration & performance
Included in dope test (drug for abuse)
Used in attention deficit hyperactive disorder (ADHD)
Phenylephrine
alpha1 agonist
used as mydriatics, decreases ocular tension
Oral or nasal decongestant
Nasal Decongestants
Topical: Oxymetazoline, Xylometazoline, Naphazoline
alpha2 agonist, long duration of action
Use cautiously in hypertensive patients
Oral: Phenylephrine, Pseudoephedrine,
Phenylpropanolamine (PPA)
Produce vasoconstriction in mucosa & skin
Used orally as decongestant of upper respiratory tract,
nose & eustachian tubes
Avoided in hypertensive patients
 Indications:
1.Vascular Uses:
Hypotensive states (shock, spinal anaesthesia, hypotensive drugs)
Along with local anaesthetics
Control of local bleeding
Nasal Decongestants
2. Cardiac Use
Cardiac arrest (drowning, electrocution, etc.) – In combination with
external cardiac massage
Partial or complete A-V block – Isoprenaline as temporary
measure
Congestive Heart Failure
1. Bronchial asthma
2. Allergic disorders (histamine mediated)
3. Mydriatic
Fundus examination
Wide angle glaucoma
1. Insulin Hypoglycaemia
2. Nocturnal enuresis in children and urinary
incontinence – Amphetamine
3. Uterine relaxant – Ritoridine: to postpone labour –
Isosuxprine: threatened abortion and dysmenorrhoea
4. Central Uses
Attention Deficit Hyperkinetic Disorders –
Amphetamine
Narcolepsy – Amphetamine, Modafinil – Imipramine like
drugs
Epilepsy – Amphetamines
Parkinsonism – Amphetamine
Obesity – Considered in severe obesity
 Anti-adrenergic Drugs/Sympatholytics

These are the drugs that antagonize the action of

adrenaline & related drugs.
They are competitive antagonist of α or β or both
receptors.
Classification:

Alpha (α) Beta (β) blocker

blocker Nonselective
α1 selective Cardioselective
α2 selective (β1)
Nonselective
Actions:
Vasodilation (venous):- Fall in BP
Reflex tachycardia
Nasal congestion
Miosis
Increase intestinal motility
Trigone, sphincter& prostate tone is reduced:- Improve
urine flow
Inhibit ejaculation:- Impotence
Prazosin, Terzosin, Doxazosin & Tamsulosin-
These are selective competitive blockers of the α1 receptor.
Prazosin, Terzosin & Doxazosin are useful in the treatment of
hypertension as they cause dilation of artery.
It can cause first dose effect so started at low dose at
bedtime.
They are orally effective with high plasma protein bound,
metabolised in liver & excreted from bile.
Tamsulosin is uroselective (α1A & α1D) indicated for the
treatment of benign prostatic hypertrophy (BPH).
Uses: HTN, BPH, CHF, Raynaud’s disease
Yohimbine is a selective competitive α2 blocker.
It is found as a component of the bark of the yohimbe
tree.
It directly blocks α2 receptors and has been used to
relieve vasoconstriction associated with Raynaud
disease.
Yohimbine is contraindicated in CNS and cardiovascular
conditions because it is a CNS and cardiovascular
stimulant.
Phenoxybenzamine is nonselective, linking covalently to
both α1 and α2 receptors. The actions of phenoxybenzamine
last about 24 hours after a single administration.
Dose: 20-60mg/day oral
Phentolamine produces a competitive block of α1 and α2
receptors. This drug’s action lasts for approximately 4 hours
after a single administration.
Dose: 5mg i.v. repeated as required
Uses:
Pheochromocytoma
Hypertension
Secondary shock
Benign prostatic hypertrophy
Peripheral vascular disease
 Propranolol
Propanolol is the β-adrenergic antagonist and blocks
both β1 and β2 receptors with equal affinity.
Pharmacological Actions:
1. Cardio Vascular system (CVS)
Heart: HR, FOC, A-V conduction
2. Respiratory Tract
Increased bronchial resistance (β2 blockade)
3. CNS
Subtle behaviour changes, forgetfulness, increased dreaming and
nightmares
Anti-anxiety effect (peripheral action of propranolol)
4. Metabolic
Blocks adrenergically mediated lipolysis
Inhibits glygenolysis in heart, skeletal muscles, liver
May reduce carbohydrate tolerance (decreased insulin release)
5. Skeletal muscle
Inhibits adrenergically provoked tremor (β2 blockade)
Attenuate exercise capacity
6. Eye
Reduced secretion of aqueous humour and intra ocular tension
7. Uterus
Relaxant activity of β agonists blocked
Dose: 10mg BD to 160mg QID oral, 2-5mg i.v. parenteral
Timolol
Timolol blocks β1 and β2 adrenoceptors and is more potent
than propranolol.
Timolol reduces the production of aqueous humor in the
eye. It is used topically in the treatment of chronic open-
angle glaucoma and occasionally for systemic treatment of
hypertension. (0.25-5% eyedrops)
Labetalol and carvedilol
Labetalol and carvedilol are β blockers with additional
α1blocking actions that produce peripheral vasodilation,
thereby reducing blood pressure.
It is useful in treating hypertensive patients with increased
peripheral vascular resistance.
Acebutolol, Atenolol, Metoprolol & Esmolol
Cardioselective β blockers, such as acebutolol, atenolol, and
metoprolol antagonize β1 receptors. This cardio selectivity is
pronounced at low doses.
These drugs lower blood pressure in hypertension and
increase exercise tolerance in angina.
Esmolol has a very short lifetime due to metabolism of an
ester linkage.
The cardiospecific blockers have relatively little effect on
pulmonary function, peripheral resistance, and carbohydrate
metabolism.
Dose: Acebutolol 200-400mg OD, Atenolol 12.5-50mg OD
Uses:
Hypertension
Stable Angina
Cardiac arrhythmias
Myocardial infarction
Congestive heart failure
Hypertrophic obstructive cardiomyopathy
Dissecting aortic aneurysm
Pheochromocytoma
Thyrotoxicosis
Migraine
Anxiety
Essential tremor
Glaucoma
Adverse Effects:
Can accentuate myocardial insufficiency and precipitate
CHF/edema
Bradycardia
Exacerbates variant angina
Impaired Carbohydrate tolerance
Altered plasma lipid profile
Tiredness and reduced exercise capacity
Cold hands and feet
Others: G.I. upset, lack of drive, nightmares, forgetfulness,
hallucinations, sexual distress in male
Contraindications:
Sudden withdrawal : rebound hypertension, worsening of angina,
sudden death
Worsens COPD; can produce acute Bronchial asthma
Partial or complete heart block
 Glaucoma
Glaucoma is an eye disease that is associated with increased intraocular
pressure, in which damage to the eye (optic) nerve can lead to loss of
vision and even blindness.
It can be open angle glaucoma & angle closure glaucoma.
Drugs for Glaucoma:
1. Beta blockers: Timolol, Betaxolol, Levobunolol
2. Alpha agonists: Dipivefrine, Apraclonidine, Brimonidine
3. Prostaglandin analogues: Latanoprost, Travoprost
4. Carbonic anhydrase inhibitors: Acetazolamide, Dorzolamide
5. Anticholinesterase/Miotics: Pilocarpine
Thank
you!