Autonomic Nervous System

Cholinergic Drugs

Dr. ABHIPSA PATRA

Dept. of PHARMACOLOGY
 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
M1 Secretory glands salivation, stomach acid,
sweating, lacrimation

M2 Heart Decreases heart rate 

bradycardia
M3 Smooth muscle Contraction of smooth
(GI/GU/Resp) muscles (some)  diarrhea,
bronchospasm, urination

M3 Pupil and ciliary muscle Contracts  Miosis

Increased flow of
aqueous humor
Nm Skeletal muscle end Contraction of skeletal
plate muscle

Nn Autonomic ganglia, Secretion of Epinephrine

Adrenal Medulla Controls ANS
 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
Lacrimation
Urination
Bronchocon
striction
Defaecation
Decreased heart
 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
Eye:
• 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 CNS excitation, restlessness,

irritability, disorientation,
hallucinations,delirium
 Side Effects of anticholinergics
Body System Side/Adverse Effects
Eye Dilated pupils, decreased visual
accommodation, increased intraocular
pressure

Gastrointestinal Decreased salivation, decreased gastric

secretions, decreased motility
 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

α1 α2 β1 β2 β3
Synthesis:
Tyrosine
Tyrosine
hydroxyl
ase

Dopa
Amino
acid
decarbo
xylase

Dopamine
Dopami
ne β-
Hydroxyl
ase
Adrenergic drugs acts through adrenergic receptors.
Adrenergic Receptors/Adenoreceptors are of 2 types: alpha
(α) & beta (β).
Alpha receptors (α)
Receptor Tissue Response
α1 Vascular smooth muscle vasocontraction
Genitourinary tract contraction
smooth muscle

Smooth muscle Contraction

(Sphincter, radial muscle (mydriasis, secretion)
of iris, gland)
Intestinal smooth muscle Relaxation
α2 Prejunctional nerve NA release
ending
Vascular smooth muscle vasoconstriction
 Beta receptors (β)
Receptor Tissue Response
β1 Heart ↑Rate, FOC,
A-V conduction
Juxtaglomerular cells ↑Rennin release
β2 Smooth muscles Relaxation
(Bronchial,
gastrointestinal,
genitourinary, uterus)
Skeletal muscle Glycogenolysis
K+ uptake
Liver Glycogenolysis
Gluconeogenesis
β3 Adipose tissue Lipolysis
 Adrenergic drugs/Sympathomimetics
1.Direct Adrenaline,
sympathomimetics NorAdrenaline,
Isoprenaline,
Phenylephrine,
Xylometazoline

2.Indirect Amphetamine, Cocaine,

sympathomimetics Sellegilline, Entacapone

3.Mixed action Ephedrine,

 Clinical classification of Adrenergic drugs
Pressor agents Dopamine, NA, Mephentermine, Ephedrine
Cardiac Dobutamine, Adr, Iso
stimulant
Bronchodilators Salbutamol (albuterol), Salmeterol, Terbutaline, Iso,
Adr
Nasal Xylometazoline, Oxymetazoline, Phenylephrine
decongestant Pseudoephedrine

CNS stimulants Amphetamine, Dexamphetamine

Anorectics Fenfluramine, Sibutramine
Uterine relaxant Ritodrine, Isoxsuprine, salbutamol, Terbutaline
 Pharmacological Actions:
Adrenaline (Adr) α1+ α2 + β1+ β2+weak β3 action
Noradrenaline (NA) α1+ α2+ β1+ β3 but no β2action
Isoprenaline (Iso) β1+ β2+ β3 action but no α
action

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.
Heart Positive ionotropic effect (increase in force of contraction)
Positive chronotropic effect (increase in heart rate)
Positive dromotropic effect (increase in heart conduction)

Respiration Bronchodilation , Nasal decongestion

Blood Vasoconstriction
vessels

Blood Increases
pressure

GIT Relaxation but sphincter contracts so peristalsis decreases

Eye Mydriasis (Dilation of pupils)

Uterus Non-pregnant-Contraction; Pregnant-Relaxation

Skeletal Tremor, glycogenolysis

muscle
Metabolic Hyperglycemia, Lipolysis, Hypokalemia
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. Binding of dopamine
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
3. Bronchial asthma
4. Allergic disorders (histamine mediated)
5. Mydriatic
• Fundus examination
• Wide angle glaucoma
6. Insulin Hypoglycaemia
7. Nocturnal enuresis in children and urinary
incontinence – Amphetamine
8. Uterine relaxant – Ritoridine: to postpone labour –
Isosuxprine: threatened abortion and dysmenorrhoea
9. 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) blocker Beta (β) blocker

•α1 selective •Nonselective
•α2 selective •Cardioselective (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!