Pharmacology of

Ganglion stimulants, blockers and

Glaucoma

Dr.U.P.Rathnakar
MD.DIH.PGDHM
www.scribd.com
www.pharmacologyfordummies.blogspot.com
 Autonomic tone & effect of ganglionic blockade

Organ Dominant tone Effect

Heart Para Symp Tachycardia

BV Symp Dilatation

Iris Para symp Mydriasis

Ciliary muscles Parasymp Cycloplegia

Intestines Parasymp Decreased motility

Bladder Para-symp Decreased tone

Sexual function Para symp Inhibition of

erection&ejaculation
Salivary glands Parasymp Dryness

Sweat Symp Anhydrosis

 Ganglion blocking agents:
Competitive blockers:
• Hexamethonium
• Trimethaphan camphor sulfonate
• Mecamylamine
Persistent depolarising blockers:
• Nicotine ( Large doses)
• Anticholinesterases ( Large doses)
 Therapeutic uses of ganglion blockers:

Trimethaphan, because of its very brief action is

given by IV infusion for producing controlled
hypotension for short periods during
- Surgery.
- Dissection of aorta.
 Ganglionic stimulants:
Selective nicotinic agonists:
• Nicotine- (Transdermal patches for smoking
cessation)
• Varenicline – (NN partial agonist for smoking
cessation)
• Lobeline
Nonselective muscarinic/nicotinic agonists:
• Acetylcholine
• Carbachol
• Anticholinesterases
 Glaucoma
[Silent thief of sight]
• Group of diseases
• Progressive optic nerve damage
• Characteristic loss of field of vision
• Often associated with raised IOT
• Exact etiology is not known.
• Treatment is to reduce IOT
 Glaucoma-Types
• Open angle[wide angle, chronic simple]
 Genetic??
 Insidious and progressive
 Ocular hypotensives
• Angle closure [Narrow angle, Acute congestive]
 Acute attack
 Precipitated by mydriatics
 Emergency-Drug therapy and surgery
 Aqueous humor dynamics

Increased drainage
• Pilocarpine
w
• PG analogues l fl o
ra
cle
S
e o-
Uv Inhibitors of AH production
• Beta blockers
• CAH inhibitors
• A2 agonists
 AH-Synthesis
Ciliary body
α2-Receptor
Stimulation
Reduced secretion

Ciliary Vessels Carbonic anhydrase

ß 2-Receptor
Blockade-decreases secretion

α1-Receptor
Stimulation
Reduction of synthesis
AH- Outflow
 Drugs for glaucoma
1. Prostaglandin analogues 4. Carbonic anhydrase
 Latanaprost inhibitors
 Unoprostone, Travoprost, Bimatoprost • Acetazolamide, Dorzolamide,
2. β Adrenergic blockers Brinzolamide
• Timolol, levobunolol, carteolol, 5. Miotics
• Pilocarpine, anticholinesterases
metipranolol [nonselective];
betaxolol and levobetaxolol [β 1
selective]
6. Drugs used in acute
3. α Adrenergic agonists congestive
• Apraclonidine,brimonidine,
dipivefrine, adrenaline
 Prostaglandin F2α analogues
Latanaprost, Unoprostone, Travoprost, Bimatoprost
o MOA- Increases permeability of tissues in ciliary muscles
o Increases uveo-scleral outflow
o Treatment started with these
o Alone [0.005%] or in combination
o Advantage-Once a day, no systemic side effects

Side effects –Irritation, Blurring of vision, increased iris

pigmentation, thickening and darkening of eyelashes.
 ß Adrenergic blockers:
• Timolol, levobunolol, carteolol, metipranolol
[nonselective]; betaxolol and levobetaxolol [β 1 selective]
• MOA: Decreased synthesis and secretion of AH
• Equally effective as miotics, sustained action for weeks
• Ocular side effects
• Stinging, redness, dryness, allergic
Conjuctivitis, blurred vision
• Systemic side effects[absorption]
• Brocnhospasm, bradycardia[ß2/ ß1]
 Advantages of topical ß blockers over
miotics:
• No change in size of pupil.
• No induced myopia.
• No headache.
• No fluctuations in IOT.
• Convenient twice/once daily application.
 Ciliary body
α2-Receptor
Stimulation
Reduced secretion

Ciliary Vessels Carbonic anhydrase

ß 2-Receptor
α1-Receptor Blockade-decreases secretion
Stimulation
Reduction of synthesis
 α Adrenergic agonists:
• Adrenaline:
• α1 –Ciliary vasoconstriction-
Reduce AH synthesis
• α2- Ciliary epithelium-Reduce
secretion
• ß 2 – Increased U.scleral &
trabecular flow
• Not used –
• Poor penetration,ocular
intolearnce & Systemic action
• Dipivefrine –
• Prodrug of adrenaline – rarely used
• Apraclonidine –
• Primary α 2 receptor action
( Only for short term use due to
side effects)
• Brimonidine –
• More selective α2 receptor
action
• Less α1 side effects
• 3rd choice drug
 Adverse effects-adrenergic agonists

• Itching
• Mydriasis
• Dryness of mouth and nose
• Eye lid retraction.
 Carbonic Anhydrase inhibitors
• PT, Gastric mucosa, Pancreas, CILIARY
BODY, Brain, RBC

→ + -
• H2O+CO2 →CAH← H2CO3 H +HCO3
←

• AH is rich in HCO3-
• Inhibition of enzyme → decreased synthesis of AH

• More than 99% inhibition is required

 Carbonic anhydrase inhibitors….
• Acetazolamide: ( Oral route)
Used for short term indications-Angle closure, before surgery,
supplement to other drugs
Side effects – Paresthesia, hypokalemia, acidosis, anorexia.
• Dorzolamide: ( Topical application)
Add on drug
Side effects – Burning and itching sensation in the eye.
• Brinzolamide
 Miotics:
• Topical pilocarpine and antiChEs.
• They lower IOT by improving trabecular outflow
• Disadvantages:
 Short duration
 Ciliary spasm
 Vision disturbances
 Inconsistent response

Because of several drawbacks they are used only as the last

option in open angle glaucoma.
 Treatment of open angle
Start with latanoprost or a ß-blocker.
↓ (Inadequate response)
Change over to the alternative drug or
use both concurrently.
↓ (Inadequate response)
Add Brimonidine/Dorzolamide/Dipivefrine
↓ (Inadequate response)
Oral CAIs [Acetazolamide SR or methazolamide]
↓ (Inadequate response)
laser or incisional surgical treatment.
 General principles of
Glaucoma Therapy
• Asthma and COPD with a bronchospastic component are relative
contraindications to the use of topical beta adrenergic receptor antagonists
• Cardiac dysrhythmias (i.e., bradycardia and heart block) also are relative
contraindications to beta adrenergic antagonists for similar reasons;
• H/O nephrolithiasis can be a contraindication for carbonic anhydrase inhibitors
(CAIs);
• Young patients usually are intolerant of miotic therapy secondary to visual
blurring from induced myopia;
• Direct miotic agents are preferred over cholinesterase inhibitors in “phakic”
patients (i.e., those patients who have their own crystalline lens), since the latter
drugs can promote cataract formation; and
• Patients who have an increased risk of retinal detachment, miotics should be
used with caution since retinal tears could occur due to altered forces at the
vitreous base produced by drug-induced ciliary body contraction.
 Angle closure (narrow angle,acute
congestive) glaucoma:
• Occurs in individuals with a narrow iridocorneal
angle and shallow anterior chamber.
• Sudden raise in IOT
• Attack is precipitated by mydriasis -
( 40-60mm of Hg ).
• It is an emergency and failure to lower IOT
quickly may result in loss of sight.
 Drug therapy of Angle closure glaucoma:

• Hypertonic mannitol (20%) 1.5-2gm /kg or

glycerol (10%) –by IV route.
• Acetazolamide 0.5 gm IV followed by twice daily orally.
• Miotic – Pilocarpine 1-4% every 10 min initially.
• Timolol 0.5% eye drops instilled 12th hourly.
• Apraclonidine (1%) / Latanoprost ( 0.005%)
may be added.

Definitive treatment of angle closure glaucoma is surgical or laser

iridotomy.