Class 5 Cholinergic system
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Transcript of Class 5 Cholinergic system
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Pharmacology of Ganglion stimulants, blockers
andGlaucoma
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Organ Dominant tone EffectHeart 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
Autonomic tone & effect of ganglionic blockade
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G anglion blocking agents:
Competitive blockers:Hexamethonium
Trimethaphan camphor sulfonateMecamylamine
Persistent depolarising blockers:
Nicotine ( Large doses)Anticholinesterases ( Large doses)
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Therapeutic uses of ganglion blockers:
Trimethaphan, because of its very brief action isgiven by IV infusion for producing controlled
hypotension for short periods during- Surgery.- Dissection of aorta.
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G anglionic stimulants:
Selective nicotinic agonists:Nicotine- (Transdermal patches for smokingcessation)Varenicline ± (N N partial agonist for smokingcessation)Lobeline
Nonselective muscarinic/nicotinic agonists:AcetylcholineCarbachol
Anticholinesterases
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G laucoma
[Silent thief of sight]G roup of diseasesProgressive optic nerve damage
Characteristic loss of field of visionOften associated with raised IOT
Exact etiology is not known.Treatment is to reduce IOT
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G laucoma-Types
Open angle[wide angle, chronic simple]G enetic??
Insidious and progressiveOcular hypotensivesAngle closure [Narrow angle, Acute congestive]
Acute attack Precipitated by mydriaticsEmergency-Drug therapy and surgery
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Inhibitors of AH productionBeta blockers
CAH inhibitorsA2 agonists
Increased drainagePilocarpineP G analogues
Aq ueous humor dynamics
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C arbonic anhydraseC iliary Vessels
2-Receptor Stimulation
Reduced secretion
ß 2-Receptor Blockade-decreases secretion
1-Receptor Stimulation
Reduction of synthesis
AH -Synthesis
C iliary body
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AH - Outflow
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Drugs for glaucoma
1. Prostaglandin analoguesLatanaprostUnoprostone, Travoprost, Bimatoprost
2. Adrenergic blockersTimolol, levobunolol, carteolol,metipranolol [nonselective] ;
betaxolol and levobetaxolol [ 1selective]
3. Adrenergic agonistsApraclonidine,brimonidine,dipivefrine, adrenaline
4. Carbonic anhydraseinhibitorsAcetazolamide, Dorzolamide,
Brinzolamide5. Miotics
Pilocarpine, anticholinesterases
6. Drugs used in acutecongestive
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Prostaglandin F 2 analogues
Latanaprost, Unoprostone, Travoprost, Bimatoprosto MOA- Increases permeability of tissues in ciliary muscleso Increases uveo-scleral outflowo Treatment started with theseo Alone [0.005%] or in combinationo Advantage-Once a day, no systemic side effects
Side effects ± Irritation, Blurring of vision, increased iris pigmentation, thickening and darkening of eyelashes.
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ß Adrenergic blockers:
Timolol, levobunolol, carteolol, metipranolol[nonselective] ; betaxolol and levobetaxolol [ 1 selective]
MOA: Decreased synthesis and secretion of AHEqually effective as miotics, sustained action for weeksOcular side effectsStinging, redness, dryness, allergic
Conjuctivitis, blurred visionSystemic side effects[absorption]Brocnhospasm , bradycardia[ ß
2/ ß1]
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Advantages of topical ß blockers overmiotics:
No change in size of pupil.No induced myopia.
No headache.No fluctuations in IOT.Convenient twice/once daily application.
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C arbonic anhydraseC iliary Vessels
2-Receptor Stimulation
Reduced secretion
ß 2-Receptor Blockade-decreases secretion1-Receptor
StimulationReduction of synthesis
C iliary body
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Adrenergic agonists:Adrenaline:
1 ± Ciliary vasoconstriction-Reduce AH synthesis
2- Ciliary epithelium-Reduce
secretionß 2 ± Increased U.scleral &trabecular flowNot used ±
Poor penetration,ocularintolearnce & Systemic action
Dipivefrine ± Prodrug of adrenaline ± rarely usedApraclonidine ± Primary 2 receptor action( Only for short term use due to sideeffects)
Brimonidine ± More selective 2 receptoractionLess 1 side effects3rd choice drug
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Adverse effects-adrenergic agonists
ItchingMydriasis
Dryness of mouth and noseEye lid retraction.
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Carbonic Anhydrase inhibitors
PT, Gastric mucosa, Pancreas, CILI ARYBODY, Brain, RB C
H 2O+CO2 H2C O3 H++H C O3 -
AH is rich in HC O3-
Inhibition of enzyme decreased synthesis of AH
More than 99% inhibition is re q uired
C AH
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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
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Miotics:
Topical pilocarpine and antiChEs.They lower IOT by improving trabecular outflow
Disadvantages:Short durationCiliary spasmVision disturbances
Inconsistent response
Because of several drawbacks they are used only as the lastoption in open angle glaucoma.
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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.
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G eneral principles of G laucoma Therapy
A sthma and COPD with a bronchospastic component are relativecontraindications to the use of topical beta adrenergic receptor antagonistsCardiac dysrhythmias (i.e., bradycardia and heart block) also are relativecontraindications to beta adrenergic antagonists for similar reasons;
H/O nephrolithiasis can be a contraindication for carbonic anhydrase inhibitors(C A Is);Young patients usually are intolerant of miotic therapy secondary to visual blurring from induced myopia;
Direct miotic agents are preferred over cholinesterase inhibitors in ³phakic´ 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 beused with caution since retinal tears could occur due to altered forces at thevitreous base produced by drug-induced ciliary body contraction.
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Angle closure (narrow angle,acutecongestive) glaucoma:
Occurs in individuals with a narrow iridocornealangle and shallow anterior chamber.Sudden raise in IOTAttack is precipitated by mydriasis -( 40-60mm of Hg ).It is an emergency and failure to lower IOTquickly may result in loss of sight.
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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 12 th hourly.Apraclonidine (1%) / Latanoprost ( 0.005%)
may be added.
Definitive treatment of angle closure glaucoma is surgical or laseriridotomy.