Download presentation
Presentation is loading. Please wait.
Published byHarold Wilson Modified over 9 years ago
1
Asmah Nasser, M.D.
2
M1Secretory glands salivation, stomach acid, sweating, lacrimation M2HeartDecreases heart rate bradycardia M3Smooth muscle (GI/GU/Resp) Contraction of smooth muscles (some) diarrhea, bronchospasm, urination M3Pupil and ciliary muscle Contracts Miosis Increased flow of aqueous humor NmSkeletal muscle end plate Contraction of skeletal muscle NnAutonomic ganglia, Adrenal Medulla Secretion of Epinephrine Controls ANS
4
Classification and examples of direct and indirect acting Cholinergic agonists Brief discussion of few of the above examples Pathophysiology, diagnosis, and Management of ◦ Myasthenia gravis and tensilon test ◦ Glaucoma ◦ Alzheimer's disease ◦ Organo Phosphorus compound poisoning
5
Heart: Cardiac suppressant…Bradycardia, hypotension, Eye: Miosis, cycloplegia, facilitates aqueous humour drainage, lacrimation Bronchospasm Excess secretion from glands….salivary, bronchial, lacrimal glands etc….. GIT /bladder… smooth muscle contraction and relaxation of sphincters…, increased motility, diarrhea, vomiting, increased micturation (urinary urgency)
6
Often called parasympathomimetic drugs, because their action mimics the action of the PSNS commonly Also called as Cholinergic drugs or cholinomimetric Cholinergic agonists are two types : 1. Direct acting 2. Indirect acting
7
They act by binding directly to cholinoceptors Acetylcholine (Synthetic analogue of ACH) Carbachol Bethanechol Pilocarpine (naturally occurring alkaloid)
8
They act through inhibition of Acetyl cholinesterase enzyme….so increases Acetylcholine level in the synapse Reversible: ◦ Neostigmine ◦ Physostigmine ◦ Pyridostigmine ◦ Edrophonium ◦ Tacrine ◦ Danopezil Irreversible : Ecothiophate Malathion Parathion Sarin
10
It is a quaternary ammonium compound so Cannot penetrate the membrane Does not have any therapeutic importance, because of multiplicity of actions & rapid inactivation by acetylcholinesterases It has both Muscarinic & Nicotinic actions Neurotransmitter for pre-ganglionic neuron
11
Not hydrolyzed by acetylcholinesterases It has strong Muscarinic action & no Nicotinic action 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
12
An alkaloid, lipid soluble & is stable to hydrolysis by cholinsterases It has Muscarinic activity only. Actions- When applied locally to cornea Produces rapid moisis & contraction of ciliary muscle produces of spasm of accommodation & vision is fixed at particular distance making it impossible to focus for far situated objects Therapeutic Use : In Glaucoma It opens trabecular meshwork around schlemm’s canal ∴ causes drainage of aqueous humor ∴ IOP immediately decreases.
13
Cholinesterase inhibitors. Can be reversible or irreversible. Reversable: ◦ Neostigmine ◦ Physostigmine ◦ Edrophonium ◦ Tacrin ◦ Danopezil Irreversible ◦ Malathion and Parathion ◦ Sarin ◦ Ecothiopate ◦
14
Neostigmine in M.gravis Physostigmine in Glaucoma, atropine overdose Ecothiopate in glaucoma Edrophonium in M.gravis to test Tacrin, Danopezil in Alzheimer's Malathion, Parathion as insecticides
15
An autoimmune process causes production of antibodies that decrease the number of functional nicotinic receptors on the postjunctional end plates. Frequent findings are Double vision…. diplopia, Drooping of eyelids…. ptosis, Dysarthria ……Difficulty in speaking Dysphagia …..difficulty swallowing, Difficult in Daily routines Day passes, limb weakness increases. Difficulty in respiration Severe disease may affect all the muscles, including those necessary for respiration. Death
16
Immunosuppressant drugs Thymectomy Acetyl Cholinesterase inhibitors ◦ Neostigmine ◦ Pyridostigmine ◦ Ambenonium ◦ Edrophonium Other supportive measures
18
Neostigmine Has a strong influence at the neuromuscular junction Pyridostigmine: Has a longer duration of action than neostigmine Ambenonium :Available only in oral form; cannot be used if patient is unable to swallow tablets Edrophonium: Diagnostic agent for myasthenia gravis and to diffrentiate myasthenic and cholinergic crisis (Tensilon test )
19
Clinical situations in which severe myasthenia (myasthenic crisis) must be distinguished from excessive drug therapy (cholinergic crisis) usually occur in very ill myasthenic patients If excessive amounts of cholinesterase inhibitor have been used, patients may become paradoxically weak because of nicotinic depolarizing blockade of the motor end plate. Small doses of edrophonium (1–2 mg intravenously) will produce no relief or even worsen weakness if the patient is receiving excessive cholinesterase inhibitor therapy. On the other hand, if the patient improves with edrophonium, an increase in cholinesterase inhibitor dosage may be indicated.
20
A progressive disorder involving neural degeneration in the cortex Leads to a marked loss of memory and of the ability to carry on activities of daily living Cause of the disease is not yet known ◦ ?????? There is a progressive loss of ACh-producing neurons and their target neurons
21
Tacrine ◦ Side effect: HepatoToxicity ◦ First drug to treat Alzheimer ’ s dementia Rivastigmine ◦ Available in solution for swallowing ease Donepezil ◦ Has once-a-day dosing advantage
22
Only Ecothipate is used clinically in Glaucoma. This is the long acting drug used in glaucoma ◦ Rest of the drugs are used as pesticides or war gases or poisons: Malathion and Parathion
23
The dominant initial signs are those of muscarinic excess: miosis, salivation, sweating, bronchial constriction, vomiting, and diarrhea. Central nervous system involvement usually follows rapidly, accompanied by peripheral nicotinic effects, especially depolarizing neuromuscular blockade.
24
(1) maintenance of vital signs—respiration in particular may be impaired; (2) decontamination to prevent further absorption—this may require removal of all clothing and washing of the skin in cases of exposure to dusts and sprays; and (3) Atropine parenterally in large doses, given as often as required to control signs of muscarinic excess stimulation. (4)Therapy often also includes treatment with pralidoxime (Acetylcholinesterase reactivator)
25
Irreversible cholinesterate inhibitor. LONG acting Used in Glaucoma
26
Direct/indirect acting cholinergic drugs actions, adverse effects, toxicity features of OP poisoning In OP poisoning atropine used to reverse only the muscarinic effects.. Pralidoxime used to reactivate the enzyme
27
Miosis Excessive salivation Bradycardia Bronchospasm Abdominal cramps, vomiting, diarrhea, urination Sweating
28
Asmah Nasser, M.D.
29
About 70 million people are affected Worldwide ◦ 10% of these (~7 million) are blind from glaucoma US data: > 40 yrs of age, 3 million about 120, 000 Americans are blind from it. Most common cause of blindness among Black-Americans. 50% of all patients, are not aware they have it, until late
30
Types of Glaucoma: 1. Open Angle Glaucoma – Excessive production of Aqueous Humour 2. Closed Angle Glaucoma – Outflow obstruction of Aqueous Humour Two Therapy aimed at : 1. Reduce (Production, Synthesis or Secretion) Dorzolamide, Acetazolamide, Timolol, Betoxolol and Apraclonidine 2.Facilitate the drainage: Pilocarpine, Carbachol, Ecothiopate,Mannitol and Latanoprost
31
Courtesy : Katzung
32
Mannitol ◦ reduces IOP by reducing vitreous volume by inhibiting the enzyme carbonic anhydrase Reduces the secretion/synethesis ◦ Timolol topical eye drops Non-selective β blockade ◦ Betaxolol eye drops Selective β1 blockade Reduces the synthesis ◦ Acetazolamide (oral), Dorzolamide (topical ) : reduces the synthesis of aqueous humour, inhibits the enzyme carbonic anhydrase ◦ α2 receptor agonist (apraclonidine 1%, topical drops).
33
1. Pilocarpine, Carbachol, Ecothiopate and Physostigmine :Causes Ciliary muscle contraction, increases Irido-corneal angle and open trabecular meshwork. 2. Prostaglandins : Latanoprost : increase the outflow through uveoscleral meshwork
34
Excessive β adrenergic receptor mediated production and secretion of aqueous humor from the ciliary body epithelium. Best treated with betablockers
35
Results from obstruction of canal of Schlemm through which aqueous humor was supposed to be filtrated out. Caused by 1.Mydriatics : Anti-cholinergic drugs 2.Antidepressants : SSRI drugs Treatment: Pilocarpine, Carbachol, ecothiopate and physostigmine
Similar presentations
© 2025 SlidePlayer.com. Inc.
All rights reserved.