Parasympatholytics are the drugs that block or inhibit the actions of acetylcholine at postganglionic nerve endings and cholinergic receptors. They are also referred to as anticholinergics or cholinergic blocking agents or antispasmodics.
Anticholinergic drugs include atropine and related drugs- atropine is the prototype. Atropine is obtained from the plant Atropa belladonna. Atropine and scopolamine (hyoscine) are the belladonna alkaloids. They compete with acetylcholine for muscarinic receptors and block this receptors-they are muscarinic antagonists.
Med chem lecture on Anticholinergic drugs for B.Pharm level in Nepal
Content from Foye's Principle of medicinal chemistry, my own thoughts and some articles
Biosynthesis and catabolism of acetylcholine by Dheeraj gargDheeraj Aggarwal
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (and humans) as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells, such as neurons, muscle cells and gland cells.
The parasympathetic division typically acts in opposition to the sympathetic autonomic nervous system through negative feedback control.
This action is a complementary response, causing a balance of sympathetic and parasympathetic responses.
Overall, the parasympathetic outflow results in the conservation and restoration of energy, reduction in heart rate and blood pressure, facilitation of digestion and absorption of nutrients, and excretion of waste products.
These are drugs that produce actions similar to that of Acetylcholine hence known as parasympathomimetics.
They act either by directly interacting with cholinergic receptors or by increasing the availability of Acetylcholine at these sites.
Cholinergic antagonists and blockers-Dr.Jibachha Sah,M.V.Sc,LecturerDr. Jibachha Sah
Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
Parasympatholytics are the drugs that block or inhibit the actions of acetylcholine at postganglionic nerve endings and cholinergic receptors. They are also referred to as anticholinergics or cholinergic blocking agents or antispasmodics.
Anticholinergic drugs include atropine and related drugs- atropine is the prototype. Atropine is obtained from the plant Atropa belladonna. Atropine and scopolamine (hyoscine) are the belladonna alkaloids. They compete with acetylcholine for muscarinic receptors and block this receptors-they are muscarinic antagonists.
Med chem lecture on Anticholinergic drugs for B.Pharm level in Nepal
Content from Foye's Principle of medicinal chemistry, my own thoughts and some articles
Biosynthesis and catabolism of acetylcholine by Dheeraj gargDheeraj Aggarwal
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (and humans) as a neurotransmitter—a chemical message released by nerve cells to send signals to other cells, such as neurons, muscle cells and gland cells.
The parasympathetic division typically acts in opposition to the sympathetic autonomic nervous system through negative feedback control.
This action is a complementary response, causing a balance of sympathetic and parasympathetic responses.
Overall, the parasympathetic outflow results in the conservation and restoration of energy, reduction in heart rate and blood pressure, facilitation of digestion and absorption of nutrients, and excretion of waste products.
These are drugs that produce actions similar to that of Acetylcholine hence known as parasympathomimetics.
They act either by directly interacting with cholinergic receptors or by increasing the availability of Acetylcholine at these sites.
Cholinergic antagonists and blockers-Dr.Jibachha Sah,M.V.Sc,LecturerDr. Jibachha Sah
Dr. Jibachha Sah,M.V.Sc( Veterinary pharmacology, TU,Nepal),posted lecturer notes on AUTONOMIC AND SYSTEMIC PHARMACOLOGY for B.V.Sc & A.H. 6 th semester veterinary students of College of veterinary science,Nepal Polytechnique Institute, Bharatpur, Bhojard, Chitwan, Nepal.I hope this lecture notes may be beneficial for other Nepalese veterinary students. Please send your comment and suggestion .Email:jibachhashah@gmail.com,moble,00977-9845024121
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Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
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Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
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1. A SEMINAR ON
PARASYMPATHOMIMETIC AGENTS
Presented By: Ms. Kirti Vadi
17MPHCT002
M.Pharm
(pharmacolgy)
Rpcp,changa
Guided By: Dr. Jalpa Suthar
Assistant Professor
Dept. Of Pharmacology &
Toxicology
Rpcp,changa
2. CONTENT
2
Organization of nervous system
Acetycholine drug profile
Types of cholinergic receptors
Nicotinic receptors
Muscarinic receptors
Classification of drugs
Directly acting cholinergic drugs
Indirectly acting cholinergic drugs
Therapeutic uses of cholinergic drugs
AchE Poisoning (organophosphorous poisoning)
Side effects of cholinergic drugs
Reference
3. 3
ORGANIZATION OF NERVOUS SYSTEM
The chief neurotransmitter in the parasymphathetic nervous system is
acetylcholine. Hence it is also known as cholinergic system. The drugs that
produce effect similar to that of acetylcholine are termed as cholinergic agents
or parasympathomimetic agents.
5. TYPES OF CHOLINERGIC RECEPTORS
5
Cholinergic receptors
Muscarinic
receptor
M1
M2
M3
M4
M5
Nicotinic receptor
NM
NN
6. NICOTINIC RECEPTORS
6
Features NM NN
Location and function
subserved
Neuromuscular junction:
depolarization of muscle end
plate -contraction of skeletal
muscle
Autonomic ganglia:
depolarization -postganglionic
impulse,
Adrenal medulla:
catecholamine release
CNS: site specific excitation or
inhibition
Nature Has intrinsic ion channel,
pentamer of only α2 β Ɛ or
and subunits, each subunit
has 4TM
Has intrinsic ion channel,
pentamer of only αβ subunits,
each subunit has 4TM
Transducer
mechanism
Opening of cation (Na+, K+)
channels
Opening of cation (Na+, K+,
Ca++) channel
Agonist PTMA, Nicotine DMPP, Nicotine
Antagonist Tubocurarine Hexamethonium,
Trimethaphan
8. CLASSIFICATION OF DRUGS
8
The parasympathomimetic
agents are classified into the
following:
•Directly actingcholinergic
drugs-These drugs mimic the
actions of ACh at muscarinic
and nicotinic receptors by
binding directly to these
receptors.
•Indirectly acting cholinergic
drugs-These drugs act by
inhibiting the activity of
acetylcholinesterase (AchE)
enzyme which degrades ACh to
inactive products: choline and
acetic acid.
10. B. NATURAL ALKALOID
10
Pilocarpine
It is chief alkaloid obtain from the leaves of shrub Pilocarpus jaborandi. It
crosses BBB.
It has muscarinic action and also mild nicotinic action.
Therapeutic uses:-
1. Ophthalmic use:
For initial treatment of open angle glaucoma (0.5% to 4% solution),
reduction in intraocular pressure occur within few min and lasts for 4-8 hrs.
To counteract mydriasis produce by atropine
To break the adhesion between the iris and lens
2. As sialagogue – used to stimulate salivary secretion in patients after laryngeal
surgery. (5-10 mg orally)
11. C. MISCELLANEOUS AGENTS
11
TREMORINE and OXOTREMORINE are not used therapeutically, but used
only as investigated research tool to stimulate Parkinsonism like symptoms in
animal models.
Which results from activation of muscarinic receptors in basal ganglia and
elsewhere in CNS.
12. INDIRECTLYACTING CHOLINERGIC DRUGS
12
Acetylcholinesterase (AchE) is an enzyme which degrades acetylcholine to inactive
products: choline and acetic acid.
These agents act by inhibiting the AchE, by reversible or irreversible binding
which indirectly increase the concentration of acetylcholine in the synaptic cleft
and ultimately at the respective cholinergic receptors.
13. A. REVERSIBLE (COMPETITIVE) INHIBITORS OF AChE
13
• The reversible anticholinesterase
drugs have a similar structure to ACh.
• They combine with the anionic and
their esteric site of AChE.
• This complex is less readily
hydrolysed than AChE-ACh complex.
• It results in a temporary inhibition of
the enzyme.
• This inhibition prolong the duration of
action of ACh released in the synaptic
cleft.
14. 14
PHYSOSTIGMINE
Its an alkaloid obtain from the dried ripe seeds of Physostigma venenosum.
It is highly lipid soluble and shows better absorption in the all the body
compartments including CNS and can crosses BBB.
It has marked muscarinic effects and also stimulate ganglia but negligible
nicotinic effects at neuromuscular junction.
It is highly toxic and so has only limited use.
It is having intermediate duration of action. (30min-2hr)
Therapeutic uses:
Ophthalmic use
To counteract the effects of mydriatics
To prevent the adhesion between iris and the lens
for the treatment of glaucoma
Belladonna (atropine) poisoning
15. 15
Quaternary compounds
This drugs are least absorb and do not cross BBB.
This drugs have important therapeutic effects on skeletal muscle neuromuscular
junction.
Low doses moderately prolong and intensify the action of released ACh at motor
endplate, this results in strengthening of muscle weakness.
EDROPHONIUM
A quaternary ammonium compound that binds to the anionic site of the enzyme
only.
The ionic bond formed is readily reversible, and the action of the drug is very brief.
It is used mainly for diagnostic purposes, because improvement of muscle strength
by an anticholinesterase is characteristic of myasthenia gravis but does not occur
when muscle weakness is due to other causes.
Duration of action: 5-15 min
16. 16
Neostigmine
Hydrolysed by esterases in liver & plasma
Short duration of action (3-5 hours)
Direct action on nicotinic (NM) receptors present in neuromuscular junction (motor
end plate) of skeletal muscle
Antagonizes (reverses) skeletal muscle relaxation (paralysis) caused by tubocurarine
and other competitive neuromuscular blockers
Stimulates autonomic ganglia in small doses but Large doses block ganglionic
transmission
No CNS side effects.
17. COMPARATIVE FEATURES OF
PHYSOSTIGMINE AND NEOSTIGMINE
17
Physostigmine Neostigmine
Source Natural Synthetic
Chemistry Tertiary amine Quaternary ammonium
compound
Oral absorption Good Poor
CNS action Present Absent
Eye Penetrates cornea Poor penetration
Effect Ganglia Muscle
Uses Miotic Mysthenia gravis
Dose 0.5-1 mg oral/parenteral
0.1-1% eye drop
0.5-2.5 mg IM/SC
15-30 mg orally
Duration of action 4-6 Hrs 3-4 Hrs
18. B. IRREVERSIBLE INHIBITORS OF AChE
18
These agents are called irreversible blockers because they phosphorylated the esteratic site of
AChE irreversibly by forming a covalent bond.
Pentavalent organo-phosphorous compounds containing fluoride or organic group.
During the process, this group is released leaving the remaining part of drug molecule attached
covalently with the esteratic site of AChE through its phosphorous atom.
After phosphorylation, AChE becomes inactive and very stable due to covalent bonding.
Recovery depends on new synthesis (few weeks)
Ecothiophate (exception) : is having a quaternary nitrogen which can bind also to the anionic
site of the enzyme slow hydrolysis (few days) not strictly irreversible
Sometimes phosphorylated enzyme losses one alkyl group and become resistant to hydrolysis
– ageing
19. THERAPEUTIC USES OF CHOLINERGIC
DRUGS
19
Myasthenia gravis:
Edrophonium to diagnose
Neostigmine, Pyridostigmine & Distigmine to treat
To stimulate bladder & bowel after surgery:
Bethanechol, Carbachol, Distigmine
To lower IOP in chronic simple glaucoma:
Pilocarpine, Physostigmine
To improve cognitive function in Alzheimer’s disease:
Rivastigmine, Gallantamine, Donepezil
Physostigmine in Belladonna poisoning
20. MYASTHENIA GRAVIS
20
Autoimmune disorder affecting 1 in 10,000 population
Causes: Development of antibodies directed to Nicotinic receptors in muscle end plate
– reduction in number by 1/3rd of Nm receptors
Structural damage to NM junction
Symptoms: Weakness of muscle and fatigue which worsens after the exrecise but goes
off after the rest, slurring speech, diplopia, difficulty in swallowing
Treatment:
Neostigmine – 15 to 30 mg, orally, every 6 hrly
Dose requirement may fluctuate time to time – adjustment required according to
the response
Pyridostigmine – 60-120mg, 4-6hrly, orally
21. MYASTHENIC CRISIS
21
Acute weakness and respiratory paralysis
Tracheobronchial intubation and mechanical ventilation
Methylprednisolone IV with withdrawal of AChE
Gradual reintroduction of AChE
Thymectomy
Edrophonium is used for diagnosis of Myasthenic crisis (disease itself) and
cholinergic crisis (overdose of Anti-ChE)
Improvement of symptoms – myasthenic crisis
Worsening – Cholinergic crisis
22. AChE POISONING (ORGANOPHOSPHOROUS
POISONING)
22
Organophosphate poisoning is poisoning due to organophosphates(OPs).
The underlying mechanism involves the inhibition of acetylcholinesterase ,
leading to the buildup of acetylcholine in the body.
Diagnosis is typically based on the symptoms and can be confirmed by
measuring butyryl-cholinesterase activity in the blood.
Poisoning may be – Occupational, accidental, Suicidal
Symptoms:
Fall in BP, bradycardia or tachycardia, cardiac arrhythmia and vascular
collapse
Irritation of Eye, lacrimation, salivation, involuntary defection,
breathlessness, blurring of vision
Muscular fasciculations and weakness
Death due to respiratory paralysis – peripheral and central
23. 23
The treatment consist of specific antidote or Cholinesterase Reactivators
1. Specific antidotes
Atropine-All cases of AChE poisoning, 2mg IV every `10 minutes – till
muscarinic symptoms disappears
2. Cholinesterase Reactivators – Oximes
Oximes have generic formula R-CH=N-OH
Provides reactive group OH to the enzymes to reactivate the phosphorylated
enzymes eg. Pralidoxime (2-PAM), Obidoxime Diacetyl monoxime (DAM)
25. REFERENCE
25
1. Sharma HL, Sharma KK. Principles of pharmacology. Paras medical
publisher; 2007.
2. Tripathi KD. Essentials of medical pharmacology. JP Medical Ltd; 2013 Sep
30.
3. Goodman LS. Goodman and Gilman's the pharmacological basis of
therapeutics. New York: McGraw-Hill; 1996.
4. H. P. Shah, J. M. Ritter. Rang & Dale’s pharmacology. Elsevier Ltd; 2016