Cholinergic Receptors

Dr Madhuri Reddy
 Divisions of nervous system

Central Nervous
System
Human Nervous
system
Peripheral Autonomic
Nervous System Nervous System
 Nervous system
Includes neurons and Peripheral
ganglia outside of the Nervous
brain and spinal cord System

*Either “fight and *Autonomic Somatic Nervous

flight” mode or “rest Nervous System System
and digest” (involuntary) (voluntary)

With neurotransmitters Sympathetic Parasympathetic

norepinephrine and Nervous System Nervous System
acetylcholine (adrenergic) (cholinergic)
Autonomic Nervous System
• Central Nervous System (CNS) - Brain and spinal
cord
• Peripheral Nervous System (PNS) - Located outside
the brain & spinal cord
* Autonomic Nervous System (ANS) &
the somatic
• The PNS receives stimuli from the CNS & initiates
responses to the stimuli after it’s interpreted by the
brain
Autonomic Nervous System
• ANS acts on smooth muscles & glands
- Controls & regulates heart, respiratory system, GI
tract, bladder, eyes & glands
- Involuntary - person has little or no control
• Somatic - voluntary - person has control (skeletal
muscle)
 ANS

• ANS has 2 sets of neurons:

1. Afferent (sensory) - sends impulses to the CNS for
interpretation
2. Efferent - receives impulses (info.) from the brain
& transmits from the spinal cord to the effector
organ cells
- 2 branches - sympathetic &
parasympathetic nervous system
Cholinergics receptors
 Cholinergics stimulate the parasympathetic
nervous system
 Mimic the neurotransmitter acetylcholine
 2 types of cholinergic receptors
1. muscarinic - stimulates smooth muscle &
slows HR
2. nicotinic - affect skeletal muscle
 Many are nonselective & affect both receptors
 Some affect only the muscarinic receptors and
not the nicotinic receptors
• M1 M3 M5: Gq coupled– Ca++ = cause contraction
of smooth muscle n glands
• M2 M4 : Gi coupled(k+)= inhibition of
parasympathetic functions
• Ligand can be peptide/protein- lipid insoluble
• G Protein connects the ligand from outside to
action of enzyme on the inside
• G( guanine nucleotide bonding protein)
Sympathetic and Parasympathetic Effects on Body Tissues
ANS - Parasympathetic Nervous
System (Cholinergic)
• The parasympathetic division (craniosacral outflow)
consists of cell bodies from one of two locations: brainstem
(cranial nerves III, VII, IX, X) or sacral spinal cord (S2, S3,
S4)
• Parasympathetic or Cholinergic Nervous System
Acetylcholine neurotransmitter
- Drugs that mimic cholinergic drugs are
parasympathomimetics
Cholinergic agonists - initiates a response
- Drugs that block are anticholinergic, parasympatholytics
Cholinergic antagonists - prevents a response
Parasympathetic Responses
Cholinergic Agents
• Direct acting - act on the receptors to activate a
tissue response
• Indirect acting - inhibit the action of the enzyme
cholinesterase (acetylcholinesterase - ACH)
• Major uses = Stimulate bladder & GI tone,
constrict pupils (miosis).
Drug Effects of Cholinergic
Agents
• At recommended doses, the cholinergics primarily
affect the MUSCARINIC receptors.
• At high doses, cholinergics stimulate the
NICOTINIC receptors.
Drug Effects of Cholinergic
Agents
“SLUDGE”
• Salivation
• Lacrimation
• Urinary incontinence
• Diarrhea
• Gastrointestinal cramps
• Emesis
Direct acting
• Acetylcholine
• Carbachol
• Pilocarpine
• Bethanechol
• Bethanechol Function:
• 1)Bladder: contracts detrussor muscle, used for
treatment for non obstructive urinary retention
• 2) Intestine: Used for paralytic ileus
• Pilocarpine function:
• In low dose: bradycardia , Hypotension
• In high dose:stimulates M & N receptors so causes
Tachycardia
• Pilocarpine Functions:
• Topical eye drops- miotic agent ,
• So used in glaucoma
• To reverse the pupillary dilation after testing for
refraction
• Used for Xerostomia to increase salivation
Indirect-Acting Cholinergic
Agents (Cholinesterase Inhibitors)
• Reversible
• Bind to cholinesterase for a period of
minutes to hours
• Irreversible
• Bind to cholinesterase and form a permanent covalent
bond
• The body must make new cholinesterase
Anti cholinesterase
• Physostigmine
• 1) Glaucoma: Decreases IOP by producing miosis
• 2) Atropine Poisoning (DOC)
• Drugs for Alzheimer’s disease:
• Donepezil(Doc)
• Galantamine
• Rivastigmine
• Centrally acting anti cholinesterases to increase Ach
in brain which increases cognition and memory
• Neostigmine: Indirect action: inhibits
Cholinesterases- Increases Ach concentration of
NMJ
• Direct action: Stimulates Nm receptors of NMJ-
improves muscle power in Myasthenia Gravis
patients
• Pyridostigmine: longer acting
• Edrophonium: Rapid onset and short acting n used
for Diagnosing Myasthenia Gravis
Cholinergic Agents:
Therapeutic Uses
Indirect-Acting Agents
• Glaucoma as miotics
• Used for diagnosis and treatment of
myasthenia gravis
• Used to reverse neuromuscular blocking agents
• Atropine Poisoning
• Snake bite poisoning- Neostigmine( venom blocks Nm
receptors which causes skeletal muscle n Respiratory paralysis.
• Used to reverse anticholinergic poisoning (antidote)
Examples: physostigmine, pyridostigmine
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, Diarrhea
• Urination, lacrimation, Salivation
• Miosis
 Cholinergic Antagonists

Antimuscarinic Ganglionic Neuromuscular

agents Blocker Blocker
Atropine Nicotine Pancuronium
Scopolamine Mecamylamine Tubocurarine
Ipratropium Atracurium
Mivacurium
Succinylcholine
Antimuscarinic agents: Atropine

• A tertiary amine, has high affinity for muscarinic

receptors, preventing ACh from binding
• General actions last about 4 hours
Atropine: Actions
• Eye:
• Blocks all cholinergic activity, resulting in mydriasis,
unresponsiveness to light.
• Gastrointestinal (GI):
• Reduce activity of the GI tract
• Although gastric motility is reduced, Hcl is not significantly
affected.
• Urinary system:
• Reduce hypermotility states of the urinary bladder
• Cardiovascular:
• At low doses: decrease cardiac rate (bradycardia) due to blockade
of presynaptic muscuranic receptors.(M1)
• At higher doses: cardiac rate increases due to blockade of M2
receptors of the heart.
• Secretions:
• Blocks the salivary glands, producing a drying effect on the oral
mucous membranes
• Sweat and lacrimal glands are also affected
• Used as an antisecretory agent to block secretions in the upper and
lower respiratory tracts prior to surgery
• Antidote for cholinergic agonists:
• Used for the treatment of overdoses of cholinesterase
inhibitor insecticides and some types of mushroom
poisoning
• Adverse effects:
• Dry mouth, blurred vision, tachycardia, and constipation
• Effects on CNS include restlessness, confusion,
hallucinations,
• Children are sensitive to the rapid increases in body
temperature
Scopolamine
• Acts better on CNS n has longer duration of action
• Used to treat Nausea n vomiting
• It is available in patch Form which can be used for 3
days
Ganglionic Blockers: Nicotine
• A component of cigarette smoke
• No therapeutic benefit and is deleterious to health
• Depending on the dose, nicotine depolarizes
autonomic ganglia, resulting first in stimulation and
then in paralysis of all ganglia
• The stimulatory effects include increased blood
pressure and cardiac rate
• At higher doses, the blood pressure falls because of
ganglionic blockade
 Cholinergic Antagonists

Antimuscarinic Ganglionic Neuromuscular

agents Blocker Blocker
Atropine Nicotine Pancuronium
Scopolamine Mecamylamine Tubocurarine
Ipratropium Atracurium
Mivacurium
Succinylcholine
Neuromuscular Blocking Drugs

• Block cholinergic transmission between motor nerve

endings and the nicotinic receptors on the
neuromuscular end plate of skeletal muscle
• Clinically useful during surgery for producing
complete muscle relaxation
The order of paralysis of the
muscle
• Eyes
• Face
• Fingers
• Neck
• Trunk
• Limbs
• Diaphragm
• Recover in reverse manner
Nondepolarizing Blockers
• Mechanism of Action
• At low doses:
• Interact with the nicotinic receptors to prevent the
binding of acetylcholine
• Prevent depolarization of the muscle cell membrane
and inhibit muscular contraction
• At high doses:
• Block the ion channels of the end plate
• Therapeutic uses:
• Used in anesthesia during surgery
• Pharmacokinetics:
• Injected intravenously
• Quaternary amines structure, making them orally
ineffective, and do not cross the blood-brain barrier
• Many of the drugs are not metabolized
• Excreted unchanged in the bile
• Adverse effects:
• Tubocurarine: lowering blood pressure
• Pancuronium: increased heart rate
 • Succinylcholine is a short acting paralytic that is
Succinylcholine often used for short procedures requiring
intubation and in emergent situations.
References
• Kudlak M, Tadi P. Physiology, Muscarinic Receptor. [Updated 2023 Aug 8]. In:
StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.
Available from: https://www.ncbi.nlm.nih.gov/books/NBK555909/
• Ghossein N, Kang M, Lakhkar AD. Anticholinergic Medications. [Updated 2023
May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing;
2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK555893/
• Abrams P, Andersson KE, Buccafusco JJ, Chapple C, de Groat WC, Fryer AD,
Kay G, Laties A, Nathanson NM, Pasricha PJ, Wein AJ. Muscarinic receptors:
their distribution and function in body systems, and the implications for treating
overactive bladder. Br J Pharmacol. 2006 Jul;148(5):565-78. doi:
10.1038/sj.bjp.0706780. Epub 2006 Jun 5. PMID: 16751797; PMCID:
PMC1751864.