Cholinergic and Anticholinergic drugs Flashcards
(17 cards)
Where do cholinergic drugs act?
How do cholinergic drugs act?
Acetylcholine is the endogenous substance.
How does it work at receptors?
on the parasympathetic nervous system of the autonomic nervous system.
Rest and digest.
directly as an agonist (parasympathomimetics) or indirectly by inhibiting acetylcholinesterase (this increases acetylcholine).
- Acetylcholine is synthesized from choline.
- It is taken up in vesicles which also protects it from degradation.
- Ca influx causes vesicles to fuse with membrane releasing Ach.
- Ach binds and activates postsynaptic receptor.
- Ach is degraded by acetylcholinesterase.
- then taken up by neuron to be recycled.
Parasympathetic Nerves (“Rest & Digest”)
What are the effects when cholinergic drugs bind.
These are also effects when parasympathetic nervous system is stimulated.
Constrict pupils
Stimulate salivation
Slow heartbeat
Constrict airways
Stimulate activity of stomach
Inhibit release of glucose; stimulate gallbladder
Stimulate activity of intestines
Contract bladder
Promote erection of genitals
DUMBELLS
D – Diarrhea
U – Urination
M – Miosis (pupil constriction/pinpoint pupils)
B – Bradycardia (slow heart rate) and Bronchoconstriction
E – Emesis (vomiting)
L – Lacrimation (tears)
L- Lethargy
S – Salivation
What are the two types of Cholinergic Receptors or Cholinoceptors?
What are the subtypes?
Muscarinic and nicotinic receptors. Distinguish based on affinity.
Muscarinic: postsynaptically on Smooth muscle, Cardiac muscle, Glands and Effector organs.
Both muscarine and acetylcholine bind.
M1: autonomic ganglia, gastric glands and brain.
M2: heart (reduces HR)
M3: GIT, gallbladder, pupils, glands, blood vessels.
Nicotinic receptors
N1or Nm: neuromuscular junction
N2 or Nn: autonomic ganglia, CNS, adrenal medulla.
Direct Acting Cholinergic Agonists also called parasympathomimetics mimic the action of acetyl choline.
What are the two types?
- Choline esters (synthetic): bethanechol, carbachol
- Alkaloids (natural): pilocarpine
pilocarpine used for : miosis, to induce saliva in patients with xerostomia, emergency treatment of glaucoma.
SE: blurred vision, night blindness, sweating, salivation.
Indirectly acting cholinergic drugs or Anticholinesterases.
MOA
What are the two types and their subtypes?
acetylcholinesterase breaks down acetylcholine.
anticholinesterases prevent this.
Irreversible:
1. Organophosphates:
Carbaryl, Echothiophate, Parathion, Malathion, Diazinon, Tabun, Sarin, Soman
- Carbamates: Propoxur
Reversible: These bind reversibly to AChE
1. Carbamates: Neostigmine, Edrophonium Rivastigmine Donepezil Physostigmine, Pyridostigmine Galantamine
- Acridine: Tacrine
Uses:
1. miotic: Used in glaucoma to constrict pupils (miosis)
2. Myasthenia gravis
3. Postoperative paralytic ileus / urinary retention
4. Postoperative decurarization
5. Cobra bite
6. Alzheimer’s
Explain how the tensilon test is used to diagnose myasthenia gravis.
What happens if you overdose?
What is the drug of choice for MG?
Tensilon or Edrophonium is a short-acting anticholinesterase. It inhibits AChE, preventing ACh breakdown. This leads to increased ACh in the synaptic cleft which means better stimulation of muscle receptors.
A person tests positive for myasthenia gravis if their muscles get stronger after being injected with Tensilon. Intravenous injection of edrophonium leads to a rapid increase in muscle strength.
Excess can cause cholinergic crisis. Antidote: Atropine. The optimal dose is a low dose.
neostigmine and pyridostigmine
What causes Alzheimer’s disease?
What drugs are used to treat?
due to a deficiency of cholinergic neurons in the CNS.
So anti-cholinesterases used to treat since they Inhibit Ache in the brain.
Donepezil
Galantamine
Rivastigmine
Tacrine-hepatotoxic
SE : DUMBELLS
How to treat glaucoma?
1) direct agonists : pilocarpine ,carbachol
2) Acute Angle-Closure: First-line initial therapy with a direct muscarinic agonist e.g. pilocarpine to control Intraocular pressure and reduce vision loss. The patient is prepared for Laser Iridotomy a corrective surgery.
What drug is used for Postoperative Ileus, to increase LES (Lower Esophageal Sphincter) tone and for urinary retention?
Bethanechol or neostigmine
What are Neuromuscular-Blocking Drugs (NMBs)?
MOA
Uses
Types
Example and how it works.
Drugs that block neuromuscular transmission at the neuromuscular junction (NMJ) and cause Skeletal muscle paralysis.
Muscle relaxants inhibit neuron transmission to muscle by blocking the nicotinic acetylcholine receptor. Prevent ACh from triggering muscle contraction
Adjunct to anesthesia — to induce muscle paralysis
Facilitate intubation — by paralyzing vocal cords
Optimize surgical field — via muscle relaxation
Depolarizing Blocker: Succinylcholine
It Mimics ACh and binds to nAChR → causes initial depolarization → Fasciculations (brief muscle twitching)
Non-depolarizing Blocker: Curare/Tubocurare
It competitively antagonizes nicotinic acetylcholine receptors preventing acetylcholine from binding. No activation occurs — just blockade. The main toxin of curare,d-tubocurarine has equal or greater affinity than ACh.
If succinylcholine is used as a muscle relaxant it mimics acetylcholine and blocks the receptor so acetylcholine cannot bind to cause contraction. Using Neostigmine increases ACh levels by blocking acetylcholinesterase. But Succinylcholine is already activating the receptor so adding more ACh just worsens or prolongs the depolarization.
If curare is used as a muscle relaxant it competitively antagonizes acetylcholine so it cannot bind to cause contraction. Neostigmine increases ACh → displaces curare from the nicotinic receptor → restores muscle function
Neostigmine works with curare because of competitive inhibition — increased ACh can displace the blocker and restore contraction.
With succinylcholine, there’s no competition — the receptor is already over-activated and desensitized, so more ACh doesn’t help and may worsen the block.
What is Botulinum toxin (BTX)?
MOA
Clinical and Cosmetology uses.
Itis a neurotoxin produced by the bacterium
Clostridium botulinum.
Blocks presynaptic receptors and prevents acetylcholine release.
Clinical uses
Strabismus (eye misalignment)
Focal dystonias (e.g., cervical dystonia, writer’s cramp)
Hemifacial spasm
Spastic movement disorders (e.g., cerebral palsy-related spasticity)
Chronic migraines/headaches
Hypersalivation (sialorrhea)
Hyperhidrosis (excessive sweating)
Cosmetic/Dermatological Uses:
Reduces facial wrinkles and fine lines
Applied to forehead, crow’s feet, frown lines, chin, neck, chest
Popular in aesthetic dermatology and anti-aging treatments
Thiophosphate Insecticides
Examples: Parathion and Malathion
They are prodrugs
Must be converted into active oxygen analogues in the body
conversion happens rapidly in insects → leads to acetylcholinesterase inhibition
Malathion is rapidly detoxified in birds and mammals → relatively safe
Insects lack this efficient metabolism, so it remains toxic to them
“Mammals Metabolize Malathion”
→ Safer in humans, toxic in insects
Echothiophate and sarin (nerve gas)
This irreversibly inactivates AChE.
Accumulation of ACh at cholinergic synapses Leads to cholinergic crisis.
After binding, the enzyme-drug complex undergoes “aging” (loss of an ethyl group from the phosphorylated enzyme)
The enzyme is permanently inactivated so pralidoxime (AChE reactivator) is ineffective. Pralidoxime must be given before aging to reverse effects of AChE.
Pralidoxime must be given with Atropine to block effect of accumulated Ach at the site.
Actions:
Include generalized cholinergic stimulation
Paralysis of motor function (causing breathing difficulties)
Convulsions.
What do Anticholinergic Drugs do?
called cholinergic blocking agents, parasympatholytics, anticholinergics, antimuscarinics.
competitively antagonize acetylcholine
inhibit nerve transmission at these receptors.
- natural alkaloids: atropine, hyoscine
- semisynthetic derivatives: hyoscine butyl bromide
- synthetics
mydriatics: tropicamide
vasicoselective: tolterodine
antiparkinsonian: trihexyphenidyl
Uses of anticholinergics
atropine prevents actions such as the release of inositol trisphosphate (IP3) and the inhibition of adenylyl cyclase that are caused by muscarinic agonists.
Blockade by a small dose of atropine can be overcome by a larger concentration of acetylcholine or equivalent muscarinic agonist.
uses:
Atropine : increase heart rate in symptomatic bradycardia and Sinus or nodal bradycardia (due to myocardial infarction)
Parkinson’s disease –Benztropine, Trihexyphenidyl
Motion Sickness: Scopolamine
decreasing salivation, spasticity and tremors
Drug-induced extrapyramidal reactions due to antipsychotics
Asthma, COPD, Chronic Bronchitis, Exercise-induced bronchospasms: Ipratropium , Tiotropium
Solifenacin, Tolterodine: Overactive bladder and
Urinary incontinence.
Homatropine & Tropicamide: Accurate refraction testing in uncooperative patients (e.g., children) and Retinal examination.
Contraindications of Anticholinergic Drugs
🚫 Do NOT Use In:
Glaucoma (especially narrow-angle)
→ May ↑ intraocular pressure
Prostatic hypertrophy / BPH
→ Risk of urinary retention
Urinary tract obstruction
Gastrointestinal tract obstruction
→ Can worsen ileus
Infectious diarrhea
→ Slows gut motility, may retain toxins
Reflux esophagitis / GERD
→ ↓ LES tone → worsens reflux
Tachyarrhythmia
→ Anticholinergics ↑ HR
Angina pectoris
→ Increased HR may worsen chest pain
Hyperthyroidism
→ Can ↑ sensitivity to catecholamines → tachycardia
Pregnancy (use cautiously)
→ Limited safety data for some agents
Muscarinic agonists reduce intraocular pressure in glaucoma by:
Atropine blocks which of the following receptors?
A common side effect of atropine is:
Which anticholinergic drug is used for motion sickness?
In overactive bladder, which agent is preferred? Solifenacin
Which statement is TRUE about atropine’s CNS penetration? It has minimal CNS effects
Increasing aqueous humor drainage
Muscarinic
Dry mouth
Scopolamine
Solifenacin
