Pharmacologie: Partie 2: Pharmacologie du système nerveux autonome, Cholinomimétiques /Anticholinergiques Flashcards
What are cholinomimétiques?
Molecules that mimic the effect of acetylcholine
What are the two main types of cholinimimétiques?
- Action directe (bind to the receptor itself) CHAD
- Action indirecte (increase ACh that is secreted/produced) CHAID
How do CHADs work?
Effected mediated by molecule binding to and stimulating receptors
Two kinds: amines quaternaires (can’t pass BBB) and tertiaires (can pass BBB)
Susceptible to being hydrolyzed by cholinestérases
What are the two sous-types of CHADs?
- Nicotiniques
- Muscariniques (parasympathomimétiques)
Where are Nicotiniques found?
Ganglions autonomes: PNS and SNS
Neuromuscular junctions
CNS
If nicotinique (in PNS and SNS) are stimulated.. it will lead to what?
Release of Ach by postganglionary PSN neurons
Release of catecholamines by médullo-surrénales
Release of NA by postganglionnary SNS neurons
If nicotinique (neuromuscular junction) are stimulated.. it will lead to what?
Stimulation of post-synaptic receptors of neuromuscular junction
What will happen if these receptors are stimulated repeatedly and excessively? (nicotinique)
- Desensitization of neurons
- Inhibition of transmission ganglionnaire
- Diminished release of catecholamines by adrenals
What is the clinical effect of stimulation of these receptors by CHADs? (nicotinique)
Vasocontriction
Tachycardia
Increased GI motility
Incontinence/urgency (urination)
Muscle contraction
General CNS effects
CAN LEAD TO ADDICTION —> DOPAMINE RECEPTORS
What are the clinical uses of nicotinic CHADs?
Not many, other that nicotine patches or other treatments for cigarette addiction
Where are the global effects of stimulating muscarinic receptors?
Stimulation of PNS
Light inhibition of PNS and SNS (auto/heteroregulation)
Stimulation of SNS (sweatglands)
NO IMPACT ON MÉDULLO-SURRÉNALE
What are the effects of direct stimulation of muscarinic receptors? (PNS)
Myosis
Increase in lacrymal and salivary secretions
Increase in peristalsis
Vasodilation (not PNS.. but muscarinic receptors directly on vessels)
Bradycardia
Bronchoconstriction and increase in tracheal secretions
Increased GI motility
Relaxation of GI sphincters
Contraction of detrusor muscle and relaxation of vesical sphincter
What are some clinical uses for muscarinic CHADs?
Glaucoma: reduce intraocular pressure by inducing a myosis
Metacholine tests for diagnosing asthma: induce bronchoconstriction
Treating xerostomia resulting from Sjogrens or radiotherapy to increase salivary and lacrimal secretions
Correction of atonic bladder and urinary retention
What is muscarin?
Muscarinic agonist: activates the activity of the muscarinic acetylcholine receptor
Parasympathomimetic symptoms (hypersecretion, vomiting, diarrhea, dehydration, myosis)
Antidote: Atropine —> muscarinic antagonist
What is sarin gaz?
Liquid without smell or colour in the family of organophosphates
Irreversible inhibitors of acetylcholinesterase
Muscular contractions that may lead to paralysis, myosis, hypersecretions, bronchospasm, dyspnea, nausea, vomiting, incontinence
Antidotes: pralidoxime and atropine
What are the three important cholinomimétiques to know?
Methacholine, neostigmine and organophosphates (like Sarin)
What are anticholinergiques?
Antagonists for muscarinic and nicotinic receptors (ganglia, muscular)
They inhibit liberation of ACh
What are antimuscarinics?
They block muscarinic receptors (ex: atropine and glycopyrrolate)… not much selectivity for sub-types
They’re considered parasympatholytic
Tertiary (✅ BBB) and quaternary (❌ BBB) amines
Where do antimuscarinics primarily work?
Autoregulation in PSYMP and hetero in SYM (pre-synaptic)
Block post-synaptic muscarin receptors (Ach) in PSYMP
What are antimuscarinics principal effects?
Mydriasis
Cycloplegia (paralysis of the ciliary muscle)
Tachycardia
Bronchodilation
Urinary retention
What are some clinical uses of antimuscarinics?
Bradycardia treatment (atropine)
Treatment of bronchospasm in MPOC and asthma
Dilate pupils during ophthalmological exam
Preventing nausea/vomiting, reducing saliva secretion, sedation
Parkinsons: reduce shaking/rigidity
Reducing spasms but LOTS of side effects
Reversing effects of neuromuscular blockers and intoxication from cholinomimétiques (atropine)
What conditions are counter indications to prescribing antimuscarinics?
Glaucoma, urinary retention and prostatic hyperplasia, constipation, hyperthermia (fever), tachyarrhythmia
What are ganglioplégiques?
Antagonists for Ng receptors (nicotiniques ganglionnaires) (ex: triméthaphan)
Where do ganglioplégiques primarily target?
block symp >>> parasymp
inhibits transmission between preganglionic and postganglionic neurons in the autonomic nervous system, often by acting as a nicotinic receptor antagonist
What are some clinical uses of ganglioplégiques?
Treating hypertension BUT THEY SUCK DON’T USE THEM
What are neuromuscular blockers?
lead to paralysis of skeletal muscles (ex: rocuronium –> sedative)
Where do neuromuscular blockers target?
antagonist of nicotinic muscular receptors
What are some clinical uses of neuromuscular blockers?
Mostly used for paralysis: preoperatory, endotracheal intubation and in the ICU (rocuronium)
How does toxine botulinique work?
Bonds irreversibly to cholinergenic nervous fibres and stops liberation of ACh
What is botulism and how is it treated?
Rare and potentially fatal illness caused by a toxin produced by the bacterium Clostridium botulinum
Causes: vision problems, mydriasis, ptosis, difficulty swallowing, constipation, muscular weakness and paralysis BUT normal sensitivity and afebrile
Treatment: Antitoxine équine (MUST BE GIVEN VERY EARLY)
What is botox used for?
Used for: treating spasticity, aesthetics, can be injected into ureter, bladder and prostate for medical treatments
What do supratherapeutic doses of atropine cause? And how is this treated?
Can lead to intoxication… symptoms include: excitation, nervousness, hallucinations, coma
Treatment: Physostigmine (cholinesterase inhibitor that can cross BBB) which will inhibit central effects of atropine
