Autonomic Nervous System / Cholinergic Transmission Flashcards
What are the featurse of the autonomic nervous system?
- involuntary
- sympathic and parasympathetic
- handles visceral functions
- 2 neurons in series (pre and post ganglionic)
All preganglionic fibers of the autonomic nervous system release…
ACh
What are the functions of the sympathic nervous system?
- fight or flight
- runs on norepinerphrine
- increases CO, BP, RR, Blood Flow, BG
- decreases RBF, digestive processes
- fires at once
In the sympathic nervous system, there is ______ preganglions and _______ postganglions
short
long
What are the functions of the parasympathic nervous system?
- normal maintenance and anabolic metabolism
- incremental activation
- vagal stimulation
In the sympathic nervous system, there is ______ preganglions and _______ postganglions
long
short
What are the functions of the somatic nervous system?
- voluntary
- controls movement, respiration, and posture
- always excitatory
- no ganglia
What do cholinergic fibers release?
ACh
All preganglionic efferent and somatic motor fibers to skeletal muscle are ____________________ fibers
cholinergic
Most parasympathetic postganglionic fibers are…
cholinergic
Adrenergic fibers release…
norepinephrine
Most sympathetic post ganglionic fibers are…
adrenergic
What are the steps of cholinergic transmission?
- Acetyl CoA + choline = ACh
- Transported to cytoplasm, prepped for release
- Calcium triggers release
- Binds to cholinergic receptor
- Acetylcholinesterase breaks up the party: choline + acetate
What are the types of autonomic receptors?
Cholinergic receptors
Nicotinic (ganglionic)
Muscarinic
Adrenergic receptors
Alpha
Beta
Dopamine
What are the three main classes of nicotinic receptors?
- muscle
- ganglionic
- CNS
Are nicotinic receptors excitatory or inhibitory?
excitatory
What are the types of muscarinic receptors?
- M1: neural
- M2: atrial
- M3: glandular/smooth muscle
- M4 and M4: CNS
What is the function of M1 receptors?
Neural
- CNS excitation, gastric secretion
What is the function of M2 receptors?
Atrial
- cardiac and neural inhibition
What is the function of M3 receptors?
Glandular/Smooth Muscle
- gastric acid, salivary secretions, GI contraction, ocular accommodation, vasodilation
What are the types of adrenergic receptors and where are they located?
- Α1, Α2
- Β1, Β2, Β3
- DOPAMINE
- post-ganglionic sympathetic system only
What is another name fo muscarinic agonists?
cholinergics
What is the main function of cholinergic drugs?
parasympathomimetic
What are the types of cholinergic drugs?
- direct acting
— binds directly to NACH(OS) and MACH(OS) - indirect acting
— inhibits acetylcholinesterase
— amplifiers of endogenous ACh
What are the examples of direct acting cholinergics?
- Pilocarpine (salagen)
- Bethanechol (urecholine)
- Cevimiline (evoxac)
direct acting cholinergic
What is the function of pilocarpine (salagen)?
- glaucoma TX
- causes mitosis, lowers IOP
- dental use - radiation-induced xerostomia
direct acting cholinergic
What is the function of bethanechol (urecholine)?
- post-operative urinary retention
- most resistant to cholinersterase
direct acting cholinergic
What is the function of cevimiline (evoxac)?
- selective for M3
- more selective for exocrine glands
- radiation-induced xerostomia
- sjogren’s syndrome
What are the types of indirect acting cholinergic drugs?
- reversible
— stigmine agents, donepezil (aricept), galantamine (razadyne) - irreversible
— organophosphates
What is the main function of indirect acting cholinergic drugs?
acetylcholinesterase inhibitors
Indirect acting cholinergics are used for treatment of…
- myasthenia gravis
- glaucoma
- GI motility
- reversal of neuromuscular blockade
- anticholinergic toxicity
- alzheimers
What are the different types of reversible ACHE inhibitors?
- Pyridostigmine (Regonol®)
- Neostigmine (Prostigmin®)
- Physostigmine (Antilirium®)
- Edrophonium (Tensilon®)
- Galantamine, rivastigmine, donepezil
Pyridostigmine (Regonol®) is used for…
*Myasthenia gravis
*Nerve agent prophylaxis
1st line for MG
Neostigmine (Prostigmin®) is used for…
*Myasthenia gravis
*Post-op ileus / urinary retention
*Neuromuscular blockade reversal
Doesn’t enter CNS (quaternary amine)
Physostigmine (Antilirium®) is used for…
*Anticholinergic toxicity
Enters CNS (tertiary amine); not routinely used
Edrophonium (Tensilon®) is used for…
*Diagnosis of myasthenia gravis
Doesn’t enter CNS (quaternary amine); Not routinely used
Galantamine, rivastigmine, donepezil is used for…
*Mild-to-moderate Alzheimer’s disease
What are the featurs of organophosphates?
- Irreversible AChE
- Long lasting
bad!
What are examples of organophosphates?
- Insecticides
— Parathion, malathion - Nerve agents
—Sarin, soman, tabun, VX - Novichok Agents
What is the mechanism behind organophosphates?
- Phosphorous (+) attracted to serine (-)
- OP attaches to AChE, prevents ACh binding
- Cholinesterase is now blocked
- AChE is now permanently out of commission (unless hydrolyzed or regenerated)
When an organophosphate blocks cholinesterase what happens?
1 of 3 things…
1. Hydrolyze to original state (slow)
2. Regenerate with an oxime (fast)
3. Age (cannot regenerate)
What are the muscarinic symptoms of cholinergic toxicity?
Salivation
Lacrimation
Urination
Diarrhea
GI discomfort
Emesis
Miosis/muscles weak
Bronchorrhea
Bradycardia
Salivation/sweating
What are the nicotinic symptoms of cholinergic toxicity?
Muscle cramps
Tachycardia
Weakness
Twitching
Fasciculations
How much time do you have to be treated after exposure to nerve agents (organophosphates)?
Depends but anywhere from 2 minutes to 40 hours
What drugs can you treat an exposure to organophosphates?
- Pralidoxime (2-PAM; regenerates AChE)
- Atrophine (muscarinic only; requires huge amounts)
- Pyridostigmine (prophylaxis only)
What is another word for muscarinic antagonists?
anticholinergics
What is the function of anticholinergics?
binds muscarinic receptors, blocks ACh
What are the types of anticholinergics?
- tertiary amines (central effects)
— atrophine, scopolamine (scopace), benztropine (cogentin), dicyclomine (bentyl) - quaternary amines (peripheral effects)
— glycopyrrolate (robinul), tiotropium (spiriva)
What are the uses of atropine?
prototypical anticholinergic
- muscarinic selectivity
- No effect S/P heart transplant
- Indictions
— bradycardia
— OP toxicity
Why should you not used <0.5 mg of atropine in adults?
paradoxical bradycardia
anticholinergic
What are the uses of scopolamine?
- found in hyoscyamus niger (henbane)
- teritary amine
- use in
— motion sickness
— voodoo zombification
anticholinergic
What are the uses of glycopyrrolate?
- used to dry secretions
— surgery
— ketamine treatment - adjunct for reversal of neuromucsular blockers
quaternary amine; fever central effects
What negative effects do anticholinergics have on the CNS?
Drowsiness, amnesia, agitation, hallucinations, coma
What are the many uses for anticholinergics?
- ophthalmology
— mydriasis, cycloplegia, increased IOP - GI/GU
— antispasmodic, antidiarrheal, urinary incontinence - Cardio
— vagolytic (increase heart rate) - Secretions
— decrease all - Antidote
— reversal of cholinergic toxicity (organophosphates) - Pulomonary
— COPD, Asthma
What negative effects do anticholinergics have on the eyes?
Mydriasis, cycloplegia, reduced lacrimal secretion
What negative effects do anticholinergics have on the CV system?
Tachycardia (vagal inhibition)
What negative effects do anticholinergics have on the respiratory system?
Bronchodilation, reduced airway secretions
What negative effects do anticholinergics have on the GI system?
Decreased motility, xerostomia
What is another name for ganglion stimulating drugs?
nicotinic drugs
What is an example of a nicotinic drug?
varenicline (chantix)
nicotinic drug
What are the functions of varenicline (chantix)?
- inhibits
— nicotine binding
— withdrawal symptoms
— dopamine release - partial agonist/antagnoist
- long half-life and high affinity for NACH(OS)
What are the depolarizing neuromuscular blockers?
succinylcholine
What are the polarizing neuromuscular blockers?
- rocuronium
- vecuronium
- pancuronium (causes tachycardia)
- cisatricurium
What is the function of a neuromuscular blocker?
- inhibit binding of ACh and NMJ
depolarizing neuromuscular blocker
What is the use of succinylcholine?
- open sodium channels
- onset = 60 seconds
- duration = 5 minutes
- 1.5 mg/kg IV
Why do you need to be careful with succinylcholine?
hyperkalemia
- denervation supersensitivity
polarizing neuromuscular blocker
What is the use of rocuronium?
- no significatn ADR
- reversal agent
- onset = 60 seconds
- duration = 45 minutes
- 0.6-1.2 mg/kg
