Parasympathetic Flashcards
Acetylcholine
Cholinomimetic drug
Direct acting cholinergic agonist
Rapidly hydrolyzed by acetylcholinesterase.
Brief duration of action.
Synthetic choline esters.
Not very lipid soluble (poorly absorbed) Highly charged. usually administered directly to areas you want to have effect.
Bethanechol
Cholinomimetic drug Direct acting cholinergic agonist More resistant to acetylcholinesterase. Longer duration of action. Synthetic choline esters. Not very lipid soluble (poorly absorbed) Highly charged. usually administered directly to areas you want to have effect.
Carbachol
Cholinomimetic drug Direct acting cholinergic agonist More resistant to acetylcholinesterase. Longer duration of action. Synthetic choline esters. Not very lipid soluble (poorly absorbed) Highly charged. usually administered directly to areas you want to have effect.
Cevimeline
Cholinomimetic drug
Direct acting cholinergic agonist
Nicotine
Cholinomimetic drug Direct acting cholinergic agonist Cholinomimetic alkaloids- designed to be longer acting and absorb easier. Absorbed across skin. Mainly excreted by kidneys
Pilocarpine
Cholinomimetic drug
Direct acting cholinergic agonist
Cholinomimetic alkaloids- designed to be longer acting and absorb easier.
Mainly exerted by kidneys
Verenicline
Cholinomimetic drug
Direct acting cholinergic agonist
Edrophonium
Cholinomemetic drug
Indirect acting (anticholinesterases)
Short acting
Doneprzil
Cholinomemetic drug
Indirect acting (anticholinesterases)
Intermediate acting
Galantamine
Cholinomemetic drug
Indirect acting (anticholinesterases)
Intermediate acting
Neostigmine
Cholinomemetic drug
Indirect acting (anticholinesterases)
Intermediate acting
Physostigmine
Cholinomemetic drug
Indirect acting (anticholinesterases)
Intermediate acting
Pyridostigmine
Cholinomemetic drug
Indirect acting (anticholinesterases)
Intermediate acting
Rivastigmine
Cholinomemetic drug
Indirect acting (anticholinesterases)
Intermediate acting
Echothiophate
Cholinomemetic drug
Indirect acting (anticholinesterases)
Long acting
Malathion
Cholinomemetic drug
Indirect acting (anticholinesterases)
Long acting
Parathion
Cholinomemetic drug
Indirect acting (anticholinesterases)
Long acting
Sarin
Cholinomemetic drug
Indirect acting (anticholinesterases)
Long acting
Pralidoxime
Reactivation of acetylcholinesterase that has been inactivated
Atropine
Cholinoceptor-blocking drugs
ACh antagonist
Cyclopentolate (cyclogyl)
Cholinoceptor-blocking drugs
ACh antagonist
Dicyclomine
Cholinoceptor-blocking drugs
ACh antagonist
Homatropine
Cholinoceptor-blocking drugs
ACh antagonist
Ipratropium
Cholinoceptor-blocking drugs
ACh antagonist
Oxybutynin
Cholinoceptor-blocking drugs
ACh antagonist
Scopolamine
Cholinoceptor-blocking drugs
ACh antagonist
Tiotropium
Cholinoceptor-blocking drugs
ACh antagonist
Tropicamide
Cholinoceptor-blocking drugs
ACh antagonist
Cholinomimetics
Drugs that mimic acetylcholine. As if Ach is bound to the receptor.
Direct acting: Ach receptor agonist. Classified by type of receptor activated- nicotinic or muscarinic.
Indirect acting: Cholinesterase inhibitor. Inhibit hydrolysis of endogenous Ach to increase the availability of naturally occurring Ach in the synapse. Amplifies.
How are cholinergic agonists metabolized?
By cholinesterase enzyme just like Ach, in the blood and in the liver.
Method of administration must take into account the metabolism by acetyl-cholinesterase.
Synthetic choline esters
Ach, Carbachol, bethanechol.
Not lipid soluble, highly charged. Usually administered directly to area you want to effect.
Differ in susceptibility to cholinesterase
Ex: Ach is rapidly hydrolyzed. Brief duration.
Carbachol and bethanechol are more resistant to cholinesterase and have a longer duration of action.
Cholinomimetic alkaloids
Pilocarpine, nicotine, muscarine.
Readily absorbed from most sites of administration.
Nicotine can be absorbed through the skin.
Muscarine is toxic and crosses BBB.
Muscarine receptors are ____
Nicotinic receptors are ___
GPCR. Slow on/slow off. Not desensitized.
Ion channels. Fast on/fast off. Will be desensitized and have depolarizing blockede.
Depolarizing blockade.
Prolonged agonist binding causes post ganglionic neuron to stop firing. Prevents recovery and the receptor becomes desensitized to the agonist.
nicotinic cholinergic.
Muscarinic effects on the eye
Pupil will constrict due to contraction of iris sphincter
Ciliary muscle will contract
Will result in opening of TM = decreased IOP
Muscarinic effects on the heart
Decreased heart rate. Hyperpolarization of SA and AV node. The decrease in HR is often opposed by reflex sympathetic discharge (tug of war)
Muscarinic effects on respiratory system
Contract bronchial smooth muscle- bronchioconstriction
Stimulation of bronchial glands to increase secretions
Muscarinic effects on the GI tract
Increase smooth muscle motility, relax most spinsters, stimulate salivary and gastric glands to secrete.
Muscarinic effects on genitourinary and glands
Genitourinary: promote urination
Glands: Stimulate secretion of sweat, lacrimal, and nasopharyngeal glands.
What are more widespread? Nicotinic or muscarinic receptors?
Nicotinic are more widespread- you will get more side effects. Will even stimulate parasympathetic and sympathetic at the same time due to the ganglion synapse. Will also stimulate NMJ follows by depolarization blockade.
Often resembles simultaneous discharge of both para and sympathetic systems. Be careful when prescribing this!
What types of drugs have the longest duration of action?
Derivatives of phosphoric acid (organophosphates)
Some used as nerve gas or insecticides or weapons. Can have really bad side effects. Farmers may come in with this.
Absorption of organophosphates
Absorbed from skin, lung, gut, and conj. Dangerous to humors. Will cross BBB and cause CNS toxicity.
Exception is echothiophate- does not penetrate BBB.
Indirect acting cholinomemetic mechanism of action
Increase concentration of endogenous Ach by inhibiting acetylcholinesterase. Chemistry of drug molecules determines interaction with the enzyme.
The drug can be short, medium, or long lasting.
Short acting Indirect acting cholinomemetic
Edrophonium.
Forms reversible bond with the enzyme. Not actually a substrate for Acetylcholinesterase, meaning edrophonium will not be broken down by the enzyme. Instead, edrophonium will occupy the enzyme. Reversible. Aka very short acting.
Intermediate acting Indirect acting cholinomemetic
Neostigmine, physostigmine, pyridostigmine
Resistant to part of the enzyme action, so it takes acetylcholinesterase longer to break down the drug.
Long acting Indirect acting cholinomemetic
Echothophate, malathion, parathion, sarin.
Forms phosphorylated enzyme complex that strengthens the bond with the drug. Completely deactivates acetylcholinesterase. Body will not be able to recover until it can produce more of the enzyme.
Organ system effects of Indirect acting cholinomemetic
Similar to the direct acting cholinomimetics WRT eyes, respiratory tract, Gi, urinary.
NMJ: Will increase strength of muscle contraction. Especially in pts with myasthenia gravis. High or prolonged amounts will cause depolarization neuromuscular blockade.
CNS
Low concentrations: will cause an alerting response
High concentrations: Convulsions.
How can cholinomimetics be used clinically?
Eye (glaucoma)
GI and urinary tract to help with urinary retention and dry mouth
NMJ for Myasthenia gravis
Alzheimers
Main cholinomimetic used to treat glaucoma
Pilocarpine
When to and when not to use a cholinomimetic to treat GI disorders
Use to treat disorders that involve a decrease in smooth muscle activity WITHOUT obstruction. Cholinomimetic will increase GI smooth muscle motility- don’t want to move things around if there is an obstruction.
What to use for diagnosis of myasthenia gravis
Edrophonium. Very short acting indirect cholinomemetic.
why do you have to use indirect cholinomemetics on myasthenia gravis patients?
Cant use agonist on receptor that doesn’t work. But can use indirect to increase the Ach availability (amplification) hoping it binds to a receptor that does work.
Most common drug for long term treatment of Myasthenia gravis
Neostigmine.
Adverse effects of direct acting cholinomimetics
Nausea, vomiting, diarrhea
Urinary urgency, salivation, sweating.
Flushing of skin (vasodilator)
Bronchiole constriction.
Adverse effects of indirect acting cholinomimetics
Nausea, vomiting, diarrhea
Urinary urgency, salivation, sweating.
Flushing of skin (vasodilator)
Bronchiole constriction.
Muscle weakness (activity of NMJ)
Convulsions
Respiratory failure.
^^ these often result from exposure to pesticides (organophosphates)
What kind of side effects will you get with a cholinoceptor antagonist?
Will get symptoms opposite of parasympathetic. May even resemble sympathetic.
What do cholinoceptor antagonists do?
Bind to Ach receptor and block Ach from binding. Interrupt parasympathetic nerve impulses.
Divided into muscarinic and nicotinic subgroups.
Muscarinic blockers can be further divided based on affinity for certain receptor. M1-M5
Cholinoceptor antagonist
Absorption
Distribution
Elimination
Absorption: Most are well absorbed from the gut, conj, and across the skin.
Wide distribution with CNS penetration
Elimination via kidney
Mechanism of action of cholinoceptor antagonist
Block Ach action at muscarinic receptors.
Moderately selective for various muscarinic receptor subtypes (Exception is atropine. nonselective and is useful in treating cholinomimetic toxicity due to organophosphates)
Non-selective cholinoceptor antagonist drug that is useful in treating cholinomimetic toxicity by organophosphates
Atropine. Non selective and will bind to many Ach receptors to stop organophosphate toxicity.
When to use scopolamine
reversal of vestibular disturbances (treats motion sickness) Drowsiness and amnesia normal.
How do cholinoceptor antagonists affect the eye
Mydriasis- blocks the constrictor muscle. Allows unopposed sympathetic dilator activity
Cycloplegia- weakens the contraction of ciliary muscle.
Reduction in lacrimal secretion
Usually tropicamide or cyclopentolate.
Clinical uses of cholinoceptor antagonist
Accurate refraction
-Homatropine or cyclo
Dilated fundus exam
-Tropicamide or cyclo.
Treatment of uveitis
- prevent synechia
- Homatropine or cyclo
Iris synechia
Inflammation of the Uvea. Irregular pupil margin and pigment from iris may be stuck on lens.
Cyclo or homatropine will create a regular pupil shape. May have pigment left over on lens.
Duration of effect: Atropine Homatropine Cyclopentolate Tropicamide
Atropine: 1 week
Homatropine: 1-3 days
Cyclopentolate: 1 day
Tropicamide: 6 hours
Clinical treatment of anti-muscarinic drugs
Will stop parasympathetic. Increase sympathetic system.
Prevent airway constriction and secretions. bronchodilator Treat urinary urgency. Treat bradycardia. Cholinergic poisoning.
What drug type do you use for cholinergic poisoning?
Anti muscarinic drug. Atropine preferred because non-specific and will bind all muscarinic receptors. Multiple doses usually required.
Pralidoxime. How is it used in cholinergic poisoning?
Can “regenerate” phosphorylated enzyme (in the case of an indirect cholinomemetic.)
But it must be used rapidly!
Cholinoreceptor agonists cause SLUD
Salivation
Lacrimation
Urination
Diarrhea
Cholinorecptor antagonists have the opposite effect. Dry mouth Dry eyes Urinary retention Constipation
