Autonomics Flashcards
What are the 3 kinds of muscarinic receptors and where are they found?
M1, M2 and M3M1 is found in CNS and enteric nervous systemM2 is primarily in heart, decreases heart rate only at the SA nodeM3 is at the glands, bladder and smooth muscles of the eye
Explain M1 MOA.
M1 Gq - activate IP3-DAG cascade –> increased intracellular calcium;
Explain M2 MOA.
M2 is Gi, decreases cAMP
Explain M3 MOA.
M3 is Gq - activate IP3-DAG cascade –> increased intracellular calcium;
What happens in an intact endothelium when muscarinic agonist is administered
Vasodilation
What happens vasculature without endothelium when muscarinic agonist is administeredWhat disease is this phenomenon associated with?
Vasoconstriction by increasing intracellular Ca in the smooth musclesAtherosclerosis
Bethanecol
Used to treat non-obstructive gastrointestinl dysmotility (e.g. post-op ileus, neurogenic ileus - like from spinal cord injury, congenital megaocolon) and urinary retention. Muscarinic agonist increase the secretory ability and motility of the gut
Pilocarpine
Pilocarpine - increases salivation (treats fry mouth - sjograns) and treats glaucoma by contracting the ciliary muscles, facilitating the outflow of aqueous humor and causing pupillary constriction ; causes accommodation of lens
How is acute angle glaucoma treated?
For acute angle glaucoma it is important to cause contraction of sphincter papillae muscle which leads to pupillary constriction, pilocarpine can be used to achieve this
What are the 3 places where nicotinic receptors are found?
Autonomic ganglia, skeletal muscle motor end plates, and adrenal gland (post ganglionic organ)
MOA of nicotinic receptors?
transmembrane polypeptides that act as ion channels (influx of positive ions –>depolarization of skeletal muscles
What drug is used for smoking cessation
Very clean = Vernicline
Carbachol
Carbachol - both muscarinic and nicotinic agonist, causes pupillary constriction (useful in acute angle-closure glaucoma)
What are indirect cholinomimetics?
ACh esterase inhibitors
What is one disease that involves the use of indirect cholinominetics to increase ACh at the NMJ?
Myasthenia Gravis - antobodies against the ACh receptors are made
What are the different kinds of indirect cholinomimetics?
Quaternary, tertiary and phosphate derivatives. Quaternary cannot cross the BBB hence their effects are more peripheral, tertiary have more central effects
What are the examples of quaternary AChEI?
NeostigminePyridostigmineEdrophonium
What is the use of neostigmine?
Can reverse nondepolarizing neuromuscular blockade after surgery (removing effects of anesthesia); like urinary retention after surgery
What are the uses of pyridostigmine?
Long-term treatment for MG; only symptomatic treatment
What is the use of edrophonium?
Diagnosis of MG since it has a very short half life.
Describe the test that is done to dx MG?
It is called the tensilon testPt comes with worsening MG symptoms: 1. could be over treated (cholinergic crisis - too much ACh) or 2. could be undertreated (Myastenia crisis)If give edrophonium and symptoms get better, then undertreated/Myasthenia crisis
Give an example of tertiary AChEI? What are its uses?
Physostigmine, used for more of its central CNS effects since it can cross the BBB
Name two plants which are known to cause atropine poisoning.
Belladonna flower and Jimson’s weed, Jimson’s weed is also called Gardner’s mydriasis
Name drugs that are specific for nicotinic receptors at the NMJ?
Tubocurarine, Pancuronium, Cisatracurium
Explain the MOA of succinylcholine.
Nicotinic Ach receptor AGONIST; like an analogue of ACH, causes phase 1 block; potentiates depolarization
What is the most common cause of ACh esterase inhibitor toxicity?
Insecticide poisoning/occupational expsure
Name organophosphate AChEI
Parathion, Malathion, Echothiophate
What kind of paralysis does these cause? What does over activation of ACh receptors at the NMJ lead to?
Flaccid paralysis
What can be used to reverse ACh toxicity? What is its limitation?
Pralidoxime - reverses organophosphate toxicity; regenerates acetylcholinesterase at muscarinic AND nicotinic receptors - reverses cholinergic toxicity, including flaccid paralysis.However it cannot enter CNS, ONLY PERIPHERAL, ineffective once organophosphate -cholinesterase complex has occurred, a process called aging.
What drug can be used to reverse central and peripheral ACh toxicity?
Atropine - reverses both peripheral and central muscarinic toxicity from organophosphate poisoningHowever, it cannot reverses neuromuscular blockade/paralysis since it is only a muscarinic antagonist
Name drugs used in Alzheimer’s disease.
GalantamineRivastigmineDonepezil
Explain the MOA of atropine.
Non selective competitive antagonist of M1, M2 and M3
What are atropine’s effects on eyes?
Mydriasis and cycloplegia (inability to accommodate for near vision due to ciliary muscles paralysis)
What is the main muscarinic receptor found in CNS
M1
What are the effects of scopolamine?What is it used for?
prevent sea sickness/motion sickness as it crosses BBB and inhibits central M1 receptors, important to know that this is a property shared by most of the muscarinic antagonists.
What is the role of muscarinic antagonists in Parkinsons’ disease and other CNS diseases?
M1 receptors are found in CNS, it turns out that reduction in muscarinic transmission in the CNS is helpful in Parkinsons disease
What is the role of muscarinic antagonist in post MI treatment?
Block parasympathetic activation of M2 receptors on SA and AV nodes, normally parasympathetic tone to the heart determines the HR and blocking this tone can increase HR which is important usually after post MI - increased HR (tachycardia), increased AV conduction (treatment for heart block)
What is the role of muscarinic antagonist in heart block treatment?
Used for heart block therapy: Heart block can occurs when there is a delay or decreased electrical transmission to the ventricles through the AV nodes, this can be caused by numerous pathologies, IV atropine can be administered to reverse heart block in these patients since muscarinic receptor antagonists increase AV conduction
What is the role of anti muscarinics in COPD treatment?
Smooth muscles and secretory glands in the airway receive vagal innervation modulated by M3 receptors, anti muscarinic agents can be used to cause dilation of the airways and reduce secretions.
Name the drugs that are used in COPD
Ipratropium - M3 muscarinic antagonist for COPD, INHALED, bronchodilation –> decreased secretionsTiotropium - M3 muscarinic antagonist for COPD, INHALED, bronchodilation –> decreased secretions; longer bronchodilation; can be given once a day for COPD
Name the anti muscarinics used for urinary incontinence treatment?
Oxybutynin - M3 muscarinic antagonist, for incontinence, relaxes smooth muscle in ureters and bladder wallTolterodine - M3 muscarinic antagonist, for incontinence, relaxes smooth muscle in ureters and bladder wall
Benztropine
Benztropine - centrally acting M1 muscarinic antagonists, treatment for parkinson’s tremor and rigidity (loss of dopamine in basal ganglia) - blocks excess cholinergic activity, no effect on bradykinesia
Trihexyphenidyl
Trihexyphenidyl - centrally acting M1 muscarinic antagonists, treatment for parkinson’s tremor and rigidity (loss of dopamine in basal ganglia) -blocks excess cholinergic activity, no effect on bradykinesia
How can antipsychotics cause drug induced Parkinson’s?
Antipsychotic drugs are known to cause extrapyramidal side effects, antipsychotic agents stop dopaminergic transmission, just like in Parkinson’s disease so they cause similar symptoms- dystonia, akathisia
What are the side effects of anti muscarinics?
o Hot as a hare: antimuscarinics inhibit M3 receptors, sweat glands –> decreased sweating –> hyperthermiao Dry as a cracker: decreased salivation and lacrimation –> dry mouth and eyeso Blind as a bat - mydriasis and cycloplegia –blurred vision high pressure as a kettle Vignette: lady has Bradycardia after MI, then give atropine, comes back with eye pain –> induced acute angle closure glaucomao Mydriasis –> decreased outflow of aqueous humor –> acute angle closure glaucoma o Mad as a hatter - cross BBB –> antagonize M1 receptors –> sedation, agitation, hallucination, coma (esp in old pts)
What are alpha and beta receptors coupled to intracellularly?
Alpha 1,2 beta 1,2 -> QISSAlpha 1 is coupled to Gq, Alpha 2 is Gi, Beta 1 and 2 is Gs
What are the effects of alpha 1 activation?
Gq –> IP3 DAG cascade – increased calcium - activate smooth muscle –> increase in peripheral arterial resistance (vasoconstriction in arteries AND veins)
