Med Chem Cholinergic Neurotransmission

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Afferent (PNS): Sensory
Efferent (PNS): Motor
Sympathetic or Parasympathetic pregang. neuron short, postgang. neuron long: Sympathetic
Sympathetic or Parasympathetic pregang. neuron long, postgang. short: parasympathetic
endogenous chemical entities that facilitate the transmission of electrical impulses: neurotransmitters
what is the flow of a synapse?: nerve impulse --> release NT--> binds to receptor on postsynaptic neuron --> change in membrane potential
What is an ionotropic effect?: when receptor is also an ion channel binding can cause channel to change formation (immediate effect)
What is a Metabotropic effect?: when a receptor produces a second messenger (DAG, IP3)
what is the NT of all preganglionic fibers of sympathetic and p.sym division???: ACh
ACh is the NT of few postgang. fibers of parasym. division. True or False: False
What are the physiologic role of ACh in the CNS?: cognition, memory, behavior, coordination of movement
What are the physiologic role of ACh in the eyes?: constriction of pupil
What are the physiologic roles of ACh in the lungs and bronchioles?: increase constriction of the bronchioles and increase secretion
What are the phys roles of ACh on the GI tract?: stomach:increase contraction & secretion intestine: increase motility
What are the phys roles of ACh on the bladder: contration (micturition)
What are the phys roles of ACh on the exocrine glands?: increase secretions of salivary, sweat and lacrymal glands
What are the phys roles of Ach on the heart?: decrease rate of contraction, decrease force of contraction
What are the phys roles of ACh on the blood vessels?: relaxation of smooth muscles of blood vessels (vasodilation)
what are the 2 types of cholinergic receptors?: Nicotinic and muscarinic
what mushroom is muscarin found in?: Amanita muscarina
What two grps are contained in the structure of nicotine?: pyridine and pyrrolidine
T/F: The effect of nicotine receptors occurs w/in 0.1 to 10 msec?: True
How many subunits are in a glycoprotein?: 5
What are the subunits in a glycoprotein?: 2 alpha, 1beta, 1 gamma, 1 sigma
What autoimmune disease causes muscle weakness, drooping eyelids, lethargy, and possible paralysis: Myasthenia gravis
What are N1 receptors blocked by?: decamethonium, d-tubocurine, and succinylcholine
What are N2 receptors blocked by?: hexamethonium
What type of ring does muscarine contain?: tetrahydrofuran ring
What are the three types of domains in a muscarine receptor?: seven transmembrane helical protein domain, extracellular domain, and intracellular domain.
Where are M1 receptors?: mostly in the CNS, also in the GIT
Where are M2 receptors?: mostly in the heart
Where are M3 receptors?: exocrine glands and smooth muscle
Where are M4 receptors?: tracheal smooth muscle
What conformation is ACh in at the Nicotinic receptor?: anti confromation
What conformation is ACH in at the muscarinic receptor?: gauche conformation
Agents that mimic the action of ACh at muscarinic receptors are...: cholinergic agonist
Agents that block the action of ACh at muscarinic receptors are...: cholinergic antagonist
Agents that inhibit the nicotinic-receptor mediated responses at ACh at the autonomic ganglia are...: ganglionic blockers
Agents that inhibit the nicotinic-receptor responses of ACh at teh NMJ are...: skeletal muscle relaxants
What AA can be used to synthesize ACh?: serine
What causes the storage vesicle to fuse to pre-synaptic membrane and release ACh???: Ca 2+
What is the action of ACh?: bind to postsynaptic receptor to produce a response
What inactivates ACh?: AChE and BuChE
What blocks high affinity reuptake?: hemicholinium
Where is BuChE found: found in plasma
The onium grp of ACh has what interaction with which AA?: ionic interaction with ASP
The ester grp of ACh has what interaction with which AA's?: H-bonbing with Thr, Asn
The ethylene grp of ACh has what interaction?: hydrophobic
What effect does replacing the CH3 of N atom have on ACh?: it reduces the agonist activity
An alpha-alkyl grp subst. on ACh is more nicotinic or muscarinic: nicotinic
A beta-alkyl grp subst. on ACh is more nicotinic or muscarinic?: muscarinic
beta-alkyl grp subst. of ACh has what effect?: decreases the rate of hydrolysis by AChE
Why is ACh not used as a therapuetic agent?: easily hydrolyzed; poorly absorbed;readily excreted non-selective between nicotinic and muscarinic receptors
What is the brand name for methacholine chloride?: Provocholine
What is Provocholine used for?: diagnostic agent for bronchospasms
Although methacholine chloride is a racemic mixture, what form contains the activity?: S-enantiomer
What is the brand name for ACh?: Miochol
What type of activity does Miostat have?: both muscarinic and nicotinic
What is the brand name for Carbachol Chloride?: Miostat
What is Carbachol Chloride used for?: used topically for glaucoma
Is Miostat given orally?: No. it would produce widespread unwanted effects
Why is hydrolysis slower in Miostat?: it contains a Carbamyl ester
What is the brand name for Bethanechol chloride?: Urecholine
What is the MOA for Urecholine: stimulates cholinergic receptors in the smooth muscle of the urinary bladder and GIT
What is Bethanechol Chloride used for?: to treat or prevent post-surgical urinary retention and atony of muscles in GIT
Rank these three in order of hydrolysis (slowest to fastest) Provocholine, Urecholine, Miostat: Urecholine, Provocholine/Miostat
Rank these three in order of hydrolysis (fastest to slowest) Carbachol Chloride, Bethanechol chloride, Methacholine chloride: Methacholine/Carbachol, Bethanechol
Why does Urecholine have a decreased rate of hydrolysis: it contains both a beta-methyl grp and a carbamate
What is derived from Pilocarpus jaborandi or P. microphyllus: Pilocarpine HCl
What is the brand name for Pilocarpine HCl: Pilocar
What is the MOA for Pilocar: directly stimulates cholinergic receptors in the eye causing miosis, spasm of accomodation, and lowering of intraocular pressure
What % solution is Pilocarpine administered: 0.5%
What is the agent of choice for glaucoma treatment?: Pilocarpine
What are the systemic effects of Pilocarpine: copius sweating, salivation, and gastric secretion
Where does the aqueous humor reside?: the space between the cornea and the lens
What is the purpose of the aqueous humor?: maintains the intraocular pressure
What balances the intraocular pressure: rate of secretion, resistance to flow, resistance to resorption
What secretes the aqueous humor?: ciliary epithelial
What is the canal of schlemm?: A small opening in the anterior chamber which aqueous fluid flows through and enters venous circulation
T/F : Diabetes is a risk factor for glaucoma: True
What is the most common type of glaucoma?: open angle glaucoma
What causes open angle glaucoma: obstuction of trabecular mesh
What causes closed angle glaucoma?: anterior chamber becomes narrow when iris dilates which obstructs outflow of aqueous humor
What are the 2 inactive forms of pilocarpine?: Pilocarpic acid and isopilocarpine
How should pilocarpine be stored?: soln at room temp (exp 2 wks)
Where is AChE located?: NMJ and synaptic junction
What 3 AA are involved in hydrolysis of ACh: Ser, His, Glu
What is more stable the acetylated enzyme or the acylated enzyme?: acylated
How do Reversible inhibitors of AChE work?: react with enzyme to form an acylated enzyme or bind to enzyme with greater affinity than ACh
What is the brand name for physostigmine?: Eserine
What is the MOA of Eserine?: inhibits AChE
What is the kinetic potent range of a drug: the nanomolar range
What is physostigmine used for?: tmt of glaucoma; tmt of overdoses of anticholinergics; investigational Alzheimers
T/F: A monosubstituted carbamate will carbamate an enzyme faster then a disubstituted carbamate?: true
In solution, physostigmine is hydrolyzed to what?: eseroline and carbamic acid
What is the brand name neostigmine bromide?: Prostigmin
What is the location of the dimethylcarbamate grp compared to the trimethylammonium on Prostigmin?: meta
Which is more active in an acidic pH Neostigmine or physostigmine bromide: physostigmine
What is Prostigmin used for?: to prevent post-surgical atony of muscles; treat glaucoma; myasthenia gravis
What are some symptoms of Myasthenia Gravis?: diplopia, weakness of jaw, weakness of proximal muscles
What is the brand name for pyridostigmine bromide?: Mestinon
What is the Mestinon used for?: tmt of myasthenia gravis
What is the brand name for Edrophonium Chloride?: Tensilon
What is Tensilon used for?: a diagnostic agent
How is Edrophonium Chloride used in the emergency room?: as a reversal of curare overdose
what is the MOA for Tensilon?: competes with ACh for binding to AChE
How is Edrophonium chloride administered: IM and IV
What is the pharmacological challenge with with Tensilon: it has a transitory but dramatic improvement in muscle function
what is the brand name for ambenonium chloride: Mytelase
What is Mytelase used for?: tmt of myasthenia gravis for patients that don't respond to neostigmin or pyridostigmine
What is Ambenonium chloride derived from?: oxalic acid
What is the MOA for Mytelase?: competes with ACh for enzyme AChE
What is the brand name for Demecarium Bromide: Humorsol
Is Humorsol hydrophilic or lipophilic: lipophilic
What is Demecarium bromide used for: the tmt of wide angle glaucoma
What is the DOA for Humorsol: about 2 days
How is Demecarium bromide administered: topically because it is very potent
What is the brand name for Tacrine HCl: Cognex
Which drug has a tetrahydroacridine ring: Cognex/ Tacrine HCl
What is the MOA of Tacrine HCl?: centrally-acting AChE inhibitor
What is Cognex used for?: first drug approved for tmt of Alzheimers
Why is there limited use for Cognex?: it is hepatotoxic
What is the brand name for Donepezil HCl?: Aricept
What is Aricept used for?: tmt of Alzheimers and dementia
What is the MOA for Donepezil HCl: centrally acting reversible inhibitor of AChE
What enzyme is Aricept selective for?: AChE
T/F : Aricept has a greater affinity for AChE in the periphery then the brain?: False
What % of the 6-desmethyldonapezil metabolite is active?: 11%
What is the brand name for Rivastigmine: Exelon
What is the MOA of Exelon?: centrally acting AChEI
What is the DOA for Rivastigmine: 10 hours
What is Exelon used for?: tmt of Alzheimers
What is the active ingredient in Turmeric?: Curcumin
What is the MOA for organophosphates?: permits the accumulation of ACh at nerve endings and produce an exacerbation of ACh like actions
What are the 3 characteristics of Organophosphates: very lipophilic, high vapor pressure and very low therapeutic index
What are the four functional grps that make up an organophosphate?: O,S; alkoxy; alkoxy/alkyl/tertamine; good leaving grp
How do you calculate Therapeutic Index: lethal dose / effective dose
T/F : Phosphorylated enzymes are very stable to hydrolysis: True
When does aging occur?: when a phosphoester bond is cleaved
What is the brand name for Isofluorphate?: Floropryl
What is Floropryl used for?: tmt of glaucoma
T/F : Floropryl is very toxic: True
What effect does Isofluorophate have on the eye?: It reduces the intraocular pressure
What is the DOA for Floropryl: 4 weeks
What serious side effect can occur if solution of Floropryl is not dilute?: detachment of Retina
What is the brand name for Echothiophate Iodide?: Phospholine Iodide
What is Phospholine Iodide used for?: tmt of glaucoma
How is the therapeutic window determined?: TW= MTC-MEC
What is Sarin used for?: chemical warfare (nerve gas)
What are Paraoxon and Parathion used for?: agricultural insecticides
What effects does Sarin have on Humans?: depression of respiratory rate, bradycardia, hypothermia, hypotension
What is the brand name for Pralidoxime chloride: Protopam
What is Pralidoxime chloride also known as?: 2-PAM
WHat does hydroxylamine do?: can cleave a phosphate ester
When is 2-PAM effective: w/in 36-48 hours of poisoning
Why is 2-PAM ineffective after 48hours of the poisoning: the enzyme will start aging
What is a compound with affinity for the receptor but lacks intrinsic activity: cholinergic Antagonist
What are the 2 subgroups for Nicotinic Antagonists?: ganglionic blockers and neuromuscular blocking agents
Where is the site of action for cholinergic antagonists in the autonomic division in the sympathetic nervous system: at the ganglia
Where is the site of action for cholinergic antagonists in the somatic division?: and the NMJ
What are the 7 other terms for Muscarinic antagonists?: antimuscarinics; anti cholinergics; cholinergic antagonist; cholinergic blockers; parasympatholytics; parasympathatics;postganglionic blocking agents; anti spasmodics
What effect does antimuscarinics have on the heart: produces tachycardia
What effect does antimuscarinics have on the lungs: dialation of bronchioles
What effect does antimuscarinics have on the GIT: decrease secretion and decrease motility
What effect does antimuscarinics have on the bladder?: urinary retention
what effect does antimuscarinics have on the eyes: mydriasis and cycloplegia
what effect does antimuscarinics have on the skeletal muscle: relaxation
what effect does antimuscarinics have on the CNS: stimulation or depression
What effect does antimuscarinics have on the mucous membrane?: decrease salivation and decrease perspiration
define mydriasis: dialation of pupil
Define cycloplegia: temporary paralysis of ciliary muscle
Define sialorrhea: drooling
Define hyperhydrosis: exsessive sweating
What is the clinical significance of antimuscarinics?: increase cardiac output; antispasmodic effect, antisecretory effect; mydriatic and cycloplegia effects; Parkinson's disease; asthma; cholinergic poisoning; antisialoqoque; antihydrotic
What are the most common side effectts of anticholinergics?: dry mouth, mydriasis, urinary retention
What condition does mydriasis precipitate?: Glaucoma
What is BPH?: benign prostratic hyperplasia -> increased cell # of normal prostratic cell
Where is Atropine and Scopolamine found?: Atropa Belladona, Hyoscymus niger, Datura Stramonium
Give examples of Solanaceous alkaloids?: atropine, scopalamine, homatropine, ipratropium
What ring in in Atropine: tropane
What position must the 3alpha-hydroxy grp be in for activity (for atropine): axial
What makes up a tropane ring?: piperidine, pyrrolidine
What neurotropic effect does atropine have?: interfers w/ nerve impulse transmission
What musculotropic effect does Atropine have?: produced by direct depression of smooth muscle of GIT
What is the AOC for the musculotropic effect of Atropine: Papadarine
What is Atropine sulfate used for?: primarily mydriatic during refraction studies
What other effects does Atropine sulfate have?: tachycardia, constipation, xerostomia, dry eyes, CNS stimulation, decrease secretion in GIT
What are the contraindications of Atropine sulfate?: open angle glaucoma, BPH, severe hypertension
What is another name for Scopalamine?: Hyoscine
What is Scopalamine used for?: motion sickness
What are the other effects of Hyoscine?: sedation, and dry mouth
T/F: Homatropine HBr is twice as potent as atropine: False. it is 1/2
What structures make up Homatropine HBr?: tropine and Mandelic acid
What is Homatropine HBr used for?: primary for mydriatic and cycloplegic properties
What is the brand name for Ipratropium Bromide: Atrovent
What is the MOA for Atrovent: produces bronchodialation by competitive inhibition of cholinergic receptors bound to smooth muscles of bronchioles
What is Atrovent used for?: used to treat asthma and COPD
What is the brand name for Clindinium Bromide?: Quarzan
Which muscarinic receptors does Quarzan have a high affinity for?: M1 and M3
What is Quarzan used for?: antispasmodic and antisecretory effects
What drug is Quarzan combined w/ for peptic ulcers?: chlordiazepoxide
What is the brand name for Clindinium Br and Chlordiazepoxide?: Librax
What is the brand name for Dicyclomine HCl?: Bentyl
What is Bentyl used for?: spasmolytic effect on smooth muscle of GIT
T/F: Bentyl has 1/8 neurotropic activity of Atropine and 2x musculotropic activity: True
What drug is used to treat IBS?: Dicyclomine HCl
What is the brand name for Glycopyrrolate?: Robinul
What is Robinul used for?: spasmolytic and antisecretory effect
What muscarinic receptor does Robinul have a high affinity for: M1
What effect does Glycopyrrolate have if given in high doses: can block ganglionic and NMJ receptors
What is the brand name for propantheline Bromide?: Pro-Banthine
T/F: Pro-Banthine is 1/2x potent as Banthine.: False. it is 2-5x more potent
What is Pro-Banthine used for?: antispasmodic and antisecretory effects
what disease are aminoalcohol ethers and aminoalcohols primarily used to manage: Parkinson's
What are the four primary symptoms of PD?: fine tremors; rigidity or stiffness of limbs; slowness of movement; postural instability
What are some other symptoms of PD: oculogyric crisis; mask face; drooling; depression
What part of the brain is responsible for producing dopamine?: the substantia nigra
Is the pyrimidal tract inhibitory or excitatory?: excitatory
Is the extrapyrimidal tract excitatory or inhibitory?: inhibitory
Dopamine is an excitatory or inhibitory NT?: inhibitory
What is different in the brain of a PD patient?: The substantia nigra are dead
What are the characteristics of primary PD?: idiopathic; incurable; tmt is palliative
What are two infectious causes of secondary PD: encephalitis and syphilis
What drugs can induce secondary PD?: reserpine, haloperidol, and chlorpromezine
What class of drugs are used to treat PD: Dopaminergic agonist
What is the brand name for Diphenhydramine?: Benadryl
What are some side effects of Benadryl?: drowsiness, CNS depression
What is the brand name for Benztropine mesylate?: Cogentin
What patients are Cogentin targeted for?: useful in patients that can't tolerate central excitation
What patients should you take caution with when using Cogentin?: patients with glaucoma and BPH
What is the brand name for Biperiden?: Akineton
What is Akinetin used for?: useful for tmt of PD and also in a variety of spastic disorders
What effects does Biperiden have on patients?: alleviates akinesia, rigidity and tremors
What is the brand name for Procyclindine HCl?: Kemadrin
What is Kemadrin used for?: tmt of PD
what structural ring does Kemadrin contain?: a pyrrolidine ring
What is the brand name for Trihexyphenidyl HCl?: Artane
What is Artane used for?: tmt of PD
What structural ring does Artane have?: piperidine ring

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