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Cholinergic Pharm
Pharmacolgy Exam 2
Question | Answer |
---|---|
What is one of the only sites in the sympathetic nervous system where a postganglionic neuron releases acetylcholine onto a muscarinic receptor? | Sweat glands |
What are the two substrates required to produce acetylcholine? | Choline + Acetyl-CoA |
What is the function of the choline transporter? (CHT) | The choline transporter functions in bringing extracellular choline into the neuron |
What is the function of choline acetytransferase? (ChAT) | ChAT synthesizes acetylcholine by combining choline and acetyl-CoA |
What is the function of Vesicle Associated Transporters? (VAT) | VAT transports acetylcholine into the vesicles for storage. |
How is the release of Ach in the synaptic cleft initiated? | Voltage gated Ca++ channels open after an action potential passes through the cell. This causes the fusion of acetylcholine-containing vesicles with the membrane |
What enzyme terminates Ach's actions? | Acetylcholinesterase |
What is the function of heteroreceptors? | Heteroreceptors are activated by substances released from other nerve terminals that synapse with the nerve ending |
What is the function of autoreceptors? | Autoreceptors respond to their own substance release |
What are Vesicle Associated Membrane Proteins? (VAMPs) | VAMPs align vesicles with their release site on the cell membrane (inside the neuron) |
What are Synaptosomal nerve-associated proteins? (SNAPs) | SNAPs are the release site outside of the cell in the nerve terminal membrane |
What types of drugs affect the parasympathetic nervous system? | Cholinergic |
What are the two types of receptors that acetylcholine binds to? | Nicotinic & Muscarinic |
What is the rate limiting step in the synthesis of norepinephrine? | Tyrosine -------> Dopamine *Tyrosine Hydroxylase* |
How is norepinephrine released from the terminal? | Voltage gated Ca++ channels open after an action potential passes through. Increases in intracellular Ca++ causes the fusion of the norepinephrine-containing vesicles with the membrane. |
What types of drugs block the reuptake of norepinephrine? | Antidepressants and cocaine |
Once norepinephrine is release from the cell, what happens to it? | a) diffuses out of the cleft b) transported into the cytoplasm of the terminal by the Norepinephrine Transporter (NET) |
How is norepinephrine synthesized? (Describe the process) | 1. Tyrosine is brought into the cell via a sodium-dependent carrier 2. Tyrosine is converted into dopamine via tyrosine hydroxylase 3. Dopamine is transported in to a vesicle via VMAT and covnerted into norepinephrine via dopamine-beta-hydroxylase |
Compounds derived from the amino acid Tyrosine are called | catecholamines |
What types of tissues/organs do muscarinic receptors innervate? | Nerve, heart, smooth muscle, glands, endothelium |
Where are muscarinic receptors found? | Muscarinic receptors are found on ORGANS and in the brain *heart, bronchioles, stomach, intestine, pancreas, eye, mouth* |
Where are nicotinic receptors found? (what do they innervate?) | Nueromuscular end plate, skeletal muscle, & autonomic ganglion cells, |
What are the functions of muscarinic receptors 1, 3, & 5? | Muscarinic 1, 3, 5 Stimulate Phospholipase C as a second messenger |
What are the functions of muscarinic receptors 2 & 4? | Muscarinic 2 & 4 inhibit adenylate cyclase open K+ channels (hyperpolarize) close Ca++ channels (block entry of Ca++ that mediates cellular activity) |
What is chronotropy? | Chronotropy affects time or rate (i.e. heart rate) |
What is dromotropy? | Dromotropy affects conduction |
What is inotropy? | Inotropy affects the force of contraction |
What are the effects of parasympathomimetics on the heart? | 1. Bradycardia (negative chronotropy) 2. Decrease conduction (negative dromotropy) 3. Decrease force of contraction (negative inotropy) |
What are the effects of parasympathomimetics on the GI system? | In GI smooth muscle, increased tone and motility of the wall muscles and relaxation of sphincters |
What are the effects of parasympathomimetics on the bladder? | In bladder, the body (detrussor mm) contracts while sphincters relax |
What are the effects of parasympathomimetics on the lungs? | In lungs, bronchoconstriction and increase secretion |
What are the effects of parasympathomimetics on the eyes? | In the eye, contraction of the ciliary mm (lens) and circular mm of the iris (accommodate for close up vision) |
What are the effects of parasympathomimetics on the exocrine gland? | In exocrine glands, promotes secretion (anomylous) |
Muscarinic receptors cause a ___________ response. | SLUDGE S = Salivation L = Lacrimation U = Urination D = Defecation G = GI upset E = Emesis (vomiting) |
Acteylcholine and some analogues with similar chemical structures are known as ____________ | choline esters |
Parasympathomimetics include what class of drugs? | Muscarinic agonists, nicotinic agonists, choline esters |
What are the four types of choline esters? | Acetylcholine, methacholine, carbachol, & bethanechol |
Which two choline esters have negligible susceptibility to cholinesterase? What is the significance of negligible susceptibility to cholinesterase? | a. Carbachol & Bethanechol b. Longer half-lives |
What is bethanechol used in the treatment of? | Bethanechol is used in the treatment of postpartum or postoperative nonobstructive urinary bladder retention (causes the urinary sphincter to relax so that urine can be expelled) |
To which class does bethanechol belong? | Choline Ester |
To which class does carbachol belong? | Choline Ester |
What is carbachol used in the treatment of? | Mitotic agents (small pupil) Treatment for glaucoma |
What are the two types of muscarinic agonists? | Muscarine and Pilocarpine |
What class does muscarine belong to? What is it used for? | Muscarine is a muscarinic agonist. It is a toxin from mushrooms. MUSCARINE = TOXIN |
What class does pilocarpine belong to? What is it used for? | Pilocarpine is a muscarinic agonist. It is used in the treatment of glaucoma. |
What is muscarinic toxicity? What are the symptoms? | Too much muscarinic antagonist. Severe SLUDGE reactions. Death can occur due to respiratory failure. |
What is the antidote to muscarinic toxicity? | Atropine |
What are some "anti-parasympathetic" effects observed from muscarinic antagonists? | tachycardia, constipation, urinary retention, hypertension, bronchodilation, dry mouth, pupil dilation |
To which class does atropine belong? | Muscarinic Antagonist |
To which class does scopalamine belong? | Muscarinic Antagonist |
What is atropine used for? | Anti-Diarrhea cardiac support (crash cart) pre-operative antisecretory agent |
What is scopalamine used for? | Anti-nausea |
To which class does ipratropium belong? | muscarinic antagonist |
What is ipratropium used for? | bronchodilator |
What is a side effect of ipratropium? | dry mouth |
To which class does tiatropium belong? | muscarinic antagonist |
What is tiatropium used for? | bronchodilator - COPD longer half life than ipratropium |
To which class does methscopolamine belong to? | muscarinic antagonist |
What is methscopolamine used for? | GI spasms |
What is homoatropine used for? | GI Spasms, irritable bowel |
To which class does homoatropine belong? | muscarinic antagonist |
To which class does proantheline belong? | muscarinic antagonist |
What is proantheline used for? | ulcers |
To which class does glycopyrrolate belong? | muscarinic antagonist |
What is glycopyrrolate used for? | Anti-vagal during surgery stops visceral muscle movement |
To which drug class does pirenzepine belong? | Muscarinic antagonist |
What is pirenzepine used for? | anti-peptic disorder |
Which receptors is pirenzepine specific for? | M1 & M4 |
To which drug class does darifenacin belong? | Muscarinic antagonist |
What is darifenacin used for | Darifenacin (Enablex) is used in the treatment of urinary or fecal incontinence |
Which receptor is darifenacin selective for? | Darifenacin (Enablex) is specific for the M3 receptor |
To which class does oxybutnin belong? | Oxybutnin (ditropan) is a muscarinic antagonist |
What is oxybutnin used for? | Oxybutnin (ditropan) is used to relax the detrussor muscle (for bladder incontinence) |
To which class does tolterodine belong? | Tolterodine (Detrol) is a muscarinic antagonist |
What is tolterodine used for? | Tolterodine (Detrol) is used to relax the detrussor muscle (for bladder incontinence) |
Benztropine, Trihexyphenidyl, Biperiden, Procyclidine are all examples of what class of drugs? What are they used for? | Benztropine, Trihexyphenidyl, Biperiden, Procyclidine are muscarinic antagonists used in the treatment of Parkinson's |
What are indirect cholinergic agonists? | Indirect cholinergic agonists are drugs that stimulate Ach receptors because they inhibit acetylcholinesterase |
To which class does echothiophate belong? | Indirect muscarinic agonist |
To which class does diisopropylfluorophosphate (DFP) belong? | indirect muscarinic agonist |
What are indirect muscarinic agonists used in the treatment of? | glaucoma |
What is echothiophate used in the treatment of? | Glaucoma |
What is diisopropylfuorophosphate used in the treatment of? | glaucoma |
What is the significance of the quartenary amine on ipratropium and tiatropium? | The positively charged amine on ipratropium and tiatropium keep the drugs from crossing the BBB (since charged molecules can't cross) |
What is myasthenia gravis? | An autoimmune disorder in which there is a loss of nicotinic receptors on the motor end-plate of skeletal muscle. Leads to insufficient receptor stimulation and weakness. |
What medication is used to test for myasthenia gravis? | Edrophonium |
How is edrophonium used to diagnose myasthenia gravis? | If the patient immediately gets better after administration, it is a POSITIVE diagnosis of myasthenia gravis. If the patient gets worse, it's a negative diagnosis. |
What class of medications is used in the treatment of cognitive disorders of Alzheimer's? | Indirect Nicotinic Agonist |
Which medications belong to the Indirect Cholinergic Agonists / Cholinesterase Inhibitor class? | Phyostigmine, Tacrine, Donepezil, Galantamine |
To which drug class does phyostigmine belong? | Indirect Nicotinic Agonist |
To which drug class does Tacrine belong? | Indirect Nicotinic Agonist |
To which drug class does Donepezil belong? | Indirect Nicotinic Agonist |
To which drug class does Galantamine belong? | Indirect Nicotinic Agonist |
There is no quartenary amine on phyostigmine, tacrine, donepezil, or galantamine. What is the significancce? | No charge on the Nitrogen means that the drug is able to cross the BBB. |
To which class do bug poisons belong? | Indirect Nicotinic Agonist |
To which class does parathion, malathion, Sevin, and Chlorpyriphos belong? | Indirect Nicotinic Agonist |
To which class do human poisons used in war belong? | Indirect Nicotinic Agonist |
To which class does Sarin, Soman, and VX (dermal) belong? | Indirect Nicotinic Agonist |
What is the goal of cholinesterase inhibitors? | Inhibit Achase, which will in turn increase the amount of Ach concentrations and the duration of its effects. |
Inhibition of cholinesterase produces an increase in ________________ | skeletal muscle contractions AKA fasciculations |
Inhibition of cholinesterase produces an increase in skeletal muscle contractions (fasciculations), followed by _____________ | loss of control and paralysis |
Explain how cholinesterase works | see notes |
What are the three main classes of cholinesterase inhibitors? | Quarternay amines, carbamates, and organophosphates |
To what class of cholinesterase inhibitors does edrophonium belong? | Quaternary amine |
How does edrophonium work as a quarternary amine cholinesterase inhibitor? | blocks the binding site on the enzyme. the positively charged nitrogen binds to the anionic site where Ach would normally bind. |
To what class of cholinesterase inhibitors does neostigmine belong? | carbamates |
How does neostigmine work as a carbamate cholinesterase inhibitor | neostigmine attaches a hydroxyl group to the serine. the group comes off slowly, making the drug's effects last longer. |
To what class of cholinesterase inhibitors does diisofluorophosphate belong? | Organophosphate |
How does diisofluorophosphate work as a organophosphate cholinesterase inhibitor? | DFP binds to the esteratic site (where the serine is). |
Why is the binding of diisofluorophosphate to the esteratic site of cholinesterase considered irreversible? | The hydrolysis of phosphorylated esteratic site is so slow that it is considered irreversible |
How do you remove diisofluorophosphate from the esteratic site of cholinesterase? | by adding pralidoxime, which will bind to DFP, making a stronger bond than DFP had to the esteratic site. the new whole molecule can now leave cholinesterase together. |
What happens when you add water to the phosphorylated cholinesterase enzyme after diisofluorophosphate has bound? | "aged" enzyme irreversibley bound. permanent. |
If pralidoxime is added after the aging process of the cholinesterase enzyme has occurred, will it still work? | no. |
pralidoxime is classified as what? | reactivator |
Glaucoma is often treated with which muscarinic class of drugs? | Muscarinic agonist |
What molecule would block the transport of choline into the cell? | hemicholiniums |
what molecule would block the transport of Ach into the vesicles? | vesamicol |
what molecule would block the actions of VAMPs and SNAPs? | botulinum toxin |