Term
| Where is acetylcholine always released as the neurotransmitter? |
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Definition
All preganglionic efferent autonomic fibers (basically all ganglions)
and in the somatic nervous system |
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Term
| In what division(s) of the autonomic nervous system do we exclusively find muscarinic receptors? |
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Definition
| Parasympathetic nervous system |
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Term
| Acetylcholine is formed by what enzyme? |
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Definition
Choline acetyltransferase
(Acetyl CoA + Choline) |
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Term
| What triggers vesicles to release acetylcholine? |
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Definition
| Influx of Ca2+ into cell spurs vesicles to attach to plasma membrane and release Ach via exocytosis |
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Term
| What does acetylcholinesterase (AChE) degrade ACh into? |
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Definition
| Choline + Acetate (in 150 microseconds) |
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Term
| To what ions are Nicotinic receptors permeable? |
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Definition
| Sodium and Potassium (sodium predominates) |
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Term
| Whats the difference between muscle nicotinic receptors and neuronal nicotinic receptors? |
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Definition
Muscle nicotinic receptors have 4 different types of subunits (alpha, beta, epsilon, delta)
Neuronal nicotinic receptors only have alpha and beta subunits |
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Term
| To what subunit does acetylcholine bind? |
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Definition
| alpha subunit (2 binding sites) |
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Term
| Which muscarinic receptor types are inhibitory? |
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Definition
| M2 and M4 (abundant in heart and smooth muscle) |
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Term
| What are the 3 types of Muscarinic receptor agonists? |
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Definition
| Choline Esters, Natural Alkaloids, and Synthetic Derivatives |
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Term
| Describe the pharmacokinetics of Choline Esters |
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Definition
| Hydrophilic, poorly absorbed, poorly dist into CNS |
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Term
| What is the only therapeutic use of acetylcholine and what are its limitations? |
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Definition
| Intraocular injection in surgery to achieve miosis. It is very short acting. |
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Term
| How is methacholine different? What is it used for? |
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Definition
There is a beta-methyl group added in methacholine, which makes it more resistant to AChE but reduces its affinity for nicotinic receptors.
It is used as a diagnostic test for bronchial airway hyperactivity (suspected asthma) |
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Term
| How is Carbachol different and what are its uses? |
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Definition
Acetyl group is replaced with a carbamoyl group, making it resistant to AChE.
Used for glaucoma treatment and to cause miosis during surgery (ophthalmic use only) |
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Term
| Describe the pharmacokinetics and uses of Pilocarpine (natural alkaloid) |
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Definition
Well absorbed from most sites of administration, renal elimination.
Used for acute angle-closure, open-angle glaucoma and used as a sialagogue (saliva inducing agent) in pts with radiation damage and Sjogrens syndrome |
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Term
| What does DUMBELS stand for? |
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Definition
Acronym for main adverse effects of muscarinic receptor agonists.
Diarrhea & Diaphoresis; Urination; Miosis; Bronchospasm, Bronchorrhea, Bradycardia; Emesis; Lacrimation; Salvation and Seizures |
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Term
| What are the contraindications of cholinomimetics? |
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Definition
| Asthma, Ischemic heart disease, hyperthyroid, stomach ulcer, GI/Urinary surgery |
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Term
| What are the two Nicotinic receptor agonists? |
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Definition
| Nicotine and Varenicline(Chantix) |
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Term
| Describe the pharmacokinetics of Nicotine |
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Definition
| Well absorbed from many sites of admin; good distribution, crosses B-B barrier; hepatic metabolism and urinary excretion. |
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Term
| What are the biphasic effects of Nicotine? |
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Definition
1) direct actions - rapid depolarization of nerve cell
2) Desensitization- when the receptor is occupied for too long the response stops and the neuron/muscle stops firing (can cause convulsions and resp failure) |
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Term
| Describe the pharmacokinetics and pharmacodynamics of Varenicline |
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Definition
Oral, good bioavailability, min hepatic metab, renal excretion of unchanged drug
Is a partial agonist that stimulates activity on dopamine neurons of the VTA. Basically, acts as a less potent nicotine |
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Term
| What are the uses of Nicotine and Varenicline? |
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Definition
| Aid in nicotine withdrawal symptoms. Varenicline can have neuropsych adverse effects. |
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Term
| What does MTWThF stand for? |
|
Definition
Nicotinic Receptor Agonist Toxicity
Mydriasis, Tachycardia, Weakness, hyperThermia, Fasciculations |
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Term
| Which AChE inhibitor is a noncovalent inhibitor and what are its pharmacokinetics? |
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Definition
| Edrophonium - hydrophilic, does not readily permeate membranes, IV, very short duration of action and renal elimination |
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Term
| What are the reversible carbamate inhibitors and what are their chemical differences? |
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Definition
Physostigmine and Neostigmine.
Physostigmine has a tertiary amine and Neostigmine has a quaternary amine. |
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Term
| How do their pharmacokinetics differ? |
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Definition
| Physostigmine is able to cross the BB barrier. Neostigmine can be administered sub-Q and orally in addition to IV and IM |
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Term
| Describe the pharmacokinetics and pharmacodynamics of irreversible organophosphates like echothiophate |
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Definition
| Highly lipid soluble and can be absorbed through skin. Echothiophate is used as a topical ophthalmic solution |
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Term
| How does edrophonium act on AChE? |
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Definition
| Reversibly binds via electrostatic and hydrogen bonds to active site, prevents it from binding to ACh. (very short-lived) |
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Term
| How do the carbamate esters act on AChE? |
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Definition
| They are broken up by AChE just as ACh is but take much longer (30 mins-6 hours) to be completely hydrolyzed, basically keeping AChE busy so that it cant bind to ACh |
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Term
| How does echothiophate act on AChE? |
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Definition
| Bind to AChE and form very strong bond that takes very long to hydrolyze |
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Term
| Where are the most prominent effects of AChE seen? |
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Definition
| Cardiovascular, GI, Eye, and neuromuscular junction |
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Term
| What are the therapeutic uses of Edrophonium? |
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Definition
| PNS only - Diagnosis of myasthenia gravis, differentiating between a cholinergic crisis and a myasthenic crisis, and reversal of nondepolarizing neuromusc blockers |
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Term
| What are the uses of Physostigmine? |
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Definition
| Glaucoma and Reversal of PNS and CNS effects of anticholinergic drug tox: (anticholinergic drugs like atropine can cause life threatening delirium) |
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Term
| What are the uses of Neostigmine? |
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Definition
| Reversal of nondepolarizing neuromusc blockers; tx for myasthenia gravis; tx for postop bladder distention and urine retention |
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Term
| What are the uses of Echothiophate? |
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Definition
It is a long term miotic- used to tx chronic open angle glaucoma.
Can also be used in some cases of acute closed angle glaucoma |
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Term
| How do Tacrine and Donepezil help Alzheimers patients? |
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Definition
| Alzheimers pts lose neurons->lose production of ACh. Tacrine and Donepezil block AChE to increase ACh in pts brains |
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Term
| Describe the pharmacokinetics of Tacrine and Donepezil |
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Definition
Oral, 90-100% bioavailability (donepezil), some plasma protein binding and donepezil is a minor substrate of CYP2D6 and CYP3A4.
Tacrine: 4/day Donepezil: 1/day |
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Term
| Why is Donepezil given over Tacrine? |
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Definition
| Tacrine has a high risk of hepatotoxicity |
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Term
| What drug would you give for Xerostomia(dry-mouth)? |
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Definition
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Term
| What drug would you give for treatment of myasthenia gravis? |
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Definition
|
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Term
| What drugs would you give for smoking cessation? |
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Definition
|
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Term
| What drugs would you give for glaucoma? |
|
Definition
| Pilocarpine, Carbachol, Physostigmine, Echothiophate |
|
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Term
| What drug would you give for Alzheimers Disease? |
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Definition
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|
Term
| What drugs would you give for GI or Urinary bladder disorders? |
|
Definition
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Term
| What drug would you give for anticholinergic toxicity? |
|
Definition
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Term
| What drugs would you give for reversal of neuromuscular blockade? |
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Definition
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