Term
| What locations have ACh as the NT? |
|
Definition
Neuromuscular junction
all ganglion
adrenal gland
sweat glands |
|
|
Term
| What are the two reasons that ACh cannot be taken orally? |
|
Definition
it is hydrolyzed
it is charged and cannot cross the membrane |
|
|
Term
| What are the two bonds formed between ACh and it receptor? |
|
Definition
hydrogen bond between the ester and the esteratic site
ion-ion bond between the Amine and the anionic site |
|
|
Term
| Does a smaller pKa show that a natural alkaloid is strong or weak base? |
|
Definition
| weak because the pKa is of its conj acid and the smaller the pka the stronger the conj acid the stronger the conj acid the weaker the base |
|
|
Term
| What are the normal isomers for Muscarine and Nicotine? |
|
Definition
|
|
Term
| What was the first parasympathetic substance studied? |
|
Definition
|
|
Term
|
Definition
| yes even though it has the charged quaternary amine |
|
|
Term
| What can you give as an antidote to muscarine? |
|
Definition
|
|
Term
| Do muscarine, ACh, and nicotine bind to the receptor as charged or uncharged form? |
|
Definition
|
|
Term
| Differentiate muscarinic receptors(mAChR) and nicotinic receptors (nAChRs). |
|
Definition
muscarinic are g protein coupled receptors
Nicotinic are ion channel receptors |
|
|
Term
|
Definition
|
|
Term
| What is the ratio of atp:ACh inside the storage vesicle? |
|
Definition
|
|
Term
| Describe the biosynthesis of ACh. |
|
Definition
-Choline is taken up from the synaptic cleft(35-50%) or from storage forms
-Reacts with acetyl choline coenzyme A to make ACh
-It is then put into storage vesicles |
|
|
Term
| Besides ACh what else is stored in the vescicles? |
|
Definition
|
|
Term
| What is the rate limiting step of ACh synthesis? |
|
Definition
| Choline uptake from synaptic cleft |
|
|
Term
| What blocks reuptake of Choline? |
|
Definition
|
|
Term
| What converts ACh to Choline after release in to synaptic cleft? |
|
Definition
|
|
Term
| Describe the release of ACh. |
|
Definition
Action potential opens Ca channel
vesicle fuses with membrane |
|
|
Term
| How much ACh does one vescicle hold? *one quantum* |
|
Definition
|
|
Term
| How many *quantums* does one action potential release? |
|
Definition
|
|
Term
| When synthesizing choline what converts the primary amine to the quaternary amine? |
|
Definition
2 adenosyl methione
&
choline n methyl transferase |
|
|
Term
| What are the three general steps of ACh synthesis? |
|
Definition
decarboxylation of COOH
methylation of amine
acetyl transfer onto alcohol |
|
|
Term
| Where is ACh synthesized? |
|
Definition
| inside cholinergic neuron |
|
|
Term
| What is the most stable isomer of ACh? |
|
Definition
|
|
Term
| What is the stereoisomer of ACh that binds to the receptor? |
|
Definition
Anticlinal
*they used cis actm and trans actm to prove it. trans actm is anticlinal like |
|
|
Term
| What are the mechanisms of ACh agonist drugs? |
|
Definition
| either ACh memetics or AChE inhibitors |
|
|
Term
| What is the response to mACh agonists? |
|
Definition
smooth muscle constricts
vasodilation
gi secretion
miosis
decreased heart rate
force of contraction |
|
|
Term
| What are the general problems of ACh? |
|
Definition
non selective
the ester group is rapidly hydrolyzed
quaternary amine is charge and not lipophilic |
|
|
Term
| What addition can be made on ACh to make it more lipophilic? |
|
Definition
addition of methyl onto one of the ethylene group carbons
(Methacholine) |
|
|
Term
| What addition can be made on ACh to protect it from hydrolysis? |
|
Definition
Replacement of the primary carbon with a primary amine off the ester
(Carbachol) |
|
|
Term
| What ACh derivative is orally active and has both an added methyl and primary amine? |
|
Definition
|
|
Term
| Does the addition of a methyl on the ester side such as in metacholine and betanechol make it more active to muscarinic or nicotinic receptors? |
|
Definition
muscarinic
carbachol is both nicotinic and muscarinic |
|
|
Term
| Is s-metacholine or r-metacholine more active? (lipophilic) |
|
Definition
|
|
Term
| Is s-metacholine or r-metacholine more resistant to hydrolysis? |
|
Definition
R (it is not hydrolyzed by AChE at all)
S hydrolysis is reduced by half |
|
|
Term
| acetyl alpha methyl choline has an added methyl on the quatenary amine side, does this make it more active for muscarinic or nicotinic? |
|
Definition
|
|
Term
| What are the two alternatives to methyl and amine addition to help stabalize ACh? |
|
Definition
|
|
Term
| What bonds are formed between ACh and AChE? |
|
Definition
| hydrogen bonding and cation pi bonding (not ion-ion) |
|
|
Term
| What are the two common therapuetic uses of AChE inhibitors? Two non therapuetic uses? |
|
Definition
myastenia gravis and glaucoma
insecticides and war agents |
|
|
Term
|
Definition
|
|
Term
| What is Physostigmine? What is it used for? |
|
Definition
an AChE inhibitor, natural alkaloid
glaucoma, overdose of anticholinergics |
|
|
Term
| Is Physostigmine protonated at blood pH? Lipophilic? |
|
Definition
yes to both
it has a pKa of 8.2 |
|
|
Term
| Is Physostigmine blocked by the bbb? |
|
Definition
|
|
Term
| Is more stable phosphorylated AChE found in reversible or irreversible AChE inhibitors? |
|
Definition
Irreversible
reversible is more stable acetylated AChE(carbomylated) |
|
|
Term
These are all irreversible AChE inhibitors: ecothiophosphate iodide, malathion, soman, tauban, parathion, sarin, and paraoxon.
Which are insectasides and nerve agents? |
|
Definition
insect- -ions and paraoxon
nerve- sarin, tauban, soman |
|
|
Term
| What is the antidote for irreversible inhibitors of AChE? |
|
Definition
2-pam
*only effective before aging!! |
|
|
Term
| How long does it take for irreversible inhibitors of AChE to age and become irreversible even by 2-pam? |
|
Definition
|
|
Term
| Other names for muscarinic antagonists? |
|
Definition
anticholinergics
antimuscarinics
cholinergic blockers
antispasmodics
parasympatholytics |
|
|
Term
| Effects of muscarinic antagonists? |
|
Definition
decrease contraction of smooth muscle
mydriasis
reduced gi and salivary secretions |
|
|
Term
| Therapeutic uses of muscarinic antagonists? |
|
Definition
| smooth muscle spasms, overactive bladder, ophthalmic exam, gi ulcers, nasal secretions, motion sickness, parkinsons, poisoning |
|
|
Term
| What are the two main mACh antagonists? |
|
Definition
|
|
Term
| What is atropine used for? |
|
Definition
bradycardia
reduce secretions before surgery
cycloplegic agent
poising by nerve agents and insecticides
parkinsons |
|
|
Term
| What is scopolamine used for? |
|
Definition
|
|
Term
| What has a longer half life, scopolamine or atropine? |
|
Definition
|
|
Term
| Two classes of nicotinic antagonists? |
|
Definition
neurmuscular blocking agents
ganglionic blocking agents |
|
|
Term
| What would neuromuscular blocking agents be used for? |
|
Definition
| general anestesia, realignment of fracturs and dislocations |
|
|
Term
| What are the four types of Neuromuscular blocking agents? |
|
Definition
| depolarizing, non depolarizing, steroid based, tetrahydroisoquinoline based |
|
|
Term
| What are the two depolarizing neuromuscular blocking agents? |
|
Definition
decamethonium bromide
succinylchloride |
|
|
Term
| What are the two NONdepolarizing neuromuscular blocking agents? |
|
Definition
|
|
Term
| Are nondepolarizing long acting or short acting? |
|
Definition
|
|
Term
| What is the steroid based neuromuscular blocking agent? |
|
Definition
|
|
Term
| What is the tetrahydroisoquinoline based neuromuscular blocking agent? |
|
Definition
|
|
Term
| atracurium is a tetrahydroisoquinoline based neuromuscular blocking agent but is it depolarizing or not? |
|
Definition
|
|
Term
| Whats special about atracurium? |
|
Definition
| it is eliminated in liver and renal and are independent of each other so good for patients with imparied one or the other |
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