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58 Cards in this Set
- Front
- Back
What are two main TYPES of cholinergic receptors?
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NICOTINIC
MUSCARINIC |
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Muscarinic receptor subtype primarily associated with the heart:
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M2
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Acetylcholine is rapidly inactivated by synaptic
_____. |
Acetylcholine is rapidly inactivated by synaptic
acetyl-cholinesterase (AChE). |
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Cholinergic drugs mimic or
block the action of _____. |
Cholinergic drugs mimic or
block the action of Acetylcholine. |
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Effector organs of acetylcholine ?
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Effector organs:
Smooth muscle Skeletal muscle CNS |
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Which type of cholinergic receptor is:
Postsynaptic to preganglionic neurons in all autonomic ganglia including: Chromaffin cells of the adrenal medulla i.e. the perikarya of post ganglionic neurons. |
Nicotinic receptor (Nn)
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Cholinergic receptor type primarily localized at skeletal muscle neuromuscular junctions:
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nicotinic (more specifically Nm)
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Subtypes of nicotinic receptors?
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1. N^M Nicotinic muscular receptors – in neuromuscular junction. activation opens cation ch. resulting in end plate depol. and sk. muscle contractions
2. N^N postsynaptic neurons: autonomic ganglia, adrenal medulla (chromaffin cells), >coupled to activ. of cation ch. 3. CNS 4. presynaptic nerve terminals |
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Name 3 Subtypes of muscarinic receptors?
Where is body are each of these found? |
M1 - autonomic ganglia, CNS
M2 - Heart (SA node, AV node, atrial) M3 - smooth muscle, secretory glands |
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Location of different Muscarinic Receptors?
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1. On post-synaptic membrane of neuro-effector junction innervated by postganglionic parasympathetic neurons
2. On post-synaptic membrane of neuro-effector junction innervated by some postganglionic sympathetic neurons 3. On vascular endothelium - these receptors are pharmacologically important since they are not innervated, their physiological importance is unclear. 4. In autonomic ganglion 5. On pre-synaptic nerve terminal 6. In CNS |
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What receptor is responsible for signal transd. pathway associated with:
stimulation of enzyme phospholypase C and increased cytosolic Ca2+ |
Activation of M1 and M3 receptors -->
stimulation of enzyme phospholipase C and increased cytosolic Ca2+ note: increased uptake of Ca+2 --> depolarization? |
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What receptor is responsible for signal transd. pathway associated with:
associated with activation of K+ channel and inhibition of enzyme adenylyl cyclase. |
M2 receptor
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Name 4 directly-acting Cholinergic Agonists (drugs not naturally occurring)
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Methacholine, Carbachol, and bethanechol, Synthetic Choline esters
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Methacholine agents show selectivity to what organs?
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cardiovascular system
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Carbachol and Bethanechol agents show selectivity to what organs?
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smooth muscles of the GI tract and urinary bladder
is this associated with M3? |
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* Mild nicotinic, strong MUSCARINIC agonist.
* Has longer duration of action than ACh, since it is hydrolyzed at a slower rate by AChE, moreover it is almost totally resistant to hydrolysis by other cholinesterases. |
Methacholine
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* Very potent nicotinic and muscarinic agonist.
* Totally resistant to hydrolysis by AChE and other cholinesterases, therefore long duration of action. * can stimulate autonomic ganglion and some of its effects can be due to ACh release from terminals of cholinergic fibers. |
Carbachol (carbamylcholine)
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* Pure muscarinic agonist
* Used at times in treatment of GI tract atony, and detrusor atony in dog and cats. |
Bethanechol (Carbamyl-β-methylcholine)
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Localization of muscarinic cholinergic receptors:?
A. postganglionic parasympathetic effector sites B. autonomic ganglia cells C. adrenal medulla D. A & C E. A, B & C |
E. muscarinic cholinergic receptors at all these
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Highest nicotinic receptor activity among choline esters:
A. acetylcholine B. atropine C. methacholine D. carbachol |
D. carbachol
Carbachol = very potent nicotinic and muscarinic agonist. |
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Choline ester most susceptible to hydrolysis by acetylcholinesterase:
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acetylcholine
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Atony
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- loss of muscle tone
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Which directly-acting Cholinergic Agonists are similar in their selectivity?
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Bethanechol & carbachol
* both somewhat selective for smooth muscles of GI tract and urinary bladder |
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Resistant to hydrolysis by acetylcholinesterase?
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carbachol
Bethanechol |
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What do these compounds have in common?
Muscarine Arecoline Pilocarpine |
All naturally occurring, direct-acting cholinergic AGONISTS
MAP "Directs u to nature's cholon" -ine |
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Name naturally occurring alkaloid which is a directly-acting cholinergic agonists
* producing all parasympathomimetic effects * used topically to reduce intraocular pressure in canine glaucoma therapy. |
pilocarpine!!!
- topically to reduce intraocular pressure in canine glaucoma therapy. - primarily a muscarinic agonist derived from Pilocarpus plant |
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Diisopropyl-phospho-fluorodate is the prototype for ?
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Indirect, Irreversible, Cholinergic Agonists
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Indirect Cholinergic agonists are divided into what 2 groups?
What is their main mode of action? |
All are cholinesterase inhibitors:
* Anticholinesterases Divided into two groups * Reversible inhibitors * Irreversible inhibitors |
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Indirect, Irreversible, Cholinergic Agonists are used for:
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* Insecticides
* Dichlorvos (highly volatile organophosphate, widely used as a insecticide) - flea collars, antihelmintic * Nerve Gas |
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Main side effects are: intense contraction of GI tract accompanied by salivation, nausea and vomiting therefore it should be used with caution. .
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Bethanechol <-- GI side effects
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parasympathomimetics example?
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Muscarinic agonists
a drug or poison that acts by stimulating or mimicking the P.S. nervous system |
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parasympatholytics example?
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Muscarinic antagonists
Atropine and scopolamine |
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Describe 3 groups of Cholinergic Antagonists (what do they inhibit?)
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Drugs that interfere with actions of ACh by blocking cholinergic receptors.
Grouped in categories: 1. Anti-muscarinics: for receptors present on PS neuroeffectors and vascular endoth. 2. Ganglionic blockers: for receptor on post-ganglionic neurons 3. Neuro-muscular blockers: for receptors present on motor end plate of skeletal muscles |
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Associated with parasympathetic activation (direct effects):
A. increase heart rate B. decreased GI motility C. decrease cardiac contractility D. urinary retention |
C. decrease cardiac contractility
parasympathetic effects decrease both heart rate and contractility, mainly atrial contractility |
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Name 2 synthetic anti-muscarinic drugs (atropine-like agents)
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Pirenzepine
Telenzepine |
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Name this Synthetic anti-muscarinic drug:
Exibits selective for M1 receptors on post-ganglionic neurons of autonomic ganglia. It reduces gastric acid secretion. (Ulcer treatment in other country other than the US). |
Pirenzepine (anti-muscarinic)
It reduces gastric acid secretion. (Ulcer treatment in other country other than the US). |
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An analogue of pirenzepine (a more selective inhibitor of gastric secretion)
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Telenzepine
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What effect does Pirenzepine have gastric acid secretion?
How does it pull this off? |
* reduces gastric acid secretion by blocking M1 receptors in intramural ganglia of stomach and on gastric entero-chromaffin-like cells
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Mydriasis?
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dilation of the pupil
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Found in bethel nut has some nicotinic activity but is primarily muscarinic and has some CNS effects (stimulation and euphoria).
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Arecoline (naturally occurring, direct-acting cholinergic AGONISTS)
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Indirect Cholinergic agonists are reversible inhibitors of _____?
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Indirect Cholinergic agonists are reversible inhibitors of cholinesterases
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Name 4 Indirect Cholinergic agonists (REVERSIBLE inhibitors of ChE)
note: ChE = cholinesterase which break down ACh |
Reversible inhibitors of ChE: physostigmine
pyridostigmine endrophonium neostigmine fyi: 3 end w/-stigmine |
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What clinical application do these reversible cholinesterase inhibitors share?
What distinguishes them? |
Used in the treatment of myasthenia gravis.
similar pharmacologic action but duration of action different |
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Which indirect cholinergic agonists used for glaucoma, for antimuscarinic poisoning
- atropine toxicity, and is drug of choice for myasthenia gravis b/c has longer duration of action? (but discontinued in some circles b/c can cause additional poisoning) |
Physostigmine: longest duration
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Name only reversible inhibitors of ChE that does NOT end w/-stigmine??
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endrophonium
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Used to reverse neuromuscular
blockade induced by certain neuromuscular blocking agents. |
Neostigmine
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Rank 4 indirect ACh agonists based on duration of action (longest to shortest)
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1. Physostigmine: longest duration
2. Pyridostigmine 3. Neostigmine 4. Endrophonium : shortest duration |
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T/F Both Neostigmine & Physostigmine effective given orally, but Neostigmine easily penetrates BBB (causes CNS effects).
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False;
Both Neostigmine & Physostigmine effective given orally, but Physostigmine PHYSOSTIGMINE easily penetrates BBB (causes CNS effects). |
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These are example of ?
atracurium vecuronium mivacurium pancuronium |
Noncompetitive NM blockers are used in vet med:
- skeletal muscle relaxant - used adjunct. in anesthesia to facil. endotracheal intubation and sk. muscle relaxation during surgery, etc - inhibit neuron transmission to muscle by blocking NAR? (nicotinic AcH receptor) |
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What receptor(s) have these effects?
* Phospholipae C stimulation >> increased cytostolic Ca++ * Smooth muscle contraction (M3) * Secretion of exocrine gland (Cellular responses) |
Effects Mediated by M1 and M3 receptor
* Phospholipae C stimulation >> increased cytostolic Ca++ |
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Effects Mediated by M2 receptor?
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M2: Decrease adenylyl cyclase
* Increased K+ channel * Causes decreased conduction rate >> decreased heart rate |
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selective anti-muscarinic (muscarinic antagonist).
* slow onset of action, does not cross BBB * less arrhythmogenic * don't use in horses |
glycopyrrolate
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Bronchoconstriction in an asthmatic is treated with?
A. Atropine B. ACh agonist |
Atropine
Anticholinergic agents (antimuscarinic) are used in treating asthma, because block bronchioconstriction of PS. (decr. in PS activity may may decrease brochiolar smooth muscle tone) |
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What compound is a prototype of all directly acting cholinergic agonists?
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Acetylcholine
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What compound rapidly inactivates acetylcholine after it is released?
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synaptic Acetyl-cholinesterase
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What compounds inactivate non-synaptic acetylcholine?
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Liver and plasma cholinesterase
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What enzyme catalyzes the synthesis of acetylcholine from choline and acetate?
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Choline acetyl transferase
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What are some subtypes of nicotinic receptors?
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Nm - Neuromuscular junction
Nn - Autonomic ganglia, adrenal medulla, CNS |