Cholinergic agonists and antagonists-Kruse Flashcards by Kelley Perry

These direct-acting cholinergic agonists contain permanently charged quaternary NH4 groups that result in their poor absorption and distribution into the CNS

choline esters

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List the ranking of direct-acting cholinergic agonists, choline esters, from most rapid to least rapid in terms of cholinesterase metabolism

ach > methacholine > carbachol = bethanechol

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These direct-acting cholinergic agonists are uncharged tertiary amine that are well absorbed from most sites of administration

Alkaloids

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Which choline ester has the greatest muscarinic action? Nicotinic action?

Muscarinic: Methacholine

Nicotinic: Ach and Carbachol

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List the location, Structural features (2nd messenger), and mechanism of M1 receptors

location=nerves
Structural=Gq/11
Mechanism: IP3, DAG

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List the location, Structural features (2nd messenger), and mechanism of M2 receptors

location=heart, nerves, smooth m
structural=Gi/0
Mechanism=inhibition of cAMP, activate K channels

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List the location, Structural features (2nd messenger), and mechanism of M3 receptors

location=glands, smooth m., endothelium
structural=Gq/11
Mechanism=IP3, DAG

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List the location, Structural features (2nd messenger), and mechanism of M4 receptors

location=CNS
structural=Gi/0
mechanism=inhibit cAMP

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List the location, Structural features (2nd messenger), and mechanism of M5 receptors

location=CNS
structural=Gq/11
mechanism=IP3, DAG

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List the location, Structural features (2nd messenger), and mechanism of Nn receptors

location=postganglionic cell body, dendrites, CNS
structural=alpha and beta only
mechanism=Na, K depolarizing ion channel

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Nicotine has a greater affinity for __ nAChRs

Nicotine itself has a greater affinity for neuronal nAChRs than skeletal muscle nAChRs

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list the parasympathetic effects of the following:

Sphincter muscle of iris: ___
Ciliary muscle of eye: ___
Heart: ___
Blood vessels: ___
Bronchial muscle: ___
Bronchial glands: ___
GI motility: ___
GI sphincters: ___
GI secretion: ___
Urinary detrusor muscle: ___
Urinary trigone and sphincter: ___
Sweat, salivary, lacrimal, nasopharyngeal glands: ___

iris-contraction (miosis)
ciliary m.-contraction for near vision
heart-decrease rate/contractile strength/conduction velocity
blood vessels-dilation (via EDRF)
bronchial muscle-contraction (bronchoconstriction)
bronchial glands-stimulation
gi motility-increase
gi sphincters-relax
gi secretion-stimulation
detrusor-contract
trigone and sphincter-relax
glands-secretion

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the major clinical uses of the direct-acting cholinomimetics are for ___

diseases of the eye (glaucoma, accommodative esotropia), and the GI/GU tracts (post-operative atony, neurogenic bladder)

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describe the effects of muscarinic stimulants and glaucoma

cause contraction of ciliary body, which facilitates outflow of aq humor and reduces intraocular pressure

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___ is the most widely used choline ester for GI/GU disorders, including postoperative ileus, congenital megacolon, urinary retention, esophageal reflux

bethanechol

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___ are used to increase salivary secretion (eg dry mouth associated with Sjorgren syndrome

pilocarpine and cevimeline

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overdoses of pilocarpine and the choline esters cause predictable muscarinic effects (nausea, vomiting, diarrhea, urinary urgency, salivation, sweating, cutaneous vasodilation, bronchial constriction) and are blocked by antimuscarinic compounds such as __-

atropine

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what are some major contraindications to the use of mAChR agonists that are distributed systemically?

asthma
hyperthyroidism
coronary insufficiency
acid-peptic disease

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what drug combination can be used in the case of acute nicotine toxicity?

atropine –> for excess muscarinic stimulation from parasympathetic ganglia
diazepam –> parenteral anticonvultant for CNS stimulation

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__- is approved for intraocular use during surgery and causes miosis; rarely given systemically

acetylcholine

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__- is rarely used but adminstered by inhalation for the diagnosis of bronchial airway hyperreactiviy in pts who do not have clinically apparent asthma

methacholine

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___ can be used to treat pts with urinary retention and heartburn, is a selective mAChR agonist with little CV stimulation, and may produce UTI if sphincter fails to relax

bethanechol

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___ is a nonspecific cholinergic agonist that is used for tx of glaucoma or to produce miosis during surgery or ophthalmic examination

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carbachol

___ is an oral table used to treat dry mouth (xerostomia) in pts with Sjorgren syndrome. It is metabolized via P450 pathways and eliminated in urine

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cevimeline

___ is a pure mAChR agonist that is approved for xerostomia tx in pts with Sjogrens syndrome or head and neck cancer tx related xerostomia (PO), miosis during opthalmic procedures (topical), and for glaucoma (topical)

pilocarpine

Varenicline (Chantix) is a partial agonist that binds with high affinity and selectivity to what receptor? What is the most common adverse effect? The serious side effects?

alpha4beta2 (a4b2) nAChR's most common --> nausea serious --> neuropsychiatric symptoms, changes in behavior, agitation, depressed mood, suicide ideation

this drug is an indirect-acting cholinergic agonist that has an alcohol group

edrophonium

these drugs are indirect-acting cholinergic agonists that are carbamic acid esters

neostigmine, pyridostigmine, physostigmine, and cabaryl

echothiophate, parathion and malathion (insecticides), and sarin, soman, and tabun (nerve gases) are examples of what?

organophosphates--> indirect-acting cholinergic agonists binding to AChE is covalent and irreversible

Describe the effects on the CNS with low concentrations of AChE inhibitors:

diffuse activation on EEC and a subjective alerting response

Describe the effects on the CNS with high concentrations of AChE inhibitors:

generalized convulsions d/t neuronal hyperstimulation (may be followed by coma or resp. arrest)

Describe the effects on the eye, resp tract, gi tract, and urinary tract with AChE inhibitors:

similar to the direct acting cholinomimetics (bethanechol, carbachol, pilocarpine); these organs are innervated by mAChRs and stimulation results in parasympathetic responses

describe the net cardiovascular effects with moderate doses of AChE inhibitors

modest bradycardia, a fall in CO (due to bradycardia, decreased atrial contractility, and some reduction in ventricular contractility), and a modest increase in BP toxic doses of AChE inhibitors cause more marked bradycardia, occasionally tachycardia, and hypotension

These AChE inhibitors can reverse the paralysis induced by neuromuscular blocking drugs during surgical anesthesia

Neostigmine and edrophonium are preferred

Donepezil, rivastigmine, galantamine, and physostigmine are preferred for treatment of this neurological disorder

Progressive dementia of the alzheimer type

List some effects of intoxication d/t anticholinergic agents and name a drug that can reverse these effects:

``` Cutaneous vasodilation Anhidrosis Anhydrotic hyperthermia Nonreactive mydriasis Delirium Hallucinations Reduction or elimination of desire to urinate ``` -Physostigmine can reverse the above mentioned anticholinergic effects and is preferred because it crosses the BBB

Nondepolarizing neuromuscular blocking agents in combination with AChE inhibitors will diminish neuromuscular blockade. One exception is the drug ___ (metabolized by AChE), where neuromuscular blockade is prolonged

Mivacurium

This drug in combination with AChE inhibitors will enhance phase 1 block and antagonize phase 2 block

Succinylcholine

Describe the interaction between direct-acting cholinergic agonists and AChE inhibitors:

Combination will enhance the effects of cholinergic agonists

Describe the effects of beta-blockers in combination with AChE inhibitors:

Combination may enhance the bradycardic effects

Describe the effects of the combination of AChE inhibitors and systemic corticosteroids:

Coadministration with AChE inhibitors may enhance muscle weakness seen in pts with myasthenia gravis

This mAChR antagonist is the antidote recommended for cholinergic poisoning in combination with maintenance of vital signs (respiratory in particular)

Atropine Atropine is ineffective against peripheral neuromuscular stimulation (nAChRs)

List an example of a cholinesterase regenerator and describe the current antidotal therapy for organophosphate exposure resulting from warfare or terrorism:

- Pralidoxime | - Atropine, an oxime (pralidoxime), and a benzodiazepine as an anticonvulsant

Animal studies have shown that pretreatment with ___ reduces the incapacitation and mortality associated with nerve agent poisoning, especially with agents such as soman that show rapid aging. It has been approved for combat use in US military personnel

Pyridostigmine -should be discontinued at 1st sign of nerve gas exposure

___ drugs elicit their effects at the NMJ and on nAChRs in the ganglia

Antinicotinic

The prototype antimuscarinic compound is ___

Atropine

What are some mAChR antagonists that can be used to reduce the tremor associated with PD?

Benztropine and trihexyphenidyl

This drug can be useful in treating motion sickness and is one of the oldest agents for seasickness and can be administered by injection, PO, and transdermal patch

Scopolamine

This long-lasting mAChR antagonist is used to prevent synechia formation in uveitis and iritis

Homatropine

Which antimuscarinic agents can be used to treat asthma and COPD?

Ipratropium and Tiotropium

___ is used as an inhalational agent in the tx of asthma and COPD and is currently a first line therapy

Ipratropium

THe recently approved agent ___ has a longer bronchodilator action than ipratropium and can be dosed once daily in pts with COPD

Tiotropium

This mAChR antagonist is used in the tx of common travelers diarrhea. It is a combo of atropine and diphenoxylate.

Lomotil

What is the prototypical antimuscarinic agent used in disorders of the GU tract?

Oxybutynin

___ is a nonselective antagonist that is comparable in efficacy and side effects with oxybutynin

Trospium

List some antimuscarinic agents for urinary disorders that are more selective and may produce less adverse effects

Darifenacin, solifenacin, and tolterodine

What are some contraindications for antimuscarinic agents?

Pts with glaucoma (reduced secretions) and used with caution in elderly men with a history of prostatic hyperplasia

Cholinergic agonists and antagonists-Kruse Flashcards

(57 cards)