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MOD II > TBL 10 - Acetylcholine Agonists and Antagonists > Flashcards

TBL 10 - Acetylcholine Agonists and Antagonists Flashcards

1
Q

What type of nerve ending releases norepinephrine as the primary transmitter?

A

Adrenergic

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2
Q

What type of synapse uses norepinephrine as the primary transmitter?

A

Noradrenergic

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3
Q

What receptor binds to and is activated by one of the catecholamine transmitters or hormones (norepinephrine, epinephrine, or dopamine)?

A

Adrenergic receptor/Adrenoreceptor

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4
Q

What is the Baroreceptor Reflex?

A

The homeostatic mechanism that maintains a constant mean arterial BP with the sensory limb originating in the baroreceptors of the carotid sinus and aortic arch and the efferent pathways running in parasympathetic and sympathetic nerves to the heart and blood vessels.

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5
Q

What nerve ending releases acetylcholine?

A

Cholinergic

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6
Q

What receptor binds to and is activated by acetylcholine and related drugs?

A

Cholinoceptor/Cholinergic receptor

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7
Q

What nerve ending releases dopamine as the primary neurotransmitter and is also a synapse in which dopamine is the primary neurotransmitter?

A

Dopaminergic

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8
Q

What is the Homeostatic Reflex?

A

A compensatory mechanism for maintaining a body function at a predetermined level.

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9
Q

What is the Nonadrenergic/Noncholinergic (NANC) System?

A

A system that contains nerve fibers that are associated with autonomic nerves that release any transmitter other than norepinephrine or acetylcholine.

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10
Q

What constitutes the Parasympathetic Nervous System?

A

The part of the ANS that originates in CN III, VII, IX, and X (oculomotor, facial, glossopharyngeal, and vagus) and S2-4.

Craniosacral autonomic system.

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11
Q

What is a postsynaptic receptor?

A

A receptor located on the distal side of the synapse.

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12
Q

What is a presynaptic receptor?

A

A receptor located on the nerve ending from which the transmitter is released into the synapse.

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13
Q

What constitutes the Sympathetic Nervous System?

A

The part of the autonomic NS that originates in the thoracic and lumbar parts of the spinal cord.

The thoracolumbar autonomic system.

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14
Q

What does the Autonomic NS do?

A

Involuntarily regulates the activity of snooth muscles, exocrine glands, cardiac tissue, and endocrine and metabolic activities.

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15
Q

Where are the short preganglionic fibers of the sympathetic NS located?

A

Paravertebral chain

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16
Q

Where are the short preganglionic fibers of the parasympathetic NS located?

A

Innervated organs

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17
Q

What neurotransmitter acts on nicotinic and muscarinic receptors?

A

Acetylcholine

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18
Q

What NS are sweat glands part of and what neurotransmitter do they use?

A

Part of the sympathetic NS, are innervated by cholinergic fibers, and use ACh.

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19
Q

How is the adrenal medulla innervated?

A

Innervated directly by preganglionic sympathetic fibers.

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20
Q

How does Hemicholinum affect the synthesis of ACh?

A

Inhibits transport of choline into cholinergic nerve endings.

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21
Q

How does Vesamicol affect the storage of ACh?

A

Inhibits vesicle-associated transporter (VAT) which transports newly synthesized ACh into vesicles for storage.

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22
Q

How does calcium affect presynaptic neurons that hold ACh?

A

Calcium enters the neuron, depolarizing it, while also promoting the fusion of the vesicular membrane with the plasma membrane to allow for the exocytosis and release of ACh.

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23
Q

How does Botulism Toxin affect ACh release?

A

It blocks exocytosis, thereby inhibiting ACh release.

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24
Q

How do AChE inhibitors (ACEi) affect the termination of ACh?

A

They prevent the breakdown of ACh.

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25
Q

What kind of receptors are muscarinic receptors?

A

G-protein coupled receptors.

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26
Q

What type of receptors are M1?

A

Neuronal

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27
Q

What type of receptors are M2?

A

Cardiac

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28
Q

What type of receptors are M3?

A

Glandular

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29
Q

What pathway do M1, M3, and M5 receptors follow?

A

Gq:
- Activates PLC
- Increases IP3, DAG, and Ca
- PKC

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30
Q

What pathway do M2 and M4 receptors follow?

A

Gi:
- Inhibition of AC
- Decreased cAMP synthesis
- PKA

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31
Q

What type of receptors are nicotinic receptors?

A

Ligand-gated ion channels

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32
Q

Where are neuronal Nn type receptors located?

A

Ganglia, adrenal medulla, and brain.

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33
Q

Where are muscle Nm type receptors located?

A

Neuromuscular junction.

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34
Q

What are the muscarinic effects of M2 on the heart?

A
  • SA node hyperpolarization leading to a decrease in impulse generation and bradycardia.
  • AV node and PF (RP is increased causing slowing of conduction and partial/complete heart block.
  • Decrease in force of contraction of atrial fibers.
  • Decreased ventricular contractility.
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35
Q

What are the muscarinic effects of M3 on blood vessels?

A
  • Cholinergic innervations of the skin of the face and neck.
  • Vasodilation by NO release, causing a fall in BP and flushing.
  • Penile erection.
36
Q

What are the muscarinic effects of M3 on smooth muscles?

A
  • Smooth muscles are contracted.
  • Abdominal cramps and diarrhea due to increased peristalsis and relaxed sphincters.
  • Voiding or emptying of urinary bladder.
  • Bronchial SM contraction leading to dyspnea.
37
Q

What are the muscarinic effects of M3 on glands?

A
  • Increased secretions such as sweating, salivation, and lacrimation from the tracheobronchial tree and gastric, pancreatic, and intestinal glands.
38
Q

What are the muscarinic effects of M3 on the eye?

A
  • Miosis (contraction of circular fibers of the iris)
  • Spasm of accommodation (contraction of ciliary muscles)
  • Increased outflow and decreased intraocular pressure.
39
Q

What type of receptors does Methacholine bind to?

A

M or muscarinic

40
Q

What type of receptors does Carachol bind to?

A

M (muscarinic) and N (nicotinic)

41
Q

What type of receptors does Bethanechol bind to?

A

M or muscarinic

42
Q

What is methacholine used for?

A

Challenge test to help diagnose asthma.

43
Q

What is carbachol used for?

A

Topical treatment for glaucome in order to lower intraocular pressure.

44
Q

What is bethanechol used for?

A

Treatment of urinary retention and postoperative abdominal distension.

45
Q

What are some adverse effects of methacholine?

A
  • Dyspnea
  • Headache
  • Throat irritation
46
Q

What are some adverse effects of carbachol?

A
  • Retinal detachment
47
Q

What are some adverse effects of bethanechol?

A
  • Muscarinic effects such as dyspnea, diarrhea, urinary urgency, and sweating
48
Q

What type of receptors does Pilocarpine bind to?

A

M or muscarinic

49
Q

What are the clinical uses for Pilocarpine?

A
  • Lowers intraocular pressure for treatment of glaucoma.
  • Increases salivary secretion and lacrimation for treatment of Xerostomia caused by Sjogren’s Syndrome or radiation.
50
Q

What are some adverse effects of Pilocarpine?

A
  • Retinal detachment
51
Q

What type of drug is Pilocarpine?

A

Alkaloid

52
Q

What is the MOA of Nicotine?

A

Binds to nAChRs which releases a variety of neurotransmitters, including dopamine.

  • Low Doses: stimulation of parasympathetic and sympathetic ganglia via Nn receptors.
  • Large Doses: Persistant depolarization.
53
Q

What is the indication/clinical use for nicotine?

A

Short term nicotine replacement i tobacco abstinent subjects.

54
Q

How is nicotine dependence trated?

A
  • Counseling and motivation.
  • Pharmacotherapy:
    1) Nicotine replacement
    2) Varenicline
    3) Bupropion
55
Q

What type of drug is Varenicline?

A

Partial agonist of alpha4beta2 nicotinic receptors.

56
Q

What type of drug is Bupropion?

A

Antidepressant.

Norepinephrine and dopamine reuptake inhibitor.

57
Q

What type of drug is Edrophonium and what is its clinical use?

A
  • Reversible cholinesterase inhibitor.
  • Acts peripherally for a short duration to diagnose Myasthenia Gravis.
58
Q

What type of drug is Pyridostigmine and what is its clinical use?

A
  • Reversible cholinesterase inhibitor.
  • Treats Myasthenia Gravis but does not enter the CNS.
59
Q

What type of drug is Neostigmine and what is its clinical use?

A
  • Reversible cholinesterase inhibitor.
  • Treats Myasthenia Gravis and is useful for reversing non-depolarizing neuromuscular blockades.
60
Q

What type of drug is Physostigmine and what is its clinical use?

A
  • Reversible cholinesterase inhibitor.
  • It is absorbed through the gut and can penetrate the BBB to treat glaucoma and atropine overdose that causes seizures and other CNS defects.
61
Q

What type of drug is Donepezil, Galamtamine, and Rivastigmine and what are their clinical use?

A
  • Reversible cholinesterase inhibitors.
  • Act centrally to treat Alzheimer’s/
62
Q

What type of drug is Echothiopate, Isoflurophate, and Malathion and what are their MOA?

A
  • Irreversible cholinesterase inhibitors or organophosphate compounds.
  • Form covalent bonds with cholinesterase which augments cholinergic neurotransmission of central and peripheral synapses leading to cholinergic crisis and nicotinic activation with symptoms of muscle fasciculation and weakness, seizures, respiratory depression, and coma.
63
Q

What type of drug is Soman and Sarin and what are they used for?

A
  • Irreversible cholinesterase inhibitors used as nerve gases for biologic warfare.
64
Q

What is Myasthenia Gravis?

A

An autoimmune disease in which antibodies are directed against nicotinic receptors in skeletal muscle, inactivating and destroying them, which impairs neuromuscular transmission.

65
Q

What are the cholinergic effects caused by overstimulation of muscarinic receptors by irreversible cholinesterase inhibitors/organophosphates?

A

D - Defecation
U - Urination
M - Myosis
B - Bronchorrhea
B - Bronchospasm/Bradycardia
E - Emesis
L - Lacrimation
S - Salivation and Sweating

66
Q

What is used to overcome organophosphate toxicity?

A

Atropine

67
Q

What is used to overcome overstimulation of nicotinic receptors at the NMJ?

A

Pralidoxime

68
Q

What is the MOA of Pralidoxime?

A

Increases AChE activation which decreases ACh at the M and N receptors.

69
Q

What is the MOA of Scropolamine?

A

Competes with acetylcholine (ACh) and other muscarinic agonists to manage and treat postoperative nausea and vomiting (PONV) and motion sickness.

70
Q

What is the MOA of Benztropine and Trihexyphenidyl?

A

Exerts its action in the central nervous system (CNS) and smooth muscles by reducing central cholinergic effects by blocking muscarinic receptors, which appears to alleviate the symptoms of Parkinson disease.

71
Q

What is a common eye adverse effect of stropine?

A

Mydriasis, which is unopposed sympathetic dilator activity, causing loss of accommodation and sensitivity to light.

72
Q

What is the MOA and clinical use for Ipratropium and Tiotropium?

A
  • M3 blocker which decreases IP3 and DAG causing bronchodilation.
  • Used to treat COPD and asthma.
73
Q

What is the MOA of Glycopyrrolateand what is its clinical use?

A
  • Preferentially inhibits salivary and respiratory secretions.
  • Used for anesthesia although it does not cross the BBB.
74
Q

What is the MOA of Dicyclomine?

A

Relaxes intestinal smooth muscle i IBS.

75
Q

What is the MOA of Oxybutynin, Tolterodine, Darifenacin, Solifenacin, and Trospium?

A

Relaxes the detrusor muscle and constricts the internal urethral sphincter to decrease daytime urinary urgency and nosturia and decrease incontinence in overactive bladders.

76
Q

What is the MOA of Tropicamide and what is it used for?

A

Short acting mydriatic for peripheral retinal examination.

77
Q

What are some contraindications for anticholinergic agents?

A
  • BPH (urinary retention, hyperthermia, and acute closure glaucoma)
  • Elderly (delirium, GI obstruction)
78
Q

What is the MOA and clinical use for Mecamylamine?

A
  • Mecamylamine is a ganglionic blocker which prevents stimulation of postsynaptic receptors by acetylcholine released from presynaptic nerve endings.
  • The hypotensive effect of Mecamylamine is attributed to reduction in sympathetic tone, vasodilation, and reduced cardiac output, and is primarily postural.
79
Q

What is the MOA of Succinylcholine?

A

Depolarizing neuromuscular blocker.

Phase I: A strong nicotinic agent to cause sustained depolarization of Nm receptors that causes transient fasciculations followed by flaccid paralysis.

Phase II: persistent depolarization leads to desensitization of Nm and prolonged relaxation.

80
Q

What is Succinylcholine used for?

A

Skeletal muscle relaxant.

81
Q

What are some adverse effects of Succinylcholine?

A
  • Malignant hyperthermia
  • Hyperkalemia
  • Muscle pain/myalgia
  • Increases intragastric and IO pressure.
82
Q

When used parenterally for short actions, how is Succinylcholine inactivated?

A

By pseudocholinesterase.

83
Q

What are some CI for Succinylcholine use?

A
  • Genetic disorders of plasma cholinesterase.
  • Family history of malignant hyperthermia.
  • Recent burns or traumas.
84
Q

What is the MOA for Atracurium, Cisatracurium, Rocuronium, Tubocurarine, and Vecuronium, and what are they used for?

A
  • Competitive antagonists for Nm at the NMJ which prevents muscle contraction, causing muscle relaxation for use in surgery and intubation.
85
Q

What are some adverse effects of Atracurium, Cisatracurium, Rocuronium, Tubocurarine, and Vecuronium?

A
  • Respiratory paralysis
  • Hypersensitivity reactions

MOD II (8 decks)

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