Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Cholinergic Agonists & Antagonists > Flashcards

Cholinergic Agonists & Antagonists Flashcards

1
Q

Distinguish nicotinic and muscarinic receptors regarding the following characteristics:

  • structure
  • function
  • signaling mechanisms
  • location in ANS
A

MUSCARINIC

  • GPCR
  • found on smooth muscle, cardiac muscle, exocrine glands, sweat glands, CNS, vascular beds

NICOTINIC

  • ligand gated ion channel with 5 TM subunits
  • cation channel selective for Na and K
  • Nm = postganglionic, membranes of muscle cells
  • Nn = postganglionic cell membranes of autonomic system; brain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Describe the difference between parasympathetic and nicotinic effects in the body.

A
  • nicotinic receptors are found on postganglionic cells of both parasympathetic and sympathetic neurons
    => thus, nicotinic agonists activate BOTH simultaneously
  • parasympathetic effects are mostly through muscarinic receptors of the effector organs and also affected by nicotinic receptor activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the difference in MOA of direct and indirect cholinergic agonists.

A
  • direct = binds to the receptor and causes action

- indirect = inhibits cholinesterases to increase activity of ACh (reversible or irreversible

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

List the 3 key quaternary analogs of ACh and their pharmacological actions in the body.

A
  1. methacholine - bronchoconstriction
  2. carbachol - miosis (pupillary constriction)
  3. bethanechol - micturition and GI activation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

List the prototype tertiary amine muscarinic agonist and describe the major chemical feature that distinguishes it from the quaternary analogs. How does feature affect the drug’s clinical effects?

A

prototype = muscarine

  • no ester domain
  • resistant to hydrolysis by acetylcholinesterases or plasma cholinesterases
  • can have profound parasympathetic activation when ingested in wild mushrooms (muscarine poisoning)
  • treated with atropine (M antagonist)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Describe the relative susceptibility of the quaternary analog agonists to enzymatic degradation.

A

resistant to hydrolysis or slower hydrolysis

- longer duration of action

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List common clinical uses for the 4 muscarinic agonists.

A
  1. methacholine = methacholine challenge test to diagnose asthma
  2. carbachol = miosis to treat intraocular pressure of glaucoma, cataract surgery
  3. bethanechol = treat urinary retention in postoperation or postpartum; neurogenic atony of bladder
  4. pilocarpine = dry mouth, Sjogren’s, open/closed-angle glaucoma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

List 4 key representative reversible cholinesterase inhibitors. Compare their duration of action and their primary clinical applications.

A
  1. neostigmine - DOA = 1hr; more stable than ACh; myasthenia gravis and reverses neuromuscular relaxants
  2. edrophonium - short acting; diagnosis of myasthenia gravis, ddx b/w MG and cholinergic crisis
  3. physostigmine - DOA = 2hr; anti-delirium due to anticholinergic poisoning
  4. donepezil - DOA = 24hr; alzheimer’s
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe the MOA of the irreversible cholinesterase inhibitors. What does it cause?

A

MOA of irreversible cholinesterases = phosphorylation of AChE, which over time creates a stable compound; irreversibly bound
- causes cholinergic crisis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe the pharmacologic effects and the treatment for organophosphate toxicity.

A 
D - diarrhea, delirium
U - urinary frequency, incontinence
M - miosis, muscle weakness
B - bronchorrhea (increased bronchial secretions)
B - bradycardia
B - bronchoconstriction
E - emesis
L - lacrimation
L - lethargy
S - salivation, sweat
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

List uses of atropine.

A

def: competitive inhibition of muscarinic receptors (reversible); at high doses, can block Nn activity
USES
- relieve frequency and urgency of urination during UTI
- relieve hypermotility of colon
- relieve hypertonicity of SI
- treat cholinergic crisis due to AChE inhibitor poisoning
- induce mydriasis and cycloplegia (paralysis of ciliary muscle)
- reverse bradycardia of vagal origin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the symptoms of atropine poisoning and its treatment.

A

PNS Symptoms

  • dry mouth
  • difficulty swallowing
  • marked thirst
  • hot, flushed skin
  • dilated pupils
  • blurred vision and photophobia
  • tachycardia
  • increased BP
  • difficulty urinating
  • respiratory collapse

CNS Symptoms

  • nervousness
  • confusion
  • hallucinations
  • muscular incoordination and weakness
  • inappropriate laughter
  • psychosis

TX

  • gastric lavage
  • support maintenance of circulation and respiration
  • cold sponge to lower body temperature
  • catheterization for bladder
  • myosis agents and dark room
  • barbiturates for sedation
  • IV physostigmine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe how, when, and why glycopyrrolate is used during recovery from anesthesia.

A

when - after surgery, in combination with cholinesterase inhibitors
why - prevent stimulation of the gut during reversal of neuromuscular blockade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe the signaling mechanisms and functions of M1, M2, and M3 receptors.

A

M1 - Gaq => IP3/DAG => Ca2+
- activates myenteric plexus in GI

M2 (found in heart)
- opens K channels => decreased heart rate and contractility, decreased CO
- Gi => inhibits AC => reduced cAMP => reduced Ca2+
==> inhibits NE release from sympathetic nerve terminals

M3 - Gaq => IP3/DAG => Ca2+

  • contracts circular pupillary muscle = pupillary constriction
  • contracts pupillary muscle = pupillary accommodation
  • contracts bronchiole, GI, uterine, and detrusor (micturition)
  • relaxes vascular smooth muscle via NO
  • stimulates secretions of GI tract, eccrine sweat, tear, salivary, pancreas, and liver bile
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Describe nicotine.

A
  • Nn receptor agonist
  • use: smoking cessation
  • toxicity: skin irritation (patch) and dyspepsia (indigestion)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe succinylcholine.

A
  • blocks nicotinic receptors are neuromuscular junctions (Nm)
  • causes depolarization block
  • used as a muscle relaxant for intubation or during electroshock therapy
  • contraindication: familial hyperthermia, skeletal muscle myopathy
17
Q

Describe the following for acetylcholine:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A
  • Nn, Nm, M
  • easily hydrolyzed by acetylcholinesterases and plasma cholinesterases
  • no therapeutic use
18
Q

Describe the following for methacholine:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A

RECEPTOR SELECTIVITY

  • primarily M agonist activity on smooth muscle (M3), heart (M2), and glands (M3)
  • resistant to hydrolysis, longer duration of action than ACh

EFFECTS

  • constriction of bronchioles, pupillary, uterine, bladder, GI,
  • stimulates gland secretions
  • vasorelaxation in vascular beds
  • inhibits NE release from sympathetics

USE
- methacholine challenge test to diagnose asthma
=> if asthma is suspected, giving a low dose of methacholine will cause hyperreactivity in the bronchioles => increased constriction => decreased lung function

TOXICITY
- bronchoconstriction

CONTRAINDICATIONS
- pt on beta blockers b/c has M2 agonist effect => slowed conduction exacerbation

19
Q

Describe the following for carbachol:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A

RECEPTOR SELECTIVITY
- both N and M

USE
- miotic agent (pupillary constriction - M3) to relieve intraocular pressure in glaucoma pts or after cataract surgery

TOXICITY
- excessive N and M activity

20
Q

Describe the following for bethanechol:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A

RECEPTOR SELECTIVITY

  • selective M agonist
  • M1 (GI)
  • M3 (bladder)

EFFECTS

  • activation of myenteric plexus
  • contraction of the detrusor muscle (micturition)

USE

  • postoperative nonobstructive urinary retention
  • postpartum urinary retention
  • neurogenic atony of bladder

TOXICITY

  • less than carbachol because no M2 effect
  • bradycardia

CONTRAINDICATIONS

  • peptic ulcer
  • asthma
  • bradycardia
21
Q

Describe the following for pilocarpine:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A

RECEPTOR SELECTIVITY

  • pure muscarinic activity (found in leaf)
  • crosses BBB and has CNS effects
  • not resistant to enzyme degradation unlike muscarine b/c has an ester

USE

  • dry mouth due to head/neck radiotherapy
  • Sjogren’s syndrome (autoimmune against lacrimal and salivary glands)
  • open and angle-closure glaucoma

CONTRAINDICATIONS/use with care
- pts. on B blockers b/c it will exacerbate slow conduction via M2 agonist activity

22
Q

Describe the 2 endogenous cholinesterases, where they are found, and what their function is.

A

ACETYLCHOLINESTERASE (AChE, true, specific)

  • found in neurons, motor endplates of skeletal muscle, RBCs
  • fxn: hydrolysis of ACh in synaptic clefts or neuroeffectr transmisstion

BUTYRYLCHOLINESTERASE (BuChE, pseudo, nonspecific, plasma)

  • found in plasma, glial cells, and liver
  • fxn: hydrolysis of certain drugs (like succinylcholine)
23
Q

List the effects of cholinesterase inhibition or indirect-acting cholinergic agonists.

A
  1. autonomic effects (SM, glands) = increased M activity
  2. autonomic ganglia = increased Nn activity
  3. striated muscle = increased Nm activity
  4. CNS = stimulation or depression = both N and M
24
Q

Describe the following for neostigmine:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A
  • reversible AChE inhibitor; indirect agonist

RECEPTOR SELECTIVITY

  • primarily, increases Nm activity
  • no BBB access due to quaternary nitrogen

EFFECTS
- reverses neuromuscular blockade

USE

  • reverse neuromuscular relaxant therapy
  • myasthenia gravis

TOXICITY
- increased peripheral N and M activation

CONTRAINDICATION
- intestinal obstruction

25
Q

Describe the following for edrophonium:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A
  • reversible AChE/BuChE inhibitor; indirect agonist
  • rapid onset, short DOA

RECEPTOR SELECTIVITY
- Nm

USE

  • diagnose myasthenia gravis
  • differentiate b/w MG and cholinergic crisis

TOXICITY

  • excess dose can cause muscle weakness mistaken for MG
  • bradycardia

CONTRAINDICATIONS

  • intestinal blockade
  • urinary tract obstruction
26
Q

Describe the following for physostigmine:

  • receptor selectivity
  • effects
  • use
  • toxicity
  • contraindications
A
  • crosses BBB
  • inactivated by plasma ChE, but takes a long time; (DOA = 2 hrs)

USE
- counteracts delirium due to anticholinergic poisoning (when you are given too many cholinergic antagonists, you have very little ACh…need more)

TOX

  • increased ACh at N and M
  • convulsions

CONTRAINDICATIONS

  • asthma
  • cardiac insufficiency
  • intestinal obstruction
27
Q

Describe the following for donepezil:

  • site of action
  • use
A
  • reversible AChE inhibitor in the CNS; indirect-acting agonist
  • high bioavailability, long half life

USE
- alzheimer’s disease

28
Q

Define cholinergic crisis, its causes, symptoms, and treatments.

A

def = overstimulation of the NMJ due to excess ACh

CAUSE - too much AChE inhibitors => too much ACh => too much stimulation => refractory nicotinic receptors, cannot stimulate contraction

SX - flaccid paralysis, respiratory failure, sweating

DUE TO: nerve gasses, organophosphates, overdose on AChE inhibitors

TX

  • mechanical ventilation
  • suction of oral secretions
  • atropine to protect from systemic M activation
  • 2PAM to reactivate sequestered AChE => breakdown of ACh
  • physostigmine to reverse delirium (enters BBB)
29
Q

Describe the following for 2PAM:

  • action
  • use
A

ACTION

  • reactivates AChE by taking the phosphate on itself
  • breakdown of ACh

USE

  • tx for cholinergic crisis
  • tx for organophosphates
30
Q

Describe the following for echothiophate:

  • definition
  • effects
  • use
A

def: organophosphate used clinically

EFFECTS - long-term miosis

USE - open angle glaucoma; topical

31
Q

Describe the following for scopolamine:

  • use
  • contraindications
A
  • prototype, natural alkaloid
    USE
  • preparation for surgical anesthesia to minimize secretions
  • treatment for N/V associated with motion sickness or chemotherapy

CONTRAINDICATION - narrow angle glaucoma

Pharmacology (22 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions