Brainscape's Knowledge GenomeTM

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


See full index

Pharm II > ANS & Anticholinesterases > Flashcards

ANS & Anticholinesterases Flashcards

1
Q

Where is the parasympathetic nervous system origin?

A

Carniosacral origin CN III, V, VII, X

Sacral 2-4

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

What is the neurotransmitter for the sympathetic, parasympathetic and somatic systems?

A

Acetylcholine

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

What are the receptors for the autonomic nervous system?

A

Cholinergic–> nicotinic for all of the nervous systems and muscarinic for only the parasympathetic nervous system

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

What kind of action potential is acetylcholine?

A

Calcium mediated

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

What is acetylcholine made up of?

A

Choline and Acetyl CoA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is acetylcholine deactivated by?

A

Acetylcholinesterase (choline and acetate)

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

What is the origin of the sympathetic nervous system?

A

Thoracolumbar T1-L2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does acetylcholine work for the cholinergic neurons?

A

ACH binds with a post-synaptic receptor on the effector cell
ACH hydrolyzed by cholinesterase in the synaptic cleft
Choline is then recycled

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the neurotransmitter for the adrenergic neuron?

A

Norepinephrine

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

What are the post-synaptic receptors for the adrenergic neuron?

A

Alpha1, Beta1, 2, and 3

Alpha2 as well but only in the CNS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are alpha2 receptors in the PNS?

A

Presynaptic and inhibitory

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

What happens with norepinephrine with presynaptic terminal reuptake? Extraneurolan (effector cell) uptake?

A

Most is recycled, some is metabolized by MAO presynaptically.
Effector cell uptake, norepinephrine is metabolized by MAO and COMT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which type of norepinephrine reuptake is important for endogenous catecholamines? Exogenous catecholamines?

A

Endogenous: Presynaptic terminal reuptake
Exogenous: minute amount drifts away, metabolized in the liver and kidney

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

How does norepinephrine work?

A

Dopamine enters the synaptic vessel
Dopamine beta hydroxylase converts dopamine to NE
An action potential releases NE from the synaptic vessel
Signal termination (reuptake, dilution by diffusion, metabolism)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the sympathetic neuron differences between blood vessels and the heart?

A

Blood vessels: almost no reuptake of NE, highest rate of synthesis
Heart: highest rate of reuptake

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Drugs that alter ____ or ____ have more of an effect of BP. Drugs that affect ___ (___) have more of an effect on cardiac rate and rhythm

A

Biosynthesis
Storage
Reuptake
Cocaine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the co-neurotransmitters for a sympathetic neuron?

A

NE and ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What does NE and ATP act on?

A

P2 Purinoceptors & Alpha1 Adenoreceptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are P2 Purinoceptors?

A

Mediate fast component of contraction thru voltage dependent calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are Alpha1 adenoreceptors?

A

NE sustains contraction of muscles through receptor operated calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How does ATP mediate contraction of muscle?

A

By acting on the P2x receptors through voltage dependent Calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How does NE sustain contraction of muscle?

A

By acting on the Alpha1 adenoreceptors through receptor operated calcium channels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are neuromodulators?

A

Modify the process of neurotransmission

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Where do neuromodulators work?

A

Prejunctionally and postjunctionally

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Why do neuromodulators act prejunctionally?

A

To increase or decrease the amount of neurotransmitter released

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Why do neuromodulators act postjuctionally?

A

To alter the extent or time course of the neurotransmitter effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What does a Beta1 post-synaptic receptor do?

A

Increases adenylcyclase activity (cAMP)
Increases HR
Increases conduction velocity
Increases myocardial contractility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What does a Beta2 postsynaptic receptor do?

A

Stimulation leads to smooth muscle relaxation
Peripheral vasodilatation
Decreases BP
Bronchodilitation
Increases insulin secretion
Increases glycogenolysis and gluconeogenesis
Decreases GI mobility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How are Beta-2 receptors in the heart important for compensating for disease?

A

Help to maintain response to catecholamine stimulation as Beta-1 receptors are down-regulated during chronic catecholamine stimulation and CHF. NE usually activates beta1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the beta3 postsynaptic receptors?

A

Located on fat cells and suggest new therapy for obesity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What do the alpha1 postsynaptic receptors do?

A 
Activation increases intracellular calcium
Smooth muscle contraction
Peripheral vasoconstriction
Bronchoconstriction
Inhibits insulin secretion
Stimulates glycogenolysis and gluconeogenesis
Mydriasis
GI relaxation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What do alpha2 receptors do presynaptically in the PNS?

A

Inhibits adenylcyclase activity
Decreases entry of calcium into the cell
Limits the release of NE

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What do alpha2 receptors do postsynaptically in the CNS?

A

Sedation
Decreased sympathetic outflow
Decreased BP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Ubiquitous substances that are both neurotransmitters and hormones

A

Catecholamines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Where are they hydroxyl groups located on catecholamines?

A

3 and 4 positions of the benzene ring

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

What are the catecholamines?

A 
Dopamine
NE
Epi
Isoproterenol
Dobutamine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Drugs that act on adrenergic receptors can be classified as what?

A

Catecholamines and Synthetic non-catecholamines or sympathomimetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

What are all sympathomimetics derived from?

A

Beta phenylethylamine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

T/F: All sympathomimetics are catecholamines. But not all catecholamines are sympathomimetics

A

False: all catecholamines are sympathomimetics but not all symptathomimetics are catecholamines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

What do catecholamines act on?

A

Adrenergic receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

How are catecholamines metabolized?

A

Rapidly inactivated my enzymes
Monaoamine oxidase (MAO): enzyme present in liver, kidneys, Gi tract that catalyzes oxidative deamination
Catechol-o-transferase (COMT): methylates the hydroxyl group of catecholamines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Naturally occurring catecholamines (endogenous)

A

Sympathomimetics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What do indirect-acting synthetic non-catecholamines do?

A

Release endogenour neurotransmitter NE from postganglionic sympathetic nerve endings

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

What are the indirect-acting synthetic non-catecholamiens characterized by?

A

Mostly alpha and beta1 adrenergic effects because NE is a weak beta2 agonist

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

What is denervation or depletion of a neurotransmitter?

A

As with repeated doses of a sympathomimetic, blunts the pharmacologic responses normally evoked by the drug

46
Q

What are the direct acting synthetic non-catecholamines?

A

Phenylephrine and methoxamine

47
Q

What do direct acting synthetic non-catecholamines do?

A

Activate adrenergic receptors directly

48
Q

T/F: synthetic noncatecholamines are less potent than catecholamines

A

True

49
Q

T/F: Denervation or depletion of neurotransmitters prevents the activity of phenylephrine and methoxamine

A

False, does not prevent

50
Q

Receptor is a specific protein molecule in the lipid bilayer

A

Effector cell receptor

51
Q

What happens when an effector cell receptor is bound?

A

It interacts with guanine nucleotide proteins (g proteins)

52
Q

How are G proteins activated?

A

GTP is hydrolyzed to GDP activating g proteins that can interact with effector systems

53
Q

What are the 2 types of control for effector cell receptors?

A

Down regulation and up regulation

54
Q

What is down regulation?

A

Extended exposure to agonists reduces the number, but not their response. Results in tachyphylaxis

55
Q

What is up regulation?

A

Chronic depletion of catecholamines or use of antagonists increases the number of receptors but not their sensitivity. May account for w/d syndrome with beta blockers

56
Q

What is receptor uncoupling?

A 
Occurs rapidly (seconds to minutes)
Inability of the receptor to bind G protein (alters the function of the receptor) 
Uncouples the receptor from the signal transduction system.  Caused by the phosphorylation of the receptor and possibly the G protein
57
Q

What is sequestration?

A

Occurs more slowly (minutes to hours)
Movement of receptors from the cell surface to intracellular compartments
Not accessible to hydrophilic ligands

58
Q

What is downregulation?

A 
Prolonged process (hours to days)
Movement of receptors from the cell surface to intracellular compartments but then destroyed
Receptors are not available for recycling to the cell surface.  New receptor protein must be made from RNA to replace lost receptors (ex: from chronic stress or CHF)
59
Q

What is desensitization?

A

The reduction in a physiologic response to a stimulus that is constant overtime

60
Q

Interact with a receptor and cause an effect to occur

A

Agonist

61
Q

Interact with a receptor but prevents intracellular events from occurring. Inhibit in a competitive manner

A

Antagonist

62
Q

What is stroke volume?

A

Blood ejected in 1 cardiac cycle

63
Q

What is stroke volume determined by?

A

Preload, afterload and contractility

64
Q

What are the 2 types of anticholinesterase drugs?

A

Tertiary amines and quaternary amines

65
Q

What drugs are tertiary amines?

A

Physostigmine

66
Q

What drugs are quaternary amines?

A

Edrophonium
Neostigmine
Pyridostigmine

67
Q

Which anticholinesterase drugs cross the blood brain barrier?

A

Tertiary amines and are used for nonspecific antagonism of the CNS effects of certain drugs

68
Q

What actions do anticholinesterase drugs do?

A

Enzyme inhibition
Presynaptic effects
Direct effects

69
Q

How does enzyme inhibition work for anitcholinesterases?

A

Inhibit acetylcholinesterase which results in increased availability of ACh

70
Q

Where does the increased availability of ACh happen for enzyme inhibition for anticholinesterases?

A

Neuromuscular junction
Muscarinic receptors
Autonomic ganglia (sympathetic and parasympathetic)

71
Q

What is a true cholinesterase and is responsible for the hydrolysis of ACh to choline and acetic acid?

A

Acetylcholinesterase

72
Q

How does neostigmine and pyridostigmine work for enzyme inhibition?

A

Hydrolized by acetylcholinesterase
Carbamylates the enzyme in the process
Block enzyme’s ability to hydrolyze ACh

73
Q

How does edrophonium work for enzyme inhibition?

A

Forms a reversible electrostatic attachment

74
Q

How do anticholinesterase drugs work for presynaptic effects?

A

In the absence of neuromuscular blockers, acetylcholinesterase inhibitors may produce fasiculations

75
Q

How do anticholinesterases work for direct effects?

A

At doses greater than usual clinical doses, anticholinesterase drugs have been reported to produce some form of neuromuscular blockade. Excess ACh desensitizes the NMJ

76
Q

How are anticholinesterase drugs classified?

A

Reversible inhibition
Formation of Carbamyl Esters
Irreversible Inhibition

77
Q

What is reversible inhibition for anticholinesterases?

A

Electrostatic attachment to the anionic site (Edrophonium)

78
Q

What is formation of carbamyl esters?

A

Reversible formation of carbamyl ester complexes at the esteratic site

79
Q

What is irreversible inhibition of anticholinesterases?

A

Organophosphates combine with the esteratic site to form a stable inactive complex

80
Q

What is edrophonium’s predominant site of action?

A

Presynaptic

81
Q

What is the most important determinant of relative potency for anticholinesterases?

A

Affinity

82
Q

What is the onset of action for Edrophonium, Neostigmine and Pyridostigmine?

A

Edrophonium: 1-2 minutes
Neostigmine: 7-11 minutes
Pyridostigmine: up to 16 minutes

83
Q

What is the duration of action for the quaternary amines?

A

t1/2: 60-120 minutes

84
Q

What are the muscarinic effects of anticholinesterases?

A

Bradycardia, salivation, bronchoconstriction, miosis, hyperperistalsis and increased risk of PONV

85
Q

What are the nicotinic effects of anticholinesterases?

A

Act at the neuromuscular junction and autonomic ganglia

86
Q

Which drugs produce marked inhibition of plasma cholinesterase?

A

Neostigmine and pyridostigmine

87
Q

T/F: muscarinic effects occur at a lower concentration of ACh than nicotinic effects

A

True

88
Q

What are the clinical uses of anticholinesterases?

A

Antagonist-assisted reversal of neuromuscular blockade
Treatment of CNS effects of certain drugs
Treatment of myasthenia gravis
Treatment of Glaucoma

89
Q

How do anticholinesterases work for treatment of myasthenia gravis?

A

Increase ACh at the neuromuscular junction

90
Q

How do anticholinesterases work for reversing neuromuscular blockade

A

Increase the availability of ACh at the NMJ
Acts presynaptically and postsynaptically
Tips the balance of competition between ACh and NMB in favor of ACh and restores neuromuscular transmission

91
Q

What is the dosage for edrophonium? Neostigmine? Pyridostigmine?

A

Edrophonium: 0.5 mg/kg
1 mg/kg (twitch height <10%)
Neostigmine: 0.043 mg.kg
Pyridostigmine: 0.21 mg/kg

92
Q

For anticholinesterase drugs, what does potency depend on?

A

NMB being antagonized
Speed of spontaneous recovery
Depth of NMB when the reversal is initiated
End point selected

93
Q

What do you mix Edrophonium with for an anticholinergic?

A

Atropine 7 mcg/kg

10-15 mcg/kg is opioid based technique

94
Q

What do you mix Neostigmine with for an anticholinergic?

A

Atropine 20 mcg/kg

Glycopyrrolate 10 mcg/kg

95
Q

When do you administer reversal?

A

Administer reversal only after twitch height has recovered to >10%, otherwise keep patient sedated and intubated

96
Q

What factors influence reversal of neuromuscular blockade?

A

NDMR being reversed

Intensity of the blockade at the time of reversal

97
Q

Antagonism of neuromuscular blockade may be inhibited or prevented by what?

A 
Certain antibiotics
Hypothermia
Resp acidosis
Hypokalemia and metabolic acidosis
Edrophonium less effective in reversing deep NMB (twitch height <10%)
Atracurium: edrophonium may be better
Vecuronium: neostigmine may be better
98
Q

What is the standard of care for patients receiving NMBs?

A

Neuromuscular monitoring

99
Q

What is adequate neuromuscular recovery?

A

TOF ratio >0.9

100
Q

What are some potential consequences of postop residual blockade?

A

Adverse resp events such as upper airway obstruction, inadequate ventilation, hypoxemia, paralysis of laryngeal muscles and aspiration pneumonia and atelectasis

101
Q

Why is the incidence of residual block so high?

A

Lack of monitoring
Lack of reversal of neuromuscular blockade
Use of excessive large doses (which could be addressed by monitoring)

102
Q

What are some limitations of using Neo to reverse neuromuscular blockade?

A

Slow onset
Inadequate reversal of deep block
Risk of arrhythmias
Because of CV risk, must be combined with other drugs such as glycol or atropine

103
Q

What is the first selective binding agent to reverse neuromuscular blockade and reverses steroid-based neuromuscular blockers

A

Sugammadex (modified gamma-cyclodextrin)

104
Q

What does Sugammadex do to Rocuronium?

A

Strongly binds and encapsulates Rocuronium making it unavailable to the NMJ. Reverses neuromuscular blockade without relying on acetylcholinesterase inhibition

105
Q

What are the characteristics of Sugammadex that differentiate it from Neostigmine?

A

MOA: reverses NMB without relying on ACTH
Specific aminosteroidal non-depolarizing muscle relaxants
Lack of CV side effects, does not require atropine or glycol
Ability to reverse profound block
Reverses block more quickly

106
Q

Physostigmine is used to reverse what?

A

Anticholinergic drugs
Opioids
Benzos
Anesthetics

107
Q

How do Anticholinesterases work for the treatment of Myasthenia Gravis?

A

Increase the response of skeletal muscles to repetitive impulses by increasing available ACh

108
Q

What does a cholinergic crisis manifest as?

A

Skeletal muscle weakness

109
Q

What does an acute overdose of anticholinesterase manifest as for muscarinic effects?

A 
Miosis and difficulty focusing
Salivation
Bronchoconstriction
Bradycardia
Abdominal cramps
Loss of bowel and bladder control
110
Q

What are the nicotinic and CNS effects of acute overdose of anticholinesterase overdose?

A 
Skeletal muscle weakness to paralysis and apnea
Confusion
Ataxia
Seizures
Coma
Depressed ventilation
111
Q

What are organophosphate anticholinesterases?

A

Insectisides and nerve agents
Rapidly absorbed throught the skin, GI tract and across alveoli
High lipid solubility ensures that they will cross the BBB and produce intense CNS effects

112
Q

What is the treatment of an overdose of anticholinesterase drugs?

A

Atropine for antimuscarinic effects
Pralidoxime (Acetylcholinesterase reactivator)
Supportive measures

Pharm II (8 decks)

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