1 - PNS Part I Flashcards
1
Q
Most neuropharmacological agents act by altering ________
A
synaptic transmission
2
Q
Drugs that act by altering axonal conduction are _______ selective
A
less
the process of conducting an impulse along an axon is essentially the same in all neurons, so a drug that alters axonal conduction affects all nerves with pretty much no specificity
3
Q
What is an example of a drug that decreases axonal conduction?
A
Local anesthetics!
they are nonselective inhibitors of axonal conduction
4
Q
Why are drugs that alter synaptic transmission so much more selective?
A
unlike axons, synapses at different sites vary widely from one another
5
Q
The effect of a drug on a neuronally regulated process is dependent on:
A
the ability of that drug to directly or indirectly influence receptor activity on target cells
6
Q
What are the five steps of synaptic transmission?
A
- Transmitter Synthesis
- Transmitter Storage
- Transmitter Release
- Receptor Binding
- Termination of Transmission
7
Q
Transmitters can be removed from the synaptic gap by three processes:
A
Reuptake
Degradation
Diffusion
8
Q
How does a drug that increases transmitter synthesis impact receptor activation?
A
storage vesicles will contain transmitter in abnormally high amounts, causing more transmitter to be released, and more transmitter available to receptors on the postsynaptic cell
9
Q
Amphetamines are drugs that act by:
A
promoting transmitter release
10
Q
Botulinum Toxin acts by ______
A
inhibiting transmitter release
11
Q
Drugs that directly activate receptors are called:
A
agonists
12
Q
drugs that prevent receptor activation are called
A
antagonists
13
Q
Drugs can interfere with the termination of transmitter action by two mechanisms:
A
- Blockade of transmitter reuptake
- Inhibition of transmitter degradation
14
Q
For every PNS drug you should know three things:
A
The identity of the receptors at which that drug acts
The normal response to activation of those receptors
Whether the drug increases or decreases receptor activation
15
Q
The PNS has two major subdivisions:
A
Autonomic (parasympathetic and sympathetic)
Somatic (skeletal muscle movement)
16
Q
What are the three principle functions of the autonomic nervous system?
A
- Regulation of Heart
- Regulation of Secretory Glands
- Regulation of Smooth Muscle
17
Q
What are the seven main effects of Parasympathetic nervous system stimulation?
A
- Slowing HR
- Increasing gastric secretion
- Emptying the bladder
- Emptying the bowels
- Focusing the eye for near vision
- Constricting the pupil
- Contracting bronchial smooth muscle
18
Q
Therapeutic agents that alter parasympathetic function are used primarily for:
A
effects on the GI tract, bladder, and eyes
19
Q
The sympathetic nervous system has three main functions:
A
- Regulating the CV system
- Regulate temperature
- Implement the acute stress response
20
Q
By influencing heart and blood vessels, the sympathetic nervous system can achieve three homeostatic objectives:
A
Maintain blood flow to the brain
Redistribute blood flow during exercise
Compensate for blood loss by constricting vessel
21
Q
How does the sympathetic nervous system control temperature?
A
- Regulating blood flow to the skin
- stimulating sweat glands
- Inducing piloerection
22
Q
Generally speaking, stimulation of the sympathetic nervous system causes five things:
A
- Increased HR and BP
- Shunting blood away from skin and viscera into skeletal muscles
- Dilating bronchi to improve oxygenation
- Dilating pupils
- Mobilizing stored energy to provide glucose to the brain and fatty acids to the muscles
23
Q
In a reflex arc, the sensor is responsible for _____ and the effector is responsible for ______
A
monitoring the status of a physiologic process
making appropriate adjustments to the process
24
Q
In most organs, the _______ nervous system provides the predominant tone
A
Parasympathetic
25
The vascular system is regulated almost exclusively by the _______ nervous system
sympathetic
26
How many neurons are in the pathway leading from the spinal cord to organs innervated by parasympathetic nerves?
Two
Where these neurons synapse is a structure called a ganglion
27
The anatomy of the Parasympathetic Nervous System offers two general sites at which drugs can act:
1. The synapses between preganglionic neurons and postganglionic neurons
2. the junctions between postganglionic neurons and their effector organs
28
The autonomic nervous system always contains ____ neurons in any pathway.
The Somatic nervous system always contains _____ neurons in any pathway
Two (pre and post ganglionic)
One (Motor Neuron)
29
The Peripheral Nervous System employs three neurotransmitters:
Acetylcholine, Norepinephrine, Epinephrine
30
In the peripheral nervous system, acetylcholine is released at which junctions?
1. All preganglionic neurons of the ParaSNS and SNS
2. All postganglionic neurons of the ParaSNS
3. All motor neurons to skeletal muscles
4. Most postganglionic neurons of the SNS that go to sweat glands
31
In the peripheral nervous system, Norepinephrine is the transmitter released by:
1. Practically all post-ganglionic neurons of the sympathetic nervous systems
2. The only exception is sweat glands
32
Epinephrine is the major transmitter released from:
the adrenal medulla
33
There are two primary receptor types in the Peripheral Nervous System:
Cholinergic Receptors
Adrenergic Receptors
34
Cholinergic receptors mediate responses to \_\_\_\_\_
Adrenergic receptors mediate responses to \_\_\_\_\_
Acetylcholine (mediate response at all junctions where ACh is the transmitter)
Epinephrine and norepinephrine (mediate responses at all junctions where norepinephrine or epinephrine is the transmitter)
35
There are three major subtypes of cholinergic receptors:
NicotinicN
NicotinicM
Muscarinic
36
There are four major subtypes of adrenergic receptors:
Alpha 1
Alpha 2
Beta 1
Beta 2
37
Where are NicotinicN receptors located?
the cell bodies of ALL postganglionic neurons
38
Where are NicotinicM receptors located?
skeletal muscles
39
Where are muscarinic receptors located?
On ALL organs regulated by the ParaSNS AND sweat glands
40
Where are Adrenergic receptors located?
On ALL organs (except sweat glands) regulated by the SNS
AND
all organs regulated by epinephrine release from the adrenal medulla
41
Activation of NicotinicN receptors promotes:
ganglionic transmission at all ganglia of the SNS and ParaSNS
AND
release of epinephrine from the adrenal medulla
42
Activation of NicotinicM receptors causes:
Contraction of skeletal muscle
M is for muscle
43
Activation of Muscarinic Receptors causes:
an appropriate PNS response from the organ involved
* **Eyes:** pupil constriction, ciliary contraction (close vision)
* **Heart:** Decreased HR
* **Lung:** Bronchoconstriction, increased secretions
* **Bladder:** promotes voiding
* **GI:** Salivation, increase secretions, increased motility
* **Sweat:** Sweating
* **Sex:** Ejaculation
* **Blood Vessels:** Dilation
44
Most importantly, activation of muscarinic receptors causes:
1. increased glandular secretions (pulmonary, gastric, intestinal, and sweat)
2. Contraction of smooth muscle (bronchi and GI tract)
3. Slowing of the Heart Rate
4. Pupil constriction
5. ciliary contraction (focuses eye for near vision)
6. Dilation of blood vessels
7. Voiding of the bladder
45
The ParaSNS has pretty much no physiologic effect on human vasculature. So why do muscarinic drugs cause vasodilation?
Blood vessels do have muscarinic cholinergic receptors
No nerves terminate at these receptors, so they aren't related to the nervous system at all
But they're still there
So when we give drugs that activate muscarinic receptors, they do become activated, causing vasodilation and a drop in BP
46
Activation of Alpha 1 receptors causes:
Vasoconstriction
Ejaculation
Pupil Dilation
47
Alpha 2 receptors of the PNS are located where?
On nerve terminals of the ANS, NOT the organs they effect
This is why they're called presynaptic
48
What is the function of Alpha 2 receptors?
To regulate transmitter release
Stimulation of Alpha 2 receptors causes an inhibition of transmitter release
49
Where are alpha 2 receptors clinically relevant?
Really only in the CNS, not really at all in the PNS
50
Where are Beta 1 receptors located?
The heart
The Kidney
51
Activation of Beta 1 receptors causes:
increased rate, force of contraction, and AV conduction velocity
Release of Renin
52
Activation of Beta 2 receptors causes:
Bronchial Dilation
Uterine relaxation
VasoDILATION
Glycogenolysis in the liver and skeletal mm
Enhances skeletal muscle contractions
53
In the periphery, the only dopamine receptor of clinical significance is located in the \_\_\_\_\_
Kidney
Dilates renal blood vessels, increasing perfusion
54
Which cholinergic receptors can ACh activate?
How does this differ from adrenergic receptors?
All of them
On the other hand, adrenergic receptors are much more picky. Norepinephrine, for example, can't activate all adrenergic receptors
55
Which receptors can the following transmitters activate?
Epinephrine
Norepinephrine
Dopamine
E: All alpha and Beta Receptors, but not dopamine receptors
N: Alpha 1, Alpha 2, Beta 1
D: Alpha 1, Beta 1, dopamine receptors
56
Which transmitters are capable of activating dopamine receptors?
Only dopamine
57
There is only one transmitter that can activate Beta 2 receptors:
Epinephrine
58
When you think fight or flight, think:
Beta 2
The adrenal medulla is responsible for releasing epinephrine in fight or flight situations. As such, Beta 2 response is due solely to adrenal medulla action
59
Describe the life cycle of ACh
60
Norepinephrine transmission is terminated by:
Reuptake
Once inside the cell, it's either put back into a vesicle or broken down by MAO
61
Epinephrine is synthesized by ____ in the \_\_\_\_\_\_
Chromaffin cells
Adrenal Medulla
62
Termination of Epinephrine action is accomplished by:
hepatic metabolism
NOT reuptake
63
What are cholinergic drugs?
Drugs that influence the activity of cholinergic receptors
THEY MAY ENHANCE OR BLOCK CHOLINERGIC ACTION
64
Cholinergic drugs have more uses as _____ than \_\_\_\_
toxins
medication
65
What is the action of muscarinic agonists?
selectively mimic the effects of Ach at the muscarinic receptors
66
What do ganglionic stimulating agents do?
Selectively mimic the effects of acetylcholine at NicotinicN receptors of autonomic ganglia
67
The only therapeutic value of Ganglionic stimulating agents is:
Tobacco cessation drugs
68
What do ganglionic blocking agents do?
Selectively block ganglionic nicotinicN receptors
69
What do Neuromuscular Blocking Agents do (chemically)?
Block the effects of ACh at NicotinicM receptors at the neuromuscular junction
70
What do cholinesterase inhibitors do?
They increase cholinergic receptor activity indirectly by increasing the amount of ACh in the synaptic space
71
Muscarinic agonists are also known as:
parasympathomimetic agents
72
The principle structures affected by muscarinic activation are:
Heart
Exocrine glands
smooth mm
eyes
73
**Bethanecol**
Action
Effect
Therapeutic Use
Adverse Effects
Direct-acting Muscarinic Agonist
Effect: Bradycardia, sweating, salivation, bronchial secretions, gastric acid secretion, bronchial constriction, increased GI motility and tone, bladder emptying
Use: Treats urinary retention, GERD, gastric atony/distention
AE: HypoTN, bradycardia, excess salivation, excess gastric acid, abdominal cramps, diarrhea, increased urinary tract pressure, asthma exacerbation
Causes dysrhythmia in patients with hyperthyroidism
74
Why do patients with hyperthyroidism gets dysrhythmias from bethanechol, a drug that usually causes bradycardia?
when the take bethanechol, they get bradycardia and HypoTN, which releases NE from the SNS
In a normal patient this would be fine, but in a patient with Hyperthyroidism in can induce dysrhythmias BECAUSE they heart is exquisitely sensitive to NE
75
What is the prototype of a muscarinic agonist?
Bethanechol
76
What is the prototype of a cholinesterase Inhibitor?
Pyridostigmine
77
What is the prototype of a muscarinic antagonist?
Atropine
78
Muscarinic Poisoning results from an overdose of one of two drugs:
Direct-acting muscarinic agonists (bethanechol)
Indirect-Acting Cholinomimetics (pyridostigmine)
79
What are the manifestations of muscarinic poisoning?
SLUDGE and the Killer Bs:
* *S**alivation
* *L**acrimation
* *U**rination
* *D**iaphoresis/Diarrhea
* *G**I Cramping
* *E**mesis
* *B**radycardia
* *B**ronchospasm
* *B**ronchorrhea
80
For a patient who is taking bethanechol, when should it be taken?
1 hour before or 2 hours after meals to decreased N/V
81
Cholinesterase Inhibitors increase transmission in which receptors?
ALL cholinergic junctions (muscarinic, ganglionic, and neuromuscular)
They lack selectivity and elicit a broad spectrum of responses
82
Cholinesterase Inhibitors are used to treat which diseases?
Myasthenia Gravis
Alzheimer Disease
Parkinson
Poisoning by muscarinic *antagonists*
***Reversing Non-Depolarizing NMBAs***
83
There are two basic categories of cholinesterase inhibitors:
Reversible
Irreversible
84
Reversible Cholinesterase Inhibitors Include:
Pyridostigmine
Neostigmine
Physostigmine
Edrophonium
Several drugs for Alzheimer's
85
Pyridostigmine is the drug of choice for:
Myasthenia Gravis
86
How do reversible cholinesterase inhibitors work?
acts as a substrate for cholinesterase
It's broken down by cholinesterase, but it takes a long time, so it's basically tying up cholinesterase so it can't break down Ach
87
When used therapeutically, cholinesterase inhibitors usually only affect:
muscarinic receptors on organs
Nicotinic receptors at the NMJ
88
What are the muscarinic effects of Pyridostigmine?
Same as muscarinic agonists:
Bradycardia, Bronchial constriction, urinary urgency, increased glandular secretions, increased tone and motility of GI smoth mm, miosis, focusing of the lens for near vision
89
What are the neuromuscular effects of anticholinergics?
Therapeutic doses: increase the force of contraction
Toxic doses: reduce the force of contraction (excessive amounts of Ach at the NMJ keep the motor end plate in a state of constant depolarization, causing complete blockade)
90
Why is neostigmine an ideal choice for reversal of a patient with alzheimer's disease?
It carries a positive charge and cannot cross the blood brain barrier
91
Which cholinesterase inhibitor crosses the Blood Brain Barrier?
Physostigmine
Does not carry a charge
This makes it the drug of choice for treating atropine poisoning/antimuscarinic toxicity
92
Edrophonium is unique in its use:
used to diagnose, but not treat, MG (not used that much any more now that better testing is available)
Very short duration of action
93
Which three cholinesterase inhibitors are approved for management of Alzheimer Disease?
Donepezil (Aricept)
Galantamine (Razadyne)
Rivastigmine (Exelon)
94
Irreversible Cholinesterase Inhibitors only have one indication:
Treatment of Glaucoma
Echothiophate is the only drug used
95
All irreversible cholinesterase inhibitors contain:
an atom of phosphorus
This is why they are known as organophosphates
96
Almost all irreversible cholinesterase inhibitors are highly _____ soluble.
How does this impact their absorption?
lipid soluble
Can be absorbed readily from all routes of administration, including directly through the skin
97
What can be given to break the bond between an organophosphate inhibitor and cholinesterase?
Pralidoxime
A cholinesterase reactivator
98
Organophosphates are employed primarily as:
Insecticides
99
Toxic doses of organophosphates produces what condition?
Cholinergic Crisis: excessive muscarinic stimulation and depolarizing neuromuscular blockade
100
What is the treatment for cholinergic crisis?
giving atropine to reduce muscarinic stimulation
giving parlidoxime to reverse inhibition of cholinesterase at the NMJ
Benzo for seizures
101
Pralidoxime is only effective against:
Organophosphates
NOT reversible inhibitors
102
Pralidoxime is a quaternary ammonium compound. What are the implications of this?
It cannot cross the BBB
103
Anticholinesterases work in two places. Which one makes it useful in MG?
at the NMJ, but they also get accumulation at muscarinic sites (even though they don't need it there, the disease only attacks at the NMJ)
104
What drug would you give to someone in myasthenic crisis?
Neostigmine
105
When a patient has myasthenia gravis and is being treated with anticholinesterases, it can be difficult to tell if they also develop:
Cholinergic crisis from toxic levels of cholinesterase inhibitors
106
How can you distinguish myasthenia gravis from cholinergic crisis?
Look for muscarinic symptoms (bradycardia, bronchial constriction, urinary urgency, glandular secretions, increased tone and motility of GI smooth mm)
OR
administer a challenge dose of edrophonium, an ultra-short acting cholinesterase inhibitor. If edrophonium helps, it's MG. If the symptoms get worse, it's cholinergic crisis
107
Anytime you're using edrophonium to test for Myasthenia Gravis vs. Cholinergic Crisis, what should you have in the room on hand?
Atropine and oxygen
108
A patient with myasthenia gravis knows he is going to take a long walk. When should he time his cholinesterase inhibitor?
Right before the walk. The medication will make exertion easier.
109
If an MG patient misses a dose of their anticholinesterase, what should they do?
Don't take it until the next scheduled dose (don't try to “make up” the dose)
110
What symptoms should you tell your patient to look out for when beginning a cholinesterase inhibitor?
difficulty breathing
drooling
N/V/D
Excessive sweating
111
Where are alpha 1 receptors located?
Eye (constriction)
Arterioles (constriction)
Veins (constriction)
Penis (ejaculation)
Prostate (contraction)
Bladder (contraction of trigone and sphincter)
112
Where are Beta 2 receptors located?
Arterioles (dilation)
Bronchi (dilation)
Uterus (relaxation)
Liver (glycogenolysis)
Muscles (enhanced contraction)
