Exam 2 Flashcards
1
Q
What are the 2 parts of the peripheral nervous system?
A
Somatic NS- voluntary movement
Autonomic NS- involuntary
2
Q
What are some similarities between Somatic and Autonomic NS?
A
both part of PNS
signals received from higher brain levels
integrative neurons provide stimulation/inhibition of both sysytems
3
Q
What are some differences between Somatic and Autonomic NS?
A
somatic efferents go directly to their effector; neurons reach all the way to nueromuscular junction
autonomic efferents must synapse in a ganglion
neurons leaving the CNS- preganglionic
neuron that leaves the ganglion- postganglionic
4
Q
What are integrative neurons?
A
complexes of neurons of the CNS, they recieve sensory input from multiple locations and throughout time
capable of processing this informatiion and determining the appropriate response
either stim/inhibt the somatic or preganglionic
5
Q
2 components of the ANS:
A
sympathetic- fight/flight
parasympathetic- rest/digest
6
Q
Where do fibers of the sympathetic nervous sysytem originate/terminate?
A
originate from the thoracic and lumbar spinal cord
enter the paravertebral chain of sympathetic ganglia
some will pass through to join ganglia elsewhere in the body
7
Q
Give and example of sympathetic nerve fiber and its path:
A
Adrenal medulla
pregang fibers leave the T/L spinal segments, travel through the paravertebral chain synapse in the adrenal medulla
the cells of the medulla are considered the “post ganglionic” cells and release epinephrine
8
Q
Post ganglionic symp fibers are LONG/SHORT the distance from ganglia is SHORT/FAR
A
LONG
FAR
9
Q
What is meant by the the statement “the sympathetic is extremely reactive, and acts via mass discharge”
A
Extremely reactive: response to sympathetic stimulation is rapid and can vary moment to moment
Mass discharge: capable of mass action affecting virtually all sympathetic organs at once
10
Q
Where do parasympathetic neurons orginate?
A
from nuclei in the midbrain, medulla, and sacral spinal cord
cranial nerves 3, 7, 9 10
11
Q
Describe pre/post gang fibers of parasymp NS
A
preganglionic are long, synapse on/within effectors
therefore the post are short
12
Q
Describe the effect of the sympathetic NS on the Heart
A
increased heart rate
13
Q
Describe the effect of the sympathetic NS on the Peripheral Vasculature
A
constriction- decreases blood flow
14
Q
Describe the effect of the sympathetic NS on the Skeletal Muscle/organ vascualture
A
Alpha 1- constriction
Beta 2- dialtion
15
Q
Describe the effect of the sympathetic NS on the GI
A
Relaxation of smooth muscle
constriction of sphincter muscles
decreases secretions
16
Q
Describe the effect of the sympathetic NS on the Bronchioles
A
Relaxation
17
Q
Describe the effect of the sympathetic NS on the Urinary Bladder
A
Beta 2/3 relaxation of bladder body
alpha contraction of bladder trunk and internal sphincter
18
Q
Describe the effect of the parasympathetic NS on the Heart
A
decreased heart rate
decreased contractile force
decreased conduction velocity
19
Q
Describe the effect of the parasympathetic NS on the peripheral vascualture
A
dilation increases blood flow
20
Q
Describe the effect of the parasympathetic NS on the skeletal muscle and organ vasculature
A
dialtion
21
Q
Describe the effect of the parasympathetic NS on the GI
A
increases peristalsis
relaxation of sphincter muscles
decreased conduction velocity
22
Q
Describe the effect of the parasympathetic NS on the bronchioles
A
constriction
23
Q
Describe the effect of the parasympathetic NS on the urinary bladder
A
contraction of bladder body
relaxation of trunk and internal sphincter
24
Q
What are cholinergic receptors?
A
activated by acetylcholine
25
What are the 2 types of cholinergic receptors?
Muscarinic
nicotinic
26
What are nicotinic receptors and where are they found?
Nicotinic Ach receptors (nAchr) – stimulated by nicotine in addition to Ach
acitvate an Ion Gated Channel
Found at synapse of preganglionic neurons onto the ganglia
Found at synapse of somatic neurons onto effectors
27
What are muscarinic receptors and where are they found?
Muscarinic Ach receptors (mAchr) – stimulated by muscarine, bethanechol, and pilocarpine in addition to Ach
Found at post ganglionic synapse of parasympathetic fibers onto effectors
G-coupled protein receptor
28
What are adrenergic receptors and where are they found?
Adrenergic receptors – activated by catecholamines such as norepinephrine or epinephrine
Found at post ganglionic synapse of sympathetic fibers onto effectors
A class of 7 transmembrane receptors who, when bound by agonist, will activate an enzyme cascade, starting with activation of a G protein
29
What are non-adrenergic, non-choline receptors?
Non-adrenergic, non-cholinergic receptors
Purinergic receptors – stimulated by purines
Found dispersed throughout body – i.e. urinary bladder
30
Facts about acetylcholine (Ach)
Acetylcholine (Ach)
oCreated by multiple enzymes in a long process
Choline-acetyltransferase is the rate limiting enzyme; the activity of this enzyme will determine the availability of Ach to be released into the synapse
o Acetylcholinesterase digests Ach in the synapse
Breaks it down and transports metabolites back into presynaptic cell for recycling
oExcess Ach exposure can be treated with a cholinergic receptor antagonist OR acetylcholinesterase stimulant
31
Facts about Norepinephrine (NE):
Norepinephrine (NE)
o Classified as a catecholamine
o Tyrosine -> DOPA -> Dopamine -> Norepinephrine
Due to the relation between dopamine and NE, it is not unlikely that a dopamine agonist will likely also stimulate adrenergic receptors that bind NE
32
Facts about Epinephrine
Epinephrine (Epi)
o NOT identical to NE, thus will have a different effect on adrenergic receptors
o More resilient in blood stream – less susceptible to degradation in bloodstream
33
Alpha-1 Receptors:
Present on vascular smooth muscle for vessels feeding the skin, kidney, viscera, and skeletal muscle
When bound by agonist (i.e. NE):
- Vasoconstriction
*Note, in some locations alpha 1 will be outnumbered by beta 2 receptors; therefore stimulation with agonists of both will result in beta 2 activity
34
Alpha 2 receptors:
Pre-synaptic ganglia; When activated these will work to auto-inhibit NE release.
35
Beta 1 receptors:
Present on the SA note, Atria, and Ventricles of the heart
Agonist will induce:
- Increased contractility (contraction strength), heart rate, and conduction velocity
- Overall stimulation of the heart
36
Beta-2 receptors
Found in a variety of locations:
1. Pulmonary airway smooth muscle – bronchioles
a. Leads to dilation of airways – bronchodilation
2. Vasculature feeding skeletal muscle
a. Vasodilation
b. So, if there are more Beta 2 receptors than alpha 1 on a vessel feeding a skeletal muscle, then stimulation by agonist will result in vasodilation
3. Presynaptic neurons – within the membrane
a. Leads to auto-stimulation; presynaptic neuron releases NE, then that NE stimulates it to release more NE
37
What effects do norepinephrine/epinephrine have on the different receptor types?
- Epinephrine (Epi) is an agonist for all 4 subtypes of adrenergic receptors
- Norepinephrine (NE) is only agonistic for alpha 1,2 and beta 1
o So stimulation of Beta 2 is limited to circulating Epi
38
What are the 3 most common catecholamines we talked about?
Epi,
NE
Isoproterol
39
Clinical application of Epi/NE/Isoproterol in local anesthetic:
1. Keep it at the location you give it bc local vasoconstriction via activation of alpha-1 receptors
2. Constriction of vasculature,
3. HOWEVER- caution, decreased peripheral blood pressure could activate baroreflex, leading to bradycardia
4. Also caustion giving in poorly perfused areas- ischemia
40
Clinical application of Epi/NE/Isoproterol as a hemostatic:
Constriction to stop blood flow
41
Clinical application of Epi/NE/Isoproterol in cardiac arrest/AV blocl
a. Beta one receptor EPI to jump start the heart
| b. Complicated system
42
Clinical application of Epi/NE/Isoproterol inAnaphylactic Shock
a. EPI-Pen, allergic reactions
| b. If you stab you finger w/ epi, need alpha one antagonist, Phentolamine most common
43
Clinical application of Epi/NE/Isoproterol in Bronchial asthma
Mild doses of catecholamines will provide continuous bronchodilation to counteract constant threat of airways closing due to allergens
44
What is the clinical application of dopamine?
i. In low doses will act as a DA receptor agonist
ii. In higher doses will act as a beta adrenergic agonist (remember the similarity between DA and NE)
iii. In veterinary field had been used to treat acute renal failure
1. Reasoning being high doses mimicking NE would lead to vasodilation, increasing perfusion to kidneys
2. However, not used anymore due to uncertain efficacy
45
What are the clinical applications of Dobutamine?
i. Most likely a beta 1 agonist
1. Had been used to treat low output congestive heart failure
2. Beta 1 agonist would stimulate the heart, acting as a positive ionotrope
46
What is ephedrine?
i. Closely related to pseudoephedrine
ii. Used for alpha and beta agonistic properties
iii. Historically had been used in dietary supplements (i.e. Hydroxycut) to induce beta receptor mediated lipolysis and thermogenesis
1. 2004, the FDA banned their use due to dangerous side effects
iv. Vet met uses:
1. Urinary incontinence – not very effective
2. Rarely used to combat hypotension
47
WHat is Phenylephrine?
i. Alpha agonist
1. Used for pupillary dilation during an ophthalmic exam
2. Combats hypotension and hypovolemic shock
a. Alpha stimulation leading to vasoconstriction to increase blood pressure
48
What are some common Beta 2 agonists?
i. Albuterol – found in inhalers; fast acting beta 2 agonist (good for emergency use)
ii. Clenbuterol – commonly used to treat Chronic Obstructive Pulmonary Disease (COPD)
1. This is a banned substance in horses
2. Illegal use in horse racing to stimulate bronchodilation (higher oxygen intake) and potential beta 3 stimulation (lipolysis and increase energy availability)
iii. Terbutaline – Long lasting beta 2 agonist; takes longer to take effect than albuterol
49
What are anti-adrenergic drugs used for?
a. Beta blockers – in veterinary medicine used to decrease blood pressure
Alpha blockers: used to reduce muscle tone in urinary sphincter
50
What is propanolol
1. Beta antagonist
| 2. Negative risk of also blocking beta 2 receptors and inducing bronchoconstriction
51
What is Atenolol?
1. Beta 1 receptor specific
2. Used frequently for high blood pressure in cats
3. Anti-anxiety medication for humans
52
How often do we use alpha blockers in Vet MEd?
rarely
53
What is Phenobenzamine?
1. Both an alpha 1 and 2 antagonist
2. Veterinary use:
a. Decreases urethral sphincter tone – ideal for inappropriate urine retention cases
b. Laminitis – known that laminitis is caused by circulatory problems to the hoof; alpha 1 antagonists would lead to vasodilation of peripheral vessels, leading to increased blood flow to the hoof
54
What is phentolamine?
1. Alpha 1 and 2 antagonist
2. Veterinary use:
a. To save fingers accidentally injected with Epi
i. Epi is agonistic to alpha 1,2 receptors, causing vasoconstriction
ii. Vasoconstriction in a digit can be so severe as to completely cut off blood supply
iii. Antagonizing these receptors will allow for restoration of blood supply to the digit
b. Treats pheochromocytomas (neoplasia of the adrenal medulla leading to excess Epi secretion) – exposure of body to an alpha 1,2 antagonist will minimize the negative effects of excess Epi
55
What are the 2 types of Ach receptors?
nAchR- nicotinic
Ion channels,
Ligand-gated ion channels
mAchR- muscarinic
G-protein coupled receptor
Metabolic receptors
7 Transmembrane protein
STRUCTURALLY VERY DIFF- member thi
56
What are the 3 types of muscarinic receptors and where are they found?
Type 1 – found primarily throughout the GI tract; stimulation leads to increases in digestion, secretion, and peristalsis
Type 2 – Primarily cardiovascular; stimulation results in vasodilation and cardiac relaxation (decreased rate, contractile strength and conduction velocity)
Type 3 – Less known; Found anywhere parasympathetic system works besides GI and cardiovascular systems
i. Eye, urinary bladder, etc.
57
Where are nicotinic receptors typically found?
found at ganglionic synapses of both parasympathetic and sympathetic nervous systems
58
What are chlinergic/cholinomemetic drugs?
drugs that produce acetylcholine effects
59
What are parasympathomimetic drugs?
drugs that produce Ach like effects at parasympathetic neuroeffector junctions
60
What are direct acting parasympathomimetic drugs?
agonists for muscarinic receptors
61
What are cholinesterase inhibitors?
blockers of teh Acetylcholinesterases that degrade endogenous Ach
62
WHat are parasympatholytic drugs?
block/inhibit Ach-like effects at parasympathetic neuroeffector juntions
63
What effects do cholinergic receptor agonists have on the eye?
contraction of iris sphincter/ciliary muscle, which will cause constriction of the pupil
64
What effects do cholinergic receptor agonists have on the heart?
general inhibitory effects- decrease rate, contractile strength, conduction velocity
65
What effects do cholinergic receptor agonists have on the blood vessels?
indirect dialtion
66
What effects do cholinergic receptor agonists have on the Lungs?
contraction of bronchial muscles
increased secretions
67
What effects do cholinergic receptor agonists have on the GI tract
increase motility
relax sphincters
timualte secretions
68
What effects do cholinergic receptor agonists have on the Urinary bladder?
contraction of detrussor
| relaxation of trigone/sphincter
69
What effects do cholinergic receptor agonists have on the glands
Increases secretions
70
What are the 2 direct acting parasympathomimetic drugs that are resistant to acetylcholinesterase ?
Carbachol
Bethanechol
71
What is carbachol?
binds both muscarinic and nicotinic Ach receptors (all types)
Therefore, at higher concentrations, can lead to nicotinic receptor stimulation = stimulation of sympathetic ganglia
Catecholamine release from adrenal medulla
Skeletal muscle fasiculations
72
What is bethanecol?
binds ONLY muscarinic receptors; so will particularly get parasympathetic agonist response
sometimes used form bladder stimulation
73
What is pilocarpine?
Cholinomimetic alkaloid
* Used to treat keratoconjunctivitis and glaucoma
* Causes miosis (pupil constriction) and enhanced aqueous humor flow
* Binds muscarinic receptors
74
What are the toxic effects of cholinergic stimulation?
Slowing of heart rate and AV block (due to decreased conduction velocity)
Increased airway resistance Dyspnea
Constriction of bronchioles
Increased secretions
Hypotension (due to vasodilation)
SLUD syndrome
75
What does SLUD stand for?
salivation
lacrimation
urination
defecation
76
What are Indirect acting parasympathomimetic drugs ?
aka cholinesterase inhibitors – block acetylcholinesterase that degrades endogenous Ach
Indirectly attains the activity of Ach by preventing the digestion of Ach; allows Ach to act for a longer period of time within the synapse
Acetylcholinesterase terminates the action of endogenous Ach at just about every site where Ach is released
Including autonomic ganglia, parasympathetic neuroeffector junctions, somatic neuromuscular junctions, adrenal medulla, CNS
77
What are Edrophonium and Pyridostigme?
Reversible Drugs:
used for treatment of Myasthenia Gravis
* Myasthenia Gravis – hereditary condition in which postsynaptic cells lack appropriate numbers of cholinergic receptors
* Requires excessive amounts of Ach to create a normal response in the postsynaptic cell
* Use of cholinesterase inhibitors prevents digestion of Ach, allowing for the needed increase in Ach concentration
78
What are organophpsphates?
o Irreversible drugs Organophosphates
Malathion, Parathion, Dichlorvos – pesticides that use to be in flea collars; pretty much not in use anymore
Sarin, Tabun, Soman – Nerve gas used in bio warfare
• Mild exposure leads to: pupillary constriction (miosis), tightness in the chest, wheezing
• Severe exposure: Diarrhea, Urination, miosis, bronchoconstriction, salivation, sweating, excitation of skeletal muscle and CNS
79
What are Parasympatholytic agens... what is the most important one we will use as vets most likely?
drugs that act as antagonists for muscarinic receptors
1. Atropine – prototypical muscarinic antagonist
a. Used to minimize the effects of nerve gas
b. Effects:
i. Tachycardia
ii. Relax GI musculature and decrease secretion
iii. Bronchodilation and decreased airway secretion
iv. Dry oral mucosa
80
What is the parasympathetic innervation to the bladder?
a. Preganglionic fibers originate in sacral spinal cord
b. Course through the pelvic nerve
c. Join ganglion adjacent to the bladder
d. Postganglionic fibers innervate the bladder wall musculature
i. Muscarinic receptors (M3) found along body of bladder – stimulation leads to contraction of musculature – inducing urination
81
What is the sympathetic innervation to the bladder?
a. Preganglionic fibers originate in T/L spinal cord
b. Immediately form ganglia adjacent to spinal cord
c. Postganglionic fibers extend toward bladder – innervate bladder wall musculature, internal sphincter, AND parasympathetic ganglia
i. Alpha 1 adrenergic receptors found at base/neck of bladder – stimulation leads to contraction of musculature – inhibiting urination
ii. Beta 2/3 adrenergic receptors found on body – stimulation leads to relaxation of musculature – inhibiting urination
82
What is the somatic innervation to the bladder?
a. Pudendal nerve
| b. Innervates the external sphincter – skeletal muscle under voluntary control
83
What are the stages of bladder filling?
a. Primarily Sympathetic Activity
i. Internal sphincter contracted
ii. Neck of bladder contracted
iii. Body of bladder relaxed
iv. Inhibits parasympathetic ganglia activity
84
What are the stages of micturition?
(bladder emptying dumb ass)
a. Primarily Parasympathetic Activity
i. Body of bladder contracts
b. Somatic activity – decision made to urinate allows for external sphincter relaxation
85
What are common causes of urinary incontinence?
o Hormonal deficiencies
o Neurologic dysfunction – trauma to neurons or CNS involved in micturition
o Ectopic ureters – ureter links directly to the urethra, bypassing the bladder
Results in a dripping incontinence
20x more common in females
o Obstructions – urolith, stenosis, irregular sphincters
86
What type of incontinence cn pharmalogical interventions help to cure
o Hormone responsive incontinence – most commonly due to estrogen dependence
In an unknown manner, estrogen interacts with bladder neck and internal sphincter to prevent inappropriate urination
Animals that are recently spayed have sudden decrease in estrogen; in these cases, hormone therapy resolves the problem
87
What 2 drugs can be used to alleviate hormonal incontinence?
```
Oral Diethylstilbestrol (DES)
– had been used as an estrogen replacement in humans but was discovered to be a carcinogen and/or teratogen
• Used in vet med but should be avoided by pregnant women
```
Phenylpropanolamine (PPA)
– alpha receptor agonist, potentially inducing the production of estrogen
88
What is urge incontinence?
overstimulation of muscarinic receptors resulting in frequent urge to urinate
89
What 2 drugs can be used to treat urge incontinence?
Oxybutynin – M3 antagonist
• Blocks the muscarinic receptors that are being overly activated
• However, has unwanted side effect of dry mouth – most humans will prefer the incontinence over dry mouth
Tolterodine – same activity and side effects of oxybutynin
• However, there is a wider margin of dose providing relief of incontinence and causing dry mouth
90
T/F Most organs are innervated by BOTH the sympathetic and parasympathetic systems
TRUE; What receptors predominate determines what has action on it
91
T/F The adrenal gland originates from neuronal tissue
TRUE; this is why it has direct sympathetic action act on it. It is basically a synapse without post-ganglionic fibers
92
What would it look like if acetylcholinesterases were damaged?
It would look like PS activity; excess ACh would sit around in the synapse.
93
Where is nor epinephrine transformed to epinephrine?
Adrenal gland
94
What is more stable in the blood stream epinephrine or norepinephrine?
Epinephrine
95
Phentolamine is a:
alpha blocker; keep your fingers
96
Propanalol and atenalol are:
Beta blockers
97
Phenylephrine
alpha agonist
98
What 2 different types of drugs would be beneficial to control urinary incontinence?
Alpha agonists or mAChR antagonists
