Flashcards in Exam 2 Deck (98):
What are the 2 parts of the peripheral nervous system?
Somatic NS- voluntary movement
Autonomic NS- involuntary
What are some similarities between Somatic and Autonomic NS?
both part of PNS
signals received from higher brain levels
integrative neurons provide stimulation/inhibition of both sysytems
What are some differences between Somatic and Autonomic NS?
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
What are integrative neurons?
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
2 components of the ANS:
Where do fibers of the sympathetic nervous sysytem originate/terminate?
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
Give and example of sympathetic nerve fiber and its path:
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
Post ganglionic symp fibers are LONG/SHORT the distance from ganglia is SHORT/FAR
What is meant by the the statement "the sympathetic is extremely reactive, and acts via mass discharge"
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
Where do parasympathetic neurons orginate?
from nuclei in the midbrain, medulla, and sacral spinal cord
cranial nerves 3, 7, 9 10
Describe pre/post gang fibers of parasymp NS
preganglionic are long, synapse on/within effectors
therefore the post are short
Describe the effect of the sympathetic NS on the Heart
increased heart rate
Describe the effect of the sympathetic NS on the Peripheral Vasculature
constriction- decreases blood flow
Describe the effect of the sympathetic NS on the Skeletal Muscle/organ vascualture
Alpha 1- constriction
Beta 2- dialtion
Describe the effect of the sympathetic NS on the GI
Relaxation of smooth muscle
constriction of sphincter muscles
Describe the effect of the sympathetic NS on the Bronchioles
Describe the effect of the sympathetic NS on the Urinary Bladder
Beta 2/3 relaxation of bladder body
alpha contraction of bladder trunk and internal sphincter
Describe the effect of the parasympathetic NS on the Heart
decreased heart rate
decreased contractile force
decreased conduction velocity
Describe the effect of the parasympathetic NS on the peripheral vascualture
dilation increases blood flow
Describe the effect of the parasympathetic NS on the skeletal muscle and organ vasculature
Describe the effect of the parasympathetic NS on the GI
relaxation of sphincter muscles
decreased conduction velocity
Describe the effect of the parasympathetic NS on the bronchioles
Describe the effect of the parasympathetic NS on the urinary bladder
contraction of bladder body
relaxation of trunk and internal sphincter
What are cholinergic receptors?
activated by acetylcholine
What are the 2 types of cholinergic receptors?
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
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
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
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
Facts about 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
Facts about 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
Facts about Epinephrine
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
Present on vascular smooth muscle for vessels feeding the skin, kidney, viscera, and skeletal muscle
When bound by agonist (i.e. NE):
*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
Alpha 2 receptors:
Pre-synaptic ganglia; When activated these will work to auto-inhibit NE release.
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
Found in a variety of locations:
1.Pulmonary airway smooth muscle – bronchioles
a. Leads to dilation of airways – bronchodilation
2.Vasculature feeding skeletal muscle
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
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
What are the 3 most common catecholamines we talked about?
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
Clinical application of Epi/NE/Isoproterol as a hemostatic:
Constriction to stop blood flow
Clinical application of Epi/NE/Isoproterol in cardiac arrest/AV blocl
a. Beta one receptor EPI to jump start the heart
b. Complicated system
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
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
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
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
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
WHat is Phenylephrine?
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
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
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
What is propanolol
1. Beta antagonist
2. Negative risk of also blocking beta 2 receptors and inducing bronchoconstriction
What is Atenolol?
1. Beta 1 receptor specific
2. Used frequently for high blood pressure in cats
3. Anti-anxiety medication for humans
How often do we use alpha blockers in Vet MEd?
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
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
What are the 2 types of Ach receptors?
Ligand-gated ion channels
G-protein coupled receptor
7 Transmembrane protein
STRUCTURALLY VERY DIFF- member thi
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.
Where are nicotinic receptors typically found?
found at ganglionic synapses of both parasympathetic and sympathetic nervous systems
What are chlinergic/cholinomemetic drugs?
drugs that produce acetylcholine effects
What are parasympathomimetic drugs?
drugs that produce Ach like effects at parasympathetic neuroeffector junctions
What are direct acting parasympathomimetic drugs?
agonists for muscarinic receptors
What are cholinesterase inhibitors?
blockers of teh Acetylcholinesterases that degrade endogenous Ach
WHat are parasympatholytic drugs?
block/inhibit Ach-like effects at parasympathetic neuroeffector juntions
What effects do cholinergic receptor agonists have on the eye?
contraction of iris sphincter/ciliary muscle, which will cause constriction of the pupil
What effects do cholinergic receptor agonists have on the heart?
general inhibitory effects- decrease rate, contractile strength, conduction velocity
What effects do cholinergic receptor agonists have on the blood vessels?
What effects do cholinergic receptor agonists have on the Lungs?
contraction of bronchial muscles
What effects do cholinergic receptor agonists have on the GI tract
What effects do cholinergic receptor agonists have on the Urinary bladder?
contraction of detrussor
relaxation of trigone/sphincter
What effects do cholinergic receptor agonists have on the glands
What are the 2 direct acting parasympathomimetic drugs that are resistant to acetylcholinesterase ?
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
What is bethanecol?
binds ONLY muscarinic receptors; so will particularly get parasympathetic agonist response
sometimes used form bladder stimulation
What is pilocarpine?
• Used to treat keratoconjunctivitis and glaucoma
• Causes miosis (pupil constriction) and enhanced aqueous humor flow
• Binds muscarinic receptors
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
Hypotension (due to vasodilation)
What does SLUD stand for?
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
What are Edrophonium and Pyridostigme?
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
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
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
ii. Relax GI musculature and decrease secretion
iii. Bronchodilation and decreased airway secretion
iv. Dry oral mucosa
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
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
What is the somatic innervation to the bladder?
a. Pudendal nerve
b. Innervates the external sphincter – skeletal muscle under voluntary control
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
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
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
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
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
– alpha receptor agonist, potentially inducing the production of estrogen
What is urge incontinence?
overstimulation of muscarinic receptors resulting in frequent urge to urinate
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
T/F Most organs are innervated by BOTH the sympathetic and parasympathetic systems
TRUE; What receptors predominate determines what has action on it
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
What would it look like if acetylcholinesterases were damaged?
It would look like PS activity; excess ACh would sit around in the synapse.
Where is nor epinephrine transformed to epinephrine?
What is more stable in the blood stream epinephrine or norepinephrine?
Phentolamine is a:
alpha blocker; keep your fingers
Propanalol and atenalol are: