The Autonomic Nervous System; and the Adrenal Medulla Flashcards
Autonomic Nervous System
A set of efferent pathways from the central nervous system that innervates and regulates smooth muscles ,cardiac muscles and glands.
Is different from somatic nervous system, which innervates skeletal muscle
3 divisions of the autonomic nervous system
Has three divisions : sympathetic, parasympathetic and enteric
Sympathetic for ‘flight or fight’ situations
Parasympathetic for ‘relax and digest’ situations
Parasympathetic ganglia are located close to
effector organs
Sympathetic ganglia are located in the
paravertebral chain
Preganglionic neurons
have their cell bodies in CNS and synapse in autonomic ganglia
Preganglionic sympathetic fibers originates from
thoracolumbar region.
Preganglionic parasympathetic fibers originates from
craniosacral region.
Postganglionic neurons
of both divisions have their cell bodies in autonomic ganglia and synapse on effector organs (heart , blood vessels, sweat glands)
Adrenal medulla
is a specialize ganglion of the sympathetic nervous system
chromaffin cells
Preganglionic fibers synapse directly on chromaffin cells in adrenal medulla
The chromaffin cells secrete epinephrine (80%) and norepinephrine (20%) into circulation.
Adrenergic neurons release
norepinephrine as the neurotransmitter
Cholinergic neurons release
whether in sympathetic or parasympathetic nervous system, release Acetylcholine
Non adrenergic , non cholinergic neurons include some postganglionic parasympathetic neurons of the GIT which release
Non adrenergic , non cholinergic neurons include some postganglionic parasympathetic neurons of the GIT which release substance-P, vasoactive intestinal peptide (VIP) and Nitric oxide
SYNTHESIS OF NOREPINEPHRINE
hydroxylation of tyrosine is the rate limiting step
UPTAKE INTO STORAGE VESICLES (NE)
Dopamine is synthesized to norepinephrine
Transport into vesicles inhibited by reserpine
RELEASE OF NEUROTRANSMITTER (NE)
Ca++ influx leads to fusion of vesicles to cell membrane
Release block by guanethidine and bretylium
BINDING TO RECEPTOR (NE)
Activation of adenylate cyclase
Opening of ion channel/ formation of cAMP
Contraction of arterial smooth muscles, increase HR, increase contractility
REMOVAL OF NOREPINEPHRINE
Reuptake is inhibited by cocaine and TCA
METABOLISM (NE)
By COMT (in plasma )and MAO (in synaptic cleft)
physiologic anatomy of the parasympathetic nervous system
Visceral motor neurons are located in discrete brain stem nuclei and in sacral s2-s4
Parasympathetic nerves originate from cranial nerves III, VII, IX, and X and the sacral spinal cord.
Occulomotor nerve (parasympathetic)
fibers to the pupillary sphincters and ciliary muscle
Facial nerve (parasympathetic)
fibers to nasal, lacrimal and submandibular gland
Glossopharyngeal nerve (parasympathetic)
fibers to parotid gland
Vagus nerve (parasympathetic)
Vagus nerve - motor inputs to visceral organs
sacral segments
Sacral segments - fibers to descending colon, rectum, bladder and genitalia
SYNTHESIS OF ACETYLCHOLINE
Transport of choline is inhibited by hemicholinium
UPTAKE INTO STORAGE VESICALS (ACH)
Acetylcholine is protected from degradation in vesicles
RELEASE OF NEUROTRANSMITTER (ACH)
Release blocked by botulinum toxin
Black widow spider venom causes release of acetylcholine
BINDING TO RECEPTOR (ACH)
Postsynaptic receptor activated by binding of neurotransmitter
DEGRADATION OF ACETYLCHOLINE
Acetylcholine is hydrolyzed by Cholinesterase
Physostigmine inhibits acetyl cholinesterase (AChE)
RECYCLING OF CHOLINE
…
Heart
Sympathetic action
parasympathetic action
sympathetic receptor
sympathetic action-
increase heart rate
increase contractility
increase av node conduction
B1B1B1
parasympathetic action
decrease heart rate
decrease contractility
decrease av node conduction
vascular smooth muscle
sympathetic action
parasympathetic action
sympathetic receptor
sympathetic action
constricts blood vessels in skin; splanchnic. dilates blood vessels in skeletal muscles
A1B2
no parasympathetic action
GIT
Sympathetic action
parasympathetic action
sympathetic receptor
sympathetic action
decrease motility, constricts sphincters
A2B2A1
increase motility relax sphincters
bronchioles
Sympathetic action
parasympathetic action
sympathetic receptor
sympathetic action
dilates bronchiolar smooth muscles, increase secretion
B2
constrict bronchiolar smooth muscles
Male sex organ
Sympathetic action
parasympathetic action
sympathetic receptor
sympathetic action
ejaculation
A1
parasympathetic
erection
Point and shoot
bladder
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
Relax bladder wall
Constricts sphincter
B2 A1
parasympathetic action
Contracts bladder wall
Relax sphincter
Kidney
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
increase renin secretion
parasympathetic action
none
sympathetic receptor
B1
Sweat glands
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
increases sweating
parasympathetic action
none
sympathetic receptor
muscarinic sympathetic cholinergic
Pupil
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
dilation
parasympathetic action
constriction
sympathetic receptor
A1
Liver
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
glycogenolysis
gluconeogenesis
parasympathetic action
none
sympathetic receptor
B2
gallbladder
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
relaxation
parasympathetic action
B2
sympathetic receptor
contraction
Urinary Bladder
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
relaxation
parasympathetic action
contraction of detrusor muscles
sympathetic receptor
B2
Pancreas
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
increase insulin secretion
parasympathetic action
none
sympathetic receptor
B2
adipose
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
increase lipolysis
parasympathetic action
none
sympathetic receptor
B1
uterus
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
relaxation (tocolysis)
parasympathetic action
none
sympathetic receptor
B2
Na+/K+ Pump
Sympathetic action
parasympathetic action
sympathetic receptor
Sympathetic action
stimulation (decrease K)
parasympathetic action
none
sympathetic receptor
B2
Medulla
Medulla
Vasomotor center
Respiratory center
Swallowing, coughing and vomiting center
pons
Pneumotaxic center
Midbrain
Micturition center
Hypothalamus
Temperature regulation center “thermostat”
Thirst and food intake regulatory center
Function of the Adrenal Medulla
Large sympathetic ganglion
When stimulated releases epinephrine (80%) and norepinephrine (20%) into the blood
Causes prolonged activity of the substances
stimulation of cardiovascular function and metabolic rate
Helps the body deal with stress
Pheochromocytoma
Pheochromocytoma
Tumor of chromoffins cells of adrenal medulla in adults
increase secretions of norepinephrine, epinephrine and dopamine from tumor cells
increase Urinary VMA(Vanillyl mandalic acid), normetapinephrines, metanephrines
Treatment : Surgery .
Preoperatively blockers (Phenoxybenzamine) to control BP
blockade without blockade in patient with pheochromocytoma can cause heart failure
“Block receptors first”
Anesthetic Consideration(Pheochromocytoma)
Preoperative adrenergic blockade and volume replacement
Intraoperative monitoring CVP ,PCWP and urine output
Following anesthetic drugs or techniques are best avoided because they may precipitate hypertension
Eephedrine, ketamine, hypoventilation stimulate sympathetic system
Halothane potentiates the dysrhythmic effects of catecholamine
Pancuronium inhibits the parasympathetic nervous system
Atracurium and Morphine SO4 release histamine that enhances the effect of tumor.
Stress Response
Mass sympathetic discharge
increase in arterial pressure, heart rate and contractility, blood flow to muscles, blood glucose, metabolic rate, muscle strength, mental activity, blood coagulation
Prepares the body for vigorous activity need to deal with a life-threatening situation
The fight or flight response
Adrenergic Receptors
a1 Receptors location?
Postsynaptic adrenergic
Located on vascular smooth muscle of skin and splanchnic regions , GIT, bladder sphincter ,and radial muscle of iris
a2 Receptors
Are located in presynaptic membrane. They are postsynaptic in brain stem platelets, fat cells and walls of GIT
b1 receptors location?
Located in the SA node, AV node ventricular muscle
b2 receptors location?
Are located on smooth muscle of skeletal muscle blood vessel, bronchial smooth muscle and walls of GIT and bladder
b3
Receptors located in gall bladder (unknown function) and adipose tissue
Cholinergic Receptors
Nicotinic Receptors
Located in the autonomic ganglia (NN) of the sympathetic and
parasympathetic , neuromuscular junction (NM) and adrenal medulla (NN). The receptors at these locations are similar but not identical
- Are activated by Ach or nicotine
- Produce excitation
- Ganglion blockers (hexamethonium , trimethaphan) block the nicotinic receptors for Ach in autonomic ganglia but NOT at the NMJ
- M/A: opening of Na+ and K+ channels
B2 receptors produce what?
Produce relaxation ( dilation of vascular smooth muscle, dilation of bronchioles , relaxation of the pregnant uterus- tocolysis)
B2 Receptors do what to BG?
Glycogenolysis & gluconeogenesis increase BG , calorigenesis
B2 Receptors M/A
M/A : Gs protein, activation of adenylate cyclase and increase cAMP(same as B1)
B1 receptor produce
Produce EXCITATION (increase HR , increase conduction, increase contractility, increase CO)
B1 Receptor sensitive to?
Sensitive to both norepinephrine and epinephrine
B1 Receptor M/A?
M/A : GS PROTEIN, activation of adenylate cyclase and increase cAMP
Alpha 1 produce and sensitive to?
Produce excitation (contraction of vascular smooth muscles) Are equally sensitive to norepinephrine and epinephrine
Alpha 1 m/a
M/A: formation of IP3 and increase intra cellular calcium
alpha 1
cardiac effects?
Arterial vasoconstriction increase SVR, LV afterload and BP
Venous vasoconstriction increase venous return, increase SV, increase CO
a1 stimulation inhibit insulin secretion and lipolysis
alpha 2 produce?
Produce inhibition of norepi release and synthesis (relaxation and dilatation); blocks Ca++ entry
-ve feed back loop
Inhibit sympathetic out flow in brain stem
Sedation
Promotes analgesia in substantia gelatinosa
alpha 2 ma
M/A: Gi protein, inhibition of adenylate cyclase, and decrease cAMP and decrease Ca++ entry
Clonidine (catapres)
a2 is inhibitory. Stimulation decrease release of epi and norepi. Provides negative feedback.
Clonidine (Catapres) is a2 agonist – decrease BP
Clonidine does not effectRBF or GFR
decrease Sympathetic outflow by inhibiting VMC – central action
decrease Release of substance P in substantia gelatinosa – analgesic action
Prolong effect of regional anesthesia
decrease MAC of inhalation anesthetics
Treat opioid withdrawal
Use to treat shivering
Use to attenuate the hemodynamic effect of ketamine
clonidine s/e
S/E sedation, bradycardia, dry mouth and rebound (withdrawal) HTN due to catecholamine, renin and angiotensin II
Restart clonidine
Clonidine and beta blockers?
never give b-blocker WHY?
Adrenergic or sympathomimetic drugs act like
norepi and epi
Isoproterenol stimulates both
b1&b2
Chemical pacemaker
Albuterol
only b2
Ritodrine (Yutopar)
stimulate only b2 receptors
Use to relax uterus in premature contraction
S/E hyperglycemia, hypokalemia and tachycardia
Phenylephrine
only alpha receptors
Some drugs have an indirect effect by increasing the release of norepi from its storage terminals examples…
ephedrine, tyramine, and amphetamine
Ganglionic blockers- Sympathetic ganglion
effect ne and epi release
hexamethonium
Beta blockers
decrease effect of ne and epi release
b1 and b2 - propranolol, b1 - metoprolol
Alpha blockers
block the effect of norepi and epi
phentolamine and phenoxybenzamine
Monoamine oxidase type A
(MAO-A) in nerve terminal
catechol-O-methyl trasnferase
(COMT) in liver and plasma metabolize epi and norepinephrine to inactive metabolites
Selegiline (deprenyl)
selectively inhibit MAO-B
increase dopamine level in brain
Use in Parkinson’s disease
What drug should be avoided in patient taking MAO inhibitor
(Meperidine and Ketamine) Hypertensive crisis with meperidine (Demerol) or ephedrine
Drug-food or drug-drug interactions
MAO inhibitors
Tyramine containing food
Hypertension, arrhythmias, seizures , stroke
“Serotonin syndrome” with SSRI’s
Wash-out period of 2 weeks is required
Clinical uses MAO inhibitors
Atypical depression, anxiety
mao inhibitor drugs?
Phenelizine (Nardil), isocarboxazid (Marplan), tranylcypromine (Parnate)
MH Symptoms
Unexplained increase end-tidal CO2 (most sensitive indicator in OR)
High grade fever; spontaneous combustion
Skeletal muscle rigidity
Lactic acidosis (hypermetabolism)
MH cause
Triggered by anesthetics (halothane) with Sux
Familial tendency - can be tested for by muscle biopsy
Constant leak of SR Ca++ through Ryanodine receptor
Sustained contractions with increase metabolism
MH Treatement
Notify the surgeon as soon as a case of MH is suspected
Stop triggering agents
Hyperventilate patient with 100% O2
Finish or abort procedure
I/ V Dentrolene (Dentrolene prevents the release of Ca++ from SR)
2.5 mg/kg
Bicarb
Cooling
Insulin for hyperkalemia
Continue to monitor core temp
Monitor urinary output to prevent shock to kidneys or ATN
Ganglion Blocker- Trimethaphan (Arfonad)
Trimethaphan (Arfonad) is competitive antagonistic of nicotinic receptor at the autonomic ganglia (NN)
Use to lower BP in emergency situation
S/E due to histamine release
Mydriasis, cycloplegia, ileus and bronchospasm
S/S of Atropine overdose: & treatment
increase temp, rapid pulse, dry mouth, flush skin, mydriasis, disorientation and constipation
Tx: Physostigmine
Blind as bat Red as beet Mad as hatter Hot as hell Dry as bone
atropine and heart rate explain?
atropine completes with ACH for the binding sites on the SA and AV node. atropine binds instead of ACH and will speed up the heart rate.
Cholinergic drugs:
Cholinergic agonists
Decrease heart rate* and lower BP
Nausea/vomiting
Increased activity of gut increase cramping and diarrhea
Excessive sweating/salivation
Increase urination
Blurred vision due to pupillary constriction (PPP)
Shortness of breath due to bronchoconstriction
Uncontrolled muscle twitching
*Acetylcholine applies breaks on heart but accelerates gut and bladder smooth muscles
*Acetylcholine applies breaks on heart but accelerates gut and bladder smooth muscles
Pyridostigmine
Myasthenia gravis,
Block reversal
increase endogenous
increase Ach strength
Edrophonium
Dx of MG (short acting)
Block reversal
increase endogenous Ach
Physostigmine
Glaucoma and atropine overdose
Block reversal
increase endogenous Ach
Anti-cholinesterases)
Neostigmine
Post op ileus and urinary retention
Myasthenia gravis, reversal of NMJ block
increase endogenous Ach
Charbachol, Pilocarpine
Narrow angle glaucoma
Constricts pupil which facilitates drainage of AH and decrease IOP
Bethanechol
Post op paralytic ileus and urinary retention
Activates bowel and bladder smooth muscles
Adverse reactions of beta blockers
Adverse reactions of beta blockers Fatigue, hypotension Bronchospasm Bradycardia Peripheral vascular insufficiency Sexual dysfunction Arrhythmias
Pharmacotherapeutics/ Indications
Angina Hypertension Hyperthyroidism Hypertrophic cardiomyopathy Supraventricular arrhythmias Anxiety Migraine headaches Open-angle glaucoma Pheochromocytoma
Beta-adrenergic blockers
Actions
Decreased blood pressure and force of heart’s contractions
By depressing SA and AV node activities leads to bradycardia
Increased peripheral vascular resistance*
Peripheral resistance returns to normal or decreased after long term use of propranolol
Reduced stimulation of the heart
Bronchiole constriction
Adverse effects of alpha blocker
Adverse effects of alpha blocker Orthostatic hypotension (patient up; BP down) Reflex tachycardia leads to angina Vertigo Difficulty breathing Light-headedness Sexual dysfunction
Norepi
Acts on a and b1
No b2 activity
Increase in systolic BP (b1 effect)
Increase in diastolic BP (a1 mediated intense vasoconstriction leads increase in SVR
Increase in mean arterial pressure
Induces reflex bradycardia; increase vagal tone and baroreceptor reflex
Isoproterenol (b specific)
Both b1 and b2 activity , NO a activity
Increase cardiac force and rate (b1 effect)
Increase AV conduction
Decrease the SVR (vasodilation of skeletal m. blood vessels (b2 effect which is unopposed )
Moderate increase in systolic BP and greatly decrease in diastolic BP.
Mean arterial BP decreases
Epinephrine (Non-selective)
Increase rate and force of cardiac contraction (b1 stimulation of SA node)
Decreases the SVR (vasodilation of skeletal m. blood vessels (b2 effect)
Result; increase systolic BP and decrease diastolic BP. Mean arterial pressure may increase or decrease or not change depending upon alteration of systolic and diastolic BP
At low dose, b effect(vasodilation) predominate; at high dose a effect (vasoconstriction) predominate
Interaction of anesthetics with b blocker
Ketamine stimulates sympathetic NS , increase SVR . Heart failure may occur in b blocked heart
Worst to bad
Ketamine (The worst)
Enflurarne
Halothane
Opioids
Isoflurane
ephedrine
Hypotension associated with regional or inhaled anesthetics Bronchial asthma Decongestant Antiemetic Vasopressor in OBS (does not UBF)
Phenylephrine (Neosynephrine)
Stimulate a1 and a2 receptors leads to vasoconstriction
increase SVR, increase MAP, reflex bradycardia
is used to treat hypotension associated with regional or inhaled anesthetics
Topical nasal decongestant
Prolong the duration of spinal anesthesia when added to LA solution
