ANS Phys & Pharm Flashcards
ANS Reflexes - CNS:
Cushing’s Triad
1) Increased ICP
2) Bradycardia
3) Hypertension
Intracranial HTN leads to SNS mediated systemic HTN. Activation of the PSNS medullary centers via baroreflex slows HR (but not enough to reduct HTN!). This results in increased blood flow to brain & further increased ICP.
ANS Reflexes - CNS:
Autonomic HYPERreflexia
1) Disruption of efferent impulses down the SC from T5 or higher.
2) Exaggerated SNS response to bowel, bladder, or surgical stimuli d/t receptor sensitivity 2/2 denervation
3) Loss of inhibitory impulses results in pure SNS response (HTN!)
Anesthesia impact: mgmt of quads/paras consists of spinal or GA with careful manipulation of BP due to alterations in ANS.
ANS Reflexes - CNS:
Thermogenesis Reflex
1) Sweating controlled by cholinergic fibers (blocked by atropine or nerve blocks)
2) Shivering decreased in elderly, absent in newborns, blocked by NMDR’s
3) GA impair thermogenesis
All GA ________ thermogenesis reflexes.
All GA impair thermogenesis reflexes.
Sweating threshold is increased and vasoconstriction and shivering thresholds are markedly decreased. Can lead to hypothermia during surgery if heat loss thorugh radiation, convection, conduction, and evaporation are not minimized.
ANS Reflexes - Cardiac:
Baroreceptor
- stretch receptors in aorta and carotid arteries sense increased pressure
- send signals via Hering Nerve & Vagus (CNX) to medulla
- decreased HR, decreased BP, decreased contractility, decreased PVR
- Phenylephrine (a1-agonist) increases BP and reflex decreases HR
ANS Reflexes - Cardiac:
Chemoreceptor
- Instead of sensing BP (baroreflex), chemoreceptors sense increased arterial CO2 and decreased arterial pH.
- HYPERcarbia increases minute ventilation.
- Peripheral in carotid body respond to decreased PO2.
- N. Hering and Vagus increase RR and TV which increases minute ventilation
- may also see increased HR and CO.
ANS Reflexes - Cardiac:
Bainbridge Reflex
- increasd CVP activates stretch receptors in the atria
- afferent impulses through vagus inhibit PSNS output resulting in tachycardia
- seen during labor when contractions autotransfuse and increase CVP
ANS Reflexes - Cardiac:
Bezold-Jarisch
1. hypotension
2. bradycardia
3. coronary dilation
- noxious stimuli (chemical or mechanical) sensed in cardiac ventricles
- unmyelinated -fibers of vagus send signals to 1) enhance baroreflex, 2) inhibit sympathetic output and 3) decrease PVR to make it easier for heart to pump.
- increased blood flow to the myocardium to decrease the work of the heart (cardioprotective)*
ANS Reflexes - Cardiac:
Oculocardiac (Five & Dime Reflex)
- afferent impulses to pressure on the eye or pulling on eye muscle
- efferent slowing of HR via Vagus N
- muscarinic response can be blocked by atropine or glycopyrolate (so surgeon can proceed with procedure)
Five & Dime
- Afferent through CN V
- Efferent through CN X Vagus
= five and dime
Anesthetic Interactions:
A2 agonists are _______ and reduce anesthetic needs.
A2 agonists are inhibitory and reduce anesthetic needs.
Anesthetic Interactions:
Fentanyl _______ SNS tone and _______ vagal activation.
Fentanyl depresses SNS tone and promotes vagal activation.
Anesthetic Interactions:
Des _____ the ANS and _____ the SNS (so we see HTN and tachycardia)
Des depresses the ANS and stimulates the SNS
Comorbid Implications:
Aging
- HTN and orthostasis
- temperature regulation
- increased circulating NE (receptor downregulation and decreased responses to exogenous catecholamines)
- decreased renin, decreased aldosterone, increased ANP = salt wasting!
Comorbid Implications:
DM
- 20-40% IDDM have neuropathies (ANS)
- labile BP, gastroparesis, altered thermoregulation, ?vagal dysfunction
- increased aspiration risk, aggressive temp maintenance, increased CO
Comorbid Implications:
Dysautonomia
- Shy-Drager syndrome, Guillain Barre, Lambert-Eaton, Postural Orthostatic Hypotension, HR variability, BP lability
dysautonomia - umbrella term used to describe several different medical conditions that cause a malfunction of the Autonomic Nervous System.
Endogenous Catecholamines
- EPi
- NE
- Dopamine
Epi
- produced in adrenal medulla (80% Epi, 20% NE)
- Adrenal standard secretion rates:
0. 2 mcg/kg/min Epi
0. 05 mcg/kg/min NE
- Exogenous Infusion Rate:
2-10mcg/kg/min (B1, B2)
>10mcg/kg/min (A1)
Anaphylaxis 0.2-0.5 mg sub-Q
NE
- NE has >A1 and no B2 effects than Epi
- 4-12 mcg/min (A1, B)
At Low Dose: B1 dominates & BP increases 2/2 increased CO
At High Dose: A1 dominates and BP increases, but HR and CO may decrease 2/2 baroreflex
- beware effect on pulm A1 and possible pulm HTN and R HF
Dopamine
- precursor to Epi and NE
- Exogenous dopamine does not cross BBB (L-dopa for parkinson’s)
Low Dose: 1-3 mcg/kg/min = D1 activation (coronary, renal, mesenteric vasodilation)
Moderate Dose: 3-10 mcg/kg/min = B1
High: >10 mcg/kg/min = A1
Metabolism of catecholamines
- COMT is intracellular
- MAO in nerve terminal mitochondria
- Exogenous catecholamines may resist COMT and MAO metabolism
- MAOIs will cause more of these to be available*
Exogenous Catecholamines:
Dopamine D1 Receptor Agonists - Fenoldopam
- minimal D-2, a or b effects
- 10x potency of dopamine
- dosed 0.1-0.8 mcg/kg/min
- 0.1-0.2 mcg/kg/min = renal vasodilation, increased renal blood flow and GFR, and Na+ excretion
- improved outcome in CABG pts w less renal failure!
Exogenous Catecholamines:
a1 receptor agonists
- increase BP and MVO2 supply
- decrease hr
- variable CO
- this is good! increased BP and decreased HR = better perfusion to coronaries!
phenylephrine
- almost pure A agonist
- > venoconstriction than arterial (increases venous return, maintains CO, HR decreases 2/2 baroreceptors)
- NOT contraindicated in OB (but not necessarily better than ephedrine)
- neosynephrine nasal spray
methoxamine
> arterial constriction than veno; longer acting; no longer in clinical use
midodrine
- oral A1 agonist used for dialysis induced hypotension
- T1/2 3 hours
- duration 4-6 hours
Miller Figure 16-4
Predominant Physiologic Effects of A1 and Dopamine (D) Receptor Activation
A2 agonists
- decrease CNS sympathetic output
- decrease presynaptic NE release
- sedation, hypnosis, sympatholysis, neuroprotection, diuresis, inhibition of insulin and HGH secretion
- rapid delivery may increase P 2/2 postsynaptic a2b receptor mediated arterial and venoconstriction
Beneficial anesthetic effects of A2 agonists (dex)
- anxiolysis
- sedation
- decreased MAC
- decreased opioid induced chest wall rigidity
- decreased BP response to ETT, extubation and incision
- decreased post-op shivering
Dexmedetomidine
- selective A2 agonist (1620:1 a2:a1 activity)
- PACU pts on Dex require less morphine
- decreased post op analgesics, b-blockers, antiemetics,diuretics and EPI for cabg pts
dosing:
Load 1 mcg/kg/hr over 10-20 min
Infusion 0.2-0.7 mcg/kg/hr
beware: hypotension and bradycardia
clonidine
220: 1 a2:a1 activity
- oral dosing q8 hours, do NOT hold 2/2 rebound HTN
- can be used in epidural but w inconsistent results
Isoproterenol
- isopropyl derivative of EPI
- nonselective activity at B1 and B2 (works at both receptors!)
- high dose = tachycardia and hypotension (BAD!)
- may be used as “chemical” pacemaker
Dobutamine
- derivative of dopamine
- B1 agonist and A1 antagonist; minimal B2 effects
- increased CO, decreased LV filling pressure
- variable HR and SVR until dose >10-20 mcg/kg/min
- dobutamine stress tests
B1 and B2 visual
B2 agonists (lungs)
- asthma and COPD
- metaproterenol, albuterol, salmeterol, isoetharine inhalers
- bronchodilation w/o systemic effects
- overdosing = B1 effects
terbutaline and ritodrine
B2 agonists
- used for tocolysis in pregnancy
- B2 mediated relaxation of uterine smooth muscle
INDIRECT acting sympathomimetics
- cause the release of “stored” NE in the synaptic vesicles
- BEWARE pts taking TCAs (NE reuptake inhibition) and MAOIs (NE breakdown inhibition)
Ephedrine chemical structure
- chemically an alkaloid w phenethylamine skeleton
Ephedrine
- indirect and direct actions on A and B receptors
- competes w NE for reuptake in vesicles so NE stays at receptor sites longer
- increased HR, BP, CO
- tachyphylaxis
- may increase MAC 2/2 stimulatory effects on CNS
tachyphylaxis
rapidly diminishing response to successive doses of a drug, rendering it ineffective due to diminished stores and no reuptake
amphetamine and METHamphetamine
- indirect acting simpathomimetics
- CNS stimulants, A and B receptor stimulants
- cause release of an inhibit reuptake of stimulating neurotransmitters
- effects related to A and B stimulation like other SNS stimulants
- treatment of OD may include dantrolene to decrease temp
methylphenidate
- indirect acting sympathomimetic
- ritalin
- similar effects to amphetamine/meth but milder
- txs ADHD
Table 13-1 Relative Adrenergic Drug Effects on Peripheral Resistance and Capacitance Vessels
Arginine Vasopressin
- NOT a catechalamine!
- endogenous hormone that regulaes urine volume and plasma osmolality
- higher concentrations act on V1a receptors in VSM to vasoconstrict (via phosphoinositol pathway
Arginine Vasopressin Dosage
- 40 unit bolus instead of EPI 1mg in a code
- used intraoperatively in 1-8 unit doses to tx refractory hypotension, ACE/ARB induced hypotension
- 1-2 units at a dose is real nice
phenoxybenzamine
- adrenergic blocker
- act post-synaptically competitively blocking A and B receptors
- phenoxybenzamine and phetolamine block A receptors and vascular dilation occurs
- phenoxybenzamine 1st choice to produce A blockade in pheochromocytoma patients
- irreversible, non-competitive blocker T1/2 18-24 hours
- dose: 10-20 mg PO BID for pheo
- also txs neurogenic bladder and BPH
Adrenergic Blockers:
B-Blockers
- b-blockers target cardiac and vascular smooth muscle
- B1 and B2 blockade (propranolol, labetalol)
- B1 specific (atenolol, metoprolol, esmolol)
- different drugs = different results
reserpine and a-methyldopa and guanethidine
- adrenergic blockers
- reserpine and a-methyldopa block synthesis and storeage of NE
- guanethidine blocks release of NE
phentolamine
- A-adrenergic blocker
used for infiltration when NE infusion infiltrates
prazosin
- A-Adrenergic blocker
high affinity for a receptors and txs HTN. PO at bedime
doxazosin and tamulosin
a-adrenergic blocker
tx BPH
B2 Blockade
B2 blockade =
- bronchospasm and probs w PVD
- bradycardia, asystole, HF, inhibits gluconeogenesis, raynaud’s
- can cause severe HTN in pheo pts if they are given a dose prior to instituting an A blockade
- Good: can reduce surgical M and M in pts w CAD
Holding B Blockers prior to surgery?
- may lead to rebound HTN that can last up to 6 days post-op
Esmolol
- selective B1 blocker
- 90second onset, t1/2 9-10 mi
- nonspecific red cell esterase metabolism (NOT metabolized by p-cholinesterase)
- Dose: 10-20-40 mg boluses to reduce HTN
- fast BP control desired w short duration
Labetalol
- A1, B1, and B2 blockade
- a:b ratio 1:7
- peripheral vasodilation w reflex tachycardia
- peaks 5-15 min; duration 4-6 hours
- Dose: 5-10 mg boluses q 5-10 min; wait for effect
- continued BP control desired and tire of giving repeat doses of esmolol
Metoprolol
- primarily B1.
- B1:B2 30:1 ratio
- Dose: 2-5 mg q 2-5 min for total dose of 15mg
- max B-blockade seen at 0.2 mg/kg
- typically given to control HR when BP reduction not needed/desired
Cholinergic Receptors:
Activation of postjunctional muscarinic receptors by Ach
Activation of postjunctional muscarinic receptors by Ach:
- in the heart leads to bradycardia
- in smooth muscle leads to bronchoconstriction, miosis, and increased GI motility/secretion
Cholinergic Receptors:
Activation of presynaptic muscarinic receptors by Ach
at the presynaptic SNS terminals in the CV and coronaries leads to decreased NE release
Cholinergic Receptors:
Nicotinic Receptors
- nicotinic receptors activate postganglionic junctions in both SNS and PNS
- NMJ nicotinic receptors are bloced by SUX which is an agonist at these sites
Muscarinic Blockers
- anticholinergic drugs (atropine, scopolamine, glycopyrolate) competitively inhibit Ach by reversibly binding to muscarinic receptors
- atropine and scope = tertiary amine = cross BBB = CNS effects
- may augment vagal outflow and cause brady at low doses (<0.5 mg)
- glyco = quat amine = NOT cross BBB = NO CNS effects
- more potent and longer acting at peripheral muscarinic receptors than atropine
Cholinesterase Inhibitors
- AChE inhibitors act indirectly resulting in an increase in Ach at ALL RECEPTOR SITES
- directly inhibits action of both TRUE or acetylcholinesterase or PSEUDO or plasma cholinesterase
- AChE found post-synaptically so AChE inhibiors act post-synaptically
Cholinesterase Inhibitors:
NMDR Reversal Agents + eye drops
Neostigmine, Pyridostigmine, Physostigmine, Edrophonium (all NDMR reversal agents) and Echothiophate (eye drops)
- desired effects at NMJ are at nicotinic receptors on NMJ
- unwanted SE occur at muscarinic receptors so we administer a muscarinic blocking agent at the same time!
SNS Receptors
A1, A2
B1, B2
D1, D2
PSNS Receptors
Muscarinic - M 1,2,3,4
Nicotinic - N 1,2
