Lecture 1

Question 1

The Sympathetic Nervous System is AKA
The preganglia are near the ________
The postganglia secrete ______

Answer 1

Thoracolumbar origin (T1-L2)
spinal cord
norepinephrine

Question 2

What converts dopamine to norepinephrine?

Answer 2

Dopamine beta hyroxylase converts dopamine to NE

Question 3

Norepinephrine is metabolized by

Answer 3

COMT and MAO

Question 4

The adrenergic receptors are:

Answer 4

alpha 1 periphery
alpha 2 central (precedex)
beta 1 heart
beta 2 other smooth muscle

Question 5

Alpha-1 Postsynaptic Receptor:

Answer 5

Activation increases intracellular calcium
Smooth muscle contraction
Peripheral vasoconstriction
Bronchoconstriction
Inhibits Insulin secretion
Stimulates glycogenolysis and gluconeogenesis
Mydriasis
GI relaxation

Question 6

Alpha-2 Receptors:

Answer 6

Alpha-2 Receptors:
Presynaptic in the PNS
Decreases entry of calcium into the cell
Limits the release of norepinephrine
Postsynaptic in the CNS
Sedation
Decreased sympathetic outflow
Decreased BP
Platelet aggregation

Question 7

Beta-1 Postsynaptic Receptor:

Answer 7

Beta-1 Postsynaptic Receptor:

Increases HR
Increases conduction velocity
Increases myocardial contractility

Question 8

Beta-2 Postsynaptic Receptor:

Answer 8

Beta-2 Postsynaptic Receptor:

Stimulation leads to smooth muscle relaxation
Peripheral vasodilitation
Decreases BP
Bronchodilitation
Increases insulin secretion
Increases glycogenolysis and gluconeogenesis
Decreases GI mobility

Question 9

The parasympathetic nervous system is also known as
The preganglia are near ______
The post ganglia secrete _______

Answer 9

Craniosacral origin (III, V, VII, X)

Organs of innervation

ACh (Cholinergic)

Question 10

ACh activates _________

Choline + Acetyl CoA = acetylcholine via ________

ACh is deactivated by _______

Answer 10

both arms of the SNS

choline acetyletransferase
(Calcium mediated action potential)

choline and acetate

Question 11

Cholinergic receptors include

Answer 11

Muscarinic and Nicotinic

Question 12

___________: extended exposure to agonists reduces the number, but not their response. Results in tachyphylaxis.

Answer 12

Down regulation

Question 13

__________: chronic depletion of catecholamines or use of antagonists increases the number of receptors, but not their sensitivity. May account for withdrawal syndrome with beta blockers.

Answer 13

Up regulation

Question 14

Catecholamines are both _________ and ________ that act on the _________ receptors

Answer 14

neurotransmitters and hormones

adrenergic

Question 15

All sympathomimetics are derived from

___________

Answer 15

β phenylethylamine.

Presence of hydroxyl groups on the 3 and 4 position of the benzene ring of the β phenylethylamine creates a catachol. (catecholamines)

Question 16

Pharmacologic effects of sympathomimetics:

Answer 16

Vasoconstriction 
-Cutaneous and renal circulations
Vasodilation
-Skeletal muscle
Bronchodilation
Cardiac stimulation
-Increased heart rate
-Increased myocardial contractility
-Vulnerability to dysrhythmias
Hepatic 
-Glycogenolysis
Liberation of free fatty acids from adipose tissue
Modulation of hormone secretion
-Insulin
-Renin
-Pituitary
CNS stimulation

Question 17

Synthetic Non-catecholamines:

Answer 17

Lack a 3-hydroxyl group
Not metabolized by COMT
Dependent on MAO for metabolism
Metabolism is often slower than that of catechols
Inhibition of MAO may prolong their duration of action.
Patients on MAO inhibitors may manifest exaggerated responses when treated with synthetic non-catecholamines.

Question 18

Non-cardiac effects of vasoconstrictors:

Answer 18

Bronchodilate
Glycogenolysis
Insulin, renin, pituitary hormone
CNS stimulation (low lipid solubility)

Question 19

Contraindications/Complications of vasoconstrictors:

Answer 19

Can worsen LV Failure
Can exacerbate RV Failure
Can decrease renal blood flow
Can mask hypovolemia

Question 20

Natural catecholamines include

Answer 20

Epinephrine
Norepinephrine
Dopamine

Question 21

Epinephrine stimulates

Answer 21

Stimulates Alpha-1, Beta-1, and Beta-2 receptors
Most potent activator of Alpha-1 receptors
2-10X more potent than NE

Question 22

Effects/ Side effects of Epinephrine:

Answer 22

Decreases renal blood flow even in the absence of changes in systemic BP.
Decreased SVR
Maintains MAP
Increased HR/ Contractility/ CO
Increased automaticity, increased risk for dysrhythmias
Reflex bradycardia may occur

Side Effects and Monitoring
No CNS effects
Hyperglycemia, mydriasis, platelet aggregation, sweating, headache, tremor, nausea, arrhythmias
Monitor BG, RR, O2 sats, HR, BP

Question 23

Norepinephrine receptors:

Answer 23

Primarily an Alpha-1 agonist
Beta-1 effects are overshadowed by its Alpha-1 effects
Beta-2 effects are minimal

Question 24

Effects/ Side Effects of Norepinephrine:

Answer 24

Responsible for maintaining BP by adjusting SVR
Increases systolic, diastolic, and mean arterial pressure
Cardiac output may increase at low doses,
Higher doses C.O. may decrease because of increased afterload and baroreceptor-mediated reflex bradycardia
Refractory hypotension
May decrease renal blood flow and cause oliguria
May lead to mesenteric infarct
Peripheral hypoperfusion can lead to gangrene of digits

Question 25

Dopamine receptors:

Answer 25

Beta and Alpha Receptor Effects (10-20 mcg/kg/min) Over 5mcg/kg/min causes NE to be released contributing to cardiac stimulation (precursor) Over 10 mcg/kg/min Alpha effects start to predominate Alpha Receptor Effects (>20 mcg/kg/min)

Question 26

Dopamine Effects/ Side Effects:

Answer 26

``` No effect on pulmonary status Dopamine in the CNS Inc: mania Dec: Schizophrenia, ADHD, PD D2 inhibition- dec prolactin secretion Monitor BP, HR, MAP, urine output, mental status ```

Question 27

Ephedrine receptors:

Answer 27

Direct and Indirect actions Principle effect by stimulating the release of NE Works at Alpha-1 and Beta receptors Beta stimulation may evoke arrhythmias, particularly in sensitized myocardium

Question 28

Ephedrine Effects/ Side Effects:

Answer 28

Principle mechanism is increased myocardial contractility -Venoconstriction greater than arteriolar constriction increases preload and with increased heart rate and myocardial contractility, increases cardiac output (Beta-1 receptor action) -Increases Systolic and Diastolic BP as a result Tachyphylaxis can occur Preserves or increases uterine blood flow Bronchial smooth muscle relaxant Side Effects and Monitoring HTN, insomnia, urinary retention, headache, weakness, tremor, palpitations, psychosis Supportive therapy with extravasation/OD Monitor BP, pulse, urine output, mental status

Question 29

Phenylephrine receptors:

Answer 29

``` Synthetic Non-Catecholamine Direct Alpha-1 agonist Increases preload > afterload Small Beta-1 effect Increases PVR when CO is adequate May be used to improve coronary perfusion pressure without chronotropic side effects. Ok to use in pregnant patients ```

Question 30

Phenylephrine Effects:

Answer 30

Increases preload > afterload Increases PVR when CO is adequate May be used to improve coronary perfusion pressure without chronotropic side effects. Causes reflex bradycardia Decreases renal and splanchnic blood flow Increases pulmonary artery resistance and pressure No dysrrhythmias as a direct effect Reverses R to L shunt in Tetrology of Fallot

Question 31

Posterior Pituitary Hormones include:

Answer 31

Arginine Vasopressin (AVP or ADH) DDAVP (Desmopressin) Oxytocin (Pitocin)

Question 32

Vasopressin has _____ effects and ______ effects

Answer 32

vasopressor and antidiuretic Stimulates vascular V1a receptors causing intense arterial vasoconstriction. In the renal-collecting ducts increases the permeability of cell membranes resulting in the passive reabsorption of water (V2 effect).

Question 33

Unlike catecholamines, the effects of arginine vasopressin are preserved during times of _______ and _________

Answer 33

hypoxia and severe acidosis

Question 34

The advantages of vasopressin over epinephrine:

Answer 34

Advantages over Epinephrine: Epi increases myocardial oxygen consumption Contribute to risk of developing post-resuscitation MI and arrhythmias Catecholamines may not work well in an acidic environment associated with CPR In animal studies, vasopressin associated with: Better blood flow to vital organs Better delivery of cerebral oxygen Better chance of resuscitation and better neurologic outcome HUMAN DATA IS LACKING

Question 35

Is vasopressin a reasonable alternative to epinephrine in the treatment of cardiac arrest?

Answer 35

YES! Vasopressin is at least as effective as Epi, may have fewer adverse effects than Epi., and therefore is a reasonable alternative to Epi. in the treatment of cardiac arrest.

Question 36

Adverse Effects/ Drug interactions of Vasoconstrictors:

Answer 36

Adverse Effects/Drug Interactions: Cardiac dysrhythmias (Beta stimulation) Pure alpha agonists can activate baroreceptor reflex-mediated bradycardia and possibly decrease CO Antihypertensives may decrease the pressor response to indirect acting drugs or enhance the response to direct acting drugs (denervation hypersensitivity).

Question 37

Drug interaction of Vasoconstrictors and tricyclic antidepressants/ MAO inhibitors:

Answer 37

Tricyclic antidepressants and MAO Inhibitors: Increase the availability of endogenous norepinephrine. Exaggerated response with indirect acting agents Worse in the first 14-21 days of therapy (then a down regulation of receptors occurs) OK to continue these drugs in the perioperative period Use a decrease dose of direct acting drugs

Question 38

Drug Interaction of Vasoconstrictors and Cocaine:

Answer 38

Cocaine: Interferes with re-uptake of catecholamines . Both exogenous and endogenous catecholamines exhibit enhanced effects. Produces central and peripheral sympathetic stimulation, resulting in vasoconstriction, tachycardia, and potentially, arrhythmias. Acute toxicity may best be managed with adrenergic blockade. (Labetalol with alpha and beta effects

Question 39

Drug interactions of vasoconstrictors and ma huang (ephedra):

Answer 39

Natural weight loss products may contain ma huang (ephedra) Ephedra contains ephedrine, psuedoephedrine Long term use results in tachyphylaxis from depletion of endogenous catecholamine stores and may contribute to perioperative hemodynamic instability and cardiovascular collapse. Stop product at least 24 hours prior to surgery.

Question 40

What is phentolamine?

Answer 40

Extravasation: Phentolamine alpha 1 and 2 antagonist Peripheral vasodilator Treats skin necrosis secondary to norepinephrine, dopamine, and epinephrine

Question 41

Idiopathic HTN is approximately _____% of HTN. It is related to _________

Answer 41

Idiopathic Hypertension (95%) Related to overactivity of the ANS and an interaction with the Renin-Angiotensin System along with factors related to sodium homeostasis and intravascular volume. Renin-Angiotensin System is important in control, but not development

Question 42

Idiopathic HTN develops initially from ______

Answer 42

Initially, increased BP due to increased CO, (SVR normal) SVR increases to prevent the increased BP from being transmitted to the capillary bed where it would affect cell homeostasis

Question 43

Perioperative HTN may be the result of ______

Answer 43

``` Inadequate anesthesia Airway manipulation Hypercarbia Hypoxia Medications Aortic cross clamp Hypervolemia Hypothermia Pain Pre-existing disease states: -Pheochromocytoma -Hyperthyroid -Autonomic hyperreflexia -Malignant hyperthermia -Intracranial hypertension -Renal disease -Poorly controlled hypertension Type of procedure being performed ```

Question 44

The primary cause of perioperative HTN is

Answer 44

Primary cause: Increased sympathetic discharge with systemic vasoconstriction

Question 45

Complications of perioperative HTN include:

Answer 45

CVA, MI, ischemia, LV dysfunction, arrhythmias, increased suture tension, hemorrhage, pulmonary edema, cognitive dysfunction

Question 46

Vasodilator mechanisms of action include:

Answer 46

Direct smooth muscle dilatation Production of intracellular NO (SNP and nitrates) Calcium channel blockers Alpha-1 Antagonists (prazosin and labetalol) Alpha-2 Agonists (clonidine, alpha-methyldopa) A.C.E. inhibitors (captopril and enalapril)

Question 47

The hemodynamic effects of vasodilators:

Answer 47

Act primarily to cause systemic vasodilation Pure arteriole dilator causes minimal effect on preload. “Pure” venodilators are not available. NTG acts primarily on the venous circulation, but also affects arterioles. Balanced vasodilator (SNP) decreases afterload and preload.

Question 48

Hemodynamic effects of pulmonary vasodilators:

Answer 48

Pulmonary Vasodilators Inhaled NO may be only “pure” pulmonary vasodilator PGE1 is excellent pulmonary vasodilator, but also causes systemic hypotension requiring NE to maintain systemic BP

Question 49

Vasodilators have a reflex increase in _______ and a redistribution of __________.

Answer 49

HR coronary blood flow ``` Hemodynamic Effects: Reflex increase in HR (Baroreceptors) Redistribution of coronary blood flow NTG may improve collateral circulation Others may cause coronary steal ```

Question 50

70-90% of the coronary artery perfusion to the LV occurs during __________ Aortic diastolic pressure governs _________ In the presence of ischemic heart disease, the collateral arteries are maximally dilated and coronary perfusion is largely ______________

Answer 50

diastole perfusion pressure dependent

Question 51

__________: Narrowed coronary arteries are always maximally dilated to compensate for the decreased blood supply. Dilating the other arterioles causes blood to be shunted away from the coronary vessels. In the myocardium, SNP dilates both epicardial conductance and intramyocardial resistance vessels and in the presence of CAD, shunts blood away from ischemic zones. NTG preferentially dilates conductance vessels and directs more blood toward ischemic zones.

Answer 51

Coronary Steal