Olson, Sympathomimetics

Front 1

Sympathomimetic drugs work on what two receptors?

Back 1

Adrenergic and Dopaminergic receptors.

Front 2

What are the Adrenoreceptors? (5)

Back 2

Alpha 1
Alpha 2
Beta 1
Beta 2
Beta 3

Front 3

What are the effects of Dopamine 1 receptor stimulation?
- Are they pre or post synaptic

Back 3

Mediate vasodilation of renal, mesenteric, coronary, and cerebral blood vessels.
- postsynaptic

Front 4

What are the effects of Dopamine 2 receptor stimulation?
- Are they pre or post synaptic

Back 4

Inhibit release of norepinephrine.
- presynaptic

Front 5

How many subtypes of dopamine receptors exist?

Back 5

5

Front 6

What are the effects of Alpha 1 receptor stimulation?
- Are they pre or post synaptic

Back 6

Vasoconstriction
Mydriasis - dilation
Relaxation of GI tract
Contraction of GI sphincters
Contraction of bladder sphincter
- Post synaptic

Front 7

What are the effects of Alpha2 receptor stimulation?
- Are they pre or post synaptic

Back 7

There are both pre and post synaptic.
Presynaptic :
Inhibition of norepinephrine release. (ex. clonidine)

Postsynaptic :
Platelet aggregation & hyperpolarization of CNS cells

Front 8

What are the effects of Beta 1 receptor stimulation?
- Are they pre or post synaptic

Back 8

Increased conduction velocity
Increased automaticity
Increased contractility
- postsynaptic

Front 9

What are the effects of Beta2 receptor stimulation?
- Are they pre or post synaptic

Back 9

Vasodilation
Bronchodilation
GI Relaxation
Uterine relaxation
Bladder relaxation
Glycogenolysis
Lipolysis - beta3

Front 10

True or False:
Only presynaptic receptors are alpha 2 and dopamine 2 receptors, and both inhibit release of norepinephrine.

Back 10

True

Front 11

What receptor causes vasoconstriction - especially cutaneous and renal?

Back 11

Alpha 2

Front 12

What receptors cause vasodilation in skeletal muscles?

Back 12

Beta 2

Front 13

What receptors cause bronchodilation ?

Back 13

Beta 2

Front 14

What receptors cause cardiac stimulation?

Back 14

Beta 1

Front 15

What receptors cause glycogenolysis?

Back 15

Beta 2

Front 16

What receptors cause liberation of free fatty acids from adipose tissue? (2)

Back 16

Beta 2 / Beta 3

Front 17

What receptors cause CNS stimulation?

Back 17

All of them

Front 18

What are the 3 naturally occurring catecholamines?

Back 18

Epinephrine
Norepinephrine
Dopamine

Front 19

What are the 4 synthetic catecholamines ?

Back 19

Isoproterenol
Dobutamine
Fenoldopam (corlopam)
Dopexamine

Front 20

What are the synthetic non-catecholamines?

Back 20

Ephedrine
Mephentermine (Wyamine)
Phenylephrine
Amphetamine, methamphetamine, dextroamphetamine
Methoxamine (Vasoxyl)

Front 21

Name 4 selective beta-2 agonists.

Back 21

Albuterol
Metaproterenol
Terbutaline
Isoetharine

Front 22

What are the direct acting sympathomimetic drugs?

Back 22

Epinephrine
norepinephrine
dopamine
phenylephrine
methoxamine

Front 23

What are the indirect acting sympathomimetic drugs?

Back 23

Ephedrine (some direct action on beta 2)
Mephantermine
Amphetamines

Front 24

What is the mechanism of action of sympathomimetics?

Back 24

Sympathomimetic binds to receptor of cell surface activating the G-protein, diffusing through the cell membrane and activating or inhibiting the effector enzyme or opening/closing ion channel.

Front 25

Beta-adrenergic stimulation causes activation of adenylyl cyclase and an increase in ______ production

Back 25

cAMP

Beta-1 stimulation - increases cAMP - Ca++ ion influx
More forceful myocardial contractility
Beta-2 stimulation - relaxation of bronchial and vascular smooth muscles

Front 26

Ephedrine is released from where?

Back 26

adrenal medulla

Front 27

Epinephrine regulates what things? (5)

Back 27

Contractility
Heart rate
Vascular and bronchial smooth muscle tone
Glandular secretions
Metabolic processes

Front 28

What is the most potent activator of alpha-adrenergic receptors?

Back 28

Epinephrine

Front 29

What are the uses of epinephrine?

Back 29

- Resuscitation
- Continuous infusion to increase contractility and maintain B/P
- Treatment of life-threatening allergic reactions
- Addition to locals

Front 30

What are the CV effects of epinephrine?
- for small, moderate, large dosing

Back 30

- Small doses (1-2 mcg/min) stimulate mainly beta-2 receptors in peripheral vasculature (vasodilate, bronchodilate)

- Moderate dose (4 mcg/min) stimulate beta-1 receptors
increasing HR and contractility

- Large doses (10-20 mcg/min) stimulate both alpha and beta receptors

Front 31

Epinephrine Alpha-1 stimulation causes...

Back 31

Intense vasoconstriction

Front 32

Epinephrine Beta-1 stimulation causes...

Back 32

Increased systolic B/P, CO, and HR (speeds up rate of phase 4 depolarization)

Front 33

What are the respiratory effects of epinephrine?

Back 33

- Beta-2 stimulation – relaxation of bronchial smooth muscle
- Increased cAMP decreases release of vasoactive mediators associated with asthma

Front 34

What are the metabolic effects of epinephrine?

Back 34

Beta-1 – increased glycogenolysis and lipolysis

Alpha-1 – inhibits insulin release

Front 35

What electrolyte effect does epinephrine have?

Back 35

Beta-2 stimulation – activation of Na+/K+ pump
- Transfer of K+ into cell → hypokalemia
- May contribute to dysrhythmias

Front 36

What are the doses for Epinephrine?
- beta/alpha
- low/high dose

Back 36

Low dose
- 1-2 mcg/min – beta-2
- 4 mcg/min – beta 1
High dose
- 10-20 mcg/min – alpha and beta
Bolus 2-8 mcg – transient cardiac stimulation for 1-5 minutes

Front 37

Describe the potency of Norepinephrine.
- compare to epi

Back 37

- Approximately equal to epi for beta-1 receptors, little effect on beta-2
- Potent alpha agonist

Front 38

What are the effects of Norepinephrine?

Back 38

- Intense vasoconstriction in all vascular beds
- Increased SVR raises MAP
- ↓ HR from baroreceptor-reflex
- ↓ CO from ↓ HR and venous return to heart
- Clinically, alpha effects > beta effects
- Metabolic acidosis from ↓ blood flow to tissue
- Decreased pulses, risk of losing digits and extremities

Front 39

What are the indications for norepinephrine use?

Back 39

- Treatment of hypotension that persists after adequate volume replacement
- Effective in increasing B/P with little change in HR or CO

Front 40

What is the dose of Norepinephrine?

Back 40

Start at 0.5-1 mcg/min and titrate to desired response – 8-30 mcg/min usual range

Front 41

What is extravasation management for norepinephrine and Dopamine

Back 41

Phentolamine 5 mg with 9 mL of NS
Inject small amount into extravasated area
Repeat if blanching reoccurs

Front 42

Which dopamine receptors dediate vasodilation of renal, mesenteric, coronary, and cerebral vessels at low doses?

Back 42

Dopamine-1 receptors

Front 43

N/V caused by dopamine is probably R/T what receptors?

Back 43

Dopamine-2 receptors.

Reglan works centrally as dopaminergic antagonist

Front 44

What is the MOA of Dopamine?

Back 44

Stimulates both adrenergic and dopaminergic receptors

--Sm doses dopaminergic
-- Higher doses beta-1 adrenergic – cardiac stimulation
-- Lg doses alpha-adrenergic

Front 45

What are the clinical effects of Dopamine?

Back 45

To increase CO associated with hypotension, increased atrial filling pressures, and low urine OP

- increases the following
Contractility
Renal blood flow
Glomerular filtration rate
Excretion of Na+
Urine OP

Front 46

What are the cardiovascular effects of Dopamine?

Back 46

- Beta-1 stimulation increases CO

- Modest increase in HR, B/P and SVR compared to CO

Front 47

What are the respiratory effects of Dopamine?

Back 47

- Interferes with chemoreceptor response to hypoxemia

- May see depression of ventilation

Front 48

Dopamine doses.
- renal
- moderate
- severe

Back 48

Dose (range up to 20 mcg/kg/min)
-- Low-dose (renal-dose) is 1-3 mcg/kg/min

-- Beta-1 dose is 3-10 mcg/kg/min, causes increased HR and contractility

-- Doses > 10mcg/kg/min
Alpha stimulation causes peripheral vasoconstriction

Front 49

What synthetic catecholamine is the most potent of all sympathomimetics in activation of beta-1 and beta-2 receptors?

Back 49

Isoproterenol
- 2-3 times more potent than epi
- no alpha agonist effects

Front 50

What is the MOA for Isoproterenol?

Back 50

Stimulates beta-1 and beta-2 receptors – relaxation of bronchial, GI, & uterine smooth muscle, increased HR & contractility, vasodilation of peripheral vasculature

Front 51

What are the uses for Isoproterenol?

Back 51

- AV block
- Unstable bradyarrhythmias
- Bradycardias resistant to atropine and dopamine
- Bradycardia in transplanted heart (direct acting effects)

Front 52

What are the CV effects for Isoproterenol?

Back 52

- beta-1 receptors cause increase in HR and contractility
- Beta-2 receptors cause vasodilation of vasculature of skeletal muscles
- Increase in CO that’s enough to cause increase in systolic B/P
- Decrease in diastolic B/P

Front 53

What is the dose of Isoproterenol

Back 53

2 mcg/min titrated to effect

Range 2-10 mcg/min

Front 54

What is the MOA for Dobutamine?

Back 54

Stimulates beta-1 receptors – ↑ HR & contractility

- Little effect on beta-2 and alpha receptors

Front 55

Why do you use Dobutamine?

Back 55

Short-term management of cardiac decompensation
-- Improves CO
-- Addition of low dose dopamine increases renal perfusion
-- Addition of vasodilator decreases afterload

Front 56

What are the CV effects of Dobutamine?

Back 56

- Increased CO
- Inotropic effect (chronotropic)
- Decreases SVR & PVR (w/inc. PAP)
- Tachycardia & dysrhythmias at high doses

Front 57

What is the dose of Dobutamine?

Back 57

2.5-20 mcg/kg/min - titrate to response

Max dose 40mcg/kg/min

Front 58

True or False:
Dobutamine is incompatible with heparin.

Back 58

True

Front 59

What is Fenoldopam (Corlopam)?

Back 59

Selective dopamine-1 receptor agonist.
- causes vasodilation
- decreases PVR
- increases diuresis/natriuresis

Front 60

When is Fenoldopam used?

Back 60

- Short term tx of severe HTN
- Renal protection w/bypass

Front 61

What are the CV effects of Fenoldopam?

Back 61

Reflex tachycardia most common.

Front 62

What other effects of Fenoldopam occur (not CV)

Back 62

HA
Flushing
Increased IOP

Front 63

What is the dose of Fenoldopam?

Back 63

0.1 mcg/kg/min titrated to 1.6 mcg/kg/min for severe HTN

0.01-0.03 mcg/kg/min to improve renal perfusion

Front 64

Concurrent use of _____ with Fenoldopam may increase fenoldopam levels.

Back 64

Acetaminophen

Front 65

What is Dopexamine (Dopacard)?

Back 65

Synthetic Catecholamines -

-- Dopaminergic and beta-2 agonist
-- No alpha effects
-- Improves creatinine clearance in patients undergoing CPB

Front 66

Is ephedrine direct or indirect acting?

Back 66

indirect

Front 67

What is Ephedrines MOA?

Back 67

Alpha and beta stimulation
20-30% alpha
70-80% beta

-- Causes endogenous release of norepi for effect on alpha and beta-1
-- Direct action on beta-2

Front 68

Uses of Ephedrine?

Back 68

-- Increase B/P after regional
-- More specifically corrects noncardiac changes after sympathetic block than selective agonist (phenylephrine)

-- Uterine blood flow is maintained

-- Chronic oral med for bronchial asthma

Front 69

Ephedrine's stimulation of ____ receptors causes increased HR & contractility

Back 69

Beta-1

Front 70

True or False:
Ephedrine increased coronary and skeletal blood flow

Back 70

True

Front 71

Dose of Ephedrine?

Back 71

10-25mg

Front 72

Describe highlights of Mephentermine (Wyamine)

Back 72

-- Indirect acting
-- Stimulates alpha and beta
-- CV effects and dose similar to ephedrine

Front 73

Describe highlights of Amphetamine, dextroamphetamine, and methamphetamine

Back 73

-- Resemble ephedrine in stimulation of alpha and beta receptors
-- Produce significant CNS stimulation
-- Tachyphylaxis prominent

Front 74

Amphetamine and anesthesia
- Acute use

Back 74

- Increased requirements
- Norepi release in CNS
- Death from uncontrollable HTN has occurred

Front 75

Amphetamine and anesthesia
- Chronic use

Back 75

- May see decreased requirements
- Stores of catecholamines depleted

Front 76

Is Phenylephrine direct or indirecting?

Back 76

Direct acting

Front 77

Is Phenylephrine work on the Alpha, Beta, or Alpha & Beta receptors?

Back 77

Alpha (mainly Alpha-1)

Front 78

What are the CV effects of Phenylephrine?

Back 78

- Venoconstriction > arterial constriction
- Decreased CO
Peripheral vasoconstriction
- Increased SVR
- Renal, splanchnic, cutaneous blood flow ↓
- Coronary blood flow and PAP increased

Front 79

When is Phenylephrine used?

Back 79

- - Increases BP, Decreases HR
-- Reflex vagal effect has been used to slow HR in hemodynamically compromised patient

Topically - Nasal decongestant & Mydriasis

Front 80

Dose of Phenylephrine?

Back 80

50-100 mcg bolus
20-50 mcg/min infusion

Front 81

State the highlights of Methoxamine (Vasoxyl)

Back 81

-- Direct acting alpha-receptors
-- No beta

-- 5-10 mg IV causes intense arterial vasoconstriction and reflex bradycardia

-- Minimal venoconstriction

Front 82

How do Selective Beta-2 Agonists work?

Back 82

Relax bronchiole and uterine smooth muscle without stimulating beta-1

Front 83

What are Selective Beta-2 Agonists used for?

Back 83

Bronchospasms

Premature uterine contractions

Front 84

What are some side effects of Selective Beta-2 Agonists?

Back 84

Tremor
Increased HR
- Some direct stimulation
- Some by reflex
Metabolic responses:
- Hyperglycemia
- Hypokalemia
- Hypomagnesemia

Front 85

What is the usual dose of albuterol (selective beta-2 agonist)?

Back 85

MDI delivers about 100 mcg/puff (2 puffs Q4-6hr)

Nebulizer:
2.5-5 mg (0.5-1mL) in NS solution

Front 86

Name several Selective Beta-2 Agonists

Back 86

Albuterol
Metaproterenol (Alupent)
Isoetharine (Bronkosol)
Bitolterol (Tornalate)
Terbutaline (Brethine)
Ritodrine (Yutopar)

Front 87

What is Terbutaline (Brethine) used for, what is the dose, how is it delivered?

Back 87

For premature labor
-- IV 2.5-10 mcg/min
-- Oral maintenance 2.5-10 mg q 4-6 hours

Available SC, PO, MDI

Front 88

What is Ritodrine (Yutopar) used for?

Back 88

Most common use – stop premature labor

Note:
Some stimulation of beta-1
- Crosses placenta – may see CV effects in infant
- Decreased secretion of Na+, K+ and water (pulmonary edema possible with aggressive hydration
- May cause hypokalemia and hyperglycemia

Front 89

Name 2 Alpha-2 Agonists.

Back 89

Clonidine & Dexmedetomidine (Precedex)

Precedex is an adjunct to anesthesia - decreases anesthetic requirement