Lecture 14-16 - Scrogin - Adrenergics (Agonists)

Question 1

What are the direct-acting endogenous sympathomimetics?

Answer 1

NE, Epi, and dopamine

Question 2

What is isoproterenol (ISO)

Answer 2

a synthetic catecholamine that is selective for beta receptors

Question 3

Describe the efficacy of epi, NE, and ISO for alpha-1 receptors

Answer 3

Epi is greater than or equal to NE

Epi and NE are&raquo_space; ISO

Question 4

Describe the efficacy of epi, NE, and ISO for alpha-2 receptors

Answer 4

Epi is greater than or equal to NE

Epi and NE are&raquo_space; ISO

*Note: this is the same for alpha 2

Question 5

Describe the efficacy of epi, NE, and ISO for beta-2 receptors

Answer 5

Iso > Epi&raquo_space; NE

NE is a partial agonist only

Question 6

Describe the efficacy of epi, NE, and ISO for beta-1 receptors

Answer 6

Iso > Epi = NE

NE and Epi have equal potency and efficacy

Question 7

Adrenomimetic agonists can be broken into what 2 classes?

Define them.

Answer 7

Direct acting = acts on receptors directly

Indirect acting = promotes increase in endogenous NT in synaptic cleft (releasers or reuptake inhibitors)

Question 8

What receptors does epi bind?

Answer 8

alpha-1 and alpha-2
beta-1 and beta-1
*depends on concentrations

Question 9

How is epi eliminated/degraded?

Answer 9

Degraded by COMT and eliminated in urine

Question 10

Low doses/infusion rates of epi gives binding to which receptors?

Answer 10

Beta-1 and Beta-2

Question 11

What are the indications for low doses of epi?

Answer 11

Anaphylaxis and bronchospasm (acute asthma attack)

Question 12

High doses/infusion rates of epi gives binding to which receptors?

Answer 12

Alpha-1

Beta-1 and Beta-2

Question 13

What are the indications for high doses of epi?

Answer 13

Cardiac arrest and heart block

Question 14

What is the mechanism of action for low doses of epi (*at each receptor)?

Answer 14

Beta-1 = + chronotropy and inotropy (inc HR, CO, and systolic)

Beta-2 = peripheral vasodilation, dec diastolic, and bronchodilation

Question 15

What is the mechanism of action for high doses of epi (*at each receptor)?

Answer 15

Alpha-1 = peripheral vasoconstriction (this is the predominant effect) and dec bronchial secretions

*a1/b1/b2 give inc CO and TPR

Question 16

What is the side effect for epi?

Answer 16

arrhythmias

Question 17

What are the contraindications for epi?

Answer 17

Late term pregnancy

*note: this was not underlined

Question 18

What receptors does NE bind?

Answer 18

Alpha-1 and Alpha-2
Beta-1
*has little affinity for beta-2

Question 19

How is NE eliminated/degraded?

Answer 19

Degraded by COMT and MAO

Eliminated in urine

Question 20

Describe the relative half life for NE and route of administration?

Answer 20

short half life

give via controlled infusion

Question 21

What is the indication for NE?

Answer 21

Vasodilatory shock (acute HYPOtension)

Question 22

Describe the mechanism of action for NE in relation to the receptors it binds

Answer 22

Alpha-1 = vasoconstriction, inc TPR, inc diastolic

Beta-1 = inc CO, inc systolic

Baroreflex = dec HR (dominates over chronotropy)

*also gives + chronotropy and inotropy

Inc in MAP = overall

Question 23

What is the side effect of NE?

Answer 23

ischemia

Question 24

What are the contraindications for NE?

Answer 24

Ischemia and pre-existing vasoconstriction (*if NE were given, it could induce gangrene)

Question 25

What receptor does dopamine bind?

Answer 25

Dopamine-1 (D1) at low concentrations Beta-1 and Alpha-1/Alpha-2 at higher infusion rates

Question 26

What is the indication for dopamine?

Answer 26

Cardiogenic shock (HYPOtension due to low CO)

Question 27

What is the mechanism of action for Dopamine at low infusion rates?

Answer 27

Activates D1 receptors = dec TPR

Question 28

What is the mechanism of action for Dopamine at medium infusion rates?

Answer 28

Activates Beta-1 receptors = inc contractility and inc HR (inc CO)

Question 29

What is the mechanism of action for Dopamine at high infusion rates?

Answer 29

Beta-1/Alpha-1/Alpha-2 stimulation = inc BP and inc TPR

Question 30

What are the side effects of dopamine at low infusion rates? high infusion rates?

Answer 30

Low infusion rates = HYPOtension High infusion rates = Ischemia

Question 31

What is the contraindication for dopamine?

Answer 31

Uncorrected Tachyarrhythmia

Question 32

What are 6 direct-acting adrenergic agonists?

Answer 32

1. Isoproterenol (ISO) 2. Dobutamine 3/4. Terbutaline/Albuterol 5. Pheynlephrine 6. Clonidine

Question 33

What are the 6 indirect acting adrenergic agonists?

Answer 33

``` Amphetamine Methamphetamine Methylphenidate Ephedrine Pseudoephedrine Tyramine ```

Question 34

What are the indications for ISO?

Answer 34

Bradycardia | Heart block when TPR is high

Question 35

What receptor does ISO bind?

Answer 35

It is a NON-SELECTIVE Beta-agonist

Question 36

How is ISO degraded?

Answer 36

By COMT

Question 37

What is the mechanism of action for ISO, in relation to specific receptors?

Answer 37

Beta-2 = vasodilation!, bronchodilation!, dec TPR, dec diastolic/systolic Beta-1 = + inotropy and chronotropy (inc CO)

Question 38

What are the side effects for ISO?

Answer 38

Tachyarrhythmias

Question 39

What is the contraindication for ISO?

Answer 39

Angina with ARRHYTHMIA

Question 40

What receptor(s) does Dobutamine bind? with what affinity?

Answer 40

B1 > B2 > a It's a selective Beta-1 agonist

Question 41

What are the indications for Dobutamine?

Answer 41

Short term Rx for CHF (cardiac insufficiency) Cardiogenic shock (low cardiac contractility)

Question 42

What is the mechanism of action for Dobutamine?

Answer 42

Inc CO + inotropy > + chronotropy (because of no/little beta-2 reflex tachy/vasodilation)

Question 43

What is the mechanism of action for high doses of Dobutamine?

Answer 43

It'll bind Beta-2 and cause HYPOtension with reflex tachycardia

Question 44

What are the side effects for Dobutamine?

Answer 44

Hypotension (beta-2) Arrhythmias (beta-1)

Question 45

How is Dobutamine degraded?

Answer 45

Rapidly by COMT

Question 46

What receptor(s) does Terbutaline/Albuterol bind? With what selectivity?

Answer 46

It is a Beta-2 agonist

Question 47

What are the indications for Terbutaline/Albuterol?

Answer 47

Bronchospasm (asthma, bronchitis, and emphysema) Obstructive Airway Disease

Question 48

What does Terbutaline/Albuterol do?

Answer 48

Cause bronchodilation Can give some Beta-1 agonist-like response (cardio effect)

Question 49

What are the side effects for Terbutaline/Albuterol?

Answer 49

Beta-1 = tachy (@ high dose) Beta-2 = tolerance, skeletal muscle tremor, and activation of pre-synaptic cholinergic beta-2 receptors

Question 50

What receptor(s) does phenylephrine bind? Any selectivity?

Answer 50

Alpha-1 agonist

Question 51

What are the indications for Phenylephrine?

Answer 51

Paroxysmal supraventricular tachy Mydriatic agent Nasal decongestant

Question 52

Is Phenylephrine degraded by COMT?

Answer 52

No, because it's not a catecholamine

Question 53

Compare the duration of action for endogenous catecholamines and phenylephrine

Answer 53

Phenylephrine has a longer duration of action

Question 54

What is the mechanism of action/effects of Phenylephrine?

Answer 54

Peripheral vasoconstriction, inc BP, activation of baroreflex, dec HR Dilates pupil Decreases bronchial secretions

Question 55

What is the side effect of phenylephrine?

Answer 55

HTN

Question 56

What receptoronidine does clonidine bind? Any selectivity?

Answer 56

Alpha-2 agonist

Question 57

What is the indication for clonidine

Answer 57

HTN from excess symp drive

Question 58

What is the mechanism of action for clonidine?

Answer 58

Peripheral effect = mild vasoconstriction, crosses BBB to dec symp outflow (reduce vasoconstriction an bp) Central effect = dec BP Overall: DEC BP

Question 59

For clonidine, dec tonic excitatory input to sympathetic cells leads to a reduction in sympathetic output to ___

Answer 59

vascular smooth muscle

Question 60

What are the side effects of Clonidine?

Answer 60

Dry mouth Hypertensive crisis (after acute withdrawal)

Question 61

How do indirect-acting sympathomimetics increase the concentration of endogenous catecholamines?

Answer 61

1. release of cytoplasmic catecholamines | 2. blockade of re-uptake transporters

Question 62

Amphetamine-like drugs are taken up by ___ and cause ___

Answer 62

Taken up by re-uptake proteins | Cause reversal of transporter and lead to Ca2+ independent release of NT

Question 63

Do amphetamines cross the BBB?

Answer 63

Yes, this leads to high abuse potential

Question 64

What are indications of direct-acting adrenergic agonists?

Answer 64

ADD Narcolepsy Nasal Decongestion

Question 65

Name 2 indirect acting agonists that are used for ADHD

Answer 65

Amphetamine, Methylphenidate,

Question 66

Which indirect agonist is used for anesthesia?

Answer 66

Ephedrine

Question 67

Which indirect agonist is used for nasal decongestion?

Answer 67

Pseudoephedrine

Question 68

What is the therapeutic use of Tyramine?

Answer 68

There is none It displaces NE

Question 69

How is Tyramine degraded?

Answer 69

By MAO

Question 70

What are the effects of indirect adrenergic agonists?

Answer 70

NE release gives peripheral vasoconstriction, + inotropy, inc conduction velocity In the CNS it's a stimulant and anorexic agent

Question 71

What is the side effect for indirect adrenergic agonists?

Answer 71

Tachy (beta-1)

Question 72

What is the contraindications for indirect acting adrenergic agonists?

Answer 72

Rx with MAOIs within the past 2 weeks