8. Adrenergic Agonists - Direct Acting Catecholamines

Front 1

What are the catecholamine direct acting adrenergic agonists?

Back 1

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Norepi
epi
isoproterenol
dobutamine
dopamine
methyldopa

Front 2

What do the catecholamine direct acting adrenergic agonists have in common?

Back 2

They all act directly at the adrenergic receptors, and have a catechol group

Front 3

Receptor selectivity of NE

Back 3

a1, a2, b1

Front 4

3 Main effects of NE

Back 4

Cardiovascular
-increase TPR
-Increase contractility
-Reflex bradycardia

Front 5

Result of increased TPR/contractility

Back 5

TPR - increased diastolic bp
Contractility - increased systollic bp
Result = increased MAP

Front 6

How does NE cause reflex bradycardia?

Back 6

The increased BP is detected by carotid baroreceptors and stimulates vagal output to slow heartrate

Front 7

Receptor selectivity of Epi:

Back 7

All - a1/a2/b1/b2

Front 8

3 types of effects of Epi:

Back 8

-Cardiovascular
-Respiratory
-Metabolic

Front 9

How does Epi affect the heart?

Back 9

-Increases Heartrate
-Increases contractility
-Increases Cardiac output

Front 10

How does Epi effect TPR at low concentrations? Via what receptors?

Back 10

Decreases TPR by vasodilating skeletal muscle vessels - B2

Front 11

How does Epi effect TPR at high concentrations? Via what receptors?

Back 11

Increases TPR by global vasoconstriction - a1

Front 12

How does Epi affect MAP?

Back 12

-Decreases Diastolic (vasodilation of skeletal m)
-Increases Systolic (heart effects)
-No change in MAP

Front 13

What is the result of there being no change in MAP by Epi?

Back 13

There is no reflex bradycardia so the heartrate is elevated

Front 14

What are the respiratory effects of NE and via what receptor?

Back 14

Bronchodilation - via B2

Front 15

What are the 2 metabolic effects of Epi?

Back 15

-Increased gluconeogenesis and glycogenolysis
-Increased lipolysis (FFA)

Front 16

What is norepinephrine used to treat?

Back 16

Neurogenic shock

Front 17

3 uses of Epinephrine:

Back 17

-Tx Cardiovascular collapse
-Tx Anaphylactic shock
-Prolong effects of local anesthetics

Front 18

What is the difference between Norepi/Epi and Isoproterenol?

Back 18

Isoproterenol is synthetic

Front 19

What receptors is Isoproterenol selective for?

Back 19

B1 and B2

Front 20

Where are the 2 main effects of Isoproterenol seen?

Back 20

-Cardiovascular
-Respiratory

Front 21

How does Isoproterenol affect blood pressure?

Back 21

-Increases systolic (heart contractility)
-Decreases diastolic (no alpha constriction, only b2 dilation)
-Decreases MAP

Front 22

How does Isoproterenol affect TPR?
Heartrate?
Respiration?

Back 22

TPR - decreased
Heartrate - Significantly increased
Respiration - bronchdilation

Front 23

What are 2 things Isoproterenol is used to treat?

Back 23

-Bradycardia
-AV block

Front 24

Why isn't Isoproterenol given as an inhalant for asthmatics?

Back 24

Because of the cardiac side effects - there are now more B2 selective agonists.

Front 25

What is the receptor selectivity of Dopamine?

Back 25

-Dopa1 receptors
-B1
-a1

Front 26

What determines the receptor selectivity of dopamine?

Back 26

The concentration

Front 27

What is the receptor selectivity of dopamine at low dose and what is the effect?

Back 27

low = D1 in renal vasculature; response is dilation, increased renal perfusion, decreased TPR and better urine output

Front 28

What is the receptor selectivity of dopamine at med dose and what is the effect?

Back 28

-Still renal effects
-Also B1 effects - increased HR, Contractility, and CO

Front 29

What is the receptor selectivity of dopamine at high dose and what is the effect?

Back 29

-All 3 - Dopa1, B1, and a1

Front 30

How does Dopamine affect BP at high conc then?

Back 30

-Increased Systolic BP
-Increased diastolic (a1)
-Increased MAP

Front 31

How does Dopamine affect BP at low conc then?

Back 31

-Decreased diastolic BP (renal)
-Decreased MAP

Front 32

How does Dopamine affect BP at med conc then?

Back 32

-Increased systolic BP (heart)
-Decreased diastolic BP (renal)
-No change in MAP

Front 33

What is Dopamine used to treat?

Back 33

Acute cardiogenic shock - it temporarily gets the patient through

Front 34

What is the receptor selectivity of Dobutamine?

Back 34

B1

Front 35

So what effect will Dobutamine have?

Back 35

Only cardiovascular
-increased HR, contractility, CO

Front 36

How does dobutamine change BP?

Back 36

Minimally increases it

Front 37

What is the main use of Dobutamine then?

Back 37

Cardiogenic shock - to increase cardiac output

Front 38

What is something else Dobutamine is often used in?

Back 38

Cardiac stress testing for patients that can't exercise, to see if they have CAD

Front 39

What is the method of administration for all of the direct acting adrenergic agonists except methyldopa?

Back 39

IV - given in an inpatient setting and via constant infusion

Front 40

Why do the direct acting catechol agonists have to be given via IV?

Back 40

Because they are all quickly metabolized by MAO and COMT

Front 41

Which direct acting catechol adrenergic agonist can be given orally?

Back 41

Methyldopa

Front 42

What is Methyldopa?

Back 42

A prodrug

Front 43

How is the prodrug Methyldopa activated?

Back 43

By replacing NE in the presynaptic nerve terminals and being metabolized by the same enzymes that synthesize NE

Front 44

What are the steps in Methyldopa activation and what is the final active metabolite?

Back 44

1. Methyldopa is acted on by Aromatic AA decarboxylase
2. alpha-Methyldopamine accumulates in synaptic vesicles and is acted on by Dopamine B-hydroxylase
3. A-methylnorepinephrine is released

Front 45

So the final active metabolite of Methyldopa is?

Back 45

A-methylnorepinephrine

Front 46

Where is the predominant site of a-methylnorepinephrine action?
-What receptors
-What is its effect

Back 46

In the CNS on a2 receptors
-Effect is reduced sympathetic outflow, decreased symp tone, bradycardia

Front 47

What is Methyldopa primarily used to treat?

Back 47

Hypertension