NE

- neurotransmitter in periphery which mediates the effects of sympathetatic  stimulation;

- not as potent as Epi; reduces renal and hepatic blood flow

Alpha Agonist Uses

- hypotension

- local vasoconstriction

- nasal decongestion

-paroxymal atrial tachycardia

NE

-alpha agonist; reduces renal/hepatic/muscle blood flow- vessels have a lot of alpha receptors in arterioles and NE produces vasoconstriction (reduce the flow of blood through these tissues). 

Increases MABP; Reflex bradycardia 

Nasal decongestion

Alpha agonist uses

 - an alpha agonist will combat paroxysmal atrial tachycardia b/c it increases PS stimulation to the heart by causing vasoconstriction;

- it has ability to produce reflex bradycardia 

NE Precautions

- tissue necrosis (slough) due to alpha stimulation (infuse centrally, high on limb)

- hyperthyroidism

- sensitization of myocardium

- contraction of gravid uterus, NOT to use in PG

NE Precautions

NE is a very potent vasoconstrictor so it

can produce tissue necrosis, when it’s

administered or applied to an end organ

Isoproterenol 

non-selective beta agonist 

Isoproterenol effects

- vascular and nonvascular smooth muscle

beta-2 stimulation;

- metabolic: hyperglycemia, FFA release;

- cardiac stimulation;

- bronchoconstriction

Dopamine low dose effects

Dopamine agonist effects:

- increases renal blood flow (interacts with

dopamine receptors in renal vasculature)

- increases glomerular filtration;

- increases sodium excretion

Dopamine moderate dose effects

Dopamine agonist plus beta-1 plus IAS action:

- increased cardiac output

- increased systolic BP

- increased coronary blood flow

- no change in tissue peripheral

resistance or diastolic BP

Dopamine high dose effects

Dopamine + beta-1 + indirect (can promote the release of NE) + alpha:

- increased PR, increase in HR; the heart is pumping against the increase in PR

- renal vasoconstriction, as you see alpha

effects in SC;

- indirect action, promoting the release

of NE from adrenergic nerves

Dopamine use

- shock by continuous infusion, superior to

NE b/c NE produces vasoconstriction, it’s

going to produce decrease in heart rate.

- increases blood flow to kidneys &

enhances glomerular filtration     

Dopamine- adverse effects

Overdose- similar to those due to

sympathetic stimulation 

-nausea, hypertension, arrhythmia

Dobutamine

 - selective beta 1 agonist. It is a cardiac stimulant, synthetic catecholamine, Isoproterenolol derivative.

- produces cardiac beta 1 effects, slight alpha and beta 2 activity

- made up of 2 isomers w/ either beta 2 or alpha agonism.

As you increase the dose, you lose the potential to produce

a + iontropic effect w/o producing a chronotropic effect.

So at at high doses it resembles ISO . 

Dobutamine effects

- improved over other catecholamines; less tachycardia,

increase in systolic BP, less effect on oxygen demand,

no decrease in cardiac efficiency. It increases Systolic

BP b/c it increases CO, but less tachycardia.

It will NOT cause a decrease in cardiac efficiency

b/c this is due to beta 2 agonists activity. 

Comparison at equipotent

beta-1 doses 

Isoproterenol has NO alpha-1 effects

but has a lot of beta-2 agonist activity (+5)

NE has a lot of alpha-1 effects (+5)

but no beta-2 effects

Dobutamine has the same low

alpha-1 and beta-2 effects (+1)

Dobutamine uses

-some type of shock w/ oliguria

Dobutamine adverse effects

- cathecolamine adverse effects; miocardial

effects with halogenated hydrocarbons,

cardiac arrhythmias, tachycardia

(approx. 10%- like ISO)

NE

- given IV causes a reflex bradycardia

b/c ofit’s alpha agonist activity.

No beta 1 agonist activity is observed

when given IV

NE, EPI and ISO

In vitro D/R plots

Arterial smooth muscle

EPI> NE >>>>> ISO

Bronchial smooth muscle

ISO> EPI >>>>>> NE

Cardiac Inotropism

ISO > EPI = NE

EPI, NE and ISO D/R plots 

w/ & w/o Antagonist

Arterial smooth muscle

NE=NE + Propanolol >>>>NE + Phentolamine

Bronchial smooth muscle

ISO= ISO +Phentolamine>>>>ISO + Propanolol

Cardiac Inotropism

NE=NE+ Phentolamine>>>NE+Propanolol

In vitro

 In arterial smooth muscle Epi is much more

potent than NE and NE is way more potent

than ISO, because ISO has no alpha agonist

activity. EPI is the most potent of those catecholamines so its ED50 would be much

smaller than that of NE.

ISO

- the most potent beta agonist;

-not taken up into adrenergic nerves

(reuptake is not important)

Inotropism

- refers to force of attraction; + iontropism increases the force

of attraction and - iontropism decreases the force of attraction.

So administration of a beta 1 agonist, normally you don’t have

any reflexes acting, drop it right on the heart, you'll have

a + ionitropic effect. Administer a muscarinic agonist drop

it right on the heart will cause a - iontropic effect, b/c

it’s going to reduce the contractile response  

Chronotropism

+ speeds up, - chronotropism it slows down. A drug which

has beta 1 agonist activity put it right on the heart it

speeds up the heart, it’s + chronotopism. A drug

put on the heart that slows it down, is -

chronotropism. Administration of an adrenergic neuron

blocker in vivo would exibit - chronotropism

Alpha 1 agonist

 -given IV will cause reflex bradycardia and hypertension  

Adrenergic neuron blocker

- causes a reduction in sympathetic stimulation 

Beta 1 agonist

- produce an increase in heart rate

and contraction 

NE

NE + propanolol 

NE + phentolamine

in arterial smooth muscle

NE gives the same D/R plot as NE + propanolol (beta blocker),  b/c NE doesn’t bind to beta receptors in the arterioles, to

give you contraction of the arterial smooth muscle.

NE + phentolamine (alpha receptor antagonist) will give a big

shift in the dose response curve to the right. So the EC50 will

be increased a lot by phentolamine but not by propanolol.

NE works on alpha receptors in the arterial smooth muscle.

Phentolamine 

alpha receptor antagonist

Propanolol 

- beta blocker

ISO

ISO + Phentolamine

ISO + Propanolol on

bronchial smooth muscle

On bronchial smooth muscle you have beta

2 receptors, and ISO will produce relaxation

of bronchial smooth muscle. ISO plus

phentolamine will not give you a shift

in D/R plot. ISO plus propanolol will give

a big shift in D/R plot to the right.

NE

NE + Phentolamine

NE + Propanolol

Cardiac Inotropism

 NE plus phentolamine gives no shift in D/R

plot but NE plus propanol gives you a rightward shift in D/R plot. Cardiac inotropism is

mediated via an increase in beta 1 receptor stimulation. Propanolol results in a rightward

shift in D/R plot b/c it is blocking the receptor

that NE needs to interact to produce an

incease in heart rate