natural catecholamines - PNS

synthetic - CNS or PNS

drug that promotes the release OF the agonist.

Ex. Tyramine - promotes the release of NE (which is the agonist)

a drug like 6OH dopamine will destroy the adrenergic nerve making it impossible for Tyramine to work.

Peripheral Sympathomimetic Effects (6)

• smooth muscle contraction (alpha agonist)
• increased rate/force of cardiac contraction (beta-1 agonist)
• relax GI smooth muscle (beta-2 agonist)
• Relax Pulmonary smooth muscle (beta 2 agonist)
• metabolic effects - increase in glucose (B2 agonist in liver)
• endocrine effects

• increased glycogenolyis (B2 liver)
• increased gluconeogenesis (B2 liver)
• increased lipolysis (Beta 2,3 adipose tissue)

• modulation of renin secretion (B2 kidney)
• modulation of pancreatic secretions
• secretion of anterior pituitary (dopamine)

1. Norepinephrine - (a1 and 2, beta 1 agonist) - decreases NE release
2. Alpha methyl norepinephrine - inhibits the release of NE
3. Clonidine - reduce the release of NE; also produces less of a opiate withdrawl (per. Dr. Louis' friend)

• vasodilation
• hypotension
• reflex tachycardia

• vasoconstriction
• hypertension
• reflex bradycardia

• vasodilation
• hypotension
• brady cardia - due to the effects of the agonist on the muscarinic receptors

• decreased appetite
• increased wakefullness

• alpha
• beta
• non-selective

• alpha 1
• alpha 2
• beta 1

• beta 1,2,3
• non selective beta agonist

• Low doses-dopamine receptors
• Hi doses - alpha and beta 1

• beta 1 (low doses)
• alpha (hi doses)
• beta 2 (high doses)

• vasoconstriction
• hypertension
• reflex bradycardia

• vasoconstriction
• hypertension
• no bradycardia because ACh synthesis is inhibited by the hemicholinium

Tachycardia - NE works directly on B1 receptors

No vasoconstriction or HTN or reflex bradycardia due to inhibition of alpha receptors.

vasoconstriction

tachycardia

There would be no Carotid sinus reflex because the PS and S nerve innervation doesn't occur. The NE would act directly on the alpha and beta 1 receptors

Dopamine at low doses causes effects on what receptors?

Dopamine at high doses casues effects on what receptors?

• low doses - Dopamine receptors
• hi Doses - dopamine, alpha and beta 1 receptors

Dobutamine at low doses effects what receptors?

Dobutamine at hi doses effects what receptors?

low doses - beta 1 receptors

hi doses - beta 1, alpha and beta 2

 - chronotropic

+inotropic

due to the fact that it comes in 2 isomers, and one of the isomers doesn't have +chronotropic effects.

Low dose Epinephrine Response?

Primarily due to stimulation of ___ receptors?

• tachycardia
• hypotension
• also metabolic effects

due to stimulation of beta receptors

Epinephrine Hi Dose effects?

Primarily due to stimulation of what receptors?

• vasoconstriction-increased PR(alpha)
• hypertension (alpha)
• tachycardia (b1)
• positive inotropism (b1)

due to stimulation of alpha and beta receptors

E = work done/oxygen uptake

Epi decreases E because it increases Oxygen uptake

• angina can be caused by Epi because it decreases cardiac efficiency (i.e. insufficient coronary circulation)

• alpha 1 - ciliary vessel vasoconstriction
• alpha 2 (ciliary body)

Both reduce the aqueous humor formation

(also Beta 1 antagonist)

• Epi (topically)
• dipivephrine
• apraclonidine

Thereapeutic dose of Epi causes:

PR

Pulse Rate

SBP

DBP

MABP

- PR

+Pulse Rate

+SBP

-DBP (due to activity on B receptors)

+MABP

Therapeutic dose of NE causes:

PR

Pulse rate

SBP

DBP

MABP

+PR

-Pulse Rate

+SBP

+DBP

2+MABP

Therapeutic dose of ISO causes:

PR

Pulse Rate

SBP

DBP

MABP

2- PR

2+ Pulse Rate

+ SBP

-2 DBP

- MABP

• respiratory distress as aerosol - but has potential for other systemic effects
• prolong local anesthetic action - will cause vasoconstriction to keep local anesthetic in one are vs. systemically
• topical hemostatic - vasoconstriction
• Cardia arrest (directly on heart) - increase HR
• Topical in open angle glaucoma (muscarinic agonist in narrow angle glaucoma)

• increased susceptibility to pressor effects in HTN and Hyperthyroid patients (due to alpha agonism)
• Angina - epi reduces cardiac efficiency triggering angina
• Halogenate hydrocarbons and cycloproprane cause sensitized myocardium to arrhythmogenic effects. Increase risk for MI

Comparison of NE, EPI and ISO in vitro D/R plot

• Arterial smooth muscle
• bronchial smooth muscle
• cardiac inotropism

• arterial - EPI>NE>>>>>>>>>>ISO
• bronchial smooth muscle - ISO>EPI>>>>>NE
• ISO>EPI=NE

NE=NE+propranolol>>>>NE+phentolamine

NE has no affinity for B2 receptors in the arterioles

phentolamine = alpha antagonist, blocks the effects of NE binding to the alpha receptors in the arterials.

D/R plot of ISO, ISO+Phentolamine and ISO+propranolol in bronchial smooth muscle

• ISO=ISO+Phentolamine>>>>ISO+propranolol

EPI produces its contractility response by stimulating what receptors?

what is its DR plot with propranolol and phenteramine?

alpha

EPI=EPI+propranolol>>>>>EPI+phentolamine

Effect of administering a catecholamine agonist after denervation.

initially and weeks later

Initially - response is increased due to lack of re-uptake

weeks later - the receptors become upregulated due to the absence of the agonist, therefore the response is increased

catecholamine - slight increase due to postjunctional receptor upregulation

IAS - response is reduced or abolished because it requires an intact neuron to produce response

• catecholamine effect would increase because neuronal uptake would be impaired
• IAS response would decrease or be abolished because the IAS couldn't be taken up into the nerve, and the IAS is dependent on getting into the nerve to elicit a response

Before - phenylephrine (alpha agonist) will increase SBP and DBP

After, the alpha antagonist will prevent the increase in SBP and DBP

before - histamine decreases SBP and DBP

After - if histamine is administered after, it will prevent decreases. However, if H1 antagonist is administered and no histamine is released, there will be no effect because histamine receptors are non innervated

standing up - there is a lot of TONE. Therefore if you administer an alpha antagonist you'd get a BIG response (because big tone)

lying down - not a lot of tone. Therefore you don't get as big a response

decrease sympathetic neuron firing

vasoconstriction = HTN = reflex bradycardia (decrease in Sympathetic firing)

increases sympathetic neuron firing

vasodilation=hypotension=tachycardia (increase S firing)

• increase vagal nerve activity and decreases HR

• decreases vagal nerve activity and increase HR

Epi's metabolic effects on:

• Lactate
• FFA
• Glucose
• insulin release via alpha 2
• glucagon release beta 2
• adenyl cyclase and CAMP
• adipose TG lipase

• increased lactate release from muscle
• increase release of FFA
• increase release of glucose
• inhibits insulin release (alpha 2 agonism)
• increases glucagon release via b2
• increase adenylcyclase and CAMP
• increase breakdown of fat into FFA

• Phenylephrine (prototype)
• methoxamine
• metaraminol
• mephentermine

• albuterol
• terbutaline
• formoteril
• salmeterol
• metaproterenol
• ritodrine
• levalbuterol

bronchodilation

prevent premature labor - topolytics, reduce the excitability of uterine smooth muscle

• Tyramine-pns only
• ephedrine(CNS)
• amphetamine(CNS)
• methamphetamine(CNS)