Adrenergic Agonists and Antagonists

What are the two parts of the autonomic system

parasympathetic and sympathetic

parasympathetic nervous system

the division of the autonomic nervous system that calms the body, conserving its energy

sympathetic nervous system

the division of the autonomic nervous system that arouses the body, mobilizing its energy in stressful situations

Effects of the sympathetic nervous system

dilated pupils, increased heart rate, dilated bronchi

constricted blood vessels, inhibits digestion, decreases serotonin

effects of the parasympathetic system

Decreases heart rate, constricts pupils, reduces ventilation rate, increases digestive activity, sexual arousal

increases serotonin

what is the difference between the autonomic system and somatic system ganglia

the somatic does not have ganglia and is direct to the skeletal muscle

what is the basic setup of the ganglia in the autonomic nervous system

preganglionic neuron

ganglionic transmitter: ach

receptor

postganglionic neuron

neuroeffector

effector organ

what does the sympathetic nervous system use to communicate with target orangs

Epinephrine and norepinephrine

what kind of receptor is on the effector organ for the sympathetic nervous system

adrenergic receptor

what kind of receptor is on the effector organ of the parasympathetic system

muscarinic

what kind of neuroeffector is the parasympathetic nervous system using

acetylcholine

What kind of receptors do norepinephrine and epinephrine have

use the same ones

metabotropic alpha 1/2 or beta-1/2/3

Basic mechanism of adrenergic effects

1. synthesis of norepinephrine

2. uptake into storage vesicle

3. release of neurotransmitter

4. Binding to receptor

5. Removal of norepinephrine

6. metabolism

synthesis of norepinephrine rate limiting step

hydroxylation of tyrosine is the rate limiting step

uptake into storage vesicles

dopamine enters a vesicle and is converted to norepinephrine

norepinephrine is protected

transport into the vesicle is inhibited by reserpine

what inhibits uptake into storage vesicles

reserpine

release of neurotransmitter

influx of calcium causes fusion of the vesicle with the cell membrane in a process called exocytosis

what promotes release of the neurotransmitter

amphetamines

removal of norepinephrine

released norepinephrine is rapidly taken into the neuron

what inhibits reuptake of norepinephrine

SNRIs cocaine and imipramine

metabolism

norepinephrine is methylated by COMT and oxidized by MAO

what are COMT inhibitors

entacapone and tolcapone

Modulation via Norepinephrine beta receptor upon its release

binds

G alpha activates adenylyl cyclase

conversion of ATP to cAMP

cAMP stimulates PK

phosphorylated K channel closes

cells more excited

what is a adrenergic receptor

GPCR receptors, primarily located in blood vessels, alpha and beta types whose primary ligands are epinephrine and norepinephrine

what is the function of alpha 1 adrenergic receptor

vasoconstriction

increase peripheral resistance

increased blood pressure

mydriasis

increase closure of bladder

Alpha 1 receptor has a greater affinity for

norepinephrine

Alpha 2 function

inhibits norepinephrine release

inhibits acetylcholine release

inhibits insulin release

alpha 2 receptors affinity is greater for

epinephrine

function of beta 1 receptor

increases heart rate, lipolysis, myocardial contractility

renin

beta 1 affinity is greater for

epinephrine and norepinephrine affinity is equal

function of beta 2 receptor

vasodilation

decreased peripheral resistance

bronchodilation

increased glucagon release and glycogenolysis

relaxes uterine muscle

Which organs does beta 1 associate with

heart and kidneys

Which organ(s) do beta 2 receptors associate with

lungs primarily

beta 2 has a higher affinity for

epinephrine (by a lot!)

How do a and beta receptors differ

affinity for various agonists

alpha highest for epinephrine and lowest for isoproterenol

beta highest for isoproterenol and lowest for norepinephrine

which receptor is not used clinically

alpha 2

What do selective beta blockers do and where do they act

used to decrease heart rate and blood pressure, on beta 1 receptors

where do nonselective beta blockers act and what do they do

block both B receptors, bronchoconstriction

What do direct acting adrenergic drugs do

act on postsynaptic receptors

what are examples of direct acting drugs

epinephrine

norepinephrine

isoproterenol

phenylephrine

what do mixed action drugs act on

direct stimulation of target and enhances release of NE from vesicles

Mixed action drug examples

pseudoephedrine

metaraminol

what do indirect acting drugs do

enhance the release of NE from the vesicles

examples of indirect acting drugs

amphetamines

cocaine

Affinity for B receptors increases as what gets larger

as the group on the amine nitrogen gets larger

Catecholamines

rapid onset of action

brief duration of action

not administered orally

do not pentrate the blood brain barrier

catecholamine drug examples

Epinephrine

NE

isoproterenol

dopamine

Non catecholamines

longer duration of action

orally administration or inhalation

How does epinephrine affect the heart

increases the rate and force of cardiac contraction

what is epinephrine's cumulative effect

increases systolic blood pressure

decreases diastolic pressure

respiratory effects of epinephrine

bronchodilation by acting directly on smooth muscle cells

epinephrine hyperglycemia effect

increased glycogenolysis in the liver increased release of glucagon and decreased release of insulin

what vessels does epinephrine constrict

arterioles in the skin

what vessels does epinephrine dilate

vessels to the liver and skeletal muscles

What is the onset of epinephrine

rapid onset with brief duration

what is epinephrine metabolized by

MAO and COMT

preferred route of epinephrine

intramuscular anterior thigh

Therapeutic uses of epinephrine

bronchospasm

cardiac arrest

anesthetics

duration of local anesthesia

topical

what kind of effect can a single cartridge of local at a 1:100,000 ratio with E have on plasma epinephrine concentration

doubling effect

CNS adverse effects of epinephrine

anxiety, fear, tension, headache, tremor

cardiac adverse affects of epinephrine

trigger cardiac arrythmias, especially if pt is using digoxin

Adverse effects of epinephrine in diabetic patients

release of endogenous stores triggered and may need to up the dose of insulin

Adverse effects of epinephrine in pits with hyperthyroidism

increased production of adrenergic receptors in vasculature leads to hypersensitive response

how can inhalation of epinephrine affect the heart

sensitive the heart to the effects of epinephrine

tachycardia

Why is there a risk of hypertensive episodes with nonselective B blockers

they prevent vasodilatory effects of epinephrine on B2 receptors leaving the A receptor stimulation unopposed

Which receptor blocker is responsible for vasodilation

alpha 1 blocker

Which receptor blocker is responsible for stopping norepinephrine release inhibition

alpha 2 blocker

What do Beta 1 blockers do

decrease in cardiac hyperactivity

What do B2 blockers do

lead to bronchoconstriction

why should you be cautious when using propranolol in diabetic patients

it can inhibit actions of catecholamines released in response to hypoglycemia and complicate therapy of diabetic patients and block warning signs of hypoglycemia and delay recovery

why should you be cautious when using bet blockers for pts with severe allergies

can be ineffective in patients taking beta blockers already

why should you be careful when moving a patient that is taking an adrenergic antagonist

lower blood pressure increases risk of fainting