Sympathomimetics 6, 7 & 8 Flashcards
What is a monoamine?
Has one amino group connected to aromatic ring by a two carbon chain.
What are examples of monoamines?
Serotonin, dopamine, norepinephrine, epinephrine and histamine
What is a catecholamine?
Monoamine with catechol group.
What are examples of catecholamines?
Norepinephrine, dopamine and epinephrine
Where are catecholamines synthesized come from?
L-tyrosine
What is the rate limiting step for catecholamine synthesis?
The enzyme tyrosine hydroxylase which will make L-tyrosine a catecholamine.
Where is norepinephrine made?
Presynaptic vesicle
Where is epinephrine made?
adrenal medulla by an enzyme found in the kidneys called Phenylethanolamine N-methyltransferase
What are the functional groups of the catecholamine that allow it to bind to the adrenergic receptor?
Catechol, Beta hydroxyl and amine group.
At physiological pH, NE and E are 98% ionized
Of the beta receptors which are the major and minor ones?
Major are B1 and B2.
Minor is B3.
What is the difference between direct acting and indirect acting sympathomimetic agents?
Direct acting bind to the adrenergic receptor and show activity.
-alpha and beta agonist
Indirect acting don’t bind to the adrenergic receptor or show binding.
-amphetamines (releasers) and cocaine (reuptake inhibitors)
What is alpha 1 activity?
Gq - excitatory
Vasoconstriction when activated.
Causes pupillary dilation, midriasis.
Ejaculation
Inhibit urination and GI
What is alpha 2 activity?
Gi/o - inhibitory
Vasoconstriction when activated
Prejunctionally inhibits NE release
In CNS decreases CV SNS input
What is beta 1 activity?
Gs - stimulatory
activation causes cardiac stimulation
Secretion of renin, produced from aldosterone due to decreased salt or low Blood Volume which will help regulate BP.
What is beta 2 activity?
Gs- stimulatory
activation causes cardiac stimulation
Bronchodilation
Relaxation of uterine
GI inhibition
Vasodilation
What receptor activity does NE have?
A1, B1 and A2
can’t bind B2 due to lack of methyl that epinephrine has.
What receptor activity does E have?
A1 + A2, B1 + B2
will favor Beta receptor over alpha
What happens as you add more methyl groups to the amine R1 group?
Receptor selectivity switches from alpha 1 to beta 2.
MAO activity also decreases.
What happens when you modify the catechol ring?
Normal catechol results in beta over alpha selectivity.
Making the 2 hydroxyl groups in the meta position results in B2 selectivity NO COMT
Adding a meta methyl to a hydroxyl group results in B2 selectivity NO COMT
Only meta hydroxyl group results in A1 selectivity.
What is important to know about NE?
Not orally available due to COMT quick metabolism. Parenteral
Can bind A1 (vasoconstriction leads to high BP) A2 and B1 (cardiac stimulation increase force and conduction) as agonist
Used as pressor (treat hypotension)
What is important to know about E?
Binds all 4 adrenergic receptors
A1: (vasoconstriction leads to high BP)
B1: (cardiac stimulation increase force, rate and conduction)
B2: (vasodilation leading to fall in blood pressure and bronoconstrction)
Substrate for MAO and COMT
Many dosage forms.
Used in anaphylaxis with local anesthetics
What is the action and clinical use of E?
Low [] effects B1 and B2
High [] effects a1 predominant
Clinical: acute anaphylaxis and cardiac effect with local anesthetics due to vasoconstriction.
What does NE look like for the heart rate and BP
Increase in BP
Increase in HR
What does E look like for the heart rate and BP
BP remains
Increase in HR
