Term
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Definition
NE, epi, isoproterenol
Binding Affinity:
alpha = epi > NE > iso
beta = iso > epi > NE |
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Term
| Where are adrenergic receptors? |
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Definition
strictly in sympathetic (not somatic or parasymp.)
a1=vasculature
a2=presynaptic
b1=heart
b2=vasculature and bronchi |
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Term
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Definition
alpha and beta are both:
GPCR's with 7 transmembrane domains |
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Term
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Definition
a1: Gq -> PLC pathway -> increase DAG/IP3 -> PKC -> vasoconstriction
a2: feedback inhibition of NE release
b1,2,3: -> Gs -> AC pathway -> increase cAMP -> PKA
1=increase heart rate/contraction
2=vasodilation
3=lipolysis |
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Term
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Definition
inotrope = increase heart contractility
chronotrope = increase heart rate |
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Term
| Compounds that bind adrenergic receptors are derivatives of |
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Definition
b-phenylethylamine
the catecholamines have 2 -OH groups that facilitate COMT metabolism
removal of these provide a longer duration of action |
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Term
| Endogenous Andrenergic Agonist (1st) |
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Definition
Drug: epinephrine
Therapeutic Class: asthma attack, anaphylactic shock, cardiac arrest
Pharmacologic Class: adrenergic agonist (sympathomimetic), ionotrope, chronotrope
Med Chem: methylated amine -> favors BETA
Target MOA: favors beta, but will bind alpha
Tissue MOA:
Therapeutic = increase heart rate & contractility (b1); bronchodilation & vasodilation[skeletal muscle] (b2); vasonstriction[skin] (a1)
Undesireable = tremors, hyperactivity, insomnia, arrhythmias
Interactions = diabetes, hyperthyroidism, B-blocker, cocaine |
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Term
| Endogenous Adrenergic Agonist (2nd) |
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Definition
Drug: norepinephrine
Therapeutic Class: shock (acute drop in BP)
Pharmacologic Class: adrenergic agonist (sympathomimetic), vasopressor
Med Chem: NO methylated amine -> favors ALPHA
Target MOA: favors alpha, but will bind beta
Tissue MOA:
Therapeutic = vasonstriction (a1) increase BP
Undesireable = blanching of skin at injection site due to extreme vasocobnstriction |
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Term
| Direct Adrenergic Agonists (4) [sympatho... what?] |
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Definition
sympathomimetics (except a2)
phenylephrine (a1)
clonidine (a2)
dobutamine (b1)
albuterol (b2) |
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Term
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Definition
Therapeutic Class: nasal congestion
Pharmacologic Class: direct a1 adrenergic agonist (sympathomimetic), vasopressor
Tissue MOA:
Therapeutic = tx nasal congestion, vasoconstriction |
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Term
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Definition
Therapeutic Class: antihypertensive, opiod detox aid
Pharmacologic Class: direct a2 adrenergic agonist - sympathoLYTIC
Tissue MOA:
Therapeutic = inhibits NE release to reduce overall muscle tone |
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Term
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Definition
Therapeutic Class: tx congestive heart failure
Pharmacologic Class: direct b1 adrenergic agonist (sympathomimetic), ionotrope [no change in rate]
Med Chem: metabolized by COMT (short duration)
Tissue MOA:
Therapeutic = increase contractility -> increase cardiac output |
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Term
|
Definition
Therapeutic Class: asthma, COPD
Pharmacologic Class: direct b2 adrenergic agonist (sympathomimetic)
Tissue MOA:
Therapeutic = bronchodilation |
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Term
| Direct Adrenergic Antagonists (3) [sympatho... what?] |
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Definition
sympatholytics (except a2)
prazosin (a1)
yohimbine (a2)
metoprolol (b1) |
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Term
|
Definition
Therapeutic Class: antihypertensive
Pharmacologic Class: direct a1 adrenergic antagonist (sympatholytic)
Tissue MOA:
Therapeutic = vasodilation -> lower blood pressure; tx of BPH
Undesireable = "first-dose" effect: exaggerated orthostatic hypotension... may cause fainting; nasal congestion; ED |
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Term
|
Definition
Therapeutic Class: sexual stimulant
Pharmacologic Class: direct a2 adrenergic antagonist - sympathoMIMETIC
Tissue MOA:
Therapeutic = inhibits inhibition of NE release (so NE is released)
Undesireable = increase HR and BP |
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Term
|
Definition
Therapeutic Class: antihypertensive
Pharmacologic Class: direct b1 adrenergic antagonist (sympatholytic), NEGATIVE ionotrope
Tissue MOA:
Therapeutic = decrease heart contractility (decreases BP)
Notes: good choice for diatbetics or asthmatics because it is strictly selective for b1, so there wouldn't be any orthrostatic hypotension (no a1) or any bronchoconstriction (no b2) |
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Term
| Indirect Adrenergic agonists/antagonists |
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Definition
| work by modulating the pathway for epi, NE, dopamine (not receptors) |
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Term
| catecholamines (3)? AKA? derived? |
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Definition
epi, NE, dopamine
biogenic amines
tyrosine derivatives |
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Term
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Definition
Tyrosine uptake by aromatic aa transporter
Tyrosine hydroxylated to Dopa [RATE LIMITING STEP]
Dopa decarboxylated to Dopamine
Dopamine into vesicles via monoamine transporter (monoamine meaning it can also transport recycled epi and NE)
In vesicle, DA hydroxylated to NE, NE methylated to epi |
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Term
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Definition
Ca++ influx -> release
NE and DA stored in presynaptic nerves
NE and Epi stored in chromaffin cells in adrenal medulla |
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Term
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Definition
| not relevant for Indirect Agents |
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Term
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Definition
| re-uptake via Na/K ATPase [PRIMARY MECHANISM to terminate NE] |
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Term
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Definition
COMT in synapse
MAO in presynaptic neuron (mitochondria)
*both also in gut |
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Term
| Indirect Adrenergic Agonists (5) |
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Definition
Big Effect:
amphetamine - enhance NE release - tx hyperactivity
cocaine - block NE re-uptake [1º mechanism] - anesthetic
desipramine - block NE re-uptake [1º mechanism] - antidepressant
Small Effect:
pargyline - MAO inhibitor - antidepressant
tolcapone - COMT inhibitor - Parkinson's |
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Term
| Indirect Adrenergic Antagonists (5) |
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Definition
Big effect:
a-methyltyrosine - inhibit tyrosine hydroxylase [RATE-LIMITING for NE synthesis]
Small Effect:
carbidopa - inhibit dopa decarboxylase - Parkinson's
disulfiram - inhibit dopamine hydroxylase - alcoholism
Others:
reserpine & guanethidine
(historically used for hypertension) |
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