exam 1 lecture 6-7-8 sympathomimetics Flashcards by Tandrew Nguyen

sympathomimetics

mimicking sympathetic activity
adrenergic agonists

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monoamine

amine connected to aromatic carbon by 2-carbon chain
serotonin, dopamine, norepinephrine, epinephrine

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catecholamine

monoamine with a catechol ring (benzene w/ 2-hydroxy)
DA, NE, E

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biosynthesis of catecholamines

L-tyrosine –> L-dopa –> dopamine –> NE (presynaptic vesicle) –> E (adrenal medulla)

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NE neurotransmission

tyrosine transported in –> dopa (tyrosine hyrdoxylase) –> dopamine (dopa decarboxylase)
dopamine into VMAT gets converted to NE by dopamine hydroxylase
release of NE when action potential opens Ca+ channels
NE releases and binds adrenergic R + regulatory R
NE that diffuses out of cleft gets reuptaken and metabolized by MAO
NE diffuses away from cleft metabolized by COMT

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COMT

oral drugs
high activity in liver
metabolizes catecholamines

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MAO

high neuronal
high activity in nerve terminal
metabolizes monoamines

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stereochemistry

NE + E have R conformation on B-carbon. required for high affinity binding to receptor

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A1 R

vasoconstriction
pupillary dilation
ejaculation
inhibit urination
GI inhibit

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A2 R

prejunctional inhibition of NE release
decrease in CV SNS input (CNS)
vasoconstriction (minor)

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B1 R

cardiac stimulation
secretion of renin (increase BP)

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B2 R

bronchodilation
uterine relaxation
vasodilation
GI inhibit
cardiac stimulation (minor)

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direct acting adrenergic receptor agonists

NE + E

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norepinephrine

a1(vasoconstriction), a2(inhibit NE release), B1( cardiac stim)
substrate for MAO + COMT –> fast metabolism
parenteral admin + sodium bisulfite to prevent oxidation

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epinephrine

a1(vasoconstriction), a2, B1(cardiac stim), B2 (bronchodilation)
substrate MAO + COMT
sodium bisulfite to prevent oxidation
uses: anaphylaxis /cardiac arrest
combo with local anesthetics to cause vasoconstriction –> prevent spread of anesthesia
low conc: targets B1 + B2 high conc: target A1

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dopamine

low dose: D1 - vasodilation for blood flow B1 - cardiac stimulation
high dose: A1 - vasoconstriction
uses: shock + acute heart failure

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dobutamine

B1 + a1 receptor agonist
B1 - cardiac stimulation
a1 - vasoconstriction
racemic mixture –> to exert stronger effect
metabolized by COMT not MAO
uses:

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A1 receptor subtypes (Gq)

main function mediates vasoconstriction
agonist: nasal decongestant, vascular failure in shock, supraventricular tachycardia
antagonist: hypertension, benign prostatic hyperplasia, pheochromocytoma (tumor)

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A1 direct acting receptor agonist

phenylephrine
methoxamine
oxymetazoline

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phenylephrine

1 hydroxy on benzene ring –> a1 selectivity
use: nasal decongestant, mydriasis, pressor, vasoconstriction
admin: parenteral, local, oral (not substrate for COMT)

2-aralkylimidazolines

direct a1 adrenergic agonist
vasoconstriction
r - substituted aromatic ring structure
x - methylene or amino

a2 receptor agonist

inhibit sympathetic output: inhibit release of NE + decrease CV SNS input
agonist: HTN, pain, glaucoma0
brainstem controls CV action, a2 inhibits output from brain

clonidine

selective a2 receptor agonist
decrease SNS output to heart + blood vessels

guanbenz + guanfacince

open-ring, bridge decreases pka –> unionized –> cross BBB

methyldopa + methyldopate

methyldopa: prodrug, good for CNS bc no b-hydroxy (more lipophillic), HTN methyldopate: more water soluble ester --> parenteral use

brimodine

glaucoma --> a2 R agonist in eye --> to inhibit aqueous humor production

B1 receptor function (Gs)

increase HR, conduction, contraction increase renin release agonist: shock, congestive heart failure antagonist: HTN, angina, arrthymias, congestive heart failure

B2 receptor function (Gs)

bronchodilation + vasodilation agonist: asthma + COPD antagonist: glaucoma

B3 receptor function (Gs)

urinary bladder relaxation agonist: OAB

isoproterenol

nonselective B receptor antagonist B1 (cardiac stim) + B2(vaso + bronchodilation) COMT not MAO metabolized emergency use: increase HR + bradycardia

baroreceptor - decrease BP

reflex tachycardia: increase in HR (B1) vasoconstriction (a1) net: increase BP

baroreceptor - increase BP

reflex bradycardia

baroreceptor - NE (a1 + b1)

a1 - vasoconstricts b1 - cardiac stimulation (increase HR) hr decreases; bp increase bc of reflex tachycardia

baroreceptor - E (a1, b1, b2)

a1 - vasoconstricts b1 - cardiac stim hr increase b2 - vasodilates + bronchodilates hr increase, bp stays same

baroreceptor - isoproterenol (b1 + b2)

B1 - cardiac stimulation B2 - vasodilator Hr increases, BP decreases

B2 agonist

'erol' bronchodilation not metabolized by MAO + COMT albuterol, salmeterol, formeterol, metaproterenol

SAR

MAO: NE > E > Isoproterenol > colterol catechol: B meta OH : a1 meta-hydroxymethyl: b2 two meta OH: b2

b3 agonist

mirabegron - OAB

indirect sympathomimetics

does not bind NE receptor promotes NE by reverse action PM transporter --> lot of NE at synapse

amphetamines

ADHD --> no catechol, chirality, b-hydroxy use: ADHD + nacrolepsy ejects NE to synapse for prolonged stim treatment overdose: acidify urine = increase secretion

phentermine/topiramete

approved for weightloss

ephredrine

b-hydroxy --> direct binding to a + b R --> use for weightloss + increase muscle strength increase HR + BP do not take with MAOI

sudafed

L-config of b-hydroxy --> nasal decongestant increase HR + BP no MAOI

MAOI

avoid with ephedrine + sudafed NE will not get metabolized --> hypertensive crisis

wine/cheese effect

thymine = indirect sympathomimetic agent MAOI decreases breakdown of thymine --> bolus release of thymine\

NET inhibitors

cocaine, methylphenidate, atomoxetine

cocaine

blocks NET, decreases uptake + enhance NE signalling local anesthetic sides: increase BP + HR

methylphenidate

DAT + NET inhibitor, so more DA + NE at synaptive cleft ADHD + narcolepsy

atomoxetine

NET inhib to enhance NE levels