Sympathomimetics Flashcards
Sympathomimetic drugs work at what receptors?
Adrenergic and Cholinergic
What type of receptors are Adrenergic receptors?
G protein coupled
What are 3 main classes of adrenergic receptors?
alpha-1, alpha-2, beta-1, beta-2, dopamine
What does stimulation of alpha 1 receptor with NE or epi do?
fight/flight; mydriasis, increase BP, increase HR, urinary retention, gluconeogenesis (make sugar)
What does beta-1 receptor activation with epi do?
increase conduction through SA node so increase HR, increase CO, increase BP, increase renin release.
What does stimulation of beta-2 receptor do?
bronchodilate, pancreas increase production to combat sugar.
What do agonists at the alpha-1 receptor sites do to calcium?
increase levels of calcium
What do alpha-2 agonists do to cAMP
decrease cAMP levels when stimulated by INHIBITING adenylate cyclase
What g-protein is at alpha-1 receptors?
Gq
What g-protein is at alpha-2 receptors?
Gi
What g-protein is at beta 1-2 receptors?
Gs
Which g-protein is inhibitory?
Gi, inhibits adenylate cyclase, Gi and Gs are stimulatory
What’s the effector at alpha-1 receptors?
phospholipase C
What’s the 2nd messengers at alpha-1 receptors?
IP3, Ca+, DAG
What is the effector at alpha-2 receptors?
adenylate cyclase
What are the 2nd messengers at alpha-2 receptors?
ATP, cAMP (inhibited)
What is the effector at beta 1-2 receptors?
Adenylate cyclase
What are the 2nd messengers at beta 1-2 receptors?
ATP, cAMP.
Which beta receptor has a higher affinity for epi than norepi?
beta-2, beta-1 has equal affinity for epi and norepi
What happens with action at dopamine-1 receptors?
STIMULATE adenyl cyclase due to INCREASED cAMP, causes relaxation.
What happens with action at dopamine-2 receptors?
INHIBIT adenyl cyclase, opens K channels, DECREASE calcium influx; primarily in brain
What neurons synthesize dopamine?
CNS neurons
What neurons synthesize epinephrine?
2nd order neurons of the SNS in adrenal medulla
What neurons synthesize Norepi?
2nd order neurons of the SNS in adrenal medulla and CNS neurons
How are sympathomimetics grouped?
by mode of action and spectrum of receptors they affect; direct mode, indirect mode
What’s the ratio of epi:norepi in the blood from adrenals?
80%epi:20% norepi
What are some alpha agonists?
phenylephrine/methoaxamine, clonidine
What are the mixed alpha/beta agonists?
norepi, epi
What are the beta agonists?
dobutamine, isoproterenol, terbutaline/albuterol
What are the dopamine agonists?
dopamine
What receptors does phenyl have more affinity for?
A1>A2»B
What receptors does clonidine have more affinity for?
A2>A1»B
What receptors does Norepi have more affinity for?
A1=A2; B1>B2
What receptors does Epi have more affinity for?
A1=A2; B1=B2
What receptors does dobutamine have more affinity for?
B1>B2»A
What receptors does isoproterenol have more affinity for?
B1=B2»A
What receptors does terbutaline/albuterol have more affinity for?
B2>B1»A
What receptors do dopamine agonists have more affinity for?
D1=D2»B»A
What is the parent drug that sympathomimetic drugs are derived from?
Phenylethylamine
What substitutions yield catecholamines?
subs by OH groups at the 3 and 4 positions on the benzene ring
What metabolic effects do sympathomimetics have?
enhance glycogenolysis in liver leading to increased glucose in circulation, high catecholamine presence in system can cause metabolic acidosis
What do alpha and beta receptors do to the blood vessels?
Alpha increase arterial resistance, beta promote smooth muscle relaxation
What effect do pure alpha agonists have on BP?
increase in peripheral arterial resistance and decreased venous capacitance so increase BP and slow HR due to baroreceptor mediated increase in vagal tone
What effect do pure beta agonists have on BP?
increased cardiac output, decreased peripheral vascular resistance by dilating vascular beds so increased or decreased BP with decreased DBP
What effect do mixed alpha/beta agonists have on BP?
skeletal muscle bed relaxation so decreased DBP but alpha constriction of arterial beds
Which receptor directly affects the heart?
beta-1, increased chronotropy and increased conduction velocity through AV node, increased contractility
What affects on the respiratory system do beta-2 have?
bronchodilation
What do alpha agonists do to the eye?
mydriasis (dilation) of pupil
What do alpha and betas do to the GI tract?
relaxation
What receptors are at bladder base and urethral sphincter?
alpha–promote urinary continence
Where is epi synthesized, stored, and released?
adrenal medulla
What are the clinical uses of epinephrine?
anaphylaxis, glaucoma, asthma, vasoconstrictor for LA, CPR, hemo instability, promote inotropy during weaning from bypass
Discuss synthesis of epi.
Tyrosine +tyrosine hydroxylase >dihydroxyphenylalanine (DOPA) + DOPA decarboxylase >dopamine +dopamine beta-hydroxylase >Norepi +phenylethanolamine N-methyltransferase >Epi
What is the limiting factor in the synthesis of epi?
tyrosine hydroxylase.
What reduces tyrosine hydroxylase?
too much NE
How much of the release of NE undergoes reuptake?
80%, to the presynaptic nerve
How else is norepi removed from the site of action?
reuptake by extraneuronal tissues containing MAO and COMT; diffusion away from synaptic cleft–metabolized by the kidney and liver by COMT and MAO
What does COMT metabolize epi to?
metanephrine
What does MAO metabolize epi to?
dihydroxymandelic acid
What does COMT metabolize dihydroxymandelic acid to?
Vanillylmandelic acid (VMA)
What does MAO metabolize NE to?
dihydroxymandelic acid
What does COMT metabolize NE to?
normetanephrine
What does MAO metabolize metanephrine and normetanephrine to?
Vanillylmandelic acid (VMA)
What do you do if your patient gets nauseous when you lay them down after a spinal.
treat BP…likely due to hypotension
What drug do you use if infant BP drops?
Ephedrine…stroke volume is fixed in peds so the only way to fix is by fixing heart rate
What 2 IV push meds do you have ready for a trauma coming into your room?
epi and vasopressin IV push. double dilute epi to get 10mcg/mL, draw vaso in 19cc saline to get 1u/mL
