11/2 Adrenergic Agonists_1/2- Corbett Flashcards
direct-acting adrenergic agonists
2 groups, examples within
1. endogenous catecholamines (affect both alpha and beta receptors)
- epinephrine
- norepinephrine
- dopamine
2. receptor-specific adrenergic agonists
- dobutamine
- isoproteronol
- albuterol
- phenylephrine
- clonidine
epinephrine
dose-dependent activation of adrenergic receptors
- equivalent efficacy across beta receptors (beta1 vs beta2) and alpha receptors (alpha1 vs alpha2)
- beta effects → higher affinity
significant CARDIOVASCULAR EFFECTS:
- beta1: positive inotrope and chronotrope
- issue for heart bc results in incr myocardial oxygen demand
- slight reduction in systemic vasc resistance (beta2 effect outweighs the alpha1 effect at low conc of epi)
- this effect switches up at high concentration! see overall contraction of vasc beds (see image)
overall effect: wide pulse pressure
mean arterial pressure does not change much during epi infusion
explain
MAP = 1/3 (systolic) + 2/3 (diastolic)
epi causes…
- incr systolic via beta1 receptors → pos inotropy/chronotropy
- incr diastolic via beta2 receptors → vasodilation
both effects tend to average each other out
systemic effects of epinephrine
- skeletal muscle
- metabolism
- bronchi
- heart
- gi tract
- kidney
clinical uses for epi
uses
toxicities
- # 1 drug of choice for anaphylaxis
- cardiac arrest
- asthma (esp bronchospasm)
- in combo with local anesthetic
- predominantly alpha adrenergic receptors on skin → vasoconstriction to keep an actual anesthetic local (prevents diffusion away)
- open-angle glaucoma
TOXICITY
- palpitations, HTN, tremor, anxiety
- contraindicated in pt on non-selective beta blockers and those with HYPERTHYROIDISM
norepinephrine
preference for alpha vs beta receptors? @ low conc
CV effects
dose-dependent responses
- hits alpha receptors equally (alpha1 vs alpha2), hits beta receptors UNEQUALLY (beta1 >>> beta2)
- at lower conc, preference for alpha receptors
CARDIOVASCULAR EFFECTS
- negligible direct effects on heart at low dose (bc predominant receptors in heart are beta1 and NE prefers alpha at low dose)
- alpha effect → arterial/venous constriction → increase in systemic vascular resistance
- incr systolic, incr diastolic
- net effect on MAP: increase!!! (distinct from negligible effect of epi on MAP)
- indirect baroreceptor effect: incr in bp → reflex drop in HR
effect of NE on MAP
net increase!
- incr in systolic
- incr in diastolic
dose response curve to NE
comparison of NE and epi
HR
bp
peripheral resistance
clinical uses of NE
1 for hypotension in sepsis! and cardiogenic shock
dopamine effects
DA effects are dose-dependent
- at higher doses, DA interacts promiscuously with other receptors (beta1 receptors, alpha receptors), so induces diff effects
- activation of DA1 receptors in kidney → increases renal blood flow and production of urine so overall: diuresis
- activation of beta1 receptors in heart → positive inotropy
- activation of peripheral alpha receptors → incr peripheral resistance
- increases work of heart; high HR can lead to arrythmia
clinical uses for IV dopamine
indications
toxicity
- hypotension
- low CO
but…
TOXICITY RISK: arrythmia (ventricular and supraventricular); wide QRS; angina
NE vs epi vs DA
receptor specific adrenergic agonists
nonselective alpha/alpha1 selective/alpha2 selective
nonselective beta/beta1 selective/beta2 selective
why is norepi in nonselective alpha agonist group?
- sometimes listed as that bc the alpha effects outweigh beta effects at small dose
alpha1 agonists
PHENYLEPHRINE (alpha1 selective agonist)
effects
- arterial vasoconstriction
- skin and splanchic vessels (mostly alpha)
- skeletal muscle too
- venous constriction → decr venous capacitance
- reflex decrease in HR
overall effect: increase in bp and baroreceptor reflex drop in HR
uses
- # 2 for hypotension (if unable to use NE)
- used for rhinitis (vasoconst in nose)
- mydriatic → will dilate pupils
alpha1 adrenergic agonists:
midodrine
midrodrine has a black box warning!
- rapidly absorbed after oral admin
- metabolized in liver/tissues → active metabolite (desglymidodrine)
- activates alpha1 receptors: vasoconst, incr sys/dia bp while standing/sitting/supine
indication: postural (orthostatic) hypotension when non-pharma tx fails
adverse fx: hypertension, esp when supine
i.e. increases vascular tone, but can shoot bp up when supine :(
alpha2 adrenergic agonists
effects
uses
toxicity
other drugs
CLONIDINE
key effects: act centrally to decrease SNS outflow
- decrease HR
- decrease systemic vasc resistance
- incr capacitance
uses
HTN, anxiolytic, ADHD
toxicity: dry mouth, sedation, depression
- rebound HTN
other drugs:
- guanabenz; guanfacine (not used)
- alpha-methyl-DOPA (for gestational HTN)
alpha2 and mixed adrenergic agonists
apraclonidine, brimonidine
- alpha2 agonist: decreases aqueous humor production; increased uptake
- use: glaucoma
oxymetazoline
- alpha1, alpha2 agonist
- use: OTC nasal decong and opthalmic drops to decr redness
- can lead to rebound effects
nonselective beta-adrenergic agonists
isoproterenol (IV only)
- equal beta effects (beta1 and beta2 effects are equivalent)
- beta1: incr HR, contractility, conduction vel
- beta2: decr peripheral vasc resistanct (decr afterload)
-
uses:
- Stokes Adams attack (syncope due to slow/absent pulse
- cardiac arrest, heart block, eval of tachyarrythmia
- toxicity: tachycardia, HTN, dysrhythmia
in image: note diff between peripheral resistance
- epi hits mostly beta2 but also hits alpha1 → overall drop in resistance thru dilation, but still some constriction balancing it out
- isoproterenol hits all beta2 with no counteracting balance → big drop in resistance thru dilation
beta1-selective adrenergic agonists
dobutamine (IV)
- beta1 selective; (-) isomer has some alpha1 activity
-
effects:
- pos inotropy (> chronotropic effect)
- alpha1 action: maintains peripheral resistance
-
uses:
- #1 drug for cardiogenic shock with maintained bp
- add to NE in septic show with low CO
- stress test
- toxicity: tachyarrhythmia, PVCs, HTN
beta2 selective adrenergic agonists
albuterol (short)
salmeterol (long)
- delivered via nebulizer or metered dose inhaler
- acts on beta2 receptors in lung
- uses: asthma, bronchospasm
- toxicity: tremor, nervousness
mixed-acting and indirect sympathomimetics
ephedrine, phenylpropanolamine (banned)
pseudoephedrine (decong)
atomoxetine (ADHD) : catecholamine reuptake inhibitor
amphetamine; methamphetamine
cocaine
summary chart
adrenergic agonists
