Adrenergic Agonists

Question 1

why must catecholamines be given via IV?

Answer 1

rapidly broken down by enzymes in GI tract (COMT - catechol-O-methyl transferase)

*also note catecholamines have high potency, though little penetration into the CNS

Question 2

describes the effects of alpha1 adrenergic receptor stimulation

Answer 2

increased vascular smooth muscle tone:

increased arteriolar tone —> increased arterial blood volume (less fluid leaks out in circulation) —> increased diastolic BP (vascular resistance)

increased venous tone —> increased venous return to heart —> increased SV —> increased systolic BP

minimal direct effects on heart

Question 3

where are alpha1 vs alpha2 adrenergic receptors found?

Answer 3

alpha1: found on organ system (post-synaptic)

alpha2: pre-synaptic membrane

Question 4

describe the effects of alpha2 adrenergic receptor stimulation

Answer 4

Gi —> decrease cAMP —> decrease Ca2+ influx —> decrease NE release —> decrease SNS tone —> decrease BP

effects largely in CNS in SNS motor center

Question 5

in simple terms, what is the effect of beta1 vs beta2 adrenergic receptor stimulation on the CV system?

Answer 5

beta1 (heart): increase rate, force, CO

beta2 (blood vessels): vasodilation

Question 6

describe the effects of epinephrine - which receptors does it bind, what does this cause?

Answer 6

epinephrine: endogenous catecholamine, agonist at both alpha and beta receptors, potent vasoconstrictor and cardiac stimulant —> increases SV, CO, BP (as well as myocardial O2 demand)

via beta1: positive inotropy/chronotropy
via alpha1: vasoconstriction
via beta2: vasodilation (skeletal muscle blood vessels)

at low doses, beta2 activation overrides alpha1 (—> small decrease in arteriolar resistance)

at higher doses, alpha1 activation occurs (—> increase in arteriolar resistance)

Question 7

for epinephrine, name the clinical uses (3), toxicities (4), and contraindications (2)

Answer 7

clinical uses: anaphylaxis (DOC), asthma, topical vasoconstriction

toxicities: palpitations, HTN, tremor, anxiety

contraindications:
- hyperthyroidism: have increase in adrenergic receptors, increasing sensitivity to epi
- non-selective beta-blocker use: creates un-opposed alpha receptor (vasoconstrictive) activation

Question 8

describe the effects of norepinephrine - which receptors does it bind, and what does this cause?

Answer 8

norepinephrine: endogenous catecholamine, agonist at both alpha1/alpha2 and beta1 —> increase peripheral resistance/ BP

via alpha1: vasoconstriction

induces reflex drop in HR that overcomes direct positive chronotropic effect of NE (while maintaining positive inotropic effect) —> increase in force of contraction without increase in HR

Question 9

contrast the effects of norepi and epi on peripheral resistance and BP

Answer 9

epinephrine: beta2 (vasodilation in skeletal muscle vasculature) > alpha1 (vasoconstriction) at low dose, so slight drop in peripheral resistance and no change in BP

norepinephrine: unopposed alpha1 (vasoconstriction) activation causes increase in peripheral resistance and increase in BP

Question 10

what is the clinical use of norepinephrine?

Answer 10

DOC (drug of choice) for hypotension in septic or cardiogenic shock

Question 11

describe the effects of dopamine - which receptors does it bind, and what does this cause?

Answer 11

dopamine: endogenous catecholamine, immediate precursor in synthesis of NE

low dose: binds D1 receptors in vascular beds (kidney) —> vasodilation

intermediate dose: also binds beta adrenergic receptors (heart) —> positive inotropy

high dose: also binds alpha adrenergic receptors (vasculature) —> vasoconstriction

Question 12

what are the clinical uses of dopamine? (3)

Answer 12

low blood pressure, low cardiac output, slow heart rate

caution: high doses can cause arrhythmias (ventricular, supraventricular), wide QRS, angina

Question 13

What type of receptor does phenylephrine bind to, and what is its effect?

Answer 13

phenylephrine: direct-acting (read: binds receptor) sympathomimetic, agonist of alpha1 adrenergic receptor

—> vasoconstriction —> increase in peripheral vascular resistance (arteries) and venous return (veins) —> increase BP

*note this causes reflex decrease in HR by high pressure baroreceptors

Question 14

what are the clinical uses of phenylephrine? (2)

Answer 14

Phenylephrine: direct-acting (read: binds receptor) sympathomimetic, agonist of alpha1 adrenergic receptor —> vasoconstriction

uses: #2 for hypotension if NE can’t be used, topical for rhinitis or red eyes

Question 15

Which type of receptor does clonidine bind to and what is its effect? What are its clinical uses?

Answer 15

clonidine: direct-acting (read: binds receptor) sympathomimetic, agonist of alpha2 adrenergic receptor

—> decreased SNS tone —> decreased BP, HR

clinical uses: HTN, ADHD
*note if stopped suddenly can lead to rebound HTN

Question 16

What type of receptor does alpha-methyl dopa bind and what effect does it exert? What is it specifically used for?

Answer 16

alpha-methyl dopa: alpha2 adrenergic agonist —> decreased SNS tone

clinical use for HTN in pregnancy only - known to be safe for fetus but has serous side effects (lupus-like syndrome, Direct Coombs positive hemolysis)

Question 17

What type of receptor does isoproterenol bind, and what is its effect? With this in mind, what are its clinical uses?

Answer 17

isoproterenol (isoprenaline): direct-acting (read: binds receptor) beta adrenergic agonist (beta1 or beta2)

—> positive inotropy/chronotropy (beta1), potent vasodilator (beta2) —> increased SV/CO —> increase systolic BP, but unopposed beta2 causes large drop in peripheral vascular resistance —> net effect is lower MAP

clinical use: very slow HR

caution: tachycardia, dysrhythmia, low BP

Question 18

compare the effects of norepinephrine and isoproterenol on HR

Answer 18

norepinephrine: binds alpha > beta adrenergic receptors, reflex drop in HR because of rise in BP

isoproterenol: binds beta > alpha adrenergic receptors, reflex increase in HR because of decrease in MAP

[both are agonists of these receptors]

Question 19

What type of receptor does dobutamine bind, and what is the effect of this? What are its clinical uses (2)?

Answer 19

Dobutamine: direct-acting (read: binds receptor) beta1 adrenergic agonist —> increases CO, positive inotrophy>chronotropy effect, no change in BP

clinical uses: DOC for cardiogenic shock with maintained BP, pharmacological stress test (increases myocardial O2 demand for patients who cannot do walking stress test)

Question 20

describe the mechanism and effect of cocaine on the CV system

Answer 20

cocaine: indirect sympathomimetic - doesn’t bind receptor, but inhibits NT reuptake at noradrenregic synapses

—> increased BP, ventricular wall stress, coronary vasoconstriction*

*normally alpha1 signaling doesn’t increase smooth muscle tone in coronary arteries because of larger effects of adenosine and NO (vasodilators), but cocaine can cause high enough levels of NE such that alpha1 signaling is sufficient to produce vasoconstriction of coronary arteries