Adrenergic Agonists

What does β1 receptor activation do in cardiac cells

Increases heart rate, contractility, and relaxation via cAMP and PKA signaling

What second messenger is activated by β1 receptors

cAMP

What enzyme does cAMP activate

Protein Kinase A (PKA)

What does PKA do in cardiac cells

Phosphorylates L-type Ca²⁺ channels, phospholamban, troponin I, and phospholemman

What is the result of β1 activation on cardiac function

Stronger contraction (inotropy), faster heart rate (chronotropy), and better relaxation (lusitropy)

What signaling pathway is triggered by α1 receptor activation

Gq → PLC → IP3 and DAG → Ca²⁺ release → smooth muscle contraction

What does IP3 do

Triggers Ca²⁺ release from the endoplasmic reticulum

What does DAG do

Activates Protein Kinase C (PKC)

What does Ca²⁺ bind to in smooth muscle

Calmodulin

What enzyme is activated by Ca²⁺-calmodulin

Myosin Light Chain Kinase (MLCK)

What does MLCK do

Phosphorylates myosin → enables actin-myosin cross-bridging → contraction

How does cAMP activate PKA

Binds to regulatory subunits → releases catalytic subunits → phosphorylation of targets

What are three key targets of PKA

Phospholamban, Troponin I, Phospholemman

What does EPAC stand for

Exchange Protein Activated by cAMP

What does EPAC activate

RAP GTPases

What are EPAC’s roles

Cell adhesion, cytoskeletal dynamics, proliferation, insulin secretion

How does cAMP affect pacemaker activity (chronotropy)

Binds to HCN channels → increases Na⁺ influx → faster SA node depolarization → increased heart rate

How does cAMP affect cardiac contractility (intropy)

Enhances L-type Ca²⁺ channel activity → more Ca²⁺ influx → stronger contraction

What does β1 activation in the kidney do

Increases renin secretion → activates RAAS → raises blood pressure

What does β2 activation do in skeletal muscle vasculature

Causes vasodilation

What does β2 activation do in bronchial smooth muscle

Causes bronchodilation

How do adrenergic receptors maintain continence

β2 relaxes detrusor muscle; α1 contracts internal urethral sphincter

What happens during micturition

Parasympathetic tone increases → detrusor contracts → sphincter relaxes

What does α2 activation in the pancreas do

Inhibits insulin secretion → preserves blood glucose during stress

How does α2 inhibit insulin

Via Gi protein → ↓ cAMP → ↓ PKA → ↓ insulin exocytosis

What does β2 activation in the liver do

Stimulates glycogenolysis and gluconeogenesis → increases blood glucose

Why can β2 agonists worsen hyperglycemia in diabetes

They increase hepatic glucose output while insulin remains impaired

What does α1 activation do to blood vessels

Vasoconstriction

What does β2 activation do to blood vessels

Vasodilation

Why do β2 agonists cause reflex tachycardia

Vasodilation → ↓ BP → baroreceptor reflex → ↑ HR

How does β2 stimulation cause skeletal muscle tremors

↑ cAMP → ↑ PKA → ↑ calcium handling → ↑ excitability → tremors

Why does albuterol cause tremors

Systemic β2 stimulation in skeletal muscle → increased neuromuscular sensitivity

What receptor does phenylephrine activate

Selective α1 agonist

What does phenylephrine do

Vasoconstriction → ↑ SVR → ↑ BP; also used for nasal decongestion and mydriasis

Why is phenylephrine used in hypotensive shock

Raises BP without increasing HR → avoids myocardial oxygen demand

Why is phenylephrine used cautiously in diabetes

Can increase blood glucose via hepatic α1 stimulation

How does clonidine lower BP

Activates central α2 receptors → ↓ sympathetic tone → ↓ HR and vasodilation

Why does clonidine cause dry mouth

α2 activation in salivary glands inhibits ACh → ↓ saliva production

What is the active metabolite of methyldopa

Alpha-methylnorepinephrine

What is methyldopa’s pregnancy category

Category B → safe for hypertension in pregnancy

What receptor does dobutamine target

Selective β1 agonist

How does dobutamine affect BP

↑ HR and contractility → ↑ CO and tissue perfusion

Why is albuterol preferred over isoproterenol in asthma

Albuterol is β2 selective → bronchodilation without cardiac stimulation

Why is mirabegron used for overactive bladder

β3 agonist → relaxes bladder with minimal cardiovascular effects

How does cocaine increase NE signaling

Inhibits NE reuptake transporter (NET) → NE accumulates in synapse

Why is cocaine used as a local anesthetic

Blocks voltage-gated Na⁺ channels → inhibits nerve conduction

Why isn’t amphetamine used as a local anesthetic

It increases NE release but doesn’t block nerve conduction

How does amphetamine increase NE release

Reverses NET, SERT, DAT → forces NE out of presynaptic neuron

What is the half-life of cocaine

About 1 hour

What is the half-life of amphetamine

About 12 hours

What is pseudoephedrine’s mechanism

Mixed agonist → binds α1/α2 and releases NE → vasoconstriction

Why is pseudoephedrine effective for congestion

Vasoconstriction reduces mucus production and nasal swelling