Week 6 - Sympathetic Nervous System Drugs

What is epinephrine?

What is salbutamol?

What is dopamine?

What is xylometazoline?

What is norepinephrine?

What is phenylephrine?

What is dobutamine?

What is labetalol?

What metoprolol?

What is midodrine?

What is tamsulosin?

What is terazosin?

What is atenolol?

What is bisoprolol?

Where is epinephrine synthesized from norepinephrine?

adrenal medulla

What is the principal mechanism for removal of the norepinephrine from the synaptic cleft?

neuronal re-uptake transporter (NET)

Where is the NET located?

pre-synaptic membrane

True or false: some of the norepinephrine in the junctional space of the synaptic cleft is metabolized within the extracellular space before even reaching the capillaries.

true

Which enzymes metabolize norepinephrine and epinephrine?

• catecho-O-methyltransferase (COMT)

• monoamine oxidase (MAO)

What is the first step of norepinephrine synthesis/release?

tyrosine (Tyr) is transported into the sympathetic nerve axon

What is tyrosine (Tyr) converted to after it reaches the sympathetic nerve axon?

DOPA

What is DOPA?

the rate-limiting step of norepinephrine synthesis

What is DOPA converted to?

dopamine

What happens in the norepinephrine synthesis/release process after DOMA converts to dopamine?

dopamine is transported into vesicles

What happens after dopamine is transported into vesicles?

it is converted into norepinephrine

What happens after dopamine is converted into norepinephrine?

an action potential (traveling down the axon) depolarizes the membrane and causes calcium to enter the axon

What does the increased intracellular calcium do in the process of norepinephrine synthesis/release?

causes the vesicles to migrate to the axonal membrane and fuse with the membrane

What happens after the vesicles and axonal membrane fuse together?

norepinephrine diffuses out of the vesicle → extracellular (junctional) space

What happens after norepinephrine diffuses out of the vesicles and into the junctional space?

norepinephrine binds to the post-junctional receptor and stimulates effector organ response

What are the neurotransmitter(s) of the sympathetic nervous system (SNS)?

• acetylcholine (ACh)

• norepinephrine

True or false: norepinephrine is a pre-ganglionic neurotransmitter.

false

What is the primary hormone of the sympathetic nervous system (SNS)?

epinephrine

What is the physiological purpose of the sympathetic nervous system (SNS)?

• fight or flight response (stress situations → stimulates endocrine system)

  • cold

  • trauma

  • hunger

  • exercise

  • fear

• continuous regulation/maintenance of blood vessel tone

Which fibers are longer: pre-ganglionic or post-ganglionic?

post-ganglionic

True or false: post-ganglionic fibers are long and have extensive branching.

true

What stimulates the release of acetylcholine (ACh)?

activation of pre-ganglionic fibers

What happens after the pre-ganglonic fibers release a

What are adrenergic receptors?

What are the different sub-types of adrenergic receptors?

• α₁

• α₂

• β₁

• β₂

• β₃

• DA1

What are the major functions of β₁ receptors?

• ↑ heart rate (chronotropy)

• ↑ contractility/stroke volume (inotropy)

• ↑ renin secretion

What are the major effector targets of β₁ receptors?

• cardiac muscle

• kidney

True or false: β₁ receptor activation within the kidneys causes the juxtaglomerular cells to synthesize/release renin.

true

What are the major functions of β₂ receptors?

• relaxation of smooth muscle (incld. bronchi)

• ↑ gluconeogenesis

• ↑ glucogenolysis

  • ↑ potassium uptake

What are the major effector targets of β₂ receptors?

• smooth muscle (incld. bronchi)

• liver

• skeletal muscle

What are the major functions of α₁ receptors?

contraction and constriction of smooth muscles and sphincters

What are the major functions of β₃ receptors?

↑ lipolysis

What are the major effector targets of α₁ receptors?

• smooth muscle

• sphincters

What are the major functions of α₂ receptors?

↓ transmitter release

What are the major effector targets of β₃ receptors?

adipose

What are the major effector targets of DA1 receptors?

• smooth muscle (especially renal)

• cardiac tissue

• mesenteric tissue

What are the major functions of DA1 receptors?

• relax renal vascular smooth muscle

  • higher doses activate α₁ and β₁ receptors

True or false: higher doses of DA1 activate both α₁ and β₁ receptors?

true

What are adrenergic agonists?

drugs that mimic the actions of norepinephrine or epinephrine

How are adrenergic agonists classified?

by their actions (direct, indirect, mixed) on α and β receptors

What is a sympathomimetic drug?

drugs that mimic the effects of sympathetic nervous system activation on the heart

In which conditions would sympathomimetic drugs be used?

Short term treatment of refractory heart failure and shock

What are catecholamines?

Where are adrenergic receptors located?

cell’s surface

True or false: β₃ is highly responsive compared to the other adrenergic receptors.

false

What happens if all of the receptors are activated simultaneously?

stimulation of adenylyl cyclase → increased conversion of ATP to cAMP

What is inotropy?

What is chronotropy?

What is dromotropy?

What is lusitropy?

True or false: adrenergic agonists are not usually household drugs.

false

What are some examples of adrenergic agonists that are household drugs?

• salbutamol

• salmeterol

• formoterol

• clonidine

• midodrine

• xylometazoline

• pseudoephedrine

What are cardiac indications for use of beta blockers?

• angina

• CHF

• HTN

• tachydysrhythmias

• acute myocardial infarction

• aortic dissection

• hypertrophic cardiomyopathy

What are non-cardiac indications for use of beta blockers?

• migraines

• PTSD

• glaucoma (eye drops)

• thyrotoxicosis

• pheochromocytoma

What are the cardiovascular adverse side effects of beta blocker usage?

• AV block

• bradycardia

• heart failure

• peripheral vascular insufficiency

What are the hematological adverse side effects of beta blocker usage?

• agranulocytosis

• thrombocytopenia

What are the CNS-related adverse side effects of beta blocker usage?

• dizziness

• mental depression

• lethargy

• hallucinations

What are the GI-related adverse side effects of beta blocker usage?

• nausea

• dry mouth

• vomiting

• diarrhea

• cramps

• ischemic colitis

True or false: impotence, rash, alopecia, and broncospasms are possible adverse side effects of beta blocker usage?

true