College of Nursing

1st Semester (S.Y. 2019-2020)

Sympathomimetics and
Sympatholytics
Terro Nikko M. Baluyut, RN, CRN, MD
Clinical Instructor
OVERVIEW
 Must Know Terms
• Anorexiant

• Catecholamine

• Decongestant

• Mydriatic
 Must Know Terms
• Selective alpha or beta adrenoceptor agonist

• Sympathomimetic

• Reuptake Inhibitor
 Must Know Terms
• Anorexiant

– Drug that decreases appetite

• Catecholamine

– Dihydroxyphenlethylamine derivative readily

metabolized by catechol-o-methyltransferase
 Must Know Terms
• Decongestant

– Alpha agonist drug that reduces conjunctival, nasal, or

oropharyngeal mucosal vasodilation by constricting
blood vessels in the submucosal tissue

• Mydriatic

– Drug that causes dilation of the pupil; opposite of miotic

 Must Know Terms
• Selective alpha or beta adrenoceptor agonist

– Drugs that have greater effects on alpha or beta

adrenoceptors; none are absolutely specific

• Sympathomimetic

– Drug that mimics stimulation of the sympathetic

autonomic nervous system
 Must Know Terms
• Reuptake Inhibitor

– Drug that increases activity of transmitters in the

synapse by inhibiting their reuptake into the
presynaptic nerve ending
RECEPTORS
 Sympathomimetics
• Mimic the effects of norepinephrine (NE) and
epinephrine (EPI)
 Sympathomimetics
• Located throughout the body

• Receptors for sympathetic neurotransmitters

Alpha adrenergic receptors  norepinephrine

Beta adrenergic receptors  epinephrine

 Alpha Adrenergic Receptors
• Divided into alpha1 and alpha2 receptors
(based on their locations on nerves)

– Alpha1  postsynaptic effector cells (cell, muscle,

organ that nerves stimulate)

– Alpha2  presynaptic nerve terminals (control

release of neurotransmitters)
 Alpha Adrenergic Receptors
• Predominant response:

– Vasoconstriction

– CNS stimulation
 Beta Adrenergic Receptors
• Divided based on their locations:

– Beta1 adrenergic receptors  heart (primarily)

– Beta2 adrenergic receprots  smooth muscles of

bronchioles, arterioles, and visceral organs
 Beta Adrenergic Receptors
• Primary response:

– Smooth muscle relaxation (bronchial,

gastrointestinal, and uterine smooth muscle
relaxation)

– Glycogenolysis

– Cardiac stimulation
 Dopaminergic Receptors
• Additional adrenergic receptor

• Stimulated by dopamine
 Dopaminergic Receptors
• Primary response: dilation (increased blood flow)

– Renal

– Mesenteric

– Coronary

– Cerebral
SYMPATHOMIMETICS
 Catecholamines
• Produce a sympathomimetic response

– Endogenous (epinephrine, norepinephrine,

dopamine)

– Synthetic (isoproterenol, dobutamine,

phenylephrine)
 Classification
• Spectrum of Action

• Mode of Action
 Classification
• Spectrum of Action

– Alpha, beta, or dopamine receptors (further into

subgroups)

– Prototypes: epinephrine (alpha & beta agonist)

phenylephrine (alpha agonist)
isoproterenol (beta agonist)

little effect on dopamine receptors

 Classification
• Spectrum of Action

– Dopamine (given as a drug itself) also activates:

• beta receptors (moderate doses)

• alpha receptors (higher doses)

 Classification
• Mode of Action

– Direct activation

– Indirect activation
 Classification
• Mode of Action

– Direct activation (binds directly to the receptor

and causes a physiologic response)
 Classification
• Mode of Action

– Indirect activation (increase concentration of the

endogenous catecholamine transmitter in the
synapse)
 Classification
• Indirect activation:

– Cause release of stored catecholamines

(amphetamines and tyramine)

– Inhibit reuptake of catecholamines (cocaine and TCA)

– Increase stores of catecholamine; potentiates

indirect acting agents (MAO inhibitors)
 Pharmacokinetics
• Relatively inactive by oral route; must be
given parentally

– Epinephrine

– Norepinephrine

– Dopamine
 Mechanism of Action
• Alpha receptor effects

• Beta receptor effects

• Dopamine receptor effects

 Mechanism of Action
• Alpha receptor effects

– Mediated by the trimeric coupling protein G4.

G4 activation  phospholipase C activation 

release of inositol 1,4,5-triphosphate (IP3) and
diacylglycerol (DAG) from membrane lipids 
calcium released by IP3; enzymes activated by DAG
 Mechanism of Action
• Alpha receptor effects

Note: alpha2 receptors activation results in

inhbition of adenylyl cyclase via coupling protein
Gi
 Mechanism of Action
• Beta receptor effects

– all beta receptors stimulate adenylyl cyclase via

coupling protein G3  increase in cyclic
adenosine monophosphate (cAMP) in the cell
 Mechanism of Action
• Dopamine receptor effects

– Activate adenylyl cyclase via Gs  increase cAMP

in neurons and vascular smooth muscle

Note: D2 receptors are more important in the

brain but may play possible roles in
presynaptic receptors in the peripheral nerves
 Effects
• Alpha adrenergic agents

• Beta adrenergic agents

• Dopaminergic agents
 Effects
• Alpha adrenergic agents

– Vasoconstriction of blood vessels

– Relaxation of GI smooth muscles

– Contraction of the uterus and bladder

 Effects
• Alpha adrenergic agents

– Male ejaculation

– Decreased insulin release

– Contraction of the ciliary muscles of the eye

(dilated pupils)
 Effects
• Beta adrenergic agents

– Bronchodilation

– Uterine relaxation

– Glycogenolysis (liver)
 Effects
• Beta adrenergic agents (B1)  cardiac stimulation
(myocardium, AV and SA nodes)

• Increased:

– Force of contraction (positive inotropic effect)

– Heart rate (positive chronotropic effect)

– Conduction through AV node (positive dromotropic effect)

 Effects
• Dopaminergic agents

– Depend on the dose (mixed activation of

receptors)
 Clinical Uses
• Anorexiant
• Anaphylaxis
• CNS
• Eye
• Bronchi
• Cardiovascular
• Genitourinary
 Clinical Uses
• Anorexiant

– Adjuncts to diet in the short-term management of

obesity

– Drugs: benzphetamine
phentermine
dextroamphetamine
dexedrine
 Clinical Uses
• Anaphylaxis

– Epinephrine (drug of choice for immediate

treatment of anaphylactic shock [hypotension,
bronchospasm, and angioedema])

– Antihistamines and corticosteroids are also used

but not as effective as epinephrine
 Clinical Uses
• CNS

– Amphetamine (narcolepsy, and weight reduction)

– Methylphenidate (ADHD)

– Often abused for purposes of deferring sleep and

mood-elevating, euphoria-producing effect (cocaine)
 Clinical Uses
• Eye

– Phenylephrine and tetrahydrozoline (reduce

conjunctival itching and congestion  from allergy
and irritation)

– Phenylephrine (mydriatic)

– Apraclonidine and brimonidine (glaucoma)

 Clinical Uses
• Bronchi

– Drugs of choice for acute asthmatic

bronchoconstriction

– Drugs: albuterol
metaproterenol
terbutaline
 Clinical Uses
• Cardiovascular

– Heart failure

– Septic and cardiogenic shock (norepinephrine)

 Clinical Uses
• Genitourinary

– Ritodrine and terbutaline (beta2 agonists) are

used to suppress labor

• Cardiac stimulant effect may be hazardous to the

mother and child
 Clinical Uses
• Genitourinary

– Ephedrine may be used for children (enuresis) and

elderly (urinary incontinence)
 Toxicity
• Little toxicity to the CNS because of their
limited ability to penetrate into the brain

• Effects are more evident in the periphery

ADRENOCEPTOR BLOCKERS
 Adrenergic Blockers
• Bind to adrenergic receptors but inhibit or
block stimulation of the sympathetic nervous
system

• Have opposite effect of adrenergic agents

– Adrenergic antagonists or sympatholytics

 Adrenergic Blockers
• Sympatholytics

– Inhibit or lyse sympathetic neurotransmitters

(norepinephrine and epinephrine)
 Sympatholytics
• Classified as either:

– α1 and α2 receptor blockers

– β1 and β2 receptor blockers

• Other classifications depend on reversibility

and duration of action
 Adrenoceptor
Antagonists

Alpha Blockers Beta Blockers

Alpha1 selective Alpha2 selective Beta1 selective Beta2 selective Non-selective

Non-selective
(Prazonsin) (Yohimbine) (Atenolol) (Butoxamine) (Propanolol)

Irreversible Reversible
Prazosin
(Phenoxybenzamine) (Phentolamine)
ALPHA BLOCKERS
 Adrenoceptor
Antagonists

Alpha Blockers

Alpha1 selective Alpha2 selective

Non-selective
(Prazosin) (Yohimbine)

Irreversible
Reversible
(Phenoxybenzamine
(Phentolamine)
)
 Classifications
• Phenoxybenzamine

– Irreversible, long-acting

– Prototype alpha blocker

– Slightly alpha1 selective

 Classifications
• Phentolamine

– Reversible, short-acting

– Competitive antagonist

– Does not distinguish between alpha1 and alpha2

receptors
 Classifications
• Prazosin

– Reversible

– Highly selective alpha1 blocker

– Similar drugs: Doxazosin

Terazosin
Tamsulosin
 Classifications
• Yohimbine

– Alpha2 selective blocker

– Used primarily in research applications

– Similar drug: Rauwolscine

 Pharmacokinetics
• Active through oral and parenteral route

– Phentolamine (rarely given orally)

 Mechanism of Action
• Phenoxybenzamine covalently binds to the
alpha receptor

– Irreversible blockade
 Mechanism of Action
• All the rest are competitive antagonists

– Effects can be counteracted by increased

concentrations of agonists

Note: important in the treatment of

pheochromocytoma (massive release of
catecholamines may overcome reversible
blockade)
 Effects
• Non-selective blockers

• Selective alpha blockers

 Effects
• Non-selective blockers:

– Most important are on the cardiovascular system

(reduction in vascular tone  decrease in arterial
and venous pressures)

– No significant direct cardiac effects

 Effects
• Non-selective blockers:

– Cause baroreceptor-mediated tachycardia (due to

drop in mean arterial pressure)

• May be exaggerated

• Alpha2 receptors in the heart (which reduce the net

release of norepinephrine) are also blocked
 Effects
• Selective alpha blockers

– Because they block alpha1 receptors more

effectively than alpha2 receptors, induce less
reflex tachycardia (than non-selectives)

– Useful in relaxing smooth muscles in the prostate

 Clinical Uses
• Non-selective alpha blockers

• Selective alpha blockers

 Clinical Uses
• Non-selective alpha blockers

– Limited clinical applications

– Pre-surgical management of pheochromocytoma (may have

severe hypertension and reduced blood volume  must be
corrected prior to surgery)

• Phenoxybenzamine (preparatory phase)

• Phentolamine (occasionally used during surgery)

 Clinical Uses
• Non-selective alpha blockers

– For reversal of accidental local infiltration of

alpha agonists (epinephrine) may cause severe
tissue ischemia and necrosis (uses phentolamine)

– Substance abuse/overdose (amphetamines,

cocaine, or phenylpropanolamine) may be
reversed
 Clinical Uses
• Non-selective alpha blockers

– Raynaud’s phenomenon (sometimes responds) but

efficacy is not well-documented

– Erectile dysfunction

• Phentolamine

• Yohimbine
 Clinical Uses
• Selective alpha blockers

– Hypertension (prazosin, doxazosin, and terazosin)

– Prevent urinary distention in benign prostatic

hyperplasia (+ tamsulosin, and silodosin)
 Toxicity
• Orthostatic hypotension

• Reflex tachycardia (non-selective alpha

blockers)
BETA BLOCKERS
 Adrenoceptor
Antagonists

Alpha
Beta Blockers
Blockers

Beta1 Beta2
Non-selective
selective selective
(Propanolol)
(Atenolol) (Butoxamine)
 Classification
• All are competitive antagonists

• Prototype drug is propanolol

 Classification
• Subgroups:

– Receptor selectivity

– Partial agonist activity

– Local anesthetic action

– Lipid-solubility
 Receptor Selectivity
• Beta1 selective

– Advantageous in treating asthma patients (functioning

B2 receptors are necessary to prevent bronchospasm)

– Drugs: Acebutolol
Atenolol
Esmolol
Metoprolol
 Receptor Selectivity
• Non-selective

– Nadolol

– Propanolol

– Timolol
 Receptor Selectivity
• Non-selective

Note: except for those starting with

“c” and “l”, all blockers starting with
letters from “a” to “m” are beta1 selective

Carvedilol and Labetalol have combined

alpha and beta-blocking activity
 Partial Agonist Activity
• Intrinsic sympathomimetic activity

– Advantageous in treating patients with asthma

– In theory, less likely to cause bronchospasm

– Drugs: Pindolol
Acebutolol
 Local Anesthetic Activity
• Membrane-stabilizing activity

– Disadvantage when beta blockers are used on the

eye (decreases protective reflexes  increases risk
of ulceration)

• Timolol (only one with absent local anesthetic effects,

and used in glaucoma)
 Effects and Clinical Uses
• Remarkably broad:

– Eye (open angle glaucoma)

– Heart(hypertension, angina, arrhythmia)

• maybe heart failure  labetalol, carvedilol, and

metoprolol
 Effects and Clinical Uses
• Remarkably broad:

– Pheochromocytoma  combined alpha and beta

blocker agents (when producing norepinephrine
and epinephrine)

– Infantile hemangioma  propanolol

 Toxicity
• Bradycardia

• AV blockade

• Heart failure
THANK YOU.