Adrenergic and anti-adrenergic

drugs
Divisions of human nervous system
Nervous system
• Sympathomimetic or adrenergic in
sympathetic nervous system—
neurotransmitters are ____________
• Parasympathomimetic or cholinergic are used
to describe parasympathetic system—
neurotransmitter is _____________
Drugs Acting on the Sympathetic Nervous System
Drugs Acting on the Parasympathetic Nervous System
Sympathetic:
• Eyes: pupillary dilation
• CNS: ↑ drive
↑ Alertnes
• Saliva: little, viscous
• Bronchi: dilation
• Heart: ↑ rate
↑ force
↑ blood pressure
• Skin: perspiration (cholinergic)
• Fat tissue: Lipolysis, fatty acid liberation.
• Liver: glycogenolysis, glucose release
• Bladder: ↑ Sphincter tone
↓ detrusor muscle
• GI-tract ↓peristalsis ↓ blood flow ↑ sphincter tone
• Skeletal muscle: ↑ blood flow ↑ glycogenolysis
Parasympathetic
• Eyes: Accommodation for near vision, miosis
• Saliva: copious, liquid
• Bronchi: constriction, ↑ secretion
• Heart: ↓ rate↓ blood pressure
• GI tract: ↑ secretion ↑ peristalsis ↓ sphincter tone
• Bladder: ↓ sphincter tone ↑ detrusor
 Sympathetic nervous system
Fight or flight response results in:
1. Increased BP
2. Increased blood flow to brain, heart and
skeletal muscles
3. Increased muscle glycogenolysis for energy
4. Pupil dilation

• 2. Decreased flow to viscera: Also increased rate and depth of respiration,

increased blood sugar, increased mental acuity, increased muscle strength
1 SYNTHESIS OF NOREPINEPHRINE
• Hydroxylation of tyrosine is the rate- limiting step

2 UPTAKE INTO STORAGE VESICLES

• Dopamine enters a vesicle and is converted to norepinephrine.
• Norepinephrine is protected from degradation in the vesicle.
• Transport into the vesicle is inhibited by reserpine.

3 RELEASE OF NEUROTRANSMITTER
• Influx of calcium causes fusion of the vesicle with the cell membrane in a process known as exocytosis.
• Release is blocked by quanethidine and bretylium

4 BINDING TO RECEPTOR
• Postsynaptic receptor is activated by the binding of neurotransmitter.

5 REMOVAL OF NOREPINEPHRINE
• Released norepinephrine is rapidly taken into the neuron.
• Reuptake is inhibited by cocaine and imipramine.

6 METABOLISM

• Norepinephrine is methylated by COMT and oxidized by MAO.

 Adrenergic receptors
• Alpha—A1 and A2
• Beta—B1, B2, B3

• Alpha 1 receptors are in blood vessels, kidney, liver, pregnant

uterus, male sexual organs, intestinal smooth muscle. Causes
vasoconstriction, decreased renin secretion , uterine contraction
• Alpha 2—Inhibits release of norepinephrine. affects vascular
smooth muscle, inhibits insulin secretion, platelet aggregation
• B1—affects heart and kidneys
• B2—affects lungs, liver, blood vessel vasodilation, decreased
motility and tone
• Dopamine—blood vessels of kidneys, heart, viscera; brain
 Review of functions of sympathetic
nervous system receptors
• Alpha 1—smooth muscle contraction
• Alpha 2-negative feedback causes less
norepinephrine to be released so BP is
reduced
• Beta 1—increased heart rate
• Beta 2—bronchodilation
• Beta 3—actual site for lipolysis
 Mechanisms of action and effects of
adrenergic drugs
• Direct adrenergic drug action
• Affects postsynaptic alpha 1 and beta
receptors on target effector organs
• Examples: epinephrine, norepinephrine,
phenylephrine
 Mechanisms of action cont.
• 2. Indirect adrenergic drug action occurs by
stimulation of postsynaptic alpha 1, beta 1
and beta 2 receptors.Cause release of
norepinephrine into the synapse of nerve
endings or prevent reuptake of
norepinephrine.
• Examples include cocaine and TCAs
 Mechanisms of action cont.
• 3. mixed action. Combination of direct and
indirect receptor stimulation
• Examples are ephedrine and pseudoephedrine
 Mechanisms of action cont.
• Stimulation of alpha 2 receptors in CNS is
useful in decreasing BP
• Most body tissues have both alpha and beta
receptors
• Effect occurs 2ndary to receptor activated and
number of receptors in the particular body
tissue
 Mechanisms of action cont.
• Some drugs act on both
receptors(nonselective) --dopamine
• Some are selective--Isoproterenol
 Indications for use
• Emergency drugs in treatment of acute
cardiovascular, respiratory and allergic disorders
• In children, epinephrine may be used to treat
bronchospasm due to asthma or allergic reactions
• Phenylephrine may be used to treat sinus congestion
• Stokes Adams (Syncope 2* Heart Block)
• Shock
• For vasoconstrictive and hemostatic purposes
(Epistaxis)
Note: Phenylephrine can cause rebound congestion
 Contraindications to use of
adrenergics
• Coronary Artery Diseases, Angina Pectoris
• Hypertension
• Hyperthyroidism
• Cerebrovascular disease
 Individual adrenergic drugs
• Epinephrine—prototype
• Effects include: increased BP, increased heart
rate, relaxation of bronchial smooth muscle,
vasoconstriction in peripheral blood vessels

Note: Vasoconstriction shunts blood to heart and brain

 epinephrine
• Increased glucose, lactate, and fatty acids in
the blood due to metabolic effects

• Inhibition of insulin secretion

 epinephrine
• Affects both alpha and beta receptors
• Usual doses, beta adenergic effects on heart
and vascular smooth muscle will predominate,
high doses, alpha adrenergic effects will
predominate
• Drug of choice for bronchospasm and
laryngeal edema of anaphylaxis
 epinephrine
• Excellent for cardiac stimulantion and
vasoconstrictive effects in cardiac arrest
• Added to local anesthetic
• May be given IV, inhalation, topically
• Not PO
 epinephrine
• Physiologic antagonist to histamine
• Those on beta blockers may need larger doses
• Drug of choice in Pulseless Electrical Activity
• PEA (pulse electrical activity)
 Other adrenergics
• Ephedrine is a mixed acting adrenergic drug.
Stimulates alpha and beta receptors. Longer
lasting than epinephrine.
• Seen in Primatene mist as a nasal
decongestant
 PseudophedRINE
• Used for bronchodilating and nasal
decongestant effects in OTC cold products
 isuprel (Isoproterenol)
• Synthetic catecholamine that acts on beta 1
and 2 receptors
• Stimulates heart, dilates blood vessels in
skeletal muscle and causes bronchodilation
• No alpha stimulation
• Used in heart blocks (when pacemaker not
available) and as a bronchodilator
 Toxicity of adrenergics in critically ill
patients
• Affects renal perfusion
• Can induce cardiac dysrhythmias
• Increases myocardial oxygen consumption
• May decrease perfusion of liver
 Anti-adrenergics
• Sympatholytic
• Block or decrease the effects of sympathetic
nerve stimulation, endogenous
catecholamines and adrenergic drugs
 Antiadrenergics—mechanisms of
action and effects
• Can occur by blocking alpha 1 receptors
postsynaptically
• Or by stimulation presynaptic alpha 2
receptors. Results in return of norepineprhine
to presynaptic site. Activates alpha 2 resulting
in negative feedback. Decreases release of
additional norepinephrine.
 Alpha-Adrenergic Agonists and
blocking agents
• Alpha 2 agonists inhibit release of
norepinephrine; thus, decrease effects on
entire body
• Results in decrease of BP
Alpha 1 adrenergic blocking agents
• Act on skin, mucosa, intestines, lungs and
kidneys to prevent vasoconstriction
• Effects: dilation of arterioles and veins,
decreased blood pressure and pupillary
constriction; increases motility of GI tract
Alpha 1 adrenergic blocking agents
• May activate reflexes that oppose fall in BP
such as fluid retention and increased heart
rate
• Can prevent alpha medicated contraction of
smooth muscle in nonvascular tissues
• Thus, useful in treating BPH as inhibit
contraction of muscles in prostate and
bladder
 Alpha 1 antagonists
• Minipress (prazosin)—prototype.
• Hytrin (terazosin) and Cardura (doxazosin)—
both are longer acting than Minipress.
 Alpha 1 antagonists cont.
• Flomax (tamsulosin). Used in BPH. Produces
smooth muscle relaxation of prostate gland
and bladder neck. Minimal orthostatic
hypotension.
 Alpha 2 agonists
• Catapres (clonidine). PO or patch.
• Tenex (guanfacine)
• Aldomet (methyldopa). Can give IV. Caution in
renal and hepatic impairment.
Beta adrenergic blocking medications
• Prevent receptors from responding to
sympathetic nerve impulses, catecholamines
and beta adrenergic drugs.
 Effects of beta blocking drugs
• Decreased heart rate
• Decreased force of contraction
• Decreased CO
• Slow cardiac conduction
• Decreased automaticity of ectopic
pacemakers
 Effects of beta blocking drugs
• Decreased renin secretion from kidneys
• Decreased BP
• Bronchoconstriction
 Effects of beta blocking agents
• Decreased production of aqueous humor in
eye
• May increase VLDL and decrease HDL
• Diminished portal pressure in clients with
cirrhosis
 Indications for use
• Alpha 1 blocking agents are used for tx of
hypertension, BPH, in vasospastic disorders,
and in persistent pulmonary hypertension in
the newborn
• May be useful in treating pheochromocytoma
• May be used in Raynaud’s or frostbite to
enhance blood flow
 Indications for use
• Alpha 2 agonists are used for hypertension—
Catapres=Clonidine
 Beta blocking medications
• Mainly for cardiovascular disorders (angina,
dysrhythmias, hypertension, MI and
glaucoma)
• In angina, beta blockers decrease myocardial
oxygen consumption by decreasing rate, BP
and contractility. Slow conduction both in SA
node and AV node.
 Beta blockers
• Possibly work by inhibition of renin,
decreasing cardiac output and by decreasing
sympathetic stimulation
• May worsen condition of heart failure as are
negative inotropes
• May reduce risk of “sudden death”
 Beta blockers
• Decrease remodeling seen in heart failure
• In glaucoma, reduce intraocular pressur by
binding to beta-adrenergic receptors in ciliary
body, thus decrease formation of aqueous
humor
 Beta blockers
• Inderal (propranolol) is prototype
• Useful in treatment of hypertension,
dysrhythmias, angina pectoris, MI
• Useful in pheochromocytoma in conjunction
with alpha blockers (counter catecholamine
release)
• migraines
 Receptor selectivity
• Acetutolol, atenolol, betaxolol, esmolol, and
metoprolol are relatively cardioselective
• These agents lose cardioselection at higher
doses as most organs have both beta 1 and
beta 2 receptors
 Non-Receptor selectivity
• Carteolol, levobunolol, metipranolol, nadolol,
propranolol, sotalol and timolol are all non-
selective
• Can cause bronchoconstriction, peripheral
vasoconstriction and interference with
glycogenolysis
Specific conditions-alpha agonists and
antagonists
• In tx for BPH, patient should be evaluated for
prostate cancer
• With alpha 2 agonists, sudden cessation can
cause rebound BP elevation
• With alpha 1 blockers, first dose syncope may
occurr from hypotension. Give low starting
dose and at hs. May also cause reflex
tachycardia and fluid retention.
Note: May need diuretics
 Special conditions—beta blocers
• Should be discontinued gradually. Long term
blockade results in increase receptor
sensitivity to epinephrine and norepinephrine.
Can result in severe hypertension. Taper 1-2
weeks.
• Patient with asthma, cardioselectivity is
preferred
 Ethnic considerations
• Monotherapy in African Americans is less
effective than in Caucasians.