ADRENERGIC AND ANTI-ADRENERGIC

DRUGS
 DIVISIONS OF HUMAN NERVOUS SYSTEM

Central
Nervous
Human System
Nervous system Peripheral Autonomic
Nervous Nervous
System System
NERVOUS SYSTEM

Peripheral
Includes neurons and ganglia outside of the Nervous
brain and spinal cord
System

*Autonomic Somatic Nervous

*Either “fight and flight” Nervous
mode orSystem
“rest and digest”System
(involuntary) (voluntary)

Parasympathetic
Sympathetic
With neurotransmitters Nervous System
Nervousnorepinephrine
System and acetylcholine
(cholinergic)
(adrenergic)
 Sympathomimetic or adrenergic in sympathetic
nervous system—neurotransmitters are
____________
 Parasympathomimetic or cholinergic are used to
describe parasympathetic system—
neurotransmitter is _____________
 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 glycogen for energy

4. Increased rate of coagulation

5. Pupil dilation
 ADRENERGIC RECEPTORS
 Alpha—A1 and A2
 Beta—B1, B2, B3
 Dopamine—subsets D1-5
 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, Isuprel, 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--dopamine
 Some are selective--Isuprel
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
INDICATIONS OF ADRENERGICS CONT.
 Stokes Adams
 Shock
 Inhibition of uterine contractions
 For vasoconstrictive and hemostatic purposes
CONTRAINDICATIONS TO USE OF ADRENERGICS

 Cardiac dysrhythmias, angina pectoris

 Hypertension
 Hyperthyroidism
 Cerebrovascular disease
 Distal areas with a single blood supply such as
fingers, toes, nose and ears
 Renal impairment use caution
INDIVIDUAL ADRENERGIC DRUGS
 Epinephrine—prototype
 Effects include: increased BP, increased heart
rate, relaxation of bronchial smooth muscle,
vasoconstriction in peripheral blood vessels
 EPINEPHRINE
 Increased glucose, lactate, and fatty acids in the
blood due to metabolic effects
 Increased leukocyte and increased coagulation
 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 stimulant 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 PEA. Vasopressin has now
become drug of choice in ventricular tachycardia
 Single dose of Vasopressin, 40 units IV
OTHER ADRENERGICS
 Ephedrine is a mixed acting adrenergic drug.
Stimulates alpha and beta receptors. Longer
lasting than epinephrine.
 See in Primatene mist
PSEUDOPHED
 Used for bronchodilating and nasal decongestant
effects
 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
NEOSYNEPHRINE (PHENYLEPHRINE)
 Pure alpha
 Decreases CO and renal perfusion
 No B1 or B2 effects
 Longer lasting than epinephrine
 Can cause a reflex bradycardia
 Useful as a mydriatic
 TOXICITY OF ADRENERGICS IN CRITICALLY ILL PATIENTS

 Affects renal perfusion

 Can induce cardiac dysrhythmias
 Increases myocardial oxygen consumption
 May decrease perfusion of liver
 Tissue necrosis with extravasation
 TOXICITY
 Do not give epinephrine and Isuprel at same time
or within 4 hours of each other. Could result in
serious dysrhythmias.
 ANTI-ADRENERGICS
 Sympatholytic
 Block or decrease the effects of sympathetic
nerve stimulation, endogenous catecholamines
and adrenergic drugs
 ANTIADRENERGIC S—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

in brain; thus, decrease effects on entire body
 Results in decrease of BP
 Also affects pancreatic islet cells, thus some
suppression of insulin secretion
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, pupillary constriction, and
increased 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.
 Priscoline (tolaxoline) used for vasospastic
disorders. Pulmonary hypertension in newborns.
Can be given sub Q, IM or IV.
 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
 Less effective metabolism of glucose. May result
in more pronounced hypoglycemia and early s/s
of hypoglycemia may be blocker (tachycardia)
 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
REGITINE (PHENTOLAMINE)
 Used for extravasation of potent vasoconstrictors
(dopamine, norepinephrine) into subcutaneous
tissues
 INDICATIONS FOR USE
 Alpha 2 agonists are used for hypertension—
Catapres
 Epidural route for severe pain in cancer
 Investigationally for anger management, alcohol
withdrawal, postmenopausal hot flashes, ADHD,
in opioid withdrawal and as adjunct in anesthesia
 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
 BETA BLOCKERS
 In cirrhosis, Inderal may decrease the incidence
of bleeding esophageal varices
 Used to be contraindicated in heart failure, now
are standard
 Known to reduce sudden death
 Often given with ACEIs
 Indications include: htn, angina, prevention of MI
 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
 Byetta is new agent that is cardioselective
 NON-RECEPTOR SELECTIVITY
 Carteolol, levobunolol, metipranolol, nadolol,
propranolol, sotalol and timolol are all non-
selective
 Can cause bronchoconstriction, peripheral
vasoconstriction and interference with
glycogenolysis
 COMBINATION SELECTIVITY
 Labetalol and carvedilol (Coreg) block alpha 1
receptors to cause vasodilation and beta 1 and
beta 2 receptors which affect heart and lungs
 Both alpha and beta properties contribute to
antihypertensive effects
 May cause less bradycardia but more postural
hypotension
 Less reflex tachycardia
INTRINSIC SYMPATHOMIMETIC ACTIVITY
 Have chemical structure similar to that of
catecholamines
 Block some beta receptors and stimulate others
 Cause less bradycardia
 Agents include: Sectral (acebutolol), Cartrol
(carteolol), Levatol (penbutolol) and Visken
(pindolol)
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.
 SPECIFIC CONDTIONS-BETA BLOCKERS
 With significant bradycardia, may need med with
ISA such as pindolol and penbutolol
 Patient with asthma, cardioselectivity is preferred
 For MI, start as soon as patient is
hemodynamically stable
 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.
 ETHNIC CONSIDERATIONS
 Monotherapy in African Americans is less
effective than in Caucasians.
 Trandate (labetalol) with both alpha and beta
effects has been shown to be more effective in
this population than Inderal, Toprol or timolol.