adrenergic pharmacology - wordpress.com
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Adrenergic Pharmacology
Wonder Abotsi, PhD
Department of Pharmacology, KNUSTRoom C114; [email protected]
Lecture Outline
▪Introduction
▪Pharmacology of Adrenergic Transmission
▪Adrenergic Agonists (Sympathomimetics)
▪Adrenergic Antagonists
References
▪Katzung et al, Basic & Clinical
Pharmacology
▪Rang & Dale's Pharmacology
▪Lippincott’s Illustrated Reviews
Autonomic Pharmacology
▪ Autonomic drugs are used clinically to either imitate or inhibit the normal
functions of the sympathetic and parasympathetic nervous systems
▪ used extensively in medicine for managing cardiovascular, respiratory,
renal, pulmonary and gastrointestinal disorders.
▪ Side effects and interactions associated with many drug classes can be
attributed to autonomic mechanisms
▪ A large number of drug classes interact with autonomic systems to
produce a stunning number of possible side effects
Central nervous system (CNS) Peripheral nervous system (PNS)
Motor (efferent) divisionSensory (afferent)division
Somatic nervoussystem
Autonomic nervoussystem (ANS)
Sympatheticdivision
Parasympatheticdivision
Enteric division is a specialized network of nerves and ganglia forming an independent nerve network
within the wall of the gastrointestinal (GI) tract.
Organization of the Nervous
System
Autonomic Nervous System
(ANS)
▪The ANS consists of motor neurons that:
▪Innervate smooth and cardiac muscle and
glands
▪Make adjustments to ensure optimal support
for body activities
▪Operate via subconscious control
Divisions of the ANS
1.Sympathetic division
2.Parasympathetic division
▪ Dual innervation
▪Most visceral organs are served by both
divisions; typically counterbalance each
other’s activity
Role of the Parasympathetic Division
▪Promotes maintenance activities and conserves body energy; the “resting and digesting” system
▪Its activity is illustrated in a person who relaxes, reading, after a meal▪Blood pressure, heart rate, and respiratory rates are low
▪Gastrointestinal tract activity is high
▪Pupils are constricted and lenses are accommodated for close vision
▪SSLUDD
Role of the Sympathetic Division
▪Mobilizes the body during activity; the
“fight-or-flight” system
▪Promotes adjustments during exercise, or
when threatened – physical/emotional stress
▪Blood flow is shunted to skeletal muscles and
heart
▪Bronchioles dilate
▪Liver releases glucose
Fight or flight
▪Acceleration of heart and lung action
▪Liberation of nutrients for muscular action
▪Constriction of blood vessels in many parts of
the body
▪Dilation of blood vessels for muscles
▪Dilation of pupil
▪Inhibition of stomach and intestinal action
▪Inhibition of tear glands and salivation
▪Relaxation of bladder
Division Origin of
Fibers Length of
Fibers Location
of Ganglia
Sympathetic Thoracolumbar region of the spinal cord
Short preganglionic and long postganglionic
Close to spinal cord
Parasympathetic Brain and sacral spinal cord (craniosacral)
Long preganglionic and short postganglionic
In visceral effector organs
ANS Anatomy
Salivaryglands
Eye
Skin*
Heart
Lungs
Liverand gall-bladder
Genitals
Pancreas
Eye
Lungs
Bladder
Liver andgall-bladder
Pancreas
Stomach
Cervical
Sympatheticganglia
Cranial
Lumbar
Thoracic
Genitals
Heart
Salivaryglands
Stomach
Bladder
Adrenalgland
Parasympathetic Sympathetic
Sacral
Brainstem
L1
T1
Skeletal muscle
Cell bodies in centralnervous system Peripheral nervous system Effect
+
+
Effectororgans
ACh
AChSmooth muscle
(e.g., in gut),
glands, cardiac
muscle
Ganglion
Adrenal medulla Blood vessel
ACh
ACh
ACh
NE
Epinephrine andnorepinephrine
Acetylcholine (ACh) Norepinephrine (NE)
Ganglion
Heavily myelinated axon
Lightly myelinated
preganglionic axon
Lightly myelinatedpreganglionic axons
Neuro-transmitterat effector
Unmyelinated
postganglionic
axon
Unmyelinated
postganglionic axon
Stimulatory
Stimulatory
or inhibitory,
depending
on neuro-
transmitter
and
receptors
on effector
organs
Single neuron from CNS to effector organs
Two-neuron chain from CNS to effector organs
SO
MA
TIC
NE
RV
OU
SS
YS
TE
M
AU
TO
NO
MIC
NE
RV
OU
S S
YS
TE
M
PA
RA
SY
MP
AT
HE
TIC
SY
MP
AT
HE
TIC
Motor Nerves of the Peripheral Nervous
System
Actions on Selected Effector Organs
I
StructureSympathetic Activation Parasympathetic
Activation
Iris
Radial Muscle
Sphincter Muscle
Pupil dilated--
--Pupils constricted
Glands
Lacrimal
Salivary
Sweat
--
Scanty, viscous secretion
Secretion, palms (Adren)Generalized secretion (ACh)
Secretion
Profuse, watery secretion
Heart
Rate
Force (Ventricles)
Increase
Increase
Decrease--
Blood Vessels Contraction (generally)
Dilation (some)
Slight effect; Dilation in
some
Actions on Selected Effector Organs II
Structure Sympathetic Activation Parasympathetic
Activation
Bronchi Relaxed Constricted
GI tract
Muscle wall
Sphincters
Relaxation(Tone & motility
decreased)
Contraction
Contraction (Tone &
motility increased)
Relaxation
Adrenal
Medulla
Secretion of EPI and NE --
Sex Organs Vasoconstriction,
Contraction of vas deferens,
seminal vesicle and
prostatic musculature
(ejaculation)
Vasodilation & erection
Function of Pupil
Bladder
Pharmacology of
Adrenergic Transmission
Adrenergic Transmission
▪Neurotransmission takes place at numerous beadlike
enlargements called varicosities
Adrenergic Transmission
Adrenergic Transmission
Adrenergic Transmission
▪The process involves five steps:
▪Synthesis
▪Storage
▪Release
▪Receptor binding of neurotransmitter
(Noradrenaline)
▪Removal of the neurotransmitter from the
synaptic gap
Transmission
Adrenergic Transmission
Catecholamines
Synthesis of catecholamines
Tyrosine hydroxylase
DOPA decarboxylase
Dopamine β-hydroxylase
Phenylethanolamine
N-methyltransferase
Tyrosine
DOPA
Dopamine
Noradrenaline
Adrenaline
INHIBITOR
α-methyltyrosine
(metyrosine)
carbidopa
α-methyl DOPA
rate limiting step
α-methyldopamine
α-methyl NA
= a false transmitter
amine group
catecholgroup
“nor” = one methyl group less
Adrenergic transmission: targets for drug
action
Also:
o Drugs that inhibit
enzymes e.g.
carbidopa
o Neurone blocker
agents e.g. bretylium,
guanethidine
o Indirect
sympathomimetics e.g.
tyramine
Or Uptake 1
Or Uptake 2
Metabolism of catecholamines
▪ Determination of the 24-
h excretion of
metanephrine,
normetanephrine, VMA
and other metabolites
provides a measure of
the total body
production of
catecholamines
▪ Useful in diagnosing
conditions such as
phaeochromocytoma.
used as an antidepressant
used in Parkinson’s disease
Substrates & inhibitors for MAO
Type A Type B
Preferred substrates Serotonin
Noradrenaline
Phenylethylamine
Benzylamine
Non-specific substrates Dopamine
Tyramine
Specific inhibitors Clorgyline,
moclobemide
Selegiline
Non-specific inhibitors Tranylcypromine
Phenelzine
Iproniazid
Tyramine
• Tyramine is a normal by-product of tyrosine metabolism in the body and can be produced in high
concentrations in protein-rich foods by decarboxylation of tyrosine during fermentation.
• It is readily metabolized by MAO in the liver and is normally inactive when taken orally because of a
very high first-pass effect.
A Food-Drug Interaction
Tyramine Interaction with MAO
Inhibitors: the “Cheese Reaction”
▪ Tyramine (contained in certain foods,
e.g. aged cheeses, chicken liver, beer,
and red wines) is normally inactivated
by MAO in the gut.
▪ Individuals receiving a MAO inhibitor
are unable to degrade tyramine
obtained from the diet.
▪ Tyramine enters nerve terminals (via
Uptake 1) and displaces NA from
storage vesicles.
Tyramine Interaction with MAO
Inhibitors: the “Cheese Reaction”
• Large amounts of stored catecholamines from nerve
terminals resulting in severe throbbing headache,
tachycardia, nausea, hypertension, cardiac
arrhythmias, and stroke.
• Patients must therefore be educated to avoid
tyramine-containing foods.
• Treatment: α-blocker or Labetalol (α-, β-blocker)
Reserpine
▪Herbal drug, used to treat hypertension and insanity
▪Disrupts the transport process of NA->vesicles by
inhibiting VMAT
▪Nerve impulse releases “empty” vesicles
▪Get a profound fall in blood pressure
▪Major side-effect is depression; suicide common (
NA in the brain)
Rauwolfia (Indian Snake Root)
Amphetamine
▪ an indirect sympathomimetic and drug
of abuse
▪ Mechanism of action
▪ Substrate for Uptake 1 (NET).
▪ Enters nerve terminals and displaces NA
from vesicles.
▪ The NA not destroyed by MAO, can be
counter transported out of the terminal via
Uptake 1.
▪ Amphetamine can also inhibit MAO -
further augmentation of NA actions
Amphetamine
▪ CNS actions of amphetamine
▪ CNS stimulation, Locomotor stimulation, Euphoria , Loss of appetite (leading to anorexia).
▪ Amphetamine - ‘drug of abuse’
▪ Tolerance -higher concentrations and more frequent administration are required to gain the
same “high”.
▪ Development of psychosis
▪ Addicts suffer from: auditory and visual hallucinations, paranoia and aggression.
▪ Clinically has been used to
▪ Treat narcolepsy,
▪ Postpone fatigue/sleep (in emergency situations)
▪ Treat obesity
Storage, Synthesis & Release of
Noradrenaline - Summary
▪Enhance or mimic noradrenergic transmission
▪ Release – amphetamine and tyramine
▪ Block reuptake – cocaine
▪ Agonists – phenylephrine
▪Reduce noradrenergic transmission
▪ Inhibit synthesis – α-methyltylrosine, carbidopa, disulfiram
▪ Disrupt vesicular storage – reserpine
▪ Inhibit release – guanethidine
▪ Receptor antagonist - prazosin
Adrenergic Receptor
Subtypes
Adrenergic receptors
▪Two receptor families, initially identified on the basis of their
response to the catecholamines, adrenaline (epinephrine),
noradrenaline (norepinephrine) & isoprenaline (isoproterenol).
▪ -adrenoceptor
▪ Excitatory effects on smooth muscle
▪ Order of agonist potencies: NA>ADR>>ISO
▪ -adrenoceptors
▪ Relaxant effect on smooth muscle, stimulatory effect on heart
▪ Order of agonist potencies: ISO>ADR>NA
Subdivision of -adrenoceptors
▪1-adrenoceptors: located post-synaptically i.e.
predominantly on effector cells
▪ important in mediating constriction of resistance vessels in
response to sympathomimetic amines
▪2 -adrenoceptors: located on presynaptic nerve
terminal membrane
▪ their activation by released transmitter causes negative
feedback inhibition of further transmitter release
2-adrenoceptor
circulating
AD
+
Feedback control via 2- and 2-
adrenoceptors
Subdivision of -adrenoceptors
▪1-adrenoceptors
▪cardiac muscle, juxtaglomerular cells, GI
smooth muscle
▪2-adrenoceptors
▪bronchial, vascular and uterine smooth muscle
▪-adrenoceptors
▪ fat cells, bladder detrusor muscle
Dopamine (DA) Receptors
▪DA can activate adrenergic receptors in
some tissue
▪There are specific and important
dopamine receptors in the body, e.g.
Brain, Renal and mesenteric vasculature
▪D1 type (D1&D5)
▪D2 type (D2, D3 & D4)
Responses Associated With Types Of
Adrenoceptors –
Alpha1 Alpha2
• arterial and arteriolar constriction
(cutaneous, visceral, skeletal &
pulmonary)
• venous constriction
• uterine contraction
• pupillary dilation (contraction of radial
smooth muscle of iris)
• contraction of ureter
• contraction of spleen
• contraction of pilomotor muscles
• contraction of GIT/bladder sphincters
• hepatic glycogenolysis
• smooth muscle proliferation (e.g. in
blood vessels & in the prostate gland)
• inhibition of NE release
• Inhibits sympathetic
outflow (brain stem)
• inhibition of ganglionic
transmission
• vasoconstriction• (quantitatively less
important than α1)
• Inhibition of insulin
release
• Platelet aggregation
Responses Associated With Types Of
Adrenoceptors –
Beta1 Beta2
•cardiac stimulation
(chronotropic, inotropic,
dromotropic)
•stimulation of renin
secretion
• arteriolar dilation (skeletal
muscle, coronary visceral
beds)
• intestinal relaxation
• bronchiolar relaxation
• uterine relaxation
• bladder body relaxation
• stimulation of insulin release
• skeletal muscle tremor
• stimulation of glycogenolysis
(hepatic & skeletal)
• Skeletal muscle K+ uptake
Beta3
•stimulation of lipolysis (β3)• Bladder detrusor muscle
relaxation
Therapeutic Uses
vascular smooth muscle
contraction
α1
inhibition of transmitter
release
α2
cardiac stimulation β1
vascular smooth muscle
relaxation
β2
bronchiolar smooth
muscle relaxation
β2
Adrenergic Agonists
(Sympathomimetics/Adrenomimetics)
Sympathomimetics
▪mimic the effects of endogenous
catecholamines such as
norepinephrine and epinephrine (i.e.
stimulation of the sympathetic
autonomic nervous system).
Sympathomimetics (Adrenergic Agonists)
Direct Acting Sympathomimetics
▪ 1, 2, 1, 2 — adrenaline (epinephrine)
▪ 1, 2, 1- noradrenaline (norepinephrine)
▪ 1 - phenylephrine; methoxamine
▪ 2 - clonidine
▪ 1, 2 -Oxymetazoline
▪ 1, 2 - isoprenaline (isoproterenol)
▪ 1 - dobutamine
▪ 2 - terbutaline; salbutamol (albuterol); metaproterenol
▪ Mixed Action Sympathomimetic Amines
▪ ephedrine
▪ Indirectly Acting Sympathomimetic
Agents
▪ amphetamine; tyramine
Alpha Agonists
Pharmacological
Effects
Applications
Vasoconstriction Nasal decongestion,
systemic vasoconstriction,
to retard absorption of local
anaesthetics, ophthalmic
vasoconstriction
Contraction of radial
smooth muscle of iris
Mydriasis; to permit fundic
examination
Examples: phenylephrine, metaraminol,
methoxamine
Beta Agonists
Pharmacological Effects Applications
Cardiac stimulation To treat inadequate
cardiac output
Bronchial smooth muscle
relaxation
Treat bronchospasm
Vasodilation Peripheral Vascular
Disease
Uterine relaxation Premature Labour
dobutamine, metaproterenol (orciprenaline),
terbutaline, ritodrine, salbutamol (albuterol).
Indirect Acting
Pharmacological Effects Applications
Vasoconstriction Nasal decongestion
Bronchodilation Asthma
CNS effects: stimulation Narcolepsy
Hyperkinetic Syndrome
Anorexigenic Obesity
Ephedrine, Amphetamine, Phenylpropanolamine,
Cyclopentamine, Tuaminoheptane, Naphazoline,
Tetrahydrozoline
Catecholamine & BP
Dopamine
◼ MECHANISM: Complex mixture of α and β effects (with no particular
selectivity), indirect sympathomimetic actions, and direct action on
dopamine receptors.
◼ PHARMACOLOGICAL EFFECTS
— Vasodilatation in renal and mesenteric beds, mediated by dopamine
receptors
— Cardiac Stimulation - increase in rate, force, cardiac output, mediated
by 1-receptors.
— Vasoconstriction - at high concentrations, mediated by a1 receptors.
◼ THERAPEUTIC USES: Shock/Chronic Refractory Congestive Failure
Dobutamine
▪MECHANISM: Selective for 1-receptors
▪PHARMACOLOGICAL EFFECTS
▪ Cardiac stimulation - force increases more than rate,
consequently cardiac output increases without a dramatic
increase in heart rate.
▪THERAPEUTIC USES
▪ short-term treatment of cardiac decompensation that may occur
after cardiac surgery
▪ in patients with congestive heart failure or acute myocardial
infarction.
Terbutaline
Others: Orciprenaline (metaproterenol), salbutamol
(albuterol) and ritodrine
▪MECHANISM: Selective for 2-receptors
▪PHARMACOLOGICAL EFFECTS: Smooth muscle
relaxation, esp. airway smooth muscle
▪THERAPEUTIC USES
▪Reversible bronchospasm (major use)
▪ To delay premature labor (minor use)
Ephedrine
▪ MECHANISM: indirectly acting with some direct effects on
both α and receptors
▪ PHARMACOLOGICAL EFFECTS
▪ vasoconstriction, positive inotropic effect, relaxation of bronchiolar
smooth muscle, mydriasis, CNS stimulation
▪ THERAPEUTIC USES
▪ bronchospasm, nasal decongestant, mydriatic, narcolepsy (major
uses).
▪ Relief of pain of dysmenorrhoea (minor)
Amphetamine
▪ MECHANISM: indirectly acting
▪ PHARMACOLOGICAL EFFECTS
▪ Systemic - vasoconstriction, cardiac stimulation
▪ Central - in general, stimulatory. Acts in medulla, cortex,
cerebrospinal axis. Anorexigenic.
▪ THERAPEUTIC USES: narcolepsy, hyperkinetic syndrome,
obesity, fatigue
▪ Cardiac arrest: Adrenaline intravenously, or sometimes via an endotracheal
tube.
▪ Cardiogenic shock: Dobutamine (1-agonist) by intravenous infusion for its
positive inotropic effect; low-dose dopamine to increase renal perfusion (via
dopamine receptors in renal vasculature) and maintain glomerular filtration .
▪ Heart block: symptomatic heart block is treated by electrical pacing; b-
agonists (isoprenaline) can be used temporarily while this is being
arranged.
▪ Hypotension: norepinephrine, phenylephrine, methoxamine; chronic
orthostatic hypotension: oral ephedrine, midodrine
Uses of Sympathomimetics: CVS
Uses of Sympathomimetics:Allergic Reactions
▪Acute anaphylactic (Type I hypersensitivity) reactions
▪Sudden and sometimes life-threatening immunological
reactions , usually caused by bee stings or by hypersensitivity
reactions to drugs (especially penicillin).
▪ Adrenaline is the first-line treatment, usually injected
intramuscularly; intravenous infusion requires close monitoring,
usually in an intensive care unit.
Uses of Sympathomimetics:
Respiratory System
▪ Asthma: selective 2-receptor agonists (salbutamol,
terbutaline, salmeterol) by inhalation; salbutamol by
intravenous infusion in severe attacks.
▪Nasal decongestion: drops containing oxymetazoline
or ephedrine for short-term* use.
*Rebound congestion with long-term use
Uses of Sympathomimetics:
Ophthalmic Applications
▪ Mydriatics: to facilitate examination of the
retina. E.g. phenylephrine
▪Glaucoma: Apraclonidine and brimonidine
lower intraocular pressure.(α2 )
Uses of Sympathomimetics: CNS
▪ Narcolepsy and Related Syndromes:
amphetamine, dextroamphetamine,
methamphetamine, modafinil, armodafinil
▪Attention-Deficit/Hyperactivity Disorder (ADHD):
Methylphenidate, dextroamphetamine, and
amphetamine
Uses of Sympathomimetics: Miscellaneous indications
▪Prolongation of local anaesthetic action: vasoconstrictor
agents such as adrenaline can be injected with the local
anaesthetic solution; it must not be injected into digits because
of the risk of gangrene.
▪ Inhibition of premature labour (salbutamol).
▪Miscellaneous indications for a-agonists (e.g. clonidine) include
hypertension, menopausal flushing, migraine prophylaxis;
efficacy is limited.
Adrenergic Antagonists
Adrenoceptor Antagonists
Classification of -blockers
▪Non-selective α-adrenoceptor antagonists (e.g.
phenoxybenzamine, phentolamine)
▪α1-selective antagonists (e.g. prazosin, doxazosin,
terazosin)
▪α2-selective antagonists (e.g. yohimbine, idazoxan)
▪Ergot derivatives (e.g. ergotamine, dihydroergotamine).
▪ Have many actions in addition to α-adrenoceptor block
71
-adrenoceptor antagonists
▪reduce arteriolar and venous tone, causing a
fall in peripheral resistance and hypotension
▪relaxation of the smooth muscle of the bladder
neck and prostate capsule, and inhibit
hypertrophy of these tissues
▪useful in treating urinary retention associated with
benign prostatic hypertrophy.
72
Clinical uses of -adrenoceptor
antagonists
▪Hypertension
▪ α1-selective antagonists preferred.
▪ Prazosin is short-acting. Preferred drugs are longer-acting (e.g.
doxazosin, terazosin), used either alone in mild hypertension,
or in combination with other drugs.
▪ Favorable effects on serum lipids: ↓LDL & triglycerides; ↑ HDL
▪Phaeochromocytoma
▪ Phenoxybenzamine used in conjunction with a β-receptor
antagonist in preparation for surgery
73
Clinical uses of -adrenoceptor
antagonists
▪Benign prostatic
hypertrophy
▪ Doxazosin, alfuzosin, terazosin
▪ BUT selective α1A-receptor
antagonists (e.g. tamsulosin,
silodosin) are especially
preferred.
▪ Show some selectivity for the
bladder, and causes less hypotension
than drugs such as prazosin, which
act on α1B receptors to control
vascular tone74
Yohimbine
▪a naturally occurring alkaloid found in the bark of
the tree Pausinystalia yohimbe and in Rauwolfia root
▪a competitive antagonist selective for 2 receptors
▪Has historically enjoyed notoriety as an
aphrodisiac
▪Improves sexual function(causes
vasodilatations) in male rats; evidence for this
effect in humans is limited.
76
-blockers
▪Propranolol
▪Metoprolol
▪Atenolol
▪Nadolol
▪Pindolol
▪Timolol
▪Bisoprolol
▪Esmolol
-blockers
▪Beta-adrenoceptor antagonist drugs (β-
blockers) block β-adrenoceptors in the
▪heart
▪peripheral vasculature
▪bronchi
▪pancreas
▪ liver
77
Intrinsic Sympathomimetic Activity
(ISA)
▪ISA, partial agonist activity represents the
capacity of beta-blockers to stimulate as well as
to block adrenergic receptors.
▪Examples: Oxprenolol, pindolol, acebutolol
and celiprolol
▪They tend to cause less bradycardia than the
other beta-blockers and may also cause less
coldness of the extremities
78
Lipid solubility
▪Some beta-blockers are lipid soluble and some
are water soluble.
▪E.g. Atenolol, celiprolol, nadolol, and sotalol
are the most water-soluble
▪They are less likely to enter the brain, and may
therefore cause less sleep disturbance and
nightmares
79
Pharmacological actions
▪ Heart: decreases the following: rate, contractility, cardiac output,
conduction velocity, automaticity. Reduces cardiac work & myocardial
O2 demand.
▪ Applications: Antiarrhythmic and Anti-Anginal
▪ Blood Pressure: Acutely, not much affected. Chronically, BP is reduced.
Possible or Suggested Explanations for ↓BP
a) ↓Cardiac Output
b) ↓Plasma renin
c) Central Action, reducing sympathetic activity
d) Presynaptic β-receptors.
▪ Application: antihypertensives. 80
Actions contd
▪ Intraocular Pressure: reduced
▪ reduced production of aqueous humor
▪ Application: therapy of glaucoma
▪Bronchiolar Smooth Muscle: Increase in airway
resistance
▪Glycogenolysis: blocked
▪ increases the likelihood of exercise-induced hypoglycaemia in
diabetics, because the normal adrenaline-induced release of
glucose from the liver is diminished
81
Clinical uses of -adrenoceptor antagonists
▪Cardiovascular system
▪Hypertension
▪ labetalol is used to treat hypertension in pregnancy.
▪Angina pectoris
▪ Following myocardial infarction (e.g. long-term timolol,
propranolol or metoprolol prolongs survival )
▪Cardiac dysrhythmias (e.g. esmolol, satolol)
▪Clinically stable cardiac failure
82
Clinical uses of -adrenoceptor antagonists
▪Other uses
▪ Glaucoma e.g. timolol eye drops
▪ Thyrotoxicosis, as adjunct to definitive treatment (e.g.
preoperatively)
▪ Anxiety states, to control somatic symptoms associated with
sympathetic overactivity, such as palpitations and tremor
▪ Migraine prophylaxis (e.g. propranolol)
▪ Benign essential tremor (a familial disorder)
83
-adrenoceptor antagonists
▪ Unwanted Effects: Bronchoconstriction , cardiac depression , bradycardia,
hypoglycaemia (blunt recognition/delay recovery), fatigue, cold extremities, sleep
disturbances with nightmares, sexual dysfunction
▪ Contra-Indications: Asthma/bronchospasms, cardiac conduction disturbances
(heart block), worsening unstable heart failure, hypoglycaemia
▪ Route of Administration – All of the -blockers available for oral
administration
▪ Propranolol available for IV and in a long-acting oral tablet
▪ Timolol and Betaxolol available as an ophthalmic solution
84
QUESTIONS
▪Nursingpharmacology.info