Adrenergic Pharmacology

Wonder Abotsi, PhD

Department of Pharmacology, KNUSTRoom C114; wkmabotsi.pharm@knust.edu.gh

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