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Revision of
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A large variety of drugs, both topical and systemic, are used in the diagnosis and
treatment of ocular disease. Although the intended target for the action of these
drugs is the ocular tissue, many will affect other systems in the body.
Understanding how drugs used in ophthalmic practice exert their effects will
explain the side-effects of these agents and the contraindication to their use in
certain groups of people.

For a drug to exert a pharmacological effect, it

must reach a receptor with which it can interact.
The receptor for drug interaction can take many
forms. For example, it may be an autonomic
receptor on a post-synaptic membrane, an
enzyme or even a substrate if the drug itself is
an enzyme. The results of drug-receptor
interaction vary widely being dependent upon
numerous factors including:

Drug concentration at receptor

Drugs affinity for the receptor
Drugs action at receptor
Mechanisms terminating the action of the
drug
Presence of other drugs at the receptor site
Availability of receptor sites
Drug selectivity
Sensitivity of receptor
Function of receptor

Figure 1 is a diagrammatic representation of

neurohumoral transmission and Figure 2 shows
the steps involved in neurohumoral transmission
in the peripheral parasympathetic and
sympathetic nervous systems. Examples of
parasympathetic and sympathetic
neurotransmission will be used to look at the
factors listed more closely.

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Figure 1 - Diagrammatic representation of neurohumoral transmission

1

1. Action potential travels

along axon

axon

2. Neurotransmitter
stored in pre-synaptic
vesicles is released
into synaptic cleft
3. Neurotransmitter binds
to specific receptors
on post-synaptic
membrane

Pre-synaptic
nerve terminal

4. Transmitter-receptor
interaction e.g.
increased membrane
permeability to
sodium, potassium
and calcium ions and
an excitatory
post-synaptic potential

Pre-synaptic vesicles
containing neurotransmitter

Neurotransmitter
in synaptic gap

5
3

Receptor site

5. Action of transmitter is
terminated by
diffusion, enzymatic
degradation, removal
by glial cells
or reuptake into
pre-synaptic
nerve terminal

Neurotransmitter
receptor complex

Post synaptic
membrane

Figure 2 - Steps involved in neurohumoral transmission in the autonomic nervous system

Autonomic nervous system

Drug concentration
at receptor site
To exert a response, a drug must reach the
receptor in sufficient quantity to bind with a
receptor and initiate a reaction, e.g. pilocarpine
by stimulating, or atropine by blocking the
muscarinic receptor on the post-synaptic nerve
ending in the parasympathetic nervous system.
In order to achieve a good therapeutic response
to the administration of atropine for example,
we use a topical drug delivery system, e.g. a 1%
eye drop, to attain high enough concentrations
of the drug at the sphincter pupillae and ciliary
muscle to block muscarinic receptors and cause
mydriasis and cycloplegia. While the same dose
of the drug administered by injection into a
muscle or vein may cause some blurring of
vision, the concentration achieved at the
receptors in the internal ocular musculature will
be insufficient for the optometrist to perform a
cycloplegic refraction. Certain drugs do not cross
the cornea well and are modified to form
pro-drugs, which enhance lipophilicity and
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System:
Receptor:
Natural
neurotransmitter:
Stimulated by:

Non selectively
blocked by:

Broken down by:

Enzymatic
degradation
inhibited by:

adrenergic

muscarinic
acetylcholine

phenylephrine

brimonidine
alpha 1 alpha 2

prazosin
doxazosin
thymoxamine

pilocarpine,
carbachol

isoprenaline

alpha

Selectively stimulated by:

Selectively
blocked by:

Parasympathetic

noradrenaline

Receptor types:

Receptor sub types:

Sympathetic

yohimbine

phenoxybenzamine,
phentolamine, labetalol

pre-synaptic
monoamide oxidase

tranylcypromine,
phenelzine

beta
dobutamine

salbutamol

beta 1 beta 2
betaxolol
atenolol
metoprolol
trimolol, propranolol,
oxprenolol, labetalol

synaptic
catechol-Omethyltransferase

entacapone

Blocked by:
atropine
cyclopentolate
tropicamide

acetylcholinesterase

physostigmine, ecothiopate

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penetration into the eye. The active moeity is
formed when enzymes in the eye act upon the
lipophilic pro-drug. Examples of pro-drugs
include dipivefrin and latanoprost.
Oral and injection routes are sometimes used
in the treatment of ocular disease to achieve
concentrations of drugs in tissues not accessible
to topical drug delivery systems, e.g. the retina
and the choroid. However, most drugs used in
ophthalmology are formulated as topical eye
preparations or periocular (e.g. local
anaesthetics for peribulbar anaesthesia) or
intraocular injections (e.g. acetylcholine
injected into the anterior chamber, intravitreal
antibiotics) to ensure that a suitable
concentration of drug is achieved at the site of
action.
Conversely, drugs with antimuscarinic effects
administered systemically for non-ophthalmic
disease give rise to low concentrations of drug
in the eye resulting in the adverse effects of low
grade mydriasis and cycloplegia.

Drug affinity for the receptor

reaction at a receptor resulting in the build-up

of a chemical that activates another receptor.
For example, physostigmine, a cholinesterase
inhibitor, binds to acetylcholinesterase, the
enzyme responsible for the breakdown of the
natural neurotransmitter acetylcholine. The
inhibition of the enzyme results in an increase
in its natural substrate, acetylcholine, which is
then available to stimulate receptors in the iris
sphincter and in the ciliary muscle resulting in
miosis and ciliary spasm. This is known as
indirect activity, thus physostigmine is an
indirectly-acting parasympathomimetic, while
pilocarpine is a directly-acting
parasympathomimetic.

Mechanisms terminating
drug action
The length of action of a drug depends upon
how long it can remain at the site for drugreceptor interaction before its action is
terminated by one of the mechanisms listed
earlier. Normally, exogenous acetylcholine,
injected into the anterior chamber as a surgical
miotic, is rapidly destroyed by cholinesterase,
thus limiting its action and avoiding postoperative pain and inflammation. However, the
presence of an anticholinesterase drug will
prevent the destruction of endogenous and
exogenous acetylcholine resulting in a more
prolonged action.

Presence of other drugs

at the receptor site
The mydriasis produced by tropicamide, resulting
from blockade of post-synaptic muscarinic
receptors in the parasympathetic nervous system
gradually wears off and endogenous
acetylcholine molecules replace those of
tropicamide at the receptors. However, the
effect of tropicamide can be reversed more
rapidly by the administration of pilocarpine.
Here, the blockade is overcome by an
exogenously administered cholinergic stimulant.
The presence of indirectly-acting drugs which
increase the concentration of the natural
neurotransmitter may enhance the effect of
agonists and attenuate that of antagonists. As
mentioned before, the presence of an
anticholinesterase drug will prevent the
destruction of endogenous (and exogenous)
acetylcholine. Another example is cocaine, which
prevents the re-uptake of noradrenaline into the
sympathetic pre-synaptic nerve terminal and
prolongs the action of the natural
neurotransmitter noradrenaline.

Neurotransmitters can only initiate an excitatory

post-synaptic potential and drugs exert a
Availability of receptor sites
pharmacological response when bound to the
At a certain concentration of drug, when all the
receptor. When the neurotransmitter is not
receptors are occupied, introducing further drug
bound, its action is terminated by diffusion
molecules to the receptor site will not result in a
away from the receptor site, enzymatic
greater therapeutic response. Increasing the
degradation, removal by astrocytes or re-uptake
concentration of drug above this plateau does,
into the pre-synaptic axon. Certain drugs
however, give rise to an increase in sidebind to receptors with greater tenacity
effects of the drug due to stimulation or
Figure 3 - Diagrammatic representation of symphathetic
than others. While atropine has a great
blockade of receptors in other tissues.
nervous system transmission
affinity for the muscarinic receptor, that
For example, nausea and vomiting was
of tropicamide is less, resulting in a
frequently seen with intensive
shorter, less complete blockade. Similarly,
pilocarpine regimens, once popular in
the reversible cholinesterase inhibitor
the treatment of primary angle closure
physostigmine has a short duration of
glaucoma.
phenylalanine
action, while the irreversible inhibitor,
ecothiopate iodide, binds permanently
hydroxylase
Drug selectivity
with the enzyme resulting in an action
Many drugs have more than one action
tyrosine
which is only overcome when new enzyme
because different parts of the drug
tyrosine
is manufactured.
molecule have chemical similarities to
hydroxylase

different natural transmitters, thus they
DOPA
Drug action at receptor
bind with different receptors resulting in
Interaction of a drug with a receptor
a multitude of effects. For example, the
DOPA
decarboxylase

results in a reaction which either:
tricyclic antidepressants imipramine and
mimics that of the natural chemical,
dopamine
amitriptyline have marked antimuscarinic
e.g. contraction of the sphincter
activity, which has been used
dopamine - hydroxylase
pupillae and ciliary muscles in
therapeutically in the management of
noradrenaline
response to carbachol, mimicking the
the unstable bladder. Modern
natural action of acetylcholine leading
equivalents such as lofepramine are

Destroyed
Deaminated
to miosis and ciliary spasm; or
more selective, having a lower incidence
by monoamine
metabolites

oxidase
blocks that reaction resulting in
of antimuscarinic effects.
Pre-synaptic
inhibition of the action of the natural
Noradrenaline
Drug selectivity is extremely
receptor
after reuptake
stimulation inhibits
chemical, e.g. cyclopentolate blocking
important
in relation to drugs affecting
Reuptake
noradrenaline
inhibited
release
the natural action of acetylcholine
the sympathetic nervous system.
by cocaine

leading to mydriasis and cycloplegia.

Figure 3 shows that noradrenaline
Destroyed by
catechol-Ostimulates two main types of receptor,
methyltransferase
noradrenaline
Stimulated by
Certain drugs which block receptors also
- and - adrenorecptors, however both
Ophenylephrine
methylated
exhibit partial agonist activity, i.e. they
types of receptor are sub-divided further
metabolite
stimulate receptors but block the action of
into 1 and 2 and 1 and 2
Blocked by
the natural transmitter. An example of an
respectively. The selectivity of an
timolol
ophthalmic drug with this property is
ophthalmic drug not only affects its

carteolol, which exhibits intrinsic

action in the eye, but also the sidesympathomimetic activity.
effects it produces elsewhere in the
Activation of adenylate cyclase leading to increased synthesis of cyclic AMP
On occasions, a drug can block a
body. Brimonidine, a selective
2

26

January 11, 2002 OT

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2-adrenoceptor stimulant, has less ocular side

effects than the non-selective -adrenoceptor
stimulant apraclonidine. Side-effects of
apraclonidine include mydriasis, conjunctival
blanching, ciliary vasoconstriction and eyelid
retraction, due to stimulation of 1-receptors.
Betaxolol, a 1 selective -blocker produces less
fall in intraocular pressure than the non-selective
timolol which blocks both 1 and 2 receptors,
however, it has a lower incidence of
bronchoconstriction because it has less effect on
the 2 receptors of the lungs. Selectivity is dose
dependent and in high concentration, so-called
selective drugs stimulate both types of receptor.
The concentration at which loss of selectivity
occurs is used as a measurement for this aspect
of a drugs characteristics.

procaryotic cell (infectious agent i.e. bacteria)

but not those in the eucaryotic cell (host).

Enzyme inhibition
Many antimicrobial agents work by a process of
enzyme inhibition.
Aciclovir

The antiviral aciclovir is very similar in structure

to DNA, the chemical that carries the genetic
information. The drug requires the addition of
phosphate before it can exert its antibacterial
action by inhibiting an enzyme necessary for viral
replication. The addition of phosphate is under
the control of another enzyme induced in virusinfected cells. This specificity makes aciclovir a
potent antiviral without the toxicity seen with
other antiviral agents.

Sensitivity of receptor
If a tissue loses its nerve supply as a result of, for
example, surgery or trauma, the receptors in that
tissue, lacking stimulation by the natural
neurotransmitter, become supersensitive to both
endogenous and exogenous stimulation. Thus,
the denervated iris sphincter in Adies pupil
shows cholinergic supersensitivity responding to
low concentrations of pilocarpine (0.0625
0.25%) which would not illicit a response in a
normal iris. Similarly, the affected pupils of
patients with Horners syndrome will dilate in
response to adrenaline 0.1%, a concentration
ineffective in the normal eye. Denervation
supersensitivity can also be induced
pharmacologically, for example by the use of the
adrenergic neurone blocker guanethidine, to
illicit a hypotensive response to low
concentrations of adrenaline. This is used
beneficially in the Ganda products used in the
treatment of primary open angle glaucoma.

Function of receptor
The stimulation of receptors in different tissues
results in different responses. Thus stimulation of
cholinergic receptors in the sphincter pupillae of
the iris results in miosis, while in the ciliary
muscle the result is ciliary spasm. The latter
action, in turn, results in opening of the
trabecular meshwork, an increase in aqueous
outflow and a fall in intraocular pressure.
However, in the heart, cholinergic stimulation
results in bradycardia, in the lungs,
bronchoconstriction and in the bladder,
contraction of the detrusor muscle resulting in
passing of urine. This explains why bradycardia is
treated with atropine, asthma with the
antimuscarinic bronchodilator ipratropium
bromide and urinary incontinence with
antimuscarinics. It also explains why so many
drugs administered for their antimuscarinic
effects on other body systems include blurred
vision amongst their side-effects.

Trimethoprim

Trimethoprim, an antibacterial component of

Polytrim eye drops and ointment inhibits an
enzyme necessary for the synthesis of proteins
and DNA.
Quinolones

The fluorinated quinolones, ciprofloxacin,

lomefloxacin and ofloxacin (broad spectrum
antibiotics) inhibit an enzyme necessary for the
synthesis of DNA.
Certain other antibiotics which act by enzyme
inhibition do so within the process of protein
synthesis.

Inhibition of protein synthesis

Bacterial protein synthesis involves the building
of peptide chains from amino acids directed by
coding on messenger ribonucleic acid (mRNA).
This process takes place in the ribosome and
antibacterial drugs show selective toxicity against

the bacterial cell as a result of differences

between the bacterial and host ribosomes. The
bacterial ribosome, composed of ribosomal RNA
and protein is made up of two ribosomal subunits the 30S and 50S ribosome, whereas those
in host cells are composed of 40S and 60S subunits.
Protein synthesis involves three main steps,
initiation, elongation and termination of the
peptide chain. Antibiotics which inhibit protein
synthesis can interrupt this procedure by enzyme
inhibition or by binding to elongation factors or
ribosomal particles. Figure 4 shows the steps
involved in bacterial protein synthesis and the
modes of action of antibacterial agents which
inhibit the process.
Host toxicity can occur with these agents,
e.g. corneal and conjunctival toxicity with topical
and ear and kidney toxicity with systemic
gentamicin and bone marrow depression with
chloramphenicol, due to the similarity between
mitochondrial ribosomes in the host and the
bacterial ribosome.
The aminoglycosides, chloramphenicol,
chlortetracycline, fusidic acid and proamidine
and dibromopropamidine isethionates all exert
their antibacterial action by inhibition of protein
synthesis.
Polymyxin B

The other antibiotic used topically in

ophthalmology, Polymyxin, affects the bacterial
cytoplasmic membrane increasing the bacterial
cells permeability and causing leakage of
intracellular molecules.

Anti-inflammatory drugs
Several types of drugs are used in ophthalmology
to prevent or reduce inflammation. Their sites of
action are shown in Figure 5.

Figure 4 - Diagrammatic representation of bacterial protein synthesis

Amino acid
molecule

Transfer
RNA

Transfer RNA with

amino acid molecule

Aminoacyl-tRNA
synthetase

Inhibited by
tetracyclines
binding to 30S
ribosome

mRNA

Ribosome
mRNA
complex with
amino acid

30S subunit
of ribosome

50S subunit
of ribosome

Inhibited by
aminoglycosides
binding to 30S
subunit

Initiation
process
involving
initiation
factors

Inhibited by chloramphenicol
binding to 50S subunit

Pepytidyl
transferase

Antimicrobial agents
These agents act by a variety of mechanisms to
kill or inhibit the growth of microorganisms. As
many of the processes involved occur in both the
infecting organism and the host, an ideal
antimicrobial agent will effect the process in the
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Ribosome
mRNA
complex with
amino acid

Inhibited by fusidic
acid which binds to
elongation factor G

Elongation involving
elongation factors

Peptide chain continues to elongate until

terminating amino acid is attached.

27

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Corticosteroids

Hypothalamus +

Corticosteroids are widely used in

ophthalmology by local administration using
topical eye drops and ointments and local
injections, and systemically using both the oral
and parenteral routes. They are used to control
ocular inflammation which can lead to reduced
vision.
There are a number of naturally occurring
corticosteroids secreted by the cortex of the
adrenal glands which are situated above the
kidneys:
hydrocortisone (cortisol),
a glucocorticoid
aldosterone, a mineralocorticoid
sex steroids including androgens,
oestrogens

Pituitary

Stress
Glucocorticoids
Hormones
hydrocortisone (cortisol)
Synthetic e.g.
betamethasone
deflazacort
dexamethasone
methylprednisolone
prednisolone
triamcinolone

Corticotrophin
(ACTH)
Adrenal cortex

Adverse effects
ACTH

Glucorticoid
effects
Target cell

Combination
of
corticosteroid
and receptor

Drugs used for their anti-inflammatory effects

are glucocorticoids and mimic the natural
glucocorticoid hydrocortisone.
The blood levels of corticosteroids are
controlled by a negative feedback mechanism
to the pituitary (Figure 6), thus - an increase
in blood levels of corticosteroids leads to a
decrease in release of corticotrophin
(adrenocorticotrophic hormone, ACTH) and a
decrease in the release of corticosteroids.

Protein
synthesis
Steroid
response
Mineralocorticoid
effects

Protein catabolism

Muscle wasting, growth

suppression in children

Bone catabolism
Mood

Osteoporosis
Psychosis

Gastric acid and pepsin

Peptic ulceration

Na + reabsorption

Sodium and water retention

Hypokalaemia
Hypertension
Muscle weakness

Diabetes

Figure 6 Pharmacology of steroids

steroids. Following interaction with its

cytoplasmic receptor, the steroid receptorcomplex migrates into the cell nucleus and
affects protein synthesis.

Figure 5 Modes of action of anti-inflammatory agents

Allergen

Mast cell
Blocked by
mast cell
stabilisers
Degranulation

Mediators of
inflammation

Mediators of
inflammation

histamine

Blocked by steroids

leukocyte
migration
arachidonic acid
Blocked by
antihistamines
cyclooxygenase
Blocked
by
steroids
lipoxygenase
Vasoconstrictors
counteract
leukotrienes

pain and long term inflammation

January 11, 2002 OT

Steroids act as anti-inflammatory agents in a

number of ways:
Effects on the immune system

Inhibition of migration of neutrophils, the

white blood cells which phagocytose their
target, into the extracellular space
Inhibition of neutrophil adherence to the
vascular endothelium, the first stage of
neutrophil migration
Inhibition of access of macrophages, the cells
which act as the second line of defence, to
the site of inflammation
Interference with lymphocyte activity in the
specific immune response which reduces
chronic inflammation

Combination
with IgE

Tissue
damage

28

Increased susceptibility to
infection

Present evidence indicates that specific

receptor proteins mediate the effects of

prostaglandins

Inflammatory responses
Immunological responses
Liver glycogen deposition }
Gluconeogenesis }
Glucose output from liver }
Glucose utilization }

K + H excretion

Mode of action

Blocked by
NSAIDs

Adrenal suppression

Corticosteroids

Other anti-inflammatory effects

Inhibition of the synthesis of histamine, a

very important mediator of inflammation (see
later)
Inhibition of release of arachidonic acid by
inhibition of phospholipase, the enzyme
which controls the conversion of
phospholipids into arachidonic acid. This
substance is the precursor of prostaglandins,
thromboxane and leukotrienes, formerly
known as the slow reacting substance of
anaphylaxis
Reduction in capillary and fibroblast
proliferation which reduces fibrosis, thus
delaying healing
Reduction in quantity of collagen deposition
thus reducing scarring
Side-effects

vasodilation, oedema,
infiltration

Virtually every tissue has receptors for steroids,

which most likely contributes to the many
physiologic and pharmalogic effects that occur
following steroid administration, (Table 1).

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Effect of corticosteroid action:

Leading to adverse effect of:

Reduction in immunological responses

Increased susceptibility to infection

Increase in glucose output from the liver,

gluconeogenesis and liver glycogen deposition

Diabetes

Reduction in glucose utilisation

Increase in protein and bone catabolism

Osteoporosis

Mood changes

Psychosis

Increase in gastric acid and pepsin secretion

Peptic ulceration

Sodium reabsorption

Sodium and water retention

Potassium and hydrogen excretion

Hypertension, muscle weakness

Table 1

Non-steroidal
anti-inflammatory drugs

Mast cell stabilisers

This large group of drugs, commonly known as

NSAIDs and including aspirin, ibuprofen and
diclofenac, act as anti-inflammatory agents by
the inhibition of prostaglandin synthesis.
So what is achieved by inhibiting the
synthesis of prostaglandins? (Table 2).
NSAIDs are administered systemically
(orally and parenterally) and topically as
analgesics and anti-inflammatories.
Twenty-three NSAIDs (excluding aspirin) are
listed in the BNF.
In ophthalmology, systemic NSAIDs are
used in the management of inflammatory
conditions such as scleritis and episcleritis (see
forthcoming CPD article).
Topical NSAIDs are used for:
The inhibition of intraoperative miosis
during cataract surgery
Pain in epithelial corneal defects after
photorefractive keratectomy
Prophylaxis and reduction of anterior
segment inflammation following surgery
and argon laser trabeculoplasty
One of the better known side-effects of
systemic NSAIDs is gastro-intestinal ulceration.
This effect is due to the inhibition of formation
of protective prostaglandins in the gastrointestinal wall. Certain NSAIDs, e.g. Arthrotec
(diclofenac + misoprostol), Napratec
(naproxen + misoprostol), are formulated with
prostaglandins to counteract this effect.

Mast cell stabilisers include lodoxamide,

nedocromil and cromoglicate and are
historically thought to stabilise mast cells by
preventing calcium ion influx across the cell
membrane thus preventing degranulation and
release of inflammatory mediators. These drugs
have also been shown in vitro to inhibit
activation of other cell types including
neutrophils, monocytes and eosinophils.

Antihistamines
Histamine released at mast cell degranulation:
Dilates capillaries
Increases vascular permeability
Provokes spasms of smooth muscles
Has a chemotactic effect on eosinophils
Stimulates prostaglandin synthesis
Stimulates the parasympathetic nerves and
mucus secretion
Is inhibited by type H1 and, to a lesser
extent, by type H2 antihistamines
Systemic and topical antihistamines block
histamine (H1) receptors and are used in
ophthalmology.
There are a large number of systemic
antihistamines used orally for the relief of a
range of allergic disorders including allergic
conjunctivitis.
Although H1-antagonists are well absorbed
after oral administration, effective and
generally well tolerated in seasonal allergic
conjunctivitis, it may take several hours to
achieve maximum anti-histaminic effects.
Topical treatment (e.g. antazoline, azelastine,

Table 2
This is what prostaglandins do in the eye :
Ocular effects of prostaglandins

Therefore NSAIDs

Pupillary constriction

prevent miosis

Vasodilation

prevent vasodilation

Increased vascular permeability

prevent this increase

Disruption of ocular blood barriers

prevent this disruption

Alteration in intraocular pressure

prevent the rise, although some PGs e.g. the

prostaglandin F2 analogue latanoprost
causes a reduction

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emedastine and levocabastine) results in more

rapid achievement of maximum therapeutic
effects as the drug is applied directly to the
affected organ. In addition, the risk of systemic
adverse effects and drug interactions will be
considerably reduced.
The side-effects of systemic antihistamines
include sedation, psychomotor impairment,
headache and antimuscarinic effects such as dry
mouth, urinary retention, blurred vision and GI
disturbances.

Vasoconstrictors
Vasoconstrictors are sympathomimetics which
counteract the vasodilatory effect of histamine
by stimulation of -receptors in the conjunctival
blood vessels resulting in a decrease in
conjunctival hyperaemia and oedema. This effect
is seen at concentrations below those which
cause mydriasis, however, it may be seen in
susceptible eyes, particularly if the corneal
epithelium is damaged or diseased, therefore
these drugs are contra-indicated in patients with
a shallow anterior chamber because of the
danger of precipitating an attack of closed angle
glaucoma.
Vasoconstrictors used in anti-inflammatory
preparations include xylometazoline and
phenylephrine. Vasoconstriction is only one of
the effects of the group of drugs known as
sympathomimetics. These drugs mimic the
action of the sympathetic nervous system. Other
effects include mydriasis and lowering of
intraocular pressure.

Mydriatics
Mydriasis comes about in one of two ways,
stimulation of the sympathetic nervous system
causing contraction of the dilator pupillae or
blockade of the parasympathetic nervous sytem
causing relaxation of the sphincter pupillae
(Figure 7). All mydriatics give rise to the local
side-effects of blurred vision and photophobia
and are contraindicated in patients with shallow
anterior chambers because of the risk of
precipitating angle closure glaucoma.

Sympathetic mydriatics
Drugs used to produce mydriasis by acting on
the dilator pupillae do so by stimulation of the
1-receptors on the muscle. Such drugs also
affect the blood vessels of the conjunctiva
causing vasoconstriction, an action used
therapeutically as mentioned above. Other
effects of 1-sympathomimetics include eyelid
retraction and generalised vasoconstriction
(Table 3), which can result in hypertension and
coronary artery spasm. Thus these drugs are
contraindicated in patients with cardiovascular
disease. The use of sympathomimetics is also
contraindicated in patients on monoamine
oxidase inhibitors (drugs used in the treatment
of depression). Such drugs prevent the
breakdown of noradrenaline and exogenouslyadministered sympathomimetics resulting in a
greatly enhanced therapeutic effect.
Certain drugs produce mydriasis indirectly by
increasing the amount of the natural

29

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Table 3 Responses of tissues to sympathetic and parasympathetic stimulation
Cholinergic impulses (P.N.S.)

Adrenergic impulses (S.N.S.)

Effector
organ

Receptor
type

Responses

Responses

HEART
S.A. node

beta 1 & 2

Increase in heart rate

Decrease in heart rate; vagal arrest

Atria

beta 1 & 2

Increase in contractility and conduction velocity

Decrease in contractility; shortened AP duration

AV node

beta 1 & 2

Increase in automaticity and conduction velocity

Decrease in conduction velocity; AV block

His-Purkinje system

beta 1 & 2

Increase in automaticity and conduction velocity

Little effect

Ventricles

beta 1 & 2

Increase in contractility, conduction

velocity, automaticity, and rate of
idioventricular pacemakers

Slight decrease in contractility

Adrenergic
Cholinergic
impulses (S.N.S.) impulses (P.N.S.)
Effector
organ

Receptor
type

Responses

Responses

alpha 1 & 2
beta 2

Constriction
Dilatation

Constriction

ARTERIOLES
Coronary

Adrenergic
impulses (S.N.S.)
Effector
organ

Receptor
type

Cholinergic impulses
(P.N.S.)

Responses

Responses

SKIN

Skin and mucosa alpha 1 & 2

Constriction

Dilatation

Skeletal muscle

Constriction
Dilatation

Dilatation
Dilatation

alpha
beta 2

Pilomotor muscles

alpha 1

Contraction

Sweat glands

alpha 1

Localised secretion

Generalised secretion

SPLEEN
CAPSULE

alpha 1
beta 2

Contraction
Relaxation

Secretion of adrenaline
and noradrenaline

Cerebral

alpha 1

Constriction (slight)

Dilatation

Pulmonary

alpha 1
beta 2

Constriction
Dilatation

Dilatation

ADRENAL
MEDULLA

Abdominal
viscera

alpha 1
beta 2

Constriction
Dilatation

SKELETAL
MUSCLE

beta 2

Salivary glands

alpha 1 & 2

Constriction

Dilatation

Increased contractility;
glycogenolysis;
K+ uptake

Renal

alpha 1 & 2
beta 1 & 2

Constriction
Dilatation

LIVER

alpha 1
and beta 2

Glycogenolysis and
gluconeogenesis

alpha 1 & 2
beta 2

Constriction
Dilatation

Tracheal &
bronchial muscle

beta 2

Bronchial
glands

alpha 1
beta 2

VEINS
Systemic

PANCREAS
Acini

alpha

Decreased secretion

Secretion

Islets
(beta-cells)

alpha 2
beta 2

Decreased secretion
Increased secretion

Relaxation

Contraction

FAT CELLS

alpha 2
beta 1

Lipolysis

Decreased secretion
Increased secretion

Stimulation

SALIVARY
GLANDS

alpha 1
beta

K+ and water secretion

Amylase secretion

LUNG

NASOPHARYNGEAL
GLANDS

K+ and water secretion

Secretion

Motility & tone

alpha 1 & 2, beta 2 Decrease (usually)

Increase

PINEAL GLAND

beta

Melatonin synthesis

Sphincters

alpha 1

Contraction (usually)

Relaxation
(usually)

POSTERIOR
PITUITARY

beta 1

Antidiuretic hormone
secretion

Secretion

Inhibition (?)

Stimulation

alpha 1 & 2 and

Decrease

Increase

Contraction
(usually)

Relaxation
(usually)

STOMACH

INTESTINE
Motility & tone

beta 1 & 2
Sphincters

alpha 1

Secretion

alpha 2

Inhibition

Stimulation

GALLBLADDER
& DUCTS

beta 2

Relaxation

Contraction

KIDNEY
Renin
secretion

alpha 1
beta 1

Decrease
Increase

beta 2

Relaxation (usually)

Contraction

Trigone &
sphincter

alpha 1

Contraction

Relaxation

URETER

Non-pregnant

Dilator pupillae

agonist

antagonist

sympathomimetic sympatholytic
or
1-stimulant

alpha 1

Increase

Ciliary Muscle

+ve effect

-ve effect

agonist

antagonist

+ve effect

agonist

-ve effect

antagonist

1-blocker

parasympathomimetic

muscarinic

parasympatholytic parasympathomimetic parasympatholytic

anti-muscarinic

muscarinic anti-muscarinic

Increase(?)
Variable

alpha 1

Contraction

beta 2

Relaxation

beta 2

Relaxation

noradrenaline

alpha 1

Ejaculation

acetylcholine

acetylcholine

drug examples :
phenylephrine

thymoxamine

pilocarpine

atropine

pilocarpine

atropine

Ciliary spasm

Cycloplegia

outcome :
Mydriasis

SEX ORGANS,
MALE

Sphincter Pupillae

-ve effect

natural neurotransmitter :

UTERUS
Pregnant

Innervates

also
known as :

Detrusor

Motility & tone

Innervates

+ve effect
illicited by:

URINARY
BLADDER

Parasympathetic nervous system

Sympathetic nervous system

Miosis

Miosis

Mydriasis

Erection

Figure 7
Modes of action of mydriatics, mydriatic cycloplegic drugs and miotics

30

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neurotransmitter noradrenaline available to

interact with the post-synaptic receptors. In
ophthalmology, the local anaesthetic cocaine
prevents reuptake of noradrenaline into the
pre-synaptic nerve terminal thus potentiating
adrenergic transmission (Figure 3). Therefore,
in addition to its local anaesthetic activity,
cocaine causes mydriasis and vasoconstriction.
The tricyclic antidepressants e.g. imipamine and
amitriptyline also prevent noradrenaline
reuptake into the pre-synaptic nerve terminal.
These drugs also possess anti-muscarinic
properties and therefore can cause mydriasis
through more than one mechanism, thus they
are well known precipitants of acute closed
angle glaucoma.

Antimuscarinic mydriatics
These drugs prevent the miotic action of
acetylcholine on muscarinic receptors of the
sphincter pupillae. This action is accompanied by
blockade of contraction of ciliary muscle
resulting in cycloplegia. Thus antimuscarinic
agents are known as mydriatic-cycloplegic drugs
and include atropine, cyclopentolate and
tropicamide.
The wide distribution of muscarinic receptors
throughout the body gives rise to a large range
of antimuscarinic side effects from such agents
and explains the use of atropine-like drugs to
treat a wide variety of disorders (Table 4).

Drugs used in
glaucoma treatment
The third use of topical sympathomimetics in
ophthalmology is as ocular hypotensive agents
in the treatment of glaucoma. Both direct and
indirect sympathomimetics and selective and
non-selective drugs are used to lower intraocular
pressure.

Non-selective sympathomimetics
Adrenaline

Adrenaline is a non-selective sympathomimetic,

i.e. it stimulates both - and -adrenoreceptors
like the natural neurotransmitter noradrenaline
although adrenaline has more marked effects on
-adrenoreceptors than noradrenaline.
Adrenaline was the first sympathomimetic drug
to be used in the treatment of primary open
angle glaucoma. Its non-selective stimulation of
- and -receptors leads to antagonistic results
of vasoconstriction in the ciliary body, as a
result of 1-stimulation, which theoretically
leads to a reduction in aqueous humour
production, coupled with an increase in the
production of aqueous humour in the ciliary
epithelium due to -stimulation. An increase in
the outflow facility, mediated by 2receptors in
the trabecular meshwork and 2-receptors which
control uveoscleral outflow, results in a net
reduction in intraocular pressure (Figure 8).
Adrenaline causes short-lived conjunctival
vasoconstriction followed by rebound
vasodilatation and a severe red eye. As the drug
is subject to photo-oxidation, it can also cause
conjunctival pigmentation. The pigment may
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CHOLINERGIC IMPULSES (P.N.S.)

EFFECTOR ORGAN
HEART
S.A. node
Atria

RESPONSES

CLINICAL USE

Decrease in herat rate, Reduction in

vagal arrest
intra-operative
bradycardia &
Decrease in
contractility shortened hypertension
Bradycardia after M.I.
AP duration

SIDE EFFECTS

DRUGS USED
CLINICALLY

Palpitations
Arrhythmias
Tachycardia

Atropine

AV node

Decrease in
conduction velocity;
AV block

His-Purkinje system

Little effect

LUNG
Tracheal & bronchial
muscle
Bronchial glands

Contraction

Bronchodilation

Stimulation

Pre-op to dry
secretions

Increase
Relaxation (usually)
Stimulation

Motion sickness
Gastric & duodenal
ulcers

Increase

Relief of colic

Constipation

Dicyclomine
Propantheline

Contraction
Relaxation

Urinary incontinence

Desire to urinate
with inability to do
so

Flavoxate
Oxybutynin

SKIN
Sweat glands

Generalised secretion

Hyperhydrosis

Dry skin

Hyoscine
Propantheline

SALIVARY GLANDS

K+ and water

Pre-op to dry
secretions

Dry mouth

Atropine
Hyoscine

Contraction  miosis
Contraction 
accommodation

Mydriatic
Cycloplegic

Photophobia
Blurred vision

Atropine
Cyclopentolate
Homatropine
Tropicamide

STOMACH
Motility & tone
Sphincters
Secretion
INTESTINE
Motility & tone
Sphincters
Secretion
URINARY BLADDER
Detrusor
Trigone &
sphincter

EYE
Sphincter pupillae
Ciliary muscle

Ipratropium
Oxitropium
Atropine
Hyoscine

Hyoscine
(Pirenzepine)

Relaxation (usually)
Stimulation

Table 4

build up to such an extent that lacrimal stones

are formed. Another local adverse effect of
adrenaline is the occurrence of cystoid
maculopathy in aphakic patients. This effect is
less likely to occur now that the majority of
cataract extractions are undertaken using the
phacoemulsification technique in which the
posterior capsule of the lens is left intact.
Being a mydriatic drug, adrenaline is contraindicated in patients with a shallow anterior
chamber as it may precipitate a case of acute
closed angle glaucoma. Because adrenaline
exerts pharmacological actions in a large
number of tissues (Table 3), systemic effects of
adrenaline have also been reported with
incidences as high as 25%.
These unfortunate side-effects of adrenaline
have led drug companies to investigate how
they may reduce the concentration of
adrenaline applied to the eye.
Ganda

Guanethidine, an adrenergic neurone blocker,

when used alone depletes sympathetic storage
sites, initially causing release of noradrenaline
that may lead to mydriasis and lid retraction.
However, eventually guanethidine produces a
pharmacological denervation supersensitivity

resembling postganglionic Horners syndrome,

a supersensitivity to adrenaline which enables
lower concentrations of adrenaline to be used
in a combination of the two drugs.
Guanethidine 1% plus adrenaline 0.2% is as
effective as adrenaline 1%. Ganda
(Guanethidine and Adrenaline), originally
launched in concentrations of 1+0.2, 3+0.5,
5+0.5 and 5+1, is now only available as the two
lower strengths due to reports of conjunctival
scarring and corneal ulceration following use of
the higher strengths of guanethidine.
Dipivefrin

Dipivefrin, or dipivalyl adrenaline, is a lipophilic

pro-drug of adrenaline, broken down by
enzymes in the aqueous humour to release free
adrenaline. As the drugs lipophilicity enhances
penetration through the cornea, the intraocular
pressure lowering effect of 0.1% dipivefrin is
similar to that achieved with 2% adrenaline.
Although use of the pro-drug does not prevent
local side effects and the contra-indication in
patients with a shallow anterior chamber
remains, some local side effects such as the
discolouration of hydrophilic lenses do not
occur and systemic cardiovascular effects are
less common.

31

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Presynaptic
nerve
terminal

selective apraclonidine is rarely seen with the

more selective brimonidine.
An understanding of the mode of action of
sympathomimetics helps to explain what might
initially seem paradoxical, the fall in intraocular
pressure with -adrenoceptor blocking agents or
-blockers.

brimonidine
guanethidine

adrenaline

apraclonidine

2
Empty pre-synaptic vesicles

Noradrenaline in
pre- synaptic vesicles

Normal receptors

Normal response

1
Vasoconstriction in
the ciliary body

Exogenous adrenaline

Supersensitive
receptors

Enhanced response

IOP

-adrenoceptor blocking agents

Increase in
outflow facility via
uveoscleral
pathway and
reduction in
aqueous inflow by
negative feedback
effect on natural
neurotransmission
IOP

Increase in
aqueous
production

Increase in
outflow
facility in
trabecular
meshwork

IOP

IOP

Mode of action of directly acting

sympathomimetics

Mode of action of guanethidine

Figure 8 Modes of action of drugs affecting the sympathetic nervous system in the treatment
of glaucoma

Selective sympathomimetics
Following the launch of the beta-blockers, the use
of the sympathomimetics declined, however, the
introduction of the more-selective apraclonidine
renewed interest in this class of drugs.
Apraclonidine

Apraclonidine is a non-selective -agonist that

reduces intraocular pressure by reducing aqueous
humour formation. Unfortunately, tachyphylaxis,
a reduced response to the drug with time,
develops rapidly. As a result of this and an
unfavourable side effect profile, which includes
mydriasis, conjunctival blanching and eyelid
retraction, due to stimulation of
1-receptors, its place in the treatment of primary
open angle glaucoma has largely been taken by
brimonidine.

Brimonidine

Brimonidine is a highly selective 2agonist

which lowers intraocular pressure by reducing
aqueous inflow through a negative feedback
effect on the pre-synaptic nerve terminal
(Figure 8) and increasing aqueous outflow
through the non-conventional or uveo-scleral
route.
Both apraclonidine and brimonidine cause
allergic reactions but the percentage of patients
affected with brimonidine is roughly a third of
that seen with apraclonidine. Other side-effects
include dry mouth, fatigue and, not surprisingly
for derivatives of clonidine, depression. These
drugs should not be used in depressed patients,
especially those on tricyclic antidepressants or
mono-amine oxidase inhibitors. Mydriasis and
eyelid retraction encountered with the less

It can be seen from Figure 8 that if the

-adrenoreceptor is blocked leaving the
-adrenoreceptor unblocked, a fall in intraocular
pressure results due to prevention of the
increase in aqueous humour secretion mediated
by -stimulation. It has been observed that
blockade of both 1- and
2- receptors with non-selective -blockers such
as timolol and carteolol results in a fall in
intraocular pressure greater than that seen with
selective 1-blockade with betaxolol. This
suggests that the reduction in outflow facility in
the trabecular meshwork, which occurs with
non-selective -blockers, has less of a negative
effect on IOP than the positive effect imparted
by 1+2-blockade on secretion of aqueous
humour. However, combination of betaxolol, a
1-selective blocker, and adrenaline results in a
greater fall in intraocular pressure than that
seen with adrenaline and the non-selective
-blockers.
As noted with sympathomimetics and
antimuscarinics, effects of topically applied
drugs are not confined to the eyes and blockade
of -adrenoreceptors gives rise to a number of
systemic side-effects (Table 5). However, the
incidence and severity of these side effects
varies with the pharmacological profile of the
individual drug (Table 6) with betaxolol, which
is cardioselective, being less likely to cause
bronchoconstriction; carteolol, which is
hydrophilic and possesses intrinsic
sympathomimetic activity exhibiting less central
and -blockade-induced side effects and
-blockers without membrane stabilising (local

Table 5 Side effects of topical -blockers

Systemic

Ocular
Allergic blepharoconjunctivitis
Burning and itching*
Blurred vision
Conjunctival hyperaemia
Corneal anaesthesia*
Dryness*
Foreign body sensation*
Macular oedema
Pain
Punctate keratitis*
Uveitis**

Respiratory
Vascular
Bronchoconstriction Hypotension
Bradycardia
Dyspnoea
Reduced cardiac stroke volume
Arryhthmias

Endocrine
Hypoglycaemia

C.N.S.
Depression
Anxiety
Nightmares
Irritability
Fatigue
Hallucinations

2-effect, less
prominent with
-blockers with
cardioselectivity or
ISA

1-effects, less prominent with

-blockers with ISA

2-effect, less prominent with

-blockers with
cardioselectivity or ISA

Central effects,
less prominent
with hydrophilic
-blockers

Peripheral vasoconstriction

Masking of tachycardia
associated with
hypoglycaemia

2-effect, less prominent with

-blockers with cardioselectivity
or ISA

1-effect, less prominent with

-blockers with ISA

associated with membranestabilising activity

** anterior granulomatous
uveitis seen with
metipranolol

32

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Membrane
stabilising
activity Lipophilicity

Preservative
content %w/v

Frequency
of instillation

Suspension 0.25%,
Solution 0.5%

BKC 0.01
BKC 0.01

b.d.

Solution 1%, 2%

BKC 0.005

b.d.

Solution 0.5%,
S.D.U.s 0.5%

BKC 0.004
Nil

o.d. b.d.

Nil

b.d.

BKC 0.01
BDB 0.012
Nil

b.d.
o.d.
b.d.

1selectivity

ISA

Betaxolol

++

++

Carteolol

++

Levobunolol

Metipranolol

Timolol

I.S.A. = intrinsic sympathomimetic activity

BKC = benzalkonium chloride

Forms available
in UK

S.D.U.s 0.1%, 0.3%

+

Solution 0.25%, 0.5%

Gel-forming solution 0.25%, 0.5%
S.D.U.s 0.25%, 0.5%

S.D.U. = single dose unit

BDB = benzododecinium bromide

Table 6 Properties of ophthalmic -blockers

anaesthetic) activity causing less local side

effects such as burning and itching, corneal
anaesthesia, dryness, foreign body sensation
and punctate keratitis.
Latanoprost

Latanoprost is an analogue of prostaglandin F2.

Prostaglandin F2 (PG F2) is one of several natural
prostaglandins enzymatically synthesised from
arichidonic acid. Other members of the group
include PGD2, PG E2, prostacyclin (PG I2) and
thromboxane (TXA2).
Although many prostaglandins have an
inflammatory role, PG F2 and some other
prostaglandins have an ocular hypotensive
action.
Each prostaglandin preferentially interacts
with its own sub-population of receptors; PGD2
with DP receptors, PGE2 with EP receptors and so
on. Many PG receptors are found in the eye with
PGF receptors being distributed in ciliary muscle,
ciliary and lens epithelium, trabecular meshwork
and iridial melanocytes.
Latanoprost lowers intraocular pressure by
increasing the outflow of aqueous humour from
the eye by the uveoscleral pathway. It has been
suggested that this is brought about by a
reduction in hydraulic resistance to outflow by
degradation of the extracellular matrix in the
spaces among ciliary smooth muscle fibres
through a release and/or activation of matrix
metalloproteinases.
A well-known side-effect of latanoprost is
the production of selective eye colour change.
This is seen in 20% of patients with hazel eyes
with blue eyes darkening rarely and no colour
change evident in brown irides. This is thought
to be due to a prostaglandin-induced increase in
melanogenesis, which occurs both in iridial
melanocytes and those of the follicles of the
eyelashes.

Miotics
As mydriatics can be divided into those which
stimulate the sympathetic nervous system
(1-agonists) and those which block the

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parasympathetic nervous system, miotics can

act by blockade of the sympathetic nervous
system or stimulation of the parasympathetic.
Agents falling into the latter category can be
further divided into directly acting agents and
those which act indirectly through inhibition of
acetylcholinesterase.
Parasympathomimetics mimic the natural
neurotransmitter acetylcholine. Pilocarpine and
carbachol are directly acting agents which
stimulate the sphincter pupillae causing
contraction of the muscle resulting in miosis.
Concurrent stimulation of the ciliary muscle not
only results in adverse effects of ciliary spasm
and accommodation, but also in the opening of
the trabecular meshwork and a fall in
intraocular pressure.
Inhibitors of the enzyme acetylcholinesterase, such as physostigmine, which
cause the miotic effects by a build-up of the
natural neurotransmitter acetylcholine.
Blockers of the sympathetic innervation
pathway, which cause miosis are sometimes
known as mydriolytics. These drugs are
1-antagonists such as thymoxamine and
dapiprazole. Neither of these agents is
commercially available in the UK.

Carbonic anhydrase
inhibitors (CAIs)
The formation of aqueous humour involves
active secretion of sodium cations by the ciliary
epithelium into the aqueous humour followed
by the attraction of negatively charged chloride
and bicarbonate ions. These ions, especially
bicarbonate, increase the osmolar potential of
the aqueous humour, which, in turn, causes
osmosis of a significant amount of fluid through
the ciliary epithelium into the posterior
chamber.
Carbonic anhydrase (CA) is an enzyme which
exists in several forms and is found in many
body tissues, including the eye. It catalyses the
reversible reaction involving the hydration of
carbon dioxide and the dehydration of carbonic
acid with subsequent dissociation to form

hydrogen and bicarbonate ions (H+ and HCO3-).

Of the identified human isoenzymes of CA, CA II
plays a key role in controlling aqueous
production and IOP. Inhibition of carbonic
anhydrase in the ciliary processes of the eye
blocks the formation of carbonic acid and
consequently reduces the production of HCO3-.
The decreased levels of HCO3- in turn diminish
aqueous formation and ultimately lower
intraocular pressure.
The only oral carbonic anhydrase inhibitor
available in the UK, acetazolamide can
commonly cause malaise, fatigue, irritability,
depression, excitement, headache, loss of
appetite leading to weight loss, reduced libido
and gastro-intestinal disturbances including
nausea, vomiting and diarrhoea. Drowsiness and
paraesthesia involving numbness and tingling of
the face and extremities are common particularly
with high doses. Diuresis, an increase in the
amount of urine formed, generally abates after a
few days of continuous therapy. Acidosis may
develop during treatment and is generally mild
but severe metabolic acidosis has occasionally
been reported, especially in elderly or diabetic
patients or those with impaired renal function.
Changes in the cellular composition of the blood
occur rarely. Acetazolamide is a sulfonamide
derivative and therapy can give rise to crystal
formation in the urine, renal calculi and renal
colic, rash and anaphylaxis. Renal lesions,
possibly due to a hypersensitivity reaction, have
also been reported.
Other adverse effects include allergic skin
reactions, flushing, fever, thirst, dizziness,
ataxia, alterations in taste, blood in the urine or
faeces, sugar in the urine, transient myopia,
photosensitivity, tinnitus and hearing
disturbances, abnormal liver function and rarely
hepatitis or cholestatic jaundice, flaccid
paralysis and convulsions. A lowering of plasma
potassium may occur, but this is generally
transient and rarely clinically significant.
The type of adverse effects generally
experienced with acetazolamide occurs at very
low frequencies with the topical CAIs

33

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brinzolamide and dorzolamide, because the
degree of inhibition of carbonic anhydrase is
generally insufficient to produce clinically
relevant systemic side effects.
Adverse drug reactions such as nausea and
paraesthesia are rare. The most common nonocular side-effects of the topical CAIs are taste
perversion and headache.
Ocular side-effects of topical CAIs include
blurred vision, ocular discomfort (stinging,
burning and itching), foreign body sensation
and ocular hyperaemia.

Local anaesthetics
The local anaesthetics are compounds that
produce insensitivity by preventing or
diminishing the conduction of sensory nerve
impulses near to the site of their application or
injection. Their main site of action appears to be
the cell membrane, where they block the
transient increase in membrane permeability to
sodium ions. This in turn increases the threshold
value for cell firing, and thus decreases the
excitability of the cell. Blockade of the sodium
channel is thought to occur by interaction of
the local anaesthetic with a specific binding site
associated with the sodium channel. Following
application, anaesthetics cross the cell
membrane in the uncharged (lipid soluble)
form, but at the site of action, the charged form

binds to the receptor. Local anaesthetics are

generally of two chemical types: the older
compounds are esters (cocaine and lignocaine);
the more recent compounds are amides
(amethocaine and benoxinate). The esters are
less stable and more readily metabolised than
the amides.

Artificial tear solutions

Artificial tear solutions contain various polymers
which increase wettability of the hydrophobic
corneal surface, extend adhesion and increase
conjunctival sac retention time. Polymers in
current use include semisynthetic cellulose
derivatives, polyvinyl alcohol,
polyvinylpyrrolidone, dextran and polyacrylic
acid.
When excessive tear film mucin is a problem,
acetylcysteine, the N-acetyl derivative of the
amino acid L-cysteine is used to break down the
mucin. It is believed to exert its action by
opening up disulphide linkages in mucus,
thereby lowering its viscosity.

Conclusion
An understanding of the basic pharmacology of
the drugs used in ophthalmic practice will equip
the reader for discussion of these drugs in future
articles.

About the author

Lucy Titcomb is Directorate Pharmacist,
Ophthalmology, Birmingham and Midland Eye
Centre.

Further reading
1. Bartlett JD, Jaanus SD. Clinical Ocular
Pharmacology, 3rd Edition.
2. Cooper JR. Bloom FE, Roth RH The
Biochemical Basis of Neuropharmacology,
7th Edition
3. Goodman LS, Lee E. Limbird LE, Hardman JG
(Eds.) Milinoff PB, Gilman AG. Goodman and
Gilmans the Pharmacological Basis of
Therapeutics, 9th Edition
4. Titcomb LC Eye Disorders, Pharmaceutical
Journal:
Glaucoma Part 1, August 28,
1999, 324-9
Glaucoma Part 2, October 2,
1999, 526-9
Mydriatic-cycloplegic drugs and
corticosteroids December 4,
1999, 900-5
Over-the-counter ophthalmic
preparations, February 5, 2000, 212-8
Topical ocular antibiotics Part 1, February
19, 2000, 298-301
Topical ocular antibiotics Part 2,
March 13, 2000, 441-5

Multiple choice questions - A Revision of Pharmacology

1. Certain topically-administered drugs do not
cross the cornea well and are modified to
enhance penetration into the eye. Such
drugs are called pro-drugs. An example of a
pro-drug is:
a. atropine
b. pilocarpine
c. dipivefrin
d. cocaine
2. Physostigmine causes miosis by:
a. directly stimulating parasympathetic
post-synaptic receptors
b. inhibiting acetylcholinesterase
c. blocking sympathetic post-synaptic receptors
d. directly stimulating sympathetic
post-synaptic receptors
3. Pharmacological denervation supersensitivity
is used beneficially in the treatment of
glaucoma by combining the adrenergic
neurone blocker guanethidine with:
a. pilocarpine
b. brimonidine
c. dorzolamide
d. adrenaline
4. Aminoglycoside antibiotics have a variety of
effects within the bacterial cell but
principally they:

a. inhibit protein synthesis by binding to the

30S ribosomal unit
b. inhibit the activity of DNA gyrase
c. inhibit protein synthesis by binding to
elongation factor G
d. interact with phospholipids in the cell
membrane disrupting the osmotic integrity
of the cell
5.
a.
b.
c.
d

In the eye, prostaglandins cause:

mydriasis
vasoconstriction
increased vascular permeability
cycloplegia

6.
a.
b.
c.
d.

In the eye, histamine causes:

spasm of smooth muscle
vasoconstriction
decreased vascular permeability
reduced prostaglandin synthesis

7.
a.
b.
c.
d.

Vasoconstrictors used in ophthalmology are:

parasympathomimetics
antimuscarinics
sympathomimetics
-blockers

8. Latanoprost is an analogue of:

a. prostaglandin D2
b. prostaglandin E2

Please note there is only one correct answer

c. prostaglandin F2
d. prostaglandin I2
9.
a.
b.
c.
d.

Certain drugs cause miosis by:

stimulating -receptors
blocking -receptors
stimulating -receptors
blocking -receptors

10. When excessive tear mucin is a problem, the

mucin can be broken down by the N-acetyl
derivative of the amino acid:
a. D-lysine
b. L-glycine
c. D-threonine
d. L-cysteine
11. Antimuscarinics are used in organs other
than the eye:
a. to treat tachycardia
b. to treat urinary retention
c. to treat arrhythmias
d. as premedicants to dry bronchial and
salivary secretions
12. Local anaesthetics are:
a. amides and esters
b. ethers and ketones
c. amides and ketones
d. esters and ethers

An answer return form is included in this issue. It should be completed and returned to: CPD Initiatives (c4082a),
OT, Victoria House, 178180 Fleet Road, Fleet, Hampshire, GU51 4DA by February 6, 2002.

34

January 11, 2002 OT

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