Rob experienced blurred vision and an enlarged, painful left pupil after working with several chemicals including atropine in his lab. At the hospital, he was diagnosed with acute closed-angle glaucoma due to narrow drainage angles exacerbated by likely exposure to a mydriatic (pupil-dilating) agent. His intraocular pressure was successfully lowered with medication and he was advised to continue treatment until his symptoms resolved.

1. 9
Autonomic disorders
CASE STUDY 46 Rob’s ocular accident
Learning outcomes
On completion of this case study, you will be able to:
• define mydriasis and describe the autonomic control of the pupil;
• describe the factors affecting the diameter of the pupil;
• describe the consequences of an increase in intraocular pressure (IOP) and
its pharmacological management.
Part 1
Mature student Rob is 26 years old and is working in a pharmacy research laboratory
as part of his work placement module. He deals with many different chemicals on
a daily basis. One afternoon while he was getting ready to finish for the day, he
noticed that his vision was becoming blurred in the left eye and the laboratory
lights were making his eye uncomfortable. After checking his eyes in the mirror,
he noticed that the pupil of his left eye was much bigger than the other eye. His
left eye was also painful. While he was thinking about visiting a doctor, one of
Clinical Physiology and Pharmacology Farideh Javid and Janice McCurrie
 2008 John Wiley & Sons, Ltd

2. 96 CH 9 AUTONOMIC DISORDERS
the local doctors walked into the lab. Rob explained his problem and, following
questioning, it emerged that Rob had been dealing with atropine, cocaine, morphine
and phenylephrine that afternoon. Since it was late in the day, the doctor advised
him to go to the local hospital for a proper examination.
Q1 Briefly explain the control of the pupil diameter of the eye.
Q2 Define mydriasis and miosis, and explain how the diameter of the pupil can be
affected by common autonomic agonists and antagonists.
Q3 Under what circumstances could a patient have pupils of an unequal size?
Q4 Could any of the chemicals used by Rob that afternoon have caused his
symptoms?
Part 2
During an eye examination at the hospital, it was found that Rob’s IOP was above the
normal range in the left eye (33 mmHg) and in the right eye was slightly increased
(21.5 mmHg). In addition, it was found that the angle between his cornea and iris
was very narrow; this was worse in the left eye, where the pupil was dilated. Rob
confirmed that eye problems are common in his mum’s family.
The doctor made a diagnosis of an acute attack of closed-angle glaucoma, as a
result of his narrow drainage angles and the probable exposure to a mydriatic agent.
Q5 What should doctors do immediately for Rob?
Q6 What drugs can be used to lower IOP in this situation?
Q7 What is glaucoma? Comment on its pathophysiology, including the different
types of glaucoma.
Q8 What is the normal IOP and how is it maintained?
Part 3
Rob’s IOP was successfully lowered with medication, and the ophthalmologist
advised him to receive treatment to control IOP until all the presenting symptoms
had cleared up, which takes a week or so.
Q9 Comment on the drug treatments for glaucoma by explaining their mechanism
of action. Your answer should include some examples of the drugs used.
Q10 Comment on the side effects/contraindications associated with drugs used to
treat glaucoma.
Q11 Is there any alternative to drug therapy in treating glaucoma?

3. CASE STUDY 47 A SEVERE ATTACK OF GREENFLY 97
CASE STUDY 47 A severe attack of greenfly
Learning outcomes
On completion of this case study, you will be able to:
• describe the anatomical differences between the sympathetic and parasym-
pathetic systems, and the associated neurotransmitter release;
• explain the actions of anticholinesterase enzymes on organs such as the
heart, respiratory and central nervous systems, salivary glands, eyes, mucous
membrane of the mouth and skeletal neuromuscular junctions;
• review the symptoms of organophosphate toxicity and the use of antidotes.
Part 1
Jim used his redundancy money to start a small business growing pot plants to
supply local shops and offices. He had always been a very successful gardener so
he was horrified when plants in his new greenhouse suffered a severe attack of
greenfly. He collected a large container of commercial insecticide containing the
organophosphate malathion from his supplier and set to work with his spray.
After a few minutes of spraying, Jim started to feel very ill indeed and soon
collapsed. As a relative novice to commercial gardening, he had not realized that
organophosphates are very toxic, as they act as anticholinesterases. He did not
appreciate that he should have been using protective clothing when spraying these
compounds in a confined space.
Jim’s symptoms included severe intestinal cramps, drooling, sweating, lacrima-
tion, agitation, nausea and muscle twitching.
Q1 By which routes could malathion enter Jim’s body?
Q2 Which parts of the nervous system appear to have been affected by the
insecticide?
Q3 What are the anatomical differences between the sympathetic and parasympa-
thetic divisions of the autonomic nervous system?
Q4 Name the neurotransmitters in the two divisions of the autonomic nervous
system.

4. 98 CH 9 AUTONOMIC DISORDERS
Q5 Describe the events which lead to the release of transmitter in the parasympa-
thetic nervous system.
Q6 How may anticholinesterases affect neurotransmission within the autonomic
nervous system?
Q7 Identify the systems or tissues which appear to have been stimulated to produce
the symptoms that Jim experienced and the division of the nervous system
which provides innervation to the structures you describe.
Part 2
Fortunately, Jim was found by a colleague soon after collapsing. He was taken into
the fresh air and then to the local hospital where his contaminated clothing was
removed. He was given breathing support on admission and a drug, pralidoxime,
to reactivate his plasma cholinesterase activity. To be fully effective, this drug must
be given within a short time of exposure to anticholinesterases, but it can remain
active for 24 hours.
Jim was given an ‘antidote’ to help reduce his symptoms, which were very
distressing. After an overnight stay in hospital, he made a good recovery.
Q8 What effects would you expect to observe in (i) the heart, (ii) the bronchi and
(iii) the salivary glands following administration of an anticholinesterase?
Q9 Why was breathing support needed in the acute phase of Jim’s condition?
Q10 What type of drug could be used as an ‘antidote’ to relieve the symptoms Jim
was experiencing?
Q11 Would the drug you have identified in Question 10 have actions on the skeletal
neuromuscular junction? Give reasons for your answer.
Q12 Bethanechol is sometimes used therapeutically to enhance detrusor (bladder)
muscle activity when there is evidence of urinary retention. What are the
mechanism of action and adverse effects of bethanechol?
Part 3
Some months after Jim’s unpleasant experience with the insecticide, he attended
an eye clinic for a routine examination. Following the visit, his pupils were widely
dilated and he found it difficult to focus on objects.
Q13 What type of drug was likely to have been used for Jim’s eye examination to
cause these effects?
Q14 If a very large dose of this agent had been instilled into his eye by mistake and
had produced systemic actions, what effects would you expect to observe on
the heart and on the mucous membranes of the mouth?