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Introduction

This study describes an investigation into the consumption and fate of
selected PhACs (Temazepam, Amitriptyline and Carbamazepine) in Greater
Preston region. The predicted environmental concentrations of these PhACs in waste
water, and in post waste water treatment work effluents, and ultimately their
effect on the aquatic environment.

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This was achieved through analysis of prescription data from the Greater
Preston region, and hospital data from the Royal Preston Hospital

Over the past 30 years, there has been a small yet increasing number of
studies focusing the fate of pharmaceutically active compounds (PhACs) in waste
water. (Jones et al, 2005. Mompelat et al, 2009. Roberts & Thomas, 2006.
Radjenovic et al 2009). However, due to advancements in detection limits from
1 ng/L in 2011, Booker at al, 2014) a large range
of PhACs are now been detected in surface waters worldwide (Booker et al, 2014,
Kasprzyk-Hordern et al, 2009). PhACs are manufactured to cause a biological
change, and often share physio-chemical characteristics with harmful
xenobiotics (e.g. the ability to pass through membranes) (Sanderson et al,
2004), so growing public concern is of no surprise. Even though many common
PhACs (e.g. antibiotics) are used in similar quantities to many pesticides,
they do not have the same environmental safeguards in place, testing for
possible contamination. Unrestricted polluting has been happening for some time
now (Jones et al, 2005).

The
chosen area of study is the Clifton Marsh effluent along the River Ribble,
Preston, in the north west of England.

 

Figure 1 – The region of this
study, the Royal Preston Hospital, and the Clifton Marsh waste water treatment
plant, alongside the River Ribble, to which the effluent gets discharged.

NHS prescription drug data was analysed to calculate a predicted
environmental concentration (PEC) of the 3 chosen drugs of this study. Both
domestic and hospital consumption data was considered. Domestic consumption
consists of drugs prescribed to outpatients and consumed and excreted at home.
This is considered the major source for these PhACs in the aquatic environment.
Hospital consumption data consists of drugs given and ingested on Royal Preston
Hospital. 

Hermann et al, 2015 says that the main entry route for PhACs to enter the
environment is through treated waste water effluents. A study into the effect
of environmental pharmaceutical pollution was carried out by Brodin et al
(2013). In his study, the effect of the common benzodiazepine Oxazepam, on the
behaviour and feeding rate of wild European perch (Perca fluviatilis) was looked at. He found that individuals exposed
to the water, with dilute concentrations of the drug (1.8 micrograms litre–1),
exhibited increased activity, reduced sociality and higher feeding rate.

Brodin goes on to say how benzodiazepines and other PhACs are resistant
to photo degradation and continue to persist in the aquatic environment, often
passing through wastewater treatment plants without major losses and have been
found at concentrations ranging from 0.001 to 0.4 ug liter?1 in rivers and
streams. Benzodiazepines and other PhACs are designed to alter behaviour in
humans, by biding to y-aminobutyric acid (GABA) receptors. However, these
receptors are found in a wide range of animal species, so it is not bizarre to
expect other species to also undergo a behavioural change if exposed to these
drugs in treated waste water effluents, even in smaller quantities.

1.2.1 Drugs selected for this study

From 2015-2016 the usage of antidepressants increased by 6% (from 61
million to 64.7 million items. NHS Digital, 2017),
the largest growth of prescription drugs within the NHS. With this
massive increase in prescription and consumption there has been surprisingly
little research into the fate on these drugs once excreted from the human body
(via urine or faeces), and where they end up post waste water treatment works.

A wide range of
pharmaceuticals, including drugs that act on the nervous system, are being increasingly
reported in the environment and are hence of growing concern. Amitriptyline,
Carbamazepine and Temazepam are being prescribed in increasingly larger doses,
so a prediction of their environmental concentrations should be undertaken as
part of a risk assessment process. The information about these drugs, including
metabolism and biodegradation rates were all taken from research papers and
internet sources.

As seen in
Figure 2 all the drugs studies all exhibit similar chemical structures, all containing
a tricyclic ring, so may all show similar effects on marine biology exposed to
them.

1.2.2
Amitriptyline

Amitriptyline is
a dibenzocycloheptene-derivative tricyclic antidepressant, it contains a
tricyclic ring system with an alkyl amine substituent on the central ring,
(Drugbank.ca, 2017). In depressed individuals, amitriptyline causes a positive
increase in mood. Tricyclic antidepressants are potent inhibitors of serotonin
and norepinephrine reuptake, which is what causes the user to experience a
positive increase in mood. Amitriptyline is used to treat depression, chronic
pain, irritable bowel syndrome, and post-traumatic stress disorder.

1.2.3
Carbamazepine

Carbamazepine is
an anticonvulsant used to treat epilepsy and control seizures. It operated by
decreasing nerve impulses that cause seizures and pain, (https://www.drugs.com/carbamazepine.html) . Carbamazepine acts by inhibiting sustained firing
by block use-dependent sodium channels. Pain relief is believed to be
associated with blockade of synaptic transmission in the trigeminal nucleus.
Seizure control is associated with the reduction of post-tetanic potentiation
of synaptic transmission in the spinal cord (Drugbank, 2017).

 

 

1.2.4 Temazepam

Temazepam is a
Benzodiazepine that acts as a gamma-aminobutyric acid modulator and anti
anxiety agent (Drugbank, 2017). It acts by binding none specifically to
benzodiazepine receptors, causing muscle relaxation with an anticonvulsant
effect

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