Home' Australian Pharmacist : Australian Pharmacist September 2016 Contents Australian Pharmacist September 2016 I ©Pharmaceutical Society of Australia Ltd.
When this drug is used to get high,
there may also be unexpected
unpleasant signs and symptoms like
vomiting, weakness, headache, itching,
dry mouth, hives, chest pain, fainting,
hallucinations, seizures and tremors.
Moving into more elaborate
combinations – cocktails of medications
– a combination of chlorpromazine,
promethazine, meperidine and related
compounds was noted to have an
opioid-sparing effect. It allowed the use
of lower doses of opioids to achieve
sedation. However, in contemporary
practice, the use of a promethazine/
opioid combination for pre and
post-operative sedation has declined
since the 1950’s due to adverse effects and
lack of data supporting clinical efficacy.
Little is known about promethazine’s
abuse potential but, since it has
been reported to be present in fatal
opioid overdoses, abuse may occur
predominantly in combination with
opioids. Promethazine was identified
by post-mortem toxicology analysis in
25/176 (14.2%) of methadone toxicity
fatalities. Key informants in several
reports note that promethazine is use
by methadone maintenance patients to
potentiate the ‘high’ from methadone.
Promethazine may potentiate sedation
from opioids. Promethazine prolongs
the QT interval in electrocardiographic
measurement of the duration of the
repolarization of the heart. Prolongation
of the QT interval has been associated
with a potentially fatal, cardiac
arrhythmia called torsade de pointes.
Methadone also prolongs the QT
interval and appears to be associated
with torsade de pointes. Torsade de
pointes is a rare event in methadone
maintenance patients. There is an
increased risk to the patient if they have
any electrolyte abnormality, a personal
or family history of structural heart
disease, liver disease, or any other
medications that can prolong the
Cyclizine, an antihistamine, is used
(tablets and injectable solution) as an
antiemetic after surgery in Australia.
Injected in large intravenous doses
with methadone, the drug produces
hallucinations, intense stimulation,
aggression and seizures. Abuse has
occurred in teenagers and cancer patients.
Clonidine is a centrally acting
antihypertensive that eases opioid
withdrawal by decreasing sympathetic
responses. In excessive doses it causes
sedation, impairs consciousness and
seizures. Opioid abusers take it to lessen
opioid withdrawal, tolerate periods of
opioid scarcity, or for its euphoric or
psychotropic effects. It can be abused
alone or in combination with drugs
One third of all patients taking clonidine
believe that it possesses additive effects.
One addict insisted that it was better
to use clonidine than heroin because
clonidine failed to make him feel
sick afterward. Following an initial
experience with high-dose clonidine,
the man developed a behavioural
pattern to maximise his drug supply.
He established a method to have
two different pharmacies fill his
prescriptions. Because clonidine was
an atypical drug of abuse, it was easy to
persuade his physician to replace lost
prescriptions. When short of money
for illicit drugs, he used clonidine
to moderate withdrawal symptoms.
When he was unable to secure clonidine,
he increased his opiates and cocaine
usage. In a week he would use a month’s
supply of clonidine.
He was so satisfied with this system of
clonidine use that he introduced two of
his friends to this practice. He confessed
that these friends were now regular
high-dose clonidine users.
Cimetidine affects microsomal
enzymes and reduces the liver’s ability
to metabolise drugs, increasing their
bioavailability .It is particularly effective
in inhibiting the cytochrome P450
drug metabolizing system therefore
influencing the metabolism of other
drugs. It reduces liver blood flow and
the combination of effects on blood
flow and metabolism tend to decrease
the clearance of certain drugs including
caffeine, triazolam, chlordiazepoxide,
ethanol, diazepam, flurazepam and
alprazolam. By taking a high dose of
cimetidine (approximately 800 mg)
about three hours before methadone
or cocaine it strengthens or prolongs
Loperamide is a low-cost, OTC
antidiarrhoeal medication that inhibits
intestinal peristalsis via mu-opioid
receptor agonism, calmodulin inhibition,
calcium channel blockade and reduced
paracellular permeability. It was thought
that its poor oral systemic bioavailability
and CNS penetration (crossing the
blood-brain barrier) limited its potential
for abuse. To alleviate opioid withdrawal,
addicts have to take loperamide in
dosages of 70–100 mg/day (indicated
dose is 16 mg/day).
In addition to being an opioid,
loperamide is a cardiac toxin.
Two deaths have recently occurred.
Firstly a 24-year-old man with a history
of substance abuse who was discovered
in his home with seizure-like activity.
Six empty loperimide boxes were found.
CPR, naloxone and intubation proved
unsuccessful. A post-mortem autopsy
revealed pulmonary and cerebral
oedema, urinary retention, moderate
cardiomegaly and venous thrombi.
The concentration of loperamide in his
cardiac blood was 77 ng/ml (therapeutic
range 0.24–3.1 ng/ml).
The second was a 39-year-old man with
a history of opioid abuse. According
to the patient’s family, he had elected
to discontinue buprenorphine therapy
and began self-medicating with an
OTC antidiarrhoeal medication. Prior to
death he had collapsed while gasping
for breath. Asystole was identified by
emergency medical services but despite
CPR and resuscitative efforts, the man
was declared DOA. An autopsy revealed
cardiomegaly and severe pulmonary
oedema. His femoral
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